ABSTRACT
Malnutrition and sarcopenia are highly prevalent and robustly associated with reduced quality of life, disease progression, and poor outcomes, including complications and mortality, in patients with cirrhosis. Their pathophysiology is multifactorial, involving inadequate dietary intake and malabsorption, impaired liver functional reserves, altered energy, protein, and ammonia metabolism, systemic inflammation, hormonal dysregulation, and lifestyle or environmental influences. Despite extensive research, unresolved issues remain regarding optimal diagnostic criteria, as current approaches vary and lack global standardization. Regarding the diagnostic criteria for malnutrition, the usefulness of the Global Leadership Initiative on Malnutrition criteria has been proposed by international nutrition societies. However, evidence supporting their applicability in hepatology remains insufficient. For sarcopenia, differences in disease concept and diagnostic methods among societies indicate that no unified diagnostic standard exists, and clinicians should approach diagnosis with an understanding of the strengths and limitations of each method. Nutritional strategies emphasize adequate energy and protein intake, late evening snacks, and branched-chain amino acid supplementation, while deficiencies in micronutrients require tailored replacement. Nutritional therapy alone has limited effect on sarcopenia, but when combined with exercise it improves muscle mass, physical performance, and outcomes. Comprehensive approaches integrating optimized nutrition, micronutrient support, and structured exercise are essential to alleviate the burden of malnutrition and sarcopenia and to improve prognosis in patients with cirrhosis. This review addresses malnutrition and sarcopenia in cirrhosis by highlighting their prevalence, pathophysiology, clinical impact, and approaches for screening and diagnosis, and by emphasizing personalized nutritional, pharmacological, and exercise interventions to improve patient outcomes.
-
Keywords: Ammonia; Liver diseases; Exercise; Frailty; Liver cirrhosis
INTRODUCTION
Malnutrition is a clinical syndrome defined as an imbalance— whether a deficiency or an excess—of nutrients that results in measurable adverse effects on body tissues or morphology (including shape, size, and composition), physiological function, and/or clinical outcomes [
1]. The term malnutrition technically includes both overnutrition and malnutrition; however, in clinical hepatology and much of the literature, it is most commonly used to refer specifically to undernutrition. Malnutrition is common in cirrhosis, affecting about 20% of patients with compensated disease and over 50% with decompensated disease, due to impaired liver function, altered energy metabolism, and reduced dietary intake [
2-
5]. Importantly, malnutrition drives the development of sarcopenia, characterized by the progressive loss of skeletal muscle mass and strength, in 37.5% of patients with cirrhosis [
6-
10]. Malnutrition and sarcopenia are strongly linked to adverse outcomes in cirrhosis, including ascites, hepatic encephalopathy (HE), poor treatment response, and mortality [
8-
14]. Over the past decades, cirrhosis etiology has shifted from viral hepatitis to steatotic liver disease including metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with moderate alcohol consumption (MetALD), and alcohol-associated liver disease (ALD), where overnutrition is a key driver [
15-
21]. Sarcopenia and sarcopenic obesity, defined by the coexistence of sarcopenia and obesity, are known to play a pivotal role in the progression of steatotic liver disease [
22]. Despite this shift, malnutrition and sarcopenia remain the key determinants of prognosis in patients with cirrhosis [
23].
In this review, we focus on malnutrition and sarcopenia in cirrhosis. We provide an overview of the prevalence, underlying mechanisms, and clinical impact of malnutrition and sarcopenia, discuss validated tools for their screening and assessment, and highlight dietary, pharmacological, and exercise-based interventions aimed at improving patient outcomes.
PATHOPHYSIOLOGY OF MALNUTRITION AND SARCOPENIA IN CIRRHOSIS
Impaired nutrient intake and absorption
Malnutrition ultimately manifests as sarcopenia, creating a vicious cycle in which muscle loss reduces physical activity and nutrient intake, thereby further worsening nutritional decline [
9,
24]. The major factors contributing to malnutrition in cirrhosis are summarized in
Figure 1. One of the principal drivers of malnutrition in cirrhosis is impaired dietary intake and nutrient absorption due to several diseaserelated or treatment-related factors. In patients with ascites, abdominal distension and sodium restriction can contribute to decreased appetite and oral intake [
25]. Patients who develop HE with coma are unable to maintain oral intake, which further aggravates malnutrition. Nausea, gastrointestinal symptoms, and adverse effects of medications further suppress intake. Moreover, dysphagia reduces oral intake and worsens malnutrition [
26,
27]. Diuretics may cause electrolyte disturbances and dehydration, promoting anorexia, fatigue, and muscle loss [
28]. Lactulose frequently induces diarrhea and bloating, impairing nutrient absorption [
29]. Polypharmacy is common and increases the risk of adverse drug reactions, interactions, and poor adherence, which can impair nutrition, physical function, and muscle health, thereby contributing to sarcopenia [
30-
32]. Delayed gastric emptying leads to early satiety and postprandial discomfort [
25], while altered taste perception, associated with zinc deficiency, diminishes appetite and food palatability [
33-
35]. In addition, portal hypertension and cholestasis reduce fat absorption, leading to deficiencies of fat-soluble vitamins, while small intestinal bacterial overgrowth contributes to malabsorption [
36]. Especially, vitamin D deficiency is common and known to play an important role in fibrosis, to worsen sarcopenia, and to increase complications of cirrhosis [
37-
43]. Carnitine deficiency contributes to muscle weakness, fatigue, and impaired ammonia detoxification, worsening both sarcopenia and HE [
44-
48]. Socioeconomic factors such as poverty, limited healthcare access, and social isolation also contribute to malnutrition. Collectively, these multifactorial disturbances in intake, absorption, and nutrient metabolism create a burden of malnutrition that profoundly contributes to disease progression and adverse outcomes in cirrhosis.
Energy metabolism in cirrhosis is characterized by increased resting energy expenditure, reduced hepatic glycogen storage, a decrease in the nonprotein respiratory quotient (npRQ) reflecting enhanced fat oxidation, and an increased reliance on amino acids for gluconeogenesis [
49-
52]. Patients with cirrhosis enter a starvation state more rapidly than healthy individuals; indeed, after an overnight fast, their npRQ is comparable to that of healthy subjects after 2–3 days of fasting [
52]. These conditions promote severe catabolism, leading to sarcopenia, frailty, or even cachexia [
50,
53-
55]. Hyperammonemia further accelerates this process by disrupting the balance of muscle protein synthesis and degradation [
56-
58].
Branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) play a key role in muscle metabolism, while aromatic amino acids (AAAs: phenylalanine, tyrosine, and tryptophan) are primarily metabolized in the liver. In patients with cirrhosis, impaired protein metabolism leads to BCAA depletion and AAA accumulation, resulting in a reduced Fischer ratio or BCAA-to-tyrosine ratio, which has been linked to complications such as HE, hepatocellular carcinoma, acute kidney injury, and poor prognosis [
59-
64]. BCAAs serve as major substrates for energy production, ammonia detoxification, and protein synthesis, and their reduction limits albumin production and suppresses muscle protein synthesis via impaired mammalian target of rapamycin (mTOR) signaling [
59,
65,
66]. In fact, patients with cirrhosis and sarcopenia have lower serum BCAA levels than those without [
14]. In addition, decreased BCAAs and increased AAAs carry independent clinical significance in cirrhosis, serving as risk factors for complications such as hepatocellular carcinoma and acute kidney injury [
60,
63,
67]. Hyperammonemia depletes BCAAs through detoxification and disrupts muscle protein homeostasis by inducing myo-statin, which suppresses mTOR signaling and promotes autophagic proteolysis, and by activating the general control nonderepressible 2/eukaryotic initiation factor 2 alpha pathway, which inhibits protein synthesis [
56,
68-
70]. In addition, ammonia induces mitochondrial dysfunction, which impairs both protein synthesis and protein degradation [
71,
72]. The changes in energy utilization and amino acid metabolism observed in cirrhosis are collectively termed protein–energy malnutrition [
50]. In patients with cirrhosis, energy malnutrition (defined as an npRQ <0.85), protein malnutrition (serum albumin <3.5 g/dL), and protein–energy malnutrition, defined as their coexistence, were observed in 43%, 61%, and 27%, respectively [
73]. Given the high prevalence and notable involvement of malnutrition in cirrhosis, the interplay between altered energy metabolism, amino acid imbalance, and malnutrition constitutes a critical therapeutic target in the management of cirrhosis.
Alcohol is a major driver of steatohepatitis and has become a leading cause of cirrhosis. It promotes glucose intolerance through increased gluconeogenesis, enhanced glycogenolysis, and impaired insulin secretion [
74]. Alcohol also disrupts lipid metabolism by enhancing the release of free fatty acids, suppressing mitochondrial β-oxidation, and impairing triglyceride export, thereby promoting hepatic steatosis [
74]. In patients with ALD, energy–protein malnutrition is common, along with frequent deficiencies in vitamins, minerals, and trace elements [
74,
75]. Alcohol also contributes to sarcopenia by inducing nutrient deficiencies, suppressing protein synthesis via increased myostatin and impaired mTOR signaling, and enhancing muscle proteolysis through autophagy [
71,
76,
77]. Furthermore, alcohol-induced mitochondrial dysfunction reduces protein synthesis and promotes protein degradation [
78-
80]. A recent meta-analysis reported a higher prevalence of sarcopenia in patients with ALD than in those without [
10], and a retrospective study found that alcohol-associated cirrhosis was linked to more rapid muscle loss compared with viral etiologies [
81]. Overall, alcohol drives the development of sarcopenia in cirrhosis through metabolic derangements, nutrient deficiencies, and impaired protein homeostasis, leading to accelerated muscle loss and poorer outcomes.
Testosterone is an anabolic-androgenic steroid hormone that decreases glucocorticoid receptor expression and competes with cortisol [
82]. Low testosterone levels are frequently observed and are correlated with muscle mass and handgrip strength in male patients with cirrhosis [
83-
85]. Interestingly, a randomized controlled trial (RCT) including 101 male patients with cirrhosis has shown that testosterone therapy increases total lean mass relative to placebo [
86]. Furthermore, a recent retrospective study found that patients with testosterone therapy had lower mortality and decompensation rates than those without in patients with cirrhosis [
87]. Additionally, growth hormone resistance leads to reduced insulin-like growth factor-1 production, which in turn suppresses activation of the mTOR signaling pathway [
88]. Taken together, hormonal alterations such as testosterone deficiency and growth hormone resistance contribute to sarcopenia by reducing anabolic signaling, partly through impaired mTOR activation.
Systemic inflammation contributes to malnutrition and sarcopenia by increasing energy expenditure, driving muscle catabolism, and reducing the efficacy of nutritional therapy [
89]. Proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) promote muscle wasting by enhancing ubiquitin–proteasome activity, and their inhibition has been shown to prevent muscle loss in animal models [
90]. TNF-α activates the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, inducing the expression of muscle RING finger protein-1 and other atrophy-related genes that drive proteolysis [
91,
92]. In parallel, IL-6 activates the Janus kinase/signal transducer and activator of transcription 3 pathway, further promoting catabolism and muscle atrophy [
93]. In terms of muscle synthesis, elevated TNF-α leads to inhibition of the mTOR pathway through myostatin [
94,
95]. Elevated IL-6 levels have been associated with decline in muscle function assessed by the liver frailty index in patients with liver disease [
96], and serum endotoxin has also been linked to sarcopenia in alcohol-related cirrhosis [
97]. Excess adipose tissue enhances proinflammatory cytokine production, thereby amplifying the mechanisms that drive sarcopenia [
98]. Consequently, in patients with MASLD or MetALD, who typically present with higher body mass index, sarcopenia or sarcopenic obesity is a growing clinical concern [
99-
101].
Beyond systemic inflammatory pathways, alterations in the gut microbiota and disruption of gut permeability further aggravate inflammation in cirrhosis [
102]. Increased bacterial and endotoxin translocation activates immune responses, while gut dysbiosis disrupts the gut–liver–muscle axis, contributing to muscle wasting [
103-
108]. In a study including 50 patients with cirrhosis, those with sarcopenia had significantly reduced microbial diversity and a lower abundance of
Prevotella, Methanobrevibacter, and
Akkermansia than those without [
109]. Another study of 60 patients confirmed reduced Shannon index diversity in patients with sarcopenia and identified 17 microbial species with differential abundance, with
Escherichia coli, Peptostreptococcus stomatis, and
Bacteroides uniformis most strongly associated with muscle mass [
110]. Nevertheless, the causal role of dysbiosis in malnutrition and sarcopenia remains uncertain and warrants further investigation.
Figure 2 illustrates the major mechanisms by which cirrhosis promotes sarcopenia.
NUTRITIONAL SCREENING AND ASSESSMENT IN PATIENTS WITH CIRRHOSIS
Nutritional screening tools
Ideally, all patients with cirrhosis should undergo detailed nutritional assessment. Nutritional screening is the first step to identify patients at high risk of malnutrition who require further evaluation. Patients with impaired liver functional reserve, such as Child–Pugh class B/C, and/or low body mass index (BMI), are considered at high risk [
2]. When assessing BMI, fluid retention should be accounted for by estimating dry weight, subtracting 5% for mild, 10% for moderate, and 15% for severe ascites, with an additional 5% reduction if bilateral pedal edema is present [
2]. Validated screening tools provide a practical means of initial nutritional assessment, and these are summarized in
Table 1. The Royal Free Hospital-Nutritional Prioritizing Tool (RFHNPT) is a liver disease–specific tool with strong evidence, demonstrating good feasibility, applicability by non-specialist staff, and correlations with disease severity, complications, and survival [
111-
113]. When compared with the Global Leadership Initiative on Malnutrition (GLIM) criteria, its sensitivity and specificity range from 67 to 95% and 60 to 82%, respectively [
114-
117]. The Nutritional Risk Screening-2002, Mini Nutritional Assessment-Short Form, and Malnutrition Universal Screening Tool are also recommended in general practice [
118-
121]. In patients with cirrhosis, the Nutritional Risk Screening-2002 has shown sensitivities of 55–67% and specificities of 91–93%, and it is useful for short-term mortality stratification [
114-
116,
122]. The Mini Nutritional Assessment Short-Form demonstrated favorable sensitivity and specificity of 88% and 97%, respectively, for identifying malnutrition [
117]. For the Malnutrition Universal Screening Tool, the sensitivity for detecting malnutrition has been reported as 87%, whereas specificity was not available [
115]. Among these, the RFH-NPT has the strongest supporting evidence for cirrhosis, but the choice of tool should also consider generalizability to broader clinical practice.
The Subjective Global Assessment (SGA) is based on information obtained through a comprehensive nutritional evaluation [
123]. It includes an evaluation of five historical factors (changes in weight, dietary intake, gastrointestinal symptoms, functional capacity, and the impact of the disease on nutritional needs) and four physical examination findings (loss of subcutaneous fat, muscle wasting, ankle edema, sacral edema, and ascites) [
123]. Patients are classified into three categories: A, well-nourished; B, moderately malnourished; and C, severely malnourished [
123]. Reported prevalence in patients with cirrhosis is 65% for SGA-A, 33% for SGA-B, and 2% for SGA-C [
124]. The SGA has excellent reproducibility and is associated with outcomes such as hospitalization length and mortality [
2,
124,
125]. However, because it relies on subjective reporting, agreement with other nutritional assessment methods is low [
126]. Moreover, results in patients with liver disease are strongly influenced by factors such as edema, ascites, and impaired liver function, and should therefore be interpreted with caution.
The Royal Free Hospital-Global Assessment (RFH-GA) was developed to improve the reproducibility and validity of nutritional assessment in patients with liver disease by combining objective and subjective variables, thereby enhancing inter-observer agreement and correlations with body composition [
127]. The RFH-GA evaluates BMI, mid-arm muscle circumference (MAMC), and dietary intake, and classifies patients as adequately nourished, moderately malnourished, or severely malnourished [
127]. Reported prevalence in cirrhosis is 66%, 31%, and 3%, respectively, while among liver transplant candidates the corresponding rates are 53%, 38%, and 9% [
128,
129]. The RFH-GA demonstrates excellent reproducibility, correlates with total body protein and fat mass, and predicts mortality in patients with cirrhosis [
127-
129]. Furthermore, a recent study showed that its ability to predict sarcopenia was superior to that of the SGA [
128]. The RFH-GA is valued for its limited assessment items and improved objectivity; however, the requirement for MAMC calculations and the lack of well-established cutoff values restrict its wider clinical application.
To establish a universally accepted diagnostic framework, the GLIM criteria were introduced in 2018 by an international consortium of experts [
114-
116]. The GLIM criteria are a two-step model comprising screening and assessment. Any validated screening tool can be used, and individuals identified as at risk of malnutrition then undergo further assessment [
114-
116]. The assessment consists of five items: three phenotypic (non-volitional weight loss, low BMI, and reduced muscle mass) and two etiologic (reduced food intake or assimilation, and disease burden/inflammation) [
114-
116]. Malnutrition is diagnosed when at least one phenotypic and one etiologic criterion are present, and severity is classified according to weight loss, BMI, and muscle mass [
114-
116]. Recent studies show that malnutrition diagnosed with the GLIM criteria can predict short- and longterm mortality in patients with cirrhosis [
7,
130]. In addition, the GLIM criteria are useful for identifying sarcopenia, as muscle mass measurement is included as a phenotypic criterion [
7]. The prevalence of malnutrition is highly dependent on the screening tool and generally lower than that of other assessment tools such as SGA and RFH-GA [
7,
116,
131]. Because the GLIM criteria allow the use of different screening tools, methods for assessing muscle mass, and approaches to determine inflammation or disease burden, diagnostic uncertainty remains, and reproducibility has not been evaluated in patients with cirrhosis. In addition, several items of the GLIM criteria, such as the cutoff values for severity classification, have not been defined for Asian populations. Therefore, further validation studies and international collaborations are needed before the GLIM criteria can be adopted as a nutritional assessment tool. Taken together, the RFH-NPT is the most well-validated tool for screening malnutrition, and patients identified as being at risk should undergo further evaluation using assessment tools such as the SGA, RFH-GA, or GLIM criteria in clinical settings (
Fig. 3). Nutritional assessment tools are also summarized in
Table 1.
SCREENING AND ASSESSMENT OF SARCOPENIA IN PATIENTS WITH CIRRHOSIS
Sarcopenia screening tools
Although BMI is generally accepted as a marker for sarcopenia [
6], its predictive accuracy for estimating muscle mass cirrhosis is limited, particularly in those with fluid retention or obesity. Therefore, estimated dry weight should always be considered in decompensated cirrhosis, and the challenge of reliable assessment remains an unmet clinical need in the era of steatotic liver disease. The SARC-F scoring system is a self-reported questionnaire consisting of five items—strength, assistance with walking, rising from a chair, climbing stairs, and falls [
132]. In patients with cirrhosis, an SARC-F score ≥4 has been reported to predict muscle mass loss (sensitivity 81%, specificity 50%) and reduced handgrip strength (sensitivity 76%, specificity 71%) [
133]. In contrast, other studies in chronic liver disease have shown that an SARC-F score of ≥4 has low sensitivity but high specificity [
134-
136]. The finger-ring test is another simple screening method in which a participant forms a ring with their thumbs and index fingers and places it around the thickest part of the non-dominant calf while seated, classifying the calf as larger than, equal to, or smaller than the finger-ring circumference [
137]. In patients with chronic liver disease, the finger-ring test has been reported to help identify low muscle mass or sarcopenia [
138,
139]. However, due to limited robust evidence, further evaluation is required before the SARC-F and finger-ring test can be established as global screening tools for sarcopenia in cirrhosis. Sarcopenia screening tools are summarized in
Table 2.
In general population, sarcopenia has been defined by major societies such as the European Working Group on Sarcopenia in Older People (EWGSOP), the International Working Group on Sarcopenia, the Foundation for the National Institutes of Health, and the Asian Working Group for Sarcopenia (AWGS) [
140-
142]. Updated definitions emphasize muscle strength, with the EWGSOP2 identifying probable sarcopenia by low muscle strength, confirmed by low muscle quantity or quality, and severe sarcopenia when low physical performance is also present [
143]. The AWGS 2019 criteria recommend a screening step and define possible, definite, and severe sarcopenia based on combinations of strength, mass, and performance [
144]. The Sarcopenia Definitions and Outcomes Consortium excluded lean mass due to limited prognostic value and instead adopted low handgrip strength and gait speed as predictors of adverse outcomes [
145].
The diagnostic criteria of liver societies are based on the diagnostic methods for older adults in each region. Sarcopenia is recognized by the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) as a major component of malnutrition, primarily defined by reduced skeletal muscle mass [
2,
3]. Especially, the AASLD defines sarcopenia in cirrhosis primarily as the phenotypic loss of muscle mass, reflecting the fact that most studies have focused on muscle quantity rather than function, and uniquely distinguishes frailty as a separate concept characterized by decreased physiologic reserve and vulnerability, with physical frailty specifically reflecting impaired muscle function [
3]. Computed tomography (CT)-based skeletal muscle index at the level of L3 is considered the gold standard for muscle mass measurement, while magnetic resonance imaging, dual-energy X-ray absorptiometry, bioelectrical impedance analysis (BIA), and anthropometric measures such as MAMC may serve as alternatives [
2,
3,
146]. Both guidelines highlight the limitations of these methods, particularly fluid retention affecting dual-energy X-ray absorptiometry and BIA and the scarce evidence for magnetic resonance imaging [
2,
3]. Functional measures such as handgrip strength and gait speed are regarded as prognostic markers rather than primary diagnostic criteria, and frailty is distinguished as a separate but related concept [
2,
3]. In addition, phase angle measured by the BIA is introduced as a reliable method to estimate muscle mass in patients with fluid retention [
3,
147]. The guidelines also emphasize the importance of reas-sessment because sarcopenia status can rapidly change in patients with cirrhosis and severe condition [
2,
3]. The Japan Society of Hepatology (JSH) suggests simple diagnostic criteria in combination with handgrip strength and muscle mass in line with the AWGS criteria [
148,
149]. According to the JSH criteria, handgrip strength is measured first, and in patients with decreased grip strength, muscle mass is assessed using CT or BIA. Sarcopenia is then diagnosed when both reduced handgrip strength and decreased muscle mass are present [
148,
149]. Recent studies have demonstrated that handgrip strength is a stronger predictor of clinical outcomes than muscle mass, underscoring the importance of incorporating muscle function assessment into the diagnostic approach for sarcopenia in cirrhosis [
150-
152]. Therefore, measuring handgrip strength as an initial screening for sarcopenia, followed by a muscle mass measurement in those with low handgrip strength, is a reasonable approach to identify sarcopenia in clinical settings (
Fig. 3). The diagnostic criteria for sarcopenia are also summarized in
Table 2.
MEDICAL NUTRITION AND EXERCISE THERAPY IN PATIENTS WITH CIRRHOSIS
Optimizing calorie and protein intake
The fundamental principle of nutritional management in cirrhosis is to calculate energy requirements and optimize caloric intake. Indirect calorimetry with a metabolic cart is the gold standard for measuring resting energy expenditure, but its availability is limited; thus, predictive equations such as the Harris–Benedict equation are often used [
153]. Previous studies using indirect calorimetry have shown a total energy expenditure of 28–38 kcal/kg/day in cirrhosis [
154-
157], leading guidelines to recommend at least 35 kcal/kg/day based on estimated dry weight [
2,
3,
111,
158]. When oral intake is insufficient due to disease severity, enteral nutrition via tube feeding should be considered [
158]. In compensated cirrhosis with obesity, moderate calorie restriction can improve metabolism [
111]. However, calorie restriction in decompensated cirrhosis is not advisable because rapid weight loss may increase the risk of malnutrition, sarcopenia, and further decompensation. In fact, bariatric surgery is a promising method for weight loss, but is also associated with the risk of decompensation and mortality [
159]. In decompensated cirrhosis, an obesity paradox, demonstrating better survival in patients with obesity than those without, has been frequently observed [
160]. This phenomenon likely reflects the adverse impact of malnutrition and sarcopenia, which are common and prognostically significant in advanced cirrhosis, rather than a survival advantage of excess adiposity [
23]. Accordingly, appropriate caloric requirements should be carefully determined by comprehensively considering body composition and liver functional reserves.
Ammonia derived from dietary protein is normally detoxified in the liver and muscle, but impairment of the urea cycle and sarcopenia may reduce this capacity and increase the risk of HE in cirrhosis. Historically, protein restriction was commonly practiced in advanced diseases. However, an RCT in patients with overt HE showed no clinical benefit of a low-protein diet compared with a normal-protein diet, with greater protein breakdown in the low-protein group [
161]. In practice, worsening of HE due to excessive protein intake is rarely observed, whereas low protein intake is associated with HE deterioration [
162]. Accordingly, current guidelines recommend 1.2–1.5 g/kg/day of protein and up to 1.2– 2.0 g/kg/day in critically ill or postoperative patients [
2,
3,
163]. An RCT in patients with covert HE demonstrated that nutritional therapy (30–35 kcal/kg/day, 1.0–1.5 g/kg/day plantbased protein) improved covert HE and reduced progression to overt HE compared with no intervention [
164]. The source of protein, whether meat- or plant-based, is also an important factor. Plant-based proteins provide arginine to enhance urea synthesis and ammonia clearance, and are rich in fiber that promotes nitrogen excretion and colonic acidification through microbial fermentation [
165]. They also contain lower levels of methionine and tryptophan, thereby reducing neurotoxic metabolites that patients with cirrhosis cannot efficiently detoxify [
165]. A recent RCT reported that replacing one meat-based meal with a vegan or vegetarian meal reduced ammonia and improved metabolites linked to HE, with ammonia levels rising in the meat group but remaining stable in the plant-based groups [
166]. Although the role of protein quality has long been studied, definitive conclusions are lacking, and further evidence is needed to clarify the impact of protein sources on clinical outcomes in patients with cirrhosis [
163].
In patients with cirrhosis, reduced glycogen stores cause early fasting catabolism, so even a 12-hour fast increases fat and protein oxidation, gluconeogenesis, and muscle breakdown [
163]. Thus, late evening snacks (LESs) and fre-quent meals are recommended to shorten fasting periods and improve fuel metabolism [
167]. Previous studies typically provided LESs of 200–300 kcal, often as liquid nutrient formulas, carbohydrate-rich foods such as rice balls, or BCAAenriched mixtures [
168-
171]. An RCT showed that three months of LES supplementation increased total body protein compared with daytime supplementation, indicating benefits for nutritional status and sarcopenia [
172]. A meta-analysis of RCTs further demonstrated improvements in liver functional reserves and reductions in ascites and HE [
173], while a retrospective study showed that nocturnal BCAA-based LES was associated with improved survival [
174]. Overall, incorporating LES as part of daily caloric intake is considered essential in the nutritional management of cirrhosis.
Since diet alone cannot correct amino acid imbalance, decreased BCAA and increased AAA, BCAA supplementation is required in patients with cirrhosis [
175]. BCAAs enhance protein synthesis mainly via mTOR activation and by facilitating albumin translation through polypyrimidine tractbinding protein, which binds to albumin mRNA to facilitate its translation [
59]. An RCT demonstrated significant albumin increases with BCAA supplementation [
176], confirmed by a meta-analysis [
177]. Because BCAAs serve as nitrogen donors for ammonia detoxification, supplementation may improve hyperammonemia, HE, and sarcopenia [
178]. Meta-analyses confirmed benefits on ammonia and HE [
177,
179], though RCTs on sarcopenia showed mixed results [
180-
183]. Therefore, the therapeutic effect of BCAA supplementation alone on sarcopenia appears to be limited, whereas its efficacy is likely enhanced when combined with exercise [
184,
185]. BCAAs have also been implicated in suppressing hepatocarcinogenesis, partly through the improvement of insulin resistance, and a prospective observational study and an RCT have reported reduced incidence of hepatocellular carcinoma with BCAA supplementation [
62,
186]. Furthermore, an RCT has shown that BCAAs can reduce cirrhosis-related complications, and a prospective observational study has demonstrated their beneficial effect on mortality in cirrhosis [
62,
176]. Thus, partial replacement of daily protein intake with BCAAs may help prevent complications and improve outcomes in cirrhosis. However, as existing studies are heterogeneous and meta-analyses have not demonstrated consistent benefits beyond HE, further international evidence is required to clarify their effects.
Micronutrient and vitamin deficiencies are common and associated with hepatic dysfunction and complications of cirrhosis. Vitamin K deficiency should be considered in patients with impaired liver functional reserves or obstructive jaundice, and supplementation may be required, particularly in those with a bleeding tendency and prolonged prothrombin time [
2]. Vitamin D deficiency (serum 25-hydroxyvitamin D <20 ng/mL) is highly prevalent (64–92%) in cirrhosis and is linked to liver fibrosis, HE, and sarcopenia [
2,
40-
42]. Supplementation is therefore reasonable when serum levels fall below 20 ng/mL until concentrations exceed 30 ng/mL [
2]. Although evidence on outcome improvement remains inconclusive [
187], vitamin D is regarded as a fundamental component in the management of sarcopenia [
188], and small studies suggest benefits in improving muscle mass [
189,
190].
Patients with cirrhosis are prone to water-soluble vitamin deficiencies. Subclinical Wernicke’s encephalopathy is common, and thiamine (B1) supplementation should be given when suspected [
2,
3,
191]. Deficiencies of pyridoxine (B6), folate (B9), and cobalamin (B12) may develop rapidly due to reduced hepatic storage and can lead to symptoms such as peripheral neuropathy [
2,
3,
191]. Because vitamin status is difficult to assess and oral multivitamin supplementation is inexpensive and safe, routine multivitamin use can be a reasonable strategy.
Trace elements including zinc, cooper, and selenium are also important in the pathophysiology of cirrhosis [
34]. Zinc supplementation has been shown in RCTs to improve hyperammonemia and in meta-analyses to benefit HE [
192,
193]. Caution is required when administering zinc as it may induce copper deficiency and then induce anemia. In addition, copper deficiency is reported to increase infection and mortality [
194]. Selenium deficiency, with a prevalence of 24– 37%, has been linked to complications including myopathy, cardiomyopathy, infection, and HE [
163,
195,
196]. The role of trace element supplementation requires further study.
Carnitine deficiency is frequently observed in patients with cirrhosis. Carnitine supplementation has been shown in RCTs to reduce ammonia and improve covert HE [
46,
197,
198]. In addition, an RCT showed improvements in fatigue and frailty in patients with overt HE [
199]. Retrospective studies also suggest benefits for muscle preservation and survival, suggesting the potential of carnitine supplementation in patients with cirrhosis [
44,
45,
48]. Regulatory status varies across countries, as carnitine may be available as a dietary supplement or as a prescription drug. Because most trials were conducted by a single group, further well-designed RCTs are needed [
200].
The effectiveness of nutritional therapy alone in improving sarcopenia is limited, and combining it with exercise therapy is essential. Current consensus supports a combination of aerobic and resistance training, as aerobic exercise improves muscular endurance and cardiopulmonary fitness, while resistance training enhances muscle mass and strength [
3]. A recent meta-analysis of RCTs showed that exercise significantly improved 6-minute walking distance and reduced serious events, including death and cirrhosisrelated complications [
201]. Another meta-analysis demonstrated that exercise increased muscle mass compared with controls [
202]. Importantly, exercise therapy was safe and improved physical performance even in patients with Child– Pugh class B/C, who were previously discouraged from active exercise [
203-
205]. Therefore, integrating exercise with nutritional therapy is recommended to maximize therapeutic benefit in patients with cirrhosis. Interventions for malnutrition and sarcopenia are summarized in
Table 3.
Although pharmacological intervention for malnutrition and sarcopenia is challenging, several investigational approaches are emerging. Ghrelin receptor agonists, such as anamorelin, have demonstrated appetite-stimulating and anabolic effects, offering potential therapeutic benefits for malnutrition [
206]. Emerging agents targeting sarcopenia include myostatin inhibitors and activin receptor antagonists that enhance muscle growth [
207], and growth differentiation factor-15 antibodies that mitigate inflammation-related muscle wasting [
208]. Mitochondrial-targeted antioxidants such as elamipretide may also improve energy metabolism and muscle function [
209]. Further clinical trials are warranted to unveil the benefits of these therapies on malnutrition and sarcopenia.
FUTURE CHALLENGES
Malnutrition and sarcopenia in cirrhosis have been well studied, and strong evidence links them to adverse outcomes. However, several challenges remain. Diagnostic criteria vary across societies, and although comprehensive multimodal assessment is recommended, no global standard exists. Establishing internationally accepted criteria for diagnosis and treatment initiation is urgently needed. With the rising prevalence of MASLD, MetALD, and ALD, the applicability of conventional thresholds has been questioned, particularly since obesity may paradoxically confer survival benefits in patients with poor liver functional reserves, complicating weight reduction while preserving muscle mass. Further evidence is needed for nutritional and exercise therapy. In addition, simple evaluation tools and reliable biomarkers are lacking, and treatment recommendations differ across countries, partly due to regional variation in RCTs. Therefore, treatment should be selected based on regional evidence, insurance coverage, and recommendations from local guidelines. Adherence to nutrition and exercise programs is another critical barrier; thus, strategies such as home-based approaches and wearable devices for monitoring and support are warranted. Combining behavioral therapy may improve adherence to dietary and exercise interventions [
210,
211]. Given the gap between evidence and clinical practice, further research and international collaborations are required to enhance screening, assessment, and treatment of malnutrition and sarcopenia to improve cirrhosis care based on robust evidence.
FOOTNOTES
-
Authors’ contributions
T.M., M.S., and B.S. contributed to the conception and design of the review. T.M. performed the literature search. T.M. and M.S. wrote the first draft of the manuscript. B.S. critically reviewed and edited the manuscript. All authors read and approved the final manuscript.
-
Acknowledgements
This study was supported by a Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (grant number JP24K18908). This study was supported by services provided by NIH center P30 DK120515. Figures were created with a license from BioRender.com.
-
Conflicts of Interest
B.S. has been consulting for Boehringer Ingelheim Pharma, Mabwell Therapeutics and Surrozen (prior 24 months). B.S.’s institution UC San Diego has received research support from Axial Biotherapeutics, ChromoLogic, CymaBay Therapeutics, Intercept Pharmaceuticals and Prodigy Biotech (prior 24 months). B.S. is founder of Nterica Bio. UC San Diego has filed several patents with B.S. as inventor related to this work. All other authors declare that they have no conflict of interest.
Figure 1.Causes of malnutrition in patients with cirrhosis. Malnutrition in cirrhosis results from a complex interplay of impaired nutrient intake, altered digestion and absorption, metabolic abnormalities, medications, and disease-related complications. GI, gastrointestinal; SIBO, small intestinal bacterial overgrowth.
Figure 2.Mechanism of sarcopenia in patients with cirrhosis. Cirrhosis is characterized by hyperammonemia and reduced levels of BCAAs due to malnutrition. Hyperammonemia suppresses mTOR signaling and promotes autophagy through the GCN2/eIF2α pathway and via myostatin. Together with alcohol and inflammation, hyperammonemia also induces mitochondrial dysfunction, leading to impaired protein synthesis and enhanced protein degradation. Depletion of BCAAs, IGF-1, and testosterone, further inhibits mTOR activity and diminishes protein synthesis. Moreover, leaky gut and adiposity contribute to systemic inflammation, and pro-inflammatory cytokines increase myostatin expression and activate catabolic pathways, ultimately exacerbating sarcopenia. BCAA, branched-chain amino acid; eIF2α, eukaryotic initiation factor 2 alpha; GCN2, general control nonderepressible 2; IGF-1, insulin-like growth factor 1; IL-6, interleukin-6; JAK, Janus kinase; mTOR, mechanistic target of rapamycin; MuRF-1, muscle RING finger protein 1; NF-κB, nuclear factor kappa-lightchain-enhancer of activated B cells; STAT, signal transducer and activator of transcription; TNF-α, tumor necrosis factor alpha.
Figure 3.Practical strategy for screening, diagnosis, and treatment of malnutrition and sarcopenia in patients with cirrhosis. Malnutrition should be screened using the RFH-NPT, and patients identified as at risk should undergo further evaluation with comprehensive nutritional assessment tools. Although screening tools for sarcopenia remain insufficiently validated, handgrip strength is a simple and practical measure, and individuals with reduced strength should be further assessed for muscle mass. Finally, a multifaceted treatment approach— including dietary modification, late-evening snacks, branched-chain amino acids, micronutrient supplementation, hormonal therapy, ammonia-lowering therapy, and exercise interventions—should be implemented according to the underlying pathophysiology. BCAA, branched-chain amino acid; BIA, bioelectrical impedance analysis; CT, computed tomography; DEXA, dual-energy X-ray absorptiometry; RFH-GA, Royal Free Hospital-Global Assessment; RFH-NPT, Royal Free Hospital-Nutritional Prioritizing Tool; SGA, Subjective Global Assessment.
Table 1.Nutritional screening and assessment tools
Table 1.
|
Nutritional screening and assessment tools |
Included variables |
Key characteristics and strengths |
Limitations and weaknesses |
|
Screening tools |
|
|
|
|
RFH-NPT |
• Disease condition |
• Developed for liver disease |
• Limited applicability outside liver disease |
|
• Fluid retention |
• Short time assessment |
• Relatively complex and requires training |
|
• BMI |
• Ability to identify malnutrition |
|
|
• Weight change |
• Ability to predict complications |
|
|
• Dietary intake |
• Ability to predict mortality |
|
|
NRS-2002 |
• Age |
• Developed for hospital setting |
• Age adjustment required |
|
• Disease condition |
• Two step screening |
• Does not consider fluid retention |
|
• BMI |
• Evidence in various diseases |
|
|
• Weight change |
• Ability to identify malnutrition |
|
|
• Dietary intake |
• Ability to predict mortality |
|
|
• Moderate reproducibility |
|
|
MUST |
• Disease condition |
• Developed for community setting |
• Limited evidence in patients with cirrhosis |
|
• BMI |
• Evidence in various diseases |
• Does not consider fluid retention |
|
• Weight change |
• High reproducibility |
• Difficult to reflect disease severity |
|
• Dietary intake |
|
|
|
MNA-SF |
• Morbidity |
• Developed for home-care setting |
• Limited evidence in patients with cirrhosis |
|
• Disease condition |
• Evidence in various diseases |
• Does not consider fluid retention |
|
• Neuropsychological problems |
• Ability to identify malnutrition |
• Contains many subjective components |
|
• BMI |
• Moderate reproducibility |
|
|
• Weight change |
|
|
|
• Dietary intake |
|
|
|
• Calf circumference |
|
|
|
Assessment tools |
|
|
|
|
SGA |
• Morbidity |
• Use subjective assessment |
• Not quantitative |
|
• Disease condition |
• No equipment required |
• Lack independency with liver functional reserves |
|
• Weight change |
• Ability to predict mortality |
• Low agreement with other nutritional measures |
|
• Dietary intake |
• High reproducibility |
• Preferably performed by trained personnel |
|
• Subcutaneous fat mass |
|
|
|
• Muscle mass |
|
|
|
• Fluid retention |
|
|
|
RFH-GA |
• BMI |
• Developed for liver disease |
• MAMC requires calculation |
|
• MAMC |
• Ability to predict mortality |
• Reference values of MAMC is not standardized |
|
• Dietary intake |
• High reproducibility |
|
|
• Includes objective indicators of body composition |
|
|
GLIM criteria |
• BMI |
• Developed as a global consensus |
• Limited evidence in patients with cirrhosis |
|
• Weight change |
• Two step approach including screening and assessment |
• Muscle mass assessment limits practicality |
|
• Muscle mass |
• Includes objective indicators of body composition |
• Uncertain determination of inflammation/disease burden |
|
• Dietary intake |
• Ability to predict mortality |
• Uncertain cutoff values for Asian population |
|
• Inflammation/disease burden |
|
• Diagnosis differs according to the screening tool |
Table 2.Sarcopenia screening tools and diagnostic criteria
Table 2.
|
Screening tools and diagnostic criteria for sarcopenia |
Included variables |
Key characteristics and strengths |
Limitations and weakness |
Cutoff values |
|
Screening tools |
|
|
|
|
|
SARC-F |
• Strength |
• A self-reported questionnaire |
• Limited evidence in patients with cirrhosis |
• Sarcopenia: SARC-F ≥4 |
|
• Assistance with walking |
• No equipment required |
• Low sensitivity |
|
|
• Rising from a chair |
• High specificity |
|
|
|
• Climbing stairs |
|
|
|
|
• Falls |
|
|
|
|
Finger-ring test |
• Calf circumference using a finger-ring |
• No equipment required |
• Limited evidence in patients with cirrhosis |
• Calf circumference compared to finger-ring: Male, just-fits and smaller; female, smaller |
|
Diagnostic criteria for older people |
|
|
|
|
|
EWGSOP2 |
• Muscle strength |
• Developed for European older people |
• Developed for European older people |
• Handgrip strength: Male <27 kg; female <16 kg |
|
• Muscle mass or quality |
• Validated in various populations |
• Cutoffs may not apply to Asians |
• ASMI: Male <7.0 kg/m²; female <5.5 kg/m² |
|
• Physical performance |
• Accepts various methods for assessment |
|
• Gait speed <0.8 m/s |
|
• Defines severe sarcopenia |
|
• 5-time chair stand test ≥12 s |
|
|
|
• Short physical performance battery ≤9 |
|
AWGS 2019 |
• Screening for sarcopenia |
• Developed for Asian older people |
• Developed for Asian older people |
• Handgrip strength: Male <28 kg; female <18 kg |
|
• Muscle strength |
• Validated in various populations |
• Limited data in liver disease |
• ASMI (DEXA): Male <7.0 kg/m²; female <5.4 kg/m² |
|
• Physical performance |
• Includes screening and diagnosis |
|
• ASMI (BIA): Male <7.0 kg/m²; female <5.7 kg/m² |
|
• Muscle mass |
• Defines severe sarcopenia |
|
• Gait speed <1.0 m/s |
|
SDOC |
• Handgrip strength |
• Developed by the global experts |
• Excluded muscle mass |
• Handgrip strength: Male <35.5 kg; female <20 kg |
|
• Gait speed |
• Included independent factors for health-related outcomes |
• Validated mainly in North America |
• Gait speed <0.8 m/s |
|
• Excluded assessment of muscle mass |
• Limited data in liver disease |
|
|
Diagnostic criteria for patients with cirrhosis |
|
|
|
|
|
EASL |
• Muscle mass |
• Summarized for patients with cirrhosis |
• No cutoff values for functional measures |
• SMI (CT): Male <50 cm²/m²; female <39 cm²/m² |
|
• Handgrip strength as supportive |
• Accepts various methods for assessment |
|
|
|
• Frailty measures as supportive |
• Recommends reassessment |
|
|
|
AASLD |
• Muscle mass |
• Divides sarcopenia with frailty |
• No cutoff values for functional measures |
• SMI (CT): Male <50 cm²/m²; female <39 cm²/m² |
|
• Also recommends frailty assessment |
• Evidence mainly in transplant candidates |
|
|
• Accepts various methods for assessment |
|
|
|
• Recommends reassessment |
|
|
|
JSH |
• Handgrip strength |
• Developed for liver disease |
• Limited evidence outside Japan |
• Handgrip strength: Male <28 kg; female <18 kg |
|
• Muscle mass |
• Explicit diagnostic criteria |
|
• SMI (CT) : Male <42 cm²/m²; female <38 cm²/m² |
|
|
|
• ASMI (BIA): Male <7.0 kg/m²; female <5.7 kg/m² |
Table 3.Interventions for malnutrition and sarcopenia
Table 3.
|
Interventions for malnutrition and sarcopenia |
Characteristics |
Evidence and strength |
Limitations and weakness |
|
Optimizing calorie and protein intake |
• Calorie intake: 35 kcal/kg/day |
• Fundamental treatment with high-protein requirement even with hepatic encephalopathy |
• Poor appetite and ascites reduce intake |
|
• Protein intake: 1.2–1.5 g/kg/day and up to 1.2–2.0 g/kg/day in critically ill or postoperative patients |
• Low cost and widely applicable |
• Difficult balance in obesity |
|
• Oral or enteral feeding with multiple small meals |
• Improved sarcopenia measures and hepatic encephalopathy in RCT |
|
Late evening snack |
• Oral carbohydrate and/or protein before sleep to prevent overnight catabolism |
• Low cost and widely applicable |
• Long-term continuation and patient engagement |
|
• Improved total body protein in RCT |
• Risk of hyperglycemia |
|
• Improved survival in retrospective study |
• Limited evidence on survival |
|
BCAA supplementation |
• Oral BCAA granules or enteral formulas |
• Improved event free survival, serum albumin levels, and HRQOL in RCT |
• Long-term continuation and patient engagement |
|
• Improved hepatic encephalopathy in meta-analysis |
• Limited evidence on survival |
|
• Reduced hepatocellular carcinoma in prospective observational study |
• Controversial results for sarcopenia in RCTs |
|
• Evidence mainly from Japan |
|
• Availability vary according to country |
|
Zinc supplementation |
• Zinc deficiency causes taste loss, anorexia, and hyperammonemia |
• Improved hyperammonemia in RCT |
• Limited numbers of RCTs |
|
• Improved hepatic encephalopathy in meta-analysis |
• Limited evidence on survival |
|
• Oral or intravenous supplementation |
• Possible gastrointestinal symptoms and copper deficiency |
|
Vitamin D supplementation |
• Vitamin D deficiency is associated with osteoporosis and sarcopenia |
• Improved sarcopenia in RCT |
• Limited evidence in meta-analysis |
|
• Recommended oral supplementation in patients with vitamin D levels <20 ng/mL |
• Improved bone mineral density in RCT |
• Limited evidence on survival |
|
• Risk of hypercalcemia |
|
Carnitine supplementation |
• Oral or intravenous levocarnitine supplementation |
• Improved hepatic encephalopathy in RCT |
• Limited evidence in meta-analysis |
|
• Improved muscle mass and survival in a retrospective study |
• Limited evidence on survival |
|
• Evidence mainly from Italy |
|
• Cost and insurance vary by country |
|
Exercise therapy |
• Includes aerobic, resistance, and combined training |
• Low cost and widely applicable |
• Long-term continuation and patient engagement |
|
• Frequency: 3–5 sessions/week |
• RCTs and meta-analyses demonstrated sarcopenia improvements |
• Lack of standardized protocols for liver disease |
|
• Intensity adjusted to fatigue and tolerance |
• Consideration of safety in patients with decompensation |
|
• Limited evidence on survival |
Abbreviations
American Association for the Study of Liver Diseases
alcohol-associated liver disease
Asian Working Group for Sarcopenia
branched-chain amino acid
bioelectrical impedance analysis
European Association for the Study of the Liver
European Working Group on Sarcopenia in Older People
Global Leadership Initiative on Malnutrition
Japan Society of Hepatology
metabolic dysfunction-associated steatotic liver disease with moderate alcohol consumption
mid-arm muscle circumference
mammalian target of rapamycin
nonprotein respiratory quotient
randomized controlled trial
Royal Free Hospital-Global Assessment
Royal Free Hospital-Nutritional Prioritizing Tool
Subjective Global Assessment
tumor necrosis factor alpha
REFERENCES
- 1. Lochs H, Allison SP, Meier R, Pirlich M, Kondrup J, Schneider S, et al. Introductory to the ESPEN Guidelines on enteral nutrition: terminology, definitions and general topics. Clin Nutr 2006;25:180-186.
- 2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol 2019;70:172-193.
- 3. Lai JC, Tandon P, Bernal W, Tapper EB, Ekong U, Dasarathy S, et al. Malnutrition, frailty, and sarcopenia in patients with cirrhosis: 2021 Practice Guidance by the American Association for the study of liver diseases. Hepatology 2021;74:1611-1644.
- 4. Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, et al. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol 2021;56:593-619.
- 5. Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2020. Hepatol Res 2021;51:725-749.
- 6. Hanai T, Shiraki M, Nishimura K, Ohnishi S, Imai K, Suetsugu A, et al. Sarcopenia impairs prognosis of patients with liver cirrhosis. Nutrition 2015;31:193-199.
- 7. Miwa T, Hanai T, Nishimura K, Unome S, Maeda T, Ogiso Y, et al. Usefulness of the Global Leadership Initiative on Malnutrition criteria to predict sarcopenia and mortality in patients with chronic liver disease. Hepatol Res 2022;52:928-936.
- 8. Tandon P, Montano-Loza AJ, Lai JC, Dasarathy S, Merli M. Sarcopenia and frailty in decompensated cirrhosis. J Hepatol 2021;75 Suppl 1:S147-S162.
- 9. Bunchorntavakul C, Reddy KR. Review article: malnutrition/sarcopenia and frailty in patients with cirrhosis. Aliment Pharmacol Ther 2020;51:64-77.
- 10. Tantai X, Liu Y, Yeo YH, Praktiknjo M, Mauro E, Hamaguchi Y, et al. Effect of sarcopenia on survival in patients with cirrhosis: a meta-analysis. J Hepatol 2022;76:588-599.
- 11. Tapper EB, Zhao L, Nikirk S, Baki J, Parikh ND, Lok AS, et al. Incidence and bedside predictors of the first episode of overt hepatic encephalopathy in patients with cirrhosis. Am J Gastroenterol 2020;115:2017-2025.
- 12. Schleicher EM, Kaps L, Schattenberg JM, Galle PR, Wörns MA, Gairing SJ, et al. Higher scores in the Clinical Frailty Scale are associated with covert and overt hepatic encephalopathy in patients with cirrhosis. Dig Liver Dis 2024;56:1046-1053.
- 13. Nardelli S, Lattanzi B, Merli M, Farcomeni A, Gioia S, Ridola L, et al. Muscle alterations are associated with minimal and overt hepatic encephalopathy in patients with liver cirrhosis. Hepatology 2019;70:1704-1713.
- 14. Hanai T, Shiraki M, Watanabe S, Kochi T, Imai K, Suetsugu A, et al. Sarcopenia predicts minimal hepatic encephalopathy in patients with liver cirrhosis. Hepatol Res 2017;47:1359-1367.
- 15. Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol 2023;79:1542-1556.
- 16. Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology 2023;78:1966-1986.
- 17. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASDEASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 2024;81:492-542.
- 18. Tokushige K, Ikejima K, Ono M, Eguchi Y, Kamada Y, Itoh Y, et al. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020. J Gastroenterol 2021;56:951-963.
- 19. Tokushige K, Ikejima K, Ono M, Eguchi Y, Kamada Y, Itoh Y, et al. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020. Hepatol Res 2021;51:1013-1025.
- 20. Enomoto H, Akuta N, Hikita H, Suda G, Inoue J, Tamaki N, et al. Etiological changes of liver cirrhosis and hepatocellular carcinoma-complicated liver cirrhosis in Japan: updated nationwide survey from 2018 to 2021. Hepatol Res 2024;54:763-772.
- 21. Huang DQ, Terrault NA, Tacke F, Gluud LL, Arrese M, Bugianesi E, et al. Global epidemiology of cirrhosis - aetiology, trends and predictions. Nat Rev Gastroenterol Hepatol 2023;20:388-398.
- 22. Lee YH, Jung KS, Kim SU, Yoon HJ, Yun YJ, Lee BW, et al. Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: nationwide surveys (KNHANES 2008-2011). J Hepatol 2015;63:486-493.
- 23. Endo K, Kakisaka K, Abe T, Yusa K, Nakaya I, Watanabe T, et al. Positive impact of obesity on the prognosis of liver cirrhosis. J Gastroenterol Hepatol 2024;39:1663-1672.
- 24. Ebadi M, Bhanji RA, Mazurak VC, Montano-Loza AJ. Sarcopenia in cirrhosis: from pathogenesis to interventions. J Gastroenterol 2019;54:845-859.
- 25. Aqel BA, Scolapio JS, Dickson RC, Burton DD, Bouras EP. Contribution of ascites to impaired gastric function and nutritional intake in patients with cirrhosis and ascites. Clin Gastroenterol Hepatol 2005;3:1095-1100.
- 26. Fujishima I, Fujiu-Kurachi M, Arai H, Hyodo M, Kagaya H, Maeda K, et al. Sarcopenia and dysphagia: position paper by four professional organizations. Geriatr Gerontol Int 2019;19:91-97.
- 27. Miwa T, Hanai T, Hayashi I, Hirata S, Nishimura K, Unome S, et al. Dysphagia risk evaluated by the Eating Assessment Tool-10 is associated with health-related quality of life in patients with chronic liver disease. Nutrition 2024;124:112440.
- 28. Hanai T, Shiraki M, Miwa T, Watanabe S, Imai K, Suetsugu A, et al. Effect of loop diuretics on skeletal muscle depletion in patients with liver cirrhosis. Hepatol Res 2019;49:82-95.
- 29. Sidhu SS, Goyal O, Parker RA, Kishore H, Sood A. Rifaximin vs. lactulose in treatment of minimal hepatic encephalopathy. Liver Int 2016;36:378-385.
- 30. Milton JC, Hill-Smith I, Jackson SH. Prescribing for older people. Bmj 2008;336:606-609.
- 31. Pana A, Sourtzi P, Kalokairinou A, Velonaki VS. Sarcopenia and polypharmacy among older adults: a scoping review of the literature. Arch Gerontol Geriatr 2022;98:104520.
- 32. Hanai T, Nishimura K, Miwa T, Maeda T, Imai K, Suetsugu A, et al. Prevalence, association, and prognostic significance of polypharmacy and sarcopenia in patients with liver cirrhosis. JGH Open 2023;7:208-214.
- 33. Madden AM, Bradbury W, Morgan MY. Taste perception in cirrhosis: its relationship to circulating micronutrients and food preferences. Hepatology 1997;26:40-48.
- 34. Kodama H, Tanaka M, Naito Y, Katayama K, Moriyama M. Japan’s practical guidelines for zinc deficiency with a particular focus on taste disorders, inflammatory bowel disease, and liver cirrhosis. Int J Mol Sci 2020;21:2941.
- 35. Miwa T, Hanai T, Toshihide M, Ogiso Y, Imai K, Suetsugu A, et al. Zinc deficiency predicts overt hepatic encephalopathy and mortality in liver cirrhosis patients with minimal hepatic encephalopathy. Hepatol Res 2021;51:662-673.
- 36. Kaplan MM, Elta GH, Furie B, Sadowski JA, Russell RM. Fat-soluble vitamin nutriture in primary biliary cirrhosis. Gastroenterology 1988;95:787-792.
- 37. Petta S, Cammà C, Scazzone C, Tripodo C, Di Marco V, Bono A, et al. Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. Hepatology 2010;51:1158-1167.
- 38. Abramovitch S, Dahan-Bachar L, Sharvit E, Weisman Y, Ben Tov A, Brazowski E, et al. Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut 2011;60:1728-1737.
- 39. Ding N, Yu RT, Subramaniam N, Sherman MH, Wilson C, Rao R, et al. A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Cell 2013;153:601-613.
- 40. Triantos C, Aggeletopoulou I, Thomopoulos K, Mouzaki A. Vitamin D-liver disease association: biological basis and mechanisms of action. Hepatology 2021;74:1065-1073.
- 41. Okubo T, Atsukawa M, Tsubota A, Yoshida Y, Arai T, Iwashita AN, et al. Relationship between serum vitamin D level and sarcopenia in chronic liver disease. Hepatol Res 2020;50:588-597.
- 42. Miwa T, Hanai T, Hirata S, Nishimura K, Sahashi Y, Unome S, et al. Vitamin D deficiency stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis: a retrospective cohort study. Clin Nutr ESPEN 2024;63:267-273.
- 43. Koyano K, Atsukawa M, Tsubota A, Kondo C, Miwa T, Namisaki T, et al. Association between laboratory values and covert hepatic encephalopathy in patients with liver cirrhosis: a multicenter, retrospective study. J Clin Med 2025;14:1858.
- 44. Ohara M, Ogawa K, Suda G, Kimura M, Maehara O, Shimazaki T, et al. L-carnitine suppresses loss of skeletal muscle mass in patients with liver cirrhosis. Hepatol Commun 2018;2:906-918.
- 45. Hiramatsu A, Aikata H, Uchikawa S, Ohya K, Kodama K, Nishida Y, et al. Levocarnitine use is associated with improvement in sarcopenia in patients with liver cirrhosis. Hepatol Commun 2019;3:348-355.
- 46. Shiraki M, Shimizu M, Moriwaki H, Okita K, Koike K. Carnitine dynamics and their effects on hyperammonemia in cirrhotic Japanese patients. Hepatol Res 2017;47:321-327.
- 47. Hanai T, Shiraki M, Imai K, Suetugu A, Takai K, Shimizu M. Usefulness of carnitine supplementation for the complications of liver cirrhosis. Nutrients 2020;12:1915.
- 48. Miwa T, Hanai T, Nishimura K, Sakai Y, Imai K, Suetsugu A, et al. Survival benefit of l-carnitine supplementation in patients with cirrhosis. JPEN J Parenter Enteral Nutr 2022;46:1326-1334.
- 49. Johnson TM, Overgard EB, Cohen AE, DiBaise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract 2013;28:15-29.
- 50. Moriwaki H, Miwa Y, Tajika M, Kato M, Fukushima H, Shiraki M. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem Biophys Res Commun 2004;313:405-409.
- 51. Tajika M, Kato M, Mohri H, Miwa Y, Kato T, Ohnishi H, et al. Prognostic value of energy metabolism in patients with viral liver cirrhosis. Nutrition 2002;18:229-234.
- 52. Mozzoli MA, Moctezuma J, Paul P, et al. Nature and quantity of fuels consumed in patients with alcoholic cirrhosis. J Clin Invest 1983;72:1821-1832.
- 53. Ebadi M, Tandon P, Moctezuma-Velazquez C, Ghosh S, Baracos VE, Mazurak VC, et al. Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis. J Hepatol 2018;69:608-616.
- 54. Miwa T, Suda G, Tateishi R, Hanai T, Ohara M, Hagiwara Y, et al. Cachexia is an independent predictor of mortality in patients with cirrhosis. Hepatol Res 2025;55:859-867.
- 55. Miwa T, Suda G, Tateishi R, Hanai T, Ohara M, Hagiwara Y, et al. Cachexia and type 2 diabetes mellitus are independent factors for mortality in patients with cirrhosis. Hepatol Res 2025;55:1557-1558.
- 56. Jindal A, Jagdish RK. Sarcopenia: Ammonia metabolism and hepatic encephalopathy. Clin Mol Hepatol 2019;25:270-279.
- 57. Gallego-Durán R, Hadjihambi A, Ampuero J, Rose CF, Jalan R, Romero-Gómez M. Ammonia-induced stress response in liver disease progression and hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2024;21:774-791.
- 58. Ferrer M, Anthony TG, Ayres JS, Biffi G, Brown JC, Caan BJ, et al. Cachexia: a systemic consequence of progressive, unresolved disease. Cell 2023;186:1824-1845.
- 59. Kawaguchi T, Izumi N, Charlton MR, Sata M. Branchedchain amino acids as pharmacological nutrients in chronic liver disease. Hepatology 2011;54:1063-1070.
- 60. Miwa T, Utakata Y, Hanai T, Aiba M, Unome S, Imai K, et al. Acute kidney injury development is associated with mortality in Japanese patients with cirrhosis: impact of amino acid imbalance. J Gastroenterol 2024;59:849-857.
- 61. Fischer JE, Yoshimura N, Aguirre A, James JH, Cummings MG, Abel RM, et al. Plasma amino acids in patients with hepatic encephalopathy. Effects of amino acid infusions. Am J Surg 1974;127:40-47.
- 62. Kawaguchi T, Shiraishi K, Ito T, Suzuki K, Koreeda C, Ohtake T, et al. Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis. Clin Gastroenterol Hepatol 2014;12:1012-1018 e1.
- 63. Stepien M, Duarte-Salles T, Fedirko V, Floegel A, Barupal DK, Rinaldi S, et al. Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: findings from a prospective cohort study. Int J Cancer 2016;138:348-360.
- 64. Kinny-Köster B, Bartels M, Becker S, Scholz M, Thiery J, Ceglarek U, et al. Plasma amino acid concentrations predict mortality in patients with end-stage liver disease. PLoS One 2016;11:e0159205.
- 65. Holeček M. Muscle amino acid and adenine nucleotide metabolism during exercise and in liver cirrhosis: speculations on how to reduce the harmful effects of ammonia. Metabolites 2022;12:971.
- 66. Yoon MS. mTOR as a key regulator in maintaining skeletal muscle mass. Front Physiol 2017;8:788.
- 67. Bajaj JS, Garcia-Tsao G, Reddy KR, O’Leary JG, Vargas HE, Lai JC, et al. Admission urinary and serum metabolites predict renal outcomes in hospitalized patients with cirrhosis. Hepatology 2021;74:2699-2713.
- 68. Qiu J, Thapaliya S, Runkana A, Yang Y, Tsien C, Mohan ML, et al. Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB-mediated mechanism. Proc Natl Acad Sci U S A 2013;110:18162-18167.
- 69. Dasarathy S, McCullough AJ, Muc S, Schneyer A, Bennett CD, Dodig M, et al. Sarcopenia associated with portosystemic shunting is reversed by follistatin. J Hepatol 2011;54:915-921.
- 70. Davuluri G, Krokowski D, Guan BJ, Kumar A, Thapaliya S, Singh D, et al. Metabolic adaptation of skeletal muscle to hyperammonemia drives the beneficial effects of l-leucine in cirrhosis. J Hepatol 2016;65:929-937.
- 71. Allen SL, Quinlan JI, Dhaliwal A, Armstrong MJ, Elsharkawy AM, Greig CA, et al. Sarcopenia in chronic liver disease: mechanisms and countermeasures. Am J Physiol Gastrointest Liver Physiol 2021;320:G241-G257.
- 72. Jacobsen EB, Hamberg O, Quistorff B, Ott P. Reduced mitochondrial adenosine triphosphate synthesis in skeletal muscle in patients with Child-Pugh class B and C cirrhosis. Hepatology 2001;34:7-12.
- 73. Shiraki M, Nishiguchi S, Saito M, Fukuzawa Y, Mizuta T, Kaibori M, et al. Nutritional status and quality of life in current patients with liver cirrhosis as assessed in 2007-2011. Hepatol Res 2013;43:106-112.
- 74. Tadokoro T, Morishita A, Himoto T, Masaki T. Nutritional support for alcoholic liver disease. Nutrients 2023;15:1360.
- 75. McClain CJ, Barve SS, Barve A, Marsano L. Alcoholic liver disease and malnutrition. Alcohol Clin Exp Res 2011;35:815-820.
- 76. Steiner JL, Lang CH. Alcohol impairs skeletal muscle protein synthesis and mTOR signaling in a time-dependent manner following electrically stimulated muscle contraction. J Appl Physiol (1985) 2014;117:1170-1179.
- 77. Thapaliya S, Runkana A, McMullen MR, Nagy LE, McDonald C, Naga Prasad SV, et al. Alcohol-induced autophagy contributes to loss in skeletal muscle mass. Autophagy 2014;10:677-690.
- 78. Mansouri A, Demeilliers C, Amsellem S, Pessayre D, Fromenty B. Acute ethanol administration oxidatively damages and depletes mitochondrial DNA in mouse liver, brain, heart, and skeletal muscles: protective effects of antioxidants. J Pharmacol Exp Ther 2001;298:737-743.
- 79. Lang CH, Lynch CJ, Vary TC. Alcohol-induced IGF-I resistance is ameliorated in mice deficient for mitochondrial branched-chain aminotransferase. J Nutr 2010;140:932-938.
- 80. Dasarathy S. Nutrition and alcoholic liver disease: effects of alcoholism on nutrition, effects of nutrition on alcoholic liver disease, and nutritional therapies for alcoholic liver disease. Clin Liver Dis 2016;20:535-550.
- 81. Hanai T, Nishimura K, Unome S, Miwa T, Nakahata Y, Imai K, et al. Alcohol-associated liver disease increases the risk of muscle loss and mortality in patients with cirrhosis. J Gastroenterol 2024;59:932-940.
- 82. Chrysavgis L, Adamantou M, Angelousi A, Cholongitas E. The association of testosterone with sarcopenia and frailty in chronic liver disease. Eur J Clin Invest 2024;54:e14108.
- 83. Sinclair M, Gow PJ, Angus PW, Hoermann R, Handelsman DJ, Wittert G, et al. High circulating oestrone and low testosterone correlate with adverse clinical outcomes in men with advanced liver disease. Liver Int 2016;36:1619-1627.
- 84. Sinclair M, Grossmann M, Angus PW, Hoermann R, Hey P, Scodellaro T, et al. Low testosterone as a better predictor of mortality than sarcopenia in men with advanced liver disease. J Gastroenterol Hepatol 2016;31:661-667.
- 85. Moctezuma-Velázquez C, Low G, Mourtzakis M, Ma M, Burak KW, Tandon P, et al. Association between low testosterone levels and sarcopenia in cirrhosis: a cross-sectional study. Ann Hepatol 2018;17:615-623.
- 86. Sinclair M, Grossmann M, Hoermann R, Angus PW, Gow PJ. Testosterone therapy increases muscle mass in men with cirrhosis and low testosterone: a randomised controlled trial. J Hepatol 2016;65:906-913.
- 87. Tapper EB, Chen X, Parikh ND. Testosterone replacement reduces morbidity and mortality for most patients with cirrhosis. Clin Gastroenterol Hepatol 2025;23:2224-2231 e3.
- 88. Kaur P, Verma N, Wadhawan A, Garg P, Ralmilay S, Kalra N, et al. Insulin-like growth factor-1 levels reflect muscle and bone health and determine complications and mortality in decompensated cirrhosis. J Clin Exp Hepatol 2025;15:102402.
- 89. Cederholm T, Bosaeus I. Malnutrition in adults. N Engl J Med 2024;391:155-165.
- 90. Costamagna D, Costelli P, Sampaolesi M, Penna F. Role of Inflammation in muscle homeostasis and myogenesis. Mediators Inflamm 2015;2015:805172.
- 91. Melendez PA, Oh BC, Lidov HG, et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 2004;119:285-298.
- 92. Di Marco S, Mazroui R, Dallaire P, Chittur S, Tenenbaum SA, Radzioch D, et al. NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release. Mol Cell Biol 2005;25:6533-6545.
- 93. Martin A, Gallot YS, Freyssenet D. Molecular mechanisms of cancer cachexia-related loss of skeletal muscle mass: data analysis from preclinical and clinical studies. J Cachexia Sarcopenia Muscle 2023;14:1150-1167.
- 94. Frost RA, Lang CH. Regulation of muscle growth by pathogen-associated molecules. J Anim Sci 2008;86:E84-93.
- 95. White JP, Puppa MJ, Gao S, Sato S, Welle SL, Carson JA. Muscle mTORC1 suppression by IL-6 during cancer cachexia: a role for AMPK. Am J Physiol Endocrinol Metab 2013;304:E1042-1052.
- 96. Mehta M, Louissaint J, Parikh NS, Long MT, Tapper EB. Cognitive function, sarcopenia, and inflammation are strongly associated with frailty: a Framingham cohort study. Am J Med 2021;134:1530-1538.
- 97. Shibamoto A, Namisaki T, Suzuki J, Kubo T, Iwai S, Tomooka F, et al. Hemoglobin and endotoxin levels predict sarcopenia occurrence in patients with alcoholic cirrhosis. Diagnostics (Basel) 2023;13:2218.
- 98. Kalinkovich A, Livshits G. Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev 2017;35:200-221.
- 99. Miwa T, Francisque C, Tajirika S, Hanai T, Imamura N, Adachi M, et al. Impact of body fat accumulation on metabolic dysfunction-associated fatty liver disease and nonalcoholic fatty liver disease in Japanese male young adults. Hepatol Res 2023;53:691-700.
- 100. Alferink LJM, Trajanoska K, Erler NS, Schoufour JD, de Knegt RJ, Ikram MA, et al. Nonalcoholic fatty liver disease in the Rotterdam study: about muscle mass, sarcopenia, fat mass, and fat distribution. J Bone Miner Res 2019;34:1254-1263.
- 101. Petermann-Rocha F, Gray SR, Forrest E, Welsh P, Sattar N, Celis-Morales C, et al. Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333,295 UK Biobank participants. J Hepatol 2022;76:1021-1029.
- 102. Tranah TH, Edwards LA, Schnabl B, Shawcross DL. Targeting the gut-liver-immune axis to treat cirrhosis. Gut 2021;70:982-994.
- 103. Schnabl B, Damman CJ, Carr RM. Metabolic dysfunctionassociated steatotic liver disease and the gut microbiome: pathogenic insights and therapeutic innovations. J Clin Invest 2025;135:e186423.
- 104. Hsu CL, Schnabl B. The gut-liver axis and gut microbiota in health and liver disease. Nat Rev Microbiol 2023;21:719-733.
- 105. Schöler D, Schnabl B. The role of the microbiome in liver disease. Curr Opin Gastroenterol 2024;40:134-142.
- 106. Özdirik B, Schnabl B. Microbial players in primary sclerosing cholangitis: current evidence and concepts. Cell Mol Gastroenterol Hepatol 2024;17:423-438.
- 107. Harberts A, Schnabl B. Microbiota in alcohol-associated organ damage. Am J Pathol 2026;196:104-120.
- 108. Zhang T, Cheng JK, Hu YM. Gut microbiota as a promising therapeutic target for age-related sarcopenia. Ageing Res Rev 2022;81:101739.
- 109. Ponziani FR, Picca A, Marzetti E, Calvani R, Conta G, Del Chierico F, et al. Characterization of the gut-liver-muscle axis in cirrhotic patients with sarcopenia. Liver Int 2021;41:1320-1334.
- 110. Ren X, Hao S, Yang C, Yuan L, Zhou X, Zhao H, et al. Alterations of intestinal microbiota in liver cirrhosis with muscle wasting. Nutrition 2021;83:111081.
- 111. Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S, et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: international society for hepatic encephalopathy and nitrogen metabolism consensus. Hepatology 2013;58:325-336.
- 112. Borhofen SM, Gerner C, Lehmann J, Fimmers R, Görtzen J, Hey B, et al. The Royal Free Hospital-Nutritional Prioritizing Tool is an independent predictor of deterioration of liver function and survival in cirrhosis. Dig Dis Sci 2016;61:1735-1743.
- 113. Wu Y, Zhu Y, Feng Y, Wang R, Yao N, Zhang M, et al. Royal Free Hospital-Nutritional Prioritizing Tool improves the prediction of malnutrition risk outcomes in liver cirrhosis patients compared with Nutritional Risk Screening 2002. Br J Nutr 2020;124:1293-1302.
- 114. Zhang P, Wang Q, Zhu M, Li P, Wang Y. Differences in nutritional risk assessment between NRS2002, RFH-NPT and LDUST in cirrhotic patients. Sci Rep 2023;13:3306.
- 115. Bannert K, Sautter LF, Wiese ML, Meyer F, Ehlers L, Fromhold-Treu S, et al. Analysis of ESPEN and GLIM algorithms reveals specific drivers for the diagnosis of malnutrition in patients with chronic gastrointestinal diseases. Nutrition 2023;106:111887.
- 116. Boulhosa R, Lourenço RP, Côrtes DM, Oliveira LPM, Lyra AC, de Jesus RP. Comparison between criteria for diagnosing malnutrition in patients with advanced chronic liver disease: GLIM group proposal versus different nutritional screening tools. J Hum Nutr Diet 2020;33:862-868.
- 117. Casas Deza D, Betoré Glaria ME, Sanz-París A, Lafuente Blasco M, Fernández Bonilla EM, Bernal Monterde V, et al. Mini nutritional assessment - short form is a useful malnutrition screening tool in patients with liver cirrhosis, using the global leadership initiative for malnutrition criteria as the gold standard. Nutr Clin Pract 2021;36:1003-1010.
- 118. Cederholm T, Jensen GL, Correia M, Gonzalez MC, Fukushima R, Higashiguchi T, et al. GLIM criteria for the diagnosis of malnutrition - a consensus report from the global clinical nutrition community. Clin Nutr 2019;38:1-9.
- 119. Cederholm T, Jensen GL, Correia M, Gonzalez MC, Fukushima R, Higashiguchi T, et al. GLIM criteria for the diagnosis of malnutrition - a consensus report from the global clinical nutrition community. J Cachexia Sarcopenia Muscle 2019;10:207-217.
- 120. Jensen GL, Cederholm T, Correia M, Gonzalez MC, Fukushima R, Higashiguchi T, et al. GLIM criteria for the diagnosis of malnutrition: a consensus report from the global clinical nutrition community. JPEN J Parenter Enteral Nutr 2019;43:32-40.
- 121. Kondrup J, Allison SP, Elia M, Vellas B, Plauth M. ESPEN guidelines for nutrition screening 2002. Clin Nutr 2003;22:415-421.
- 122. He Y, Hu L, Wu S, Li L, Zhong K, Li J, et al. Nutritional screening and assessment tools for patients with cirrhosis based on the Global Leadership Initiative on Malnutrition criteria. J Hum Nutr Diet 2024;37:430-439.
- 123. Detsky AS, McLaughlin JR, Baker JP, Johnston N, Whittaker S, Mendelson RA, et al. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr 1987;11:8-13.
- 124. Miwa T, Hanai T, Nishimura K, Hirata S, Unome S, Nakahata Y, et al. Nutritional assessment using subjective global assessment identifies energy malnutrition and predicts mortality in patients with liver cirrhosis. Sci Rep 2025;15:4831.
- 125. Merli M, Giusto M, Gentili F, Novelli G, Ferretti G, Riggio O, et al. Nutritional status: its influence on the outcome of patients undergoing liver transplantation. Liver Int 2010;30:208-214.
- 126. Ferreira LG, Anastácio LR, Lima AS, Correia MI. Assessment of nutritional status of patients waiting for liver transplantation. Clin Transplant 2011;25:248-254.
- 127. Morgan MY, Madden AM, Soulsby CT, Morris RW. Derivation and validation of a new global method for assessing nutritional status in patients with cirrhosis. Hepatology 2006;44:823-835.
- 128. Hanai T, Shiraki M, Nishimura K, Ogiso Y, Imai K, Suetsugu A, et al. Nutritional assessment tool for predicting sarcopenia in chronic liver disease. JCSM Rapid Communications 2021;4:150-158.
- 129. Kalafateli M, Mantzoukis K, Choi Yau Y, Mohammad AO, Arora S, Rodrigues S, et al. Malnutrition and sarcopenia predict postliver transplantation outcomes independently of the Model for End-stage Liver Disease score. J Cachexia Sarcopenia Muscle 2017;8:113-121.
- 130. Yang W, Guo G, Cui B, Li Y, Sun M, Li C, et al. Malnutrition according to the Global Leadership Initiative on Malnutrition criteria is associated with in-hospital mortality and prolonged length of stay in patients with cirrhosis. Nutrition 2023;105:111860.
- 131. Yang W, Guo G, Mao L, Hui Y, Wang X, Yu Z, et al. Comparison of the GLIM criteria with specific screening tool for diagnosing malnutrition in hospitalized patients with cirrhosis: A descriptive cross-sectional study. JPEN J Parenter Enteral Nutr 2023;47:310-321.
- 132. Malmstrom TK, Morley JE. SARC-F: a simple questionnaire to rapidly diagnose sarcopenia. J Am Med Dir Assoc 2013;14:531-532.
- 133. Singla N, Inavolu P, Kumar BR, Macherla R, Reddy DN. SARC-F score: a quick bedside tool to screen sarcopenia in patients with cirrhosis. J Clin Exp Hepatol 2024;14:101318.
- 134. Ida S, Kojima Y, Hamaoka S, Urawa N, Araki J, Kaneko R, et al. Validity of Japanese version of SARC-F questionnaire in patients with chronic liver disease. J Gastroenterol Hepatol 2019;34:947-953.
- 135. Ichikawa T, Miyaaki H, Miuma S, Motoyoshi Y, Yamashima M, Yamamichi S, et al. Comparison of calculated body muscle mass and SARC-F as methods of screening for sarcopenia in patients with chronic liver disease. Biomed Rep 2021;14:34.
- 136. Hanai T, Hiraoka A, Shiraki M, Sugimoto R, Taniki N, Hiramatsu A, et al. Utility of the SARC-F questionnaire for sarcopenia screening in patients with chronic liver disease: a multicenter cross-sectional study in Japan. J Clin Med 2021;10:3448.
- 137. Tanaka T, Takahashi K, Akishita M, Tsuji T, Iijima K. “Yubiwakka” (finger-ring) test: A practical self-screening method for sarcopenia, and a predictor of disability and mortality among Japanese community-dwelling older adults. Geriatr Gerontol Int 2018;18:224-232.
- 138. Hiraoka A, Izumoto H, Ueki H, Yoshino T, Aibiki T, Okudaira T, et al. Easy surveillance of muscle volume decline in chronic liver disease patients using finger-circle (yubi-wakka) test. J Cachexia Sarcopenia Muscle 2019;10:347-354.
- 139. Nishikawa H, Yoh K, Enomoto H, Nishimura T, Nishiguchi S, Iijima H. Clinical impact of the finger-circle test in patients with liver diseases. Hepatol Res 2021;51:603-613.
- 140. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing 2010;39:412-423.
- 141. Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 2011;12:249-256.
- 142. Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al. Sarcopenia in Asia: consensus report of the Asian working group for sarcopenia. J Am Med Dir Assoc 2014;15:95-101.
- 143. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019;48:16-31.
- 144. Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc 2020;21:300-307.e302.
- 145. Bhasin S, Travison TG, Manini TM, Patel S, Pencina KM, Fielding RA, et al. Sarcopenia definition: the position statements of the sarcopenia definition and outcomes consortium. J Am Geriatr Soc 2020;68:1410-1418.
- 146. Carey EJ, Lai JC, Wang CW, Dasarathy S, Lobach I, Montano-Loza AJ, et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl 2017;23:625-633.
- 147. Ruiz-Margáin A, Xie JJ, Román-Calleja BM, Pauly M, White MG, Chapa-Ibargüengoitia M, et al. Phase angle from bioelectrical impedance for the assessment of sarcopenia in cirrhosis with or without ascites. Clin Gastroenterol Hepatol 2021;19:1941-1949.e1942.
- 148. Nishikawa H, Shiraki M, Hiramatsu A, Moriya K, Hino K, Nishiguchi S. Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res 2016;46:951-963.
- 149. Japan Society of Hepatology. Japan Society of Hepatology guidelines for sarcopenia in liver disease (2nd edition). Japan Society of Hepatology web site, <https://www.jsh.or.jp/lib/files/english/guidelines_en/sarcopenia.pdf>. Accessed 18 Sep 2025.
- 150. Miwa T, Hanai T, Nishimura K, Maeda T, Ogiso Y, Imai K, et al. Handgrip strength stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis. JPEN J Parenter Enteral Nutr 2022;46:858-866.
- 151. Hanai T, Shiraki M, Imai K, Suetsugu A, Takai K, Moriwaki H, et al. Reduced handgrip strength is predictive of poor survival among patients with liver cirrhosis: a sex-stratified analysis. Hepatol Res 2019;49:1414-1426.
- 152. Nishikawa H, Shiraki M, Hiramatsu A, Hara N, Moriya K, Hino K, et al. Reduced handgrip strength predicts poorer survival in chronic liver diseases: a large multicenter study in Japan. Hepatol Res 2021;51:957-967.
- 153. Eslamparast T, Vandermeer B, Raman M, Gramlich L, Den Heyer V, Belland D, et al. Are predictive energy expenditure equations accurate in cirrhosis? Nutrients 2019;11:334.
- 154. Nielsen K, Kondrup J, Martinsen L, Døssing H, Larsson B, Stilling B, et al. Long-term oral refeeding of patients with cirrhosis of the liver. Br J Nutr 1995;74:557-567.
- 155. Greco AV, Mingrone G, Benedetti G, Capristo E, Tataranni PA, Gasbarrini G. Daily energy and substrate metabolism in patients with cirrhosis. Hepatology 1998;27:346-350.
- 156. Riggio O, Angeloni S, Ciuffa L, Nicolini G, Attili AF, Albanese C, et al. Malnutrition is not related to alterations in energy balance in patients with stable liver cirrhosis. Clin Nutr 2003;22:553-559.
- 157. Guglielmi FW, Panella C, Buda A, Budillon G, Caregaro L, Clerici C, et al. Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the ‘Nutritional Problems in Gastroenterology’ Section of the Italian Society of Gastroenterology (SIGE). Dig Liver Dis 2005;37:681-688.
- 158. Plauth M, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, et al. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr 2019;38:485-521.
- 159. Mallet M, Silaghi CA, Sultanik P, Conti F, Rudler M, Ratziu V, et al. Current challenges and future perspectives in treating patients with NAFLD-related cirrhosis. Hepatology 2024;80:1270-1290.
- 160. Karagozian R, Bhardwaj G, Wakefield DB, Baffy G. Obesity paradox in advanced liver disease: obesity is associated with lower mortality in hospitalized patients with cirrhosis. Liver Int 2016;36:1450-1456.
- 161. Córdoba J, López-Hellín J, Planas M, Sabín P, Sanpedro F, Castro F, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol 2004;41:38-43.
- 162. Morgan TR, Moritz TE, Mendenhall CL, Haas R. Protein consumption and hepatic encephalopathy in alcoholic hepatitis. VA Cooperative Study Group #275. J Am Coll Nutr 1995;14:152-158.
- 163. Singal AK, Wong RJ, Dasarathy S, Abdelmalek MF, Neuschwander-Tetri BA, Limketkai BN, et al. ACG Clinical Guideline: malnutrition and nutritional recommendations in liver disease. Am J Gastroenterol 2025;120:950-972.
- 164. Maharshi S, Sharma BC, Sachdeva S, Srivastava S, Sharma P. Efficacy of nutritional therapy for patients with cirrhosis and minimal hepatic encephalopathy in a randomized trial. Clin Gastroenterol Hepatol 2016;14:454-460 e453; quiz e433.
- 165. Iqbal U, Jadeja RN, Khara HS, Khurana S. A comprehensive review evaluating the impact of protein source (vegetarian vs. meat based) in hepatic encephalopathy. Nutrients 2021;13:370.
- 166. Badal BD, Fagan A, Tate V, Mousel T, Gallagher ML, Puri P, et al. Substitution of one meat-based meal with vegetarian and vegan alternatives generates lower ammonia and alters metabolites in cirrhosis: a randomized clinical trial. Clin Transl Gastroenterol 2024;15:e1.
- 167. Miwa Y, Shiraki M, Kato M, Tajika M, Mohri H, Murakami N, et al. Improvement of fuel metabolism by nocturnal energy supplementation in patients with liver cirrhosis. Hepatol Res 2000;18:184-189.
- 168. Yamanaka-Okumura H, Nakamura T, Takeuchi H, Miyake H, Katayama T, Arai H, et al. Effect of late evening snack with rice ball on energy metabolism in liver cirrhosis. Eur J Clin Nutr 2006;60:1067-1072.
- 169. Miwa Y, Moriwaki H. Nocturnal energy and BCAA supplementation in patients with liver cirrhosis. Hepatol Res 2004;30s:63-66.
- 170. Fukushima H, Miwa Y, Shiraki M, Gomi I, Toda K, Kuriyama S, et al. Oral branched-chain amino acid supplementation improves the oxidized/reduced albumin ratio in patients with liver cirrhosis. Hepatol Res 2007;37:765-770.
- 171. Hidaka H, Nakazawa T, Kutsukake S, Yamazaki Y, Aoki I, Nakano S, et al. The efficacy of nocturnal administration of branched-chain amino acid granules to improve quality of life in patients with cirrhosis. J Gastroenterol 2013;48:269-276.
- 172. Plank LD, Gane EJ, Peng S, Muthu C, Mathur S, Gillanders L, et al. Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: a randomized 12-month trial. Hepatology 2008;48:557-566.
- 173. Chen CJ, Wang LC, Kuo HT, Fang YC, Lee HF. Significant effects of late evening snack on liver functions in patients with liver cirrhosis: a meta-analysis of randomized controlled trials. J Gastroenterol Hepatol 2019;34:1143-1152.
- 174. Hanai T, Shiraki M, Imai K, Suetsugu A, Takai K, Shimizu M. Late evening snack with branched-chain amino acids supplementation improves survival in patients with cirrhosis. J Clin Med 2020;9:1013.
- 175. Keshavarzian A, Meek J, Sutton C, Emery VM, Hughes EA, Hodgson HJ. Dietary protein supplementation from vegetable sources in the management of chronic portal systemic encephalopathy. Am J Gastroenterol 1984;79:945-949.
- 176. Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol 2005;3:705-713.
- 177. Konstantis G, Pourzitaki C, Chourdakis M, Kitsikidou E, Germanidis G. Efficacy of branched chain amino acids supplementation in liver cirrhosis: a systematic review and metaanalysis. Clin Nutr 2022;41:1171-1190.
- 178. Holecek M. Ammonia and amino acid profiles in liver cirrhosis: effects of variables leading to hepatic encephalopathy. Nutrition 2015;31:14-20.
- 179. Gluud LL, Dam G, Les I, Marchesini G, Borre M, Aagaard NK, et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev 2017;5:Cd001939.
- 180. Singh Tejavath A, Mathur A, Nathiya D, Singh P, Raj P, Suman S, et al. Impact of branched chain amino acid on muscle mass, muscle strength, physical performance, combined survival, and maintenance of liver function changes in laboratory and prognostic markers on sarcopenic patients with liver cirrhosis (BCAAS Study): a randomized clinical trial. Front Nutr 2021;8:715795.
- 181. Hernández-Conde M, Llop E, Gómez-Pimpollo L, Fernández Carrillo C, Rodríguez L, Van Den Brule E, et al. Adding branchedchain amino acids to an enhanced standard-of-care treatment improves muscle mass of cirrhotic patients with sarcopenia: a placebo-controlled trial. Am J Gastroenterol 2021;116:2241-2249.
- 182. Mohta S, Anand A, Sharma S, Qamar S, Agarwal S, Gunjan D, et al. Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia. Hepatol Int 2022;16:680-690.
- 183. Hey P, Hoermann R, Sinclair M, Chapman B, Testro A, Apostolov R, et al. Branched-chain amino acid supplementation does not improve measures of sarcopenia in cirrhosis: results of a randomised controlled trial. Aliment Pharmacol Ther 2024;59:941-952.
- 184. Kittiprachakul S, Maung ST, Poorirerngpoom N, Srinawakul A, Numpaisarn M, Tiyarattanachai T, et al. Exercise and nutrition interventions for sarcopenia in cirrhosis: a systematic review and network meta-analysis of randomized controlled trials. Eur J Clin Nutr 2025;79:1087-1098.
- 185. Hiraoka A, Michitaka K, Kiguchi D, Izumoto H, Ueki H, Kaneto M, et al. Efficacy of branched-chain amino acid supplementation and walking exercise for preventing sarcopenia in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2017;29:1416-1423.
- 186. Nojiri S, Fujiwara K, Shinkai N, Iio E, Joh T. Effects of branchedchain amino acid supplementation after radiofrequency ablation for hepatocellular carcinoma: a randomized trial. Nutrition 2017;33:20-27.
- 187. Bjelakovic G, Nikolova D, Bjelakovic M, Gluud C. Vitamin D supplementation for chronic liver diseases in adults. Cochrane Database Syst Rev 2017;11:Cd011564.
- 188. Liu X, Chen X, Cui J. Therapeutic advances in sarcopenia management: from traditional interventions to personalized medicine. Clin Nutr 2025;51:187-197.
- 189. Okubo T, Atsukawa M, Tsubota A, Ono H, Kawano T, Yoshida Y, et al. Effect of vitamin D supplementation on skeletal muscle volume and strength in patients with decompensated liver cirrhosis undergoing branched chain amino acids supplementation: a prospective, randomized, controlled pilot trial. Nutrients 2021;13:1874.
- 190. Díaz-Ruíz R, Poca M, Román E, Cuyàs B, Bañares I, Morales Á, et al. Treatment of vitamin D deficiency in decompensated patients with cirrhosis is associated with improvement in frailty. Med Sci (Basel) 2025;13:30.
- 191. Kril JJ, Butterworth RF. Diencephalic and cerebellar pathology in alcoholic and nonalcoholic patients with end-stage liver disease. Hepatology 1997;26:837-841.
- 192. Katayama K, Saito M, Kawaguchi T, Endo R, Sawara K, Nishiguchi S, et al. Effect of zinc on liver cirrhosis with hyperammonemia: a preliminary randomized, placebo-controlled double-blind trial. Nutrition 2014;30:1409-1414.
- 193. Diglio DC, Fernandes SA, Stein J, Azeredo-da-Silva A, de Mattos AA, Tovo CV. Role of zinc supplementation in the management of chronic liver diseases: a systematic review and meta-analysis. Ann Hepatol 2020;19:190-196.
- 194. Yu L, Yousuf S, Yousuf S, Yeh J, Biggins SW, Morishima C, et al. Copper deficiency is an independent risk factor for mortality in patients with advanced liver disease. Hepatol Commun 2023;7:e0076.
- 195. Nakahata Y, Hanai T, Miwa T, Maeda T, Imai K, Suetsugu A, et al. Effect of selenium deficiency on the development of overt hepatic encephalopathy in patients with chronic liver disease. J Clin Med 2023;12:2869.
- 196. Dhanda A, Atkinson S, Vergis N, Enki D, Fisher A, Clough R, et al. Trace element deficiency is highly prevalent and associated with infection and mortality in patients with alcoholic hepatitis. Aliment Pharmacol Ther 2020;52:537-544.
- 197. Malaguarnera M, Gargante MP, Cristaldi E, Vacante M, Risino C, Cammalleri L, et al. Acetyl-L-carnitine treatment in minimal hepatic encephalopathy. Dig Dis Sci 2008;53:3018-3025.
- 198. Nojiri S, Fujiwara K, Matsuura K, Iio E, Matsunami K, Nomura T, et al. L-carnitine reduces ammonia levels and alleviates covert encephalopathy: a randomized trial. J Transl Sci 2018;4:1-6.
- 199. Malaguarnera M, Vacante M, Giordano M, Pennisi G, Bella R, Rampello L, et al. Oral acetyl-L-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, doubleblind, placebo-controlled study. Am J Clin Nutr 2011;93:799-808.
- 200. Martí-Carvajal AJ, Gluud C, Arevalo-Rodriguez I, Martí-Amarista CE. Acetyl-L-carnitine for patients with hepatic encephalopathy. Cochrane Database Syst Rev 2019;1:Cd011451.
- 201. Kawaguchi T, Kawaguchi A, Hashida R, Nakano D, Tsutsumi T, Kawaguchi M, et al. Resistance exercise in combination with aerobic exercise reduces the incidence of serious events in patients with liver cirrhosis: a meta-analysis of randomized controlled trials. J Gastroenterol 2024;59:216-228.
- 202. Hsu HC, Chow LH, Chen YL, Hung HM, Yen M, Lee HF. Effects of exercise and nutrition in improving sarcopenia in liver cirrhosis patients: a systematic review and meta-analysis. Hepatobiliary Surg Nutr 2025;14:33-48.
- 203. Chen HW, Ferrando A, White MG, Dennis RA, Xie J, Pauly M, et al. Home-based physical activity and diet intervention to improve physical function in advanced liver disease: a randomized pilot trial. Dig Dis Sci 2020;65:3350-3359.
- 204. Wallen MP, Keating SE, Hall A, Hickman IJ, Pavey TG, Woodward AJ, et al. Exercise training is safe and feasible in patients awaiting liver transplantation: a pilot randomized controlled trial. Liver Transpl 2019;25:1576-1580.
- 205. Lai JC, Dodge JL, Kappus MR, Wong R, Mohamad Y, Segev DL, et al. A multicenter pilot randomized clinical trial of a home-based exercise program for patients with cirrhosis: the strength training intervention (STRIVE). Am J Gastroenterol 2021;116:717-722.
- 206. Katakami N, Uchino J, Yokoyama T, Naito T, Kondo M, Yamada K, et al. Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: Results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04). Cancer 2018;124:606-616.
- 207. Becker C, Lord SR, Studenski SA, Warden SJ, Fielding RA, Recknor CP, et al. Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol 2015;3:948-957.
- 208. Flaherty SE, Song L, Albuquerque B, Rinaldi A, Piper M, Shanthappa DH, et al. GDF15 Neutralization ameliorates muscle atrophy and exercise intolerance in a mouse model of mitochondrial myopathy. J Cachexia Sarcopenia Muscle 2025;16:e13715.
- 209. Mitchell W, Pharaoh G, Tyshkovskiy A, Campbell M, Marcinek DJ, Gladyshev VN. The mitochondria-targeted peptide therapeutic elamipretide improves cardiac and skeletal muscle function during aging without detectable changes in tissue epigenetic or transcriptomic age. Aging Cell 2025;24:e70026.
- 210. Righetti R, Cinque F, Volpe MT, Sebastiani G. Integrating behavioral interventions into a holistic approach to metabolic dysfunction-associated steatotic liver disease. Expert Rev Gastroenterol Hepatol 2024;18:303-313.
- 211. Miwa T, Tajirika S, Hanai T, Imamura N, Adachi M, Horita R, et al. Usefulness of a questionnaire for assessing the relationship between eating behavior and steatotic liver disease among Japanese male young adults. Sci Rep 2024;14:2194.
