Clinical and Molecular Hepatology

"Non-alcoholic fatty liver disease"

Original Articles

Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study: Xianhua Mao, Xinrong Zhang, Rongtao Lai, Ka-Shing Cheung, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H. Nguyen; Clin Mol Hepatol 2025;31(3):1084-1099.
Published online April 23, 2025; DOI: https://doi.org/10.3350/cmh.2024.1096

Background/Aims
Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes.
Methods
Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan^® Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI).
Results
In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39–0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86–0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86–0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64–0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77–0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60–0.77.
Conclusions
In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.

Citations

Citations to this article as recorded by

Evaluating causal protective effect of dual GLP-1R/GIPR agonists on MASLD: A Mendelian randomization and colocalization study
Yangke Cai, Siyuan Xie, Liyi Xu, Jiamin Chen, Jianting Cai
European Journal of Pharmacology.2025; 1005: 178088. CrossRef
Impaired Thyroid Hormone Sensitivity is Associated with Increased Risk of Liver Fibrosis in Euthyroid Population: A Cross-Sectional Analysis of NHANES
Xingyu Yao, Kaiwen Xiao, Hein Ko Oo
Hormone and Metabolic Research.2025; 57(09): 511. CrossRef

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High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated steatotic liver disease: Tung-Hung Su, Sheng-Shun Yang, Mei-Hsuan Lee, Wei-Yu Kao, Shang-Chin Huang, Fen-Fang Chen, Francis SK Poon, Lung-Wen Tsai, Yi-Ting Chen, Che Lin, Weichung Wang, W Ray Kim, Jia-Horng Kao; Clin Mol Hepatol 2025;31(3):796-809.
Published online January 6, 2025; DOI: https://doi.org/10.3350/cmh.2024.0822

Background/Aims
There are no hepatocellular carcinoma (HCC) surveillance recommendations for non-viral chronic liver diseases (CLD), such as metabolic dysfunction-associated steatotic liver disease (MASLD). We explored the Steatosis-Associated Fibrosis Estimator (SAFE) score to predict HCC in MASLD and other CLD etiologies.
Methods
Patients with various CLDs were included from medical centers in Taiwan. The SAFE score, consisting of age, body mass index, diabetes, and laboratory data, was calculated at baseline, and patients were traced for new development of HCC. The predictability of the SAFE score for HCC was analyzed using the sub-distribution hazard model with adjustments for competing risks.
Results
Among 12,963 CLD patients with a median follow-up of 4 years, 258 developed HCC. The SAFE score classifies 1-, 3-, and 5-year HCC risk regardless of CLD etiologies. High (≥100) and intermediate (0–100) SAFE scores increased 11 and 2 folds HCC risks compared to low (<0) SAFE scores. Combining two lower risk tiers (SAFE<100), a high SAFE score (≥100) was associated with a 7.5-fold risk of HCC (adjusted sub-distributional hazard ratio [aSHR] 7.54; 95% confidence interval (CI) 5.38–10.60). A high SAFE score increased the risks of HCC in subgroups of viral hepatitis, non-viral hepatitis (aSHR 11.10; 95% CI 3.97–31.30) and MASLD (aSHR 4.23; 95% CI 1.43–12.50). A hospital cohort (n=8,103) and a community MASLD cohort (n=120,166) validated the high SAFE score (≥100) for HCC risk prediction.
Conclusions
The SAFE score stratifies high risks for HCC in CLD patients regardless of etiologies and helps to select at-risk candidates for HCC surveillance.

Citations

Citations to this article as recorded by

HCC predictors in routine practice for patients with chronic liver diseases: Correspondence to editorial on “High SAFE scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction associated steatotic liver disease”
Tung-Hung Su, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(1): e52. CrossRef
Can SAFE score be utilized as a universal hepatocellular carcinoma prediction score?: Editorial on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated
Michael Kwan-Lung Ko, Loey Lung-Yi Mak
Clinical and Molecular Hepatology.2026; 32(1): 371. CrossRef
Risk stratification for hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: Editorial on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic
Ho Soo Chun, Minjong Lee
Clinical and Molecular Hepatology.2026; 32(1): 368. CrossRef

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Editorial

Steatotic liver disease

Vibration-controlled transient elastography in shaping the epidemiology and management of steatotic liver disease: Editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023”: Xiao-Dong Zhou, Terry Cheuk-Fung Yip, Daniel Q Huang, Mark Dhinesh Muthiah, Mazen Noureddin, Ming-Hua Zheng; Clin Mol Hepatol 2025;31(2):620-624.
Published online December 26, 2024; DOI: https://doi.org/10.3350/cmh.2024.1131

Citations

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Liver Fibrosis and the Risk of Coronary Artery Disease, Stent Thrombosis, Restenosis and Adverse Clinical Outcomes
Na Tian, Tie Xiao, Tianyi Xia, Hai‐Yang Yuan, Michael D. Shapiro, Gregory Y. H. Lip, Cheng‐Han Fanren, Li‐You Lian, Chen‐Xiao Huang, Yi‐Xuan Wei, Giovanni Targher, Christopher D. Byrne, Cheng‐Lv Hong, Shenghong Ju, Ming‐Hua Zheng
Alimentary Pharmacology & Therapeutics.2026; 63(1): 70. CrossRef
Editorial: Does Metabolic Dysfunction‐Associated Steatotic Liver Disease With Advanced Fibrosis Also Equate to Risk of Advanced Coronary Artery Disease? Authors' Reply
Xiao‐Dong Zhou, Yusuf Yilmaz, Ming‐Hua Zheng
Alimentary Pharmacology & Therapeutics.2026; 63(1): 155. CrossRef
Statins in MASLD: Challenges and Future
Xiao-Dong Zhou, Mark D. Muthiah, Ming-Hua Zheng
JHEP Reports.2025; : 101372. CrossRef
Addressing the burden of steatotic liver disease: The role of transient elastography: Correspondence to editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023”
Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed
Clinical and Molecular Hepatology.2025; 31(2): e180. CrossRef
The association of advanced lung cancer inflammation index with non-alcoholic fatty liver disease in NHANES 2017–2020
Lin Cheng, Shumeng Li, Hui Li, Jiafeng You, Mingwei Yu, Guowang Yang
Frontiers in Medicine.2025;[Epub] CrossRef
Long-Term Glycemic Control and the Risk of Liver Stiffness Progression and Liver-Related Events in MASLD
Xiao-Dong Zhou, Qin-Fen Chen, Seung Up Kim, Terry Cheuk-Fung Yip, Salvatore Petta, Atsushi Nakajima, Emmanuel Tsochatzis, Jérôme Boursier, Elisabetta Bugianesi, Hannes Hagström, Wah-Kheong Chan, Manuel Romero-Gomez, José Luis Calleja, Victor de Lédinghen,
Clinical Gastroenterology and Hepatology.2025;[Epub] CrossRef

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75 Download
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Reviews

Steatotic liver disease

Microbiome-centered therapies for the management of metabolic dysfunction-associated steatotic liver disease: Huma Saeed, Luis Antonio Díaz, Antonio Gil-Gómez, Jeremy Burton, Jasmohan S. Bajaj, Manuel Romero-Gomez, Marco Arrese, Juan Pablo Arab, Mohammad Qasim Khan; Clin Mol Hepatol 2025;31(Suppl):S94-S111.
Published online November 28, 2024; DOI: https://doi.org/10.3350/cmh.2024.0811

Abstract
PDF

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies’ potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.

Citations

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Viral hepatitis

Mechanisms of hepatocellular carcinoma and cirrhosis development in concurrent steatotic liver disease and chronic hepatitis B: Saisai Zhang, Lung-Yi Mak, Man-Fung Yuen, Wai-Kay Seto; Clin Mol Hepatol 2025;31(Suppl):S182-S195.
Published online November 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0837

Abstract
PDF

Chronic hepatitis B (CHB) poses a major global public health challenge and is a leading cause of cirrhosis and liver cancer. Hepatic steatosis is common in individuals with CHB compared to the non-CHB population and is particularly prevalent in hepatitis B virus (HBV)-endemic regions, affecting about one-third of CHB patients. The interaction between hepatic steatosis and CHB-related disease progression is complex and still under debate. Evidence demonstrates that co-existing steatosis may worsen liver fibrosis while paradoxically increasing the likelihood of achieving better HBV control. In particular, despite the association of steatotic liver disease (SLD) with lower HBV viral loads and higher rates of HBsAg seroclearance, the coexistence of CHB and SLD can potentially accelerate liver disease progression. Factors such as fat deposition, lipotoxicity, oxidative stress, and chronic inflammation in SLD may foster a pro-fibrotic and pro-carcinogenic environment, accelerating the disease progression. Additionally, loss of global DNA methylation, changes in the immune microenvironment, and genetic susceptibility further contribute to the development of CHB-related cirrhosis and hepatocellular carcinoma (HCC). This review examines the mechanisms driving liver disease progression and the heightened risk of cirrhosis and HCC in patients with concurrent CHB and steatotic liver disease, underscoring the importance of prioritizing antiviral therapy for CHB in addition to addressing SLD.

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Diagnostic Performance of Ultrasound-Derived Fat Fraction and Automated Point Shear Wave Elastography for Hepatic Steatosis and Fibrosis in Suspected Steatotic Liver Disease: A Prospective Multicenter Study
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Correspondence

Liver fibrosis, cirrhosis, and portal hypertension

Correspondence to editorial on “Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis”: Young Eun Chon, Jung Hwan Yu, Seung Up Kim; Clin Mol Hepatol 2025;31(1):e61-e63.
Published online October 15, 2024; DOI: https://doi.org/10.3350/cmh.2024.0878

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Letter to the Editor

Steatotic liver disease

Letter to the editor on “Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis”: Xiao-Song Li, Xi-Ping Shen, Hang Li; Clin Mol Hepatol 2025;31(1):e15-e16.
Published online September 12, 2024; DOI: https://doi.org/10.3350/cmh.2024.0784

Citations

Citations to this article as recorded by

Correspondence to letter to the editor on “Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis”
Yuri Cho, Dae Won Jun
Clinical and Molecular Hepatology.2025; 31(1): e103. CrossRef

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Original Article

Steatotic liver disease

Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis: Young Eun Chon, Young-Joo Jin, Jihyun An, Hee Yeon Kim, Miyoung Choi, Dae Won Jun, Mi Na Kim, Ji Won Han, Han Ah Lee, Jung Hwan Yu, Seung Up Kim; Clin Mol Hepatol 2024;30(Suppl):S117-S133.
Published online August 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0392

Background/aims
Opinions differ regarding vibration-controlled transient elastography and magnetic resonance elastography (VCTE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of VCTE and MRE for diagnosing AF.
Methods
Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating VCTE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for VCTE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated.
Results
A total of 19,199 patients from 63 studies using VCTE showed diagnostic AUC of 0.83 (95% confidence interval: 0.80–0.86), 0.83 (0.80–0.86), 0.87 (0.84–0.90), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89 (0.86–0.92), 0.92 (0.89–0.94), 0.89 (0.86–0.92), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. The diagnostic AUC for AF using VCTE was highest at 0.90 with a cut-off of 7.1–7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62–3.8 kPa.
Conclusions
VCTE (7.1–7.9 kPa) and MRE (3.62–3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

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Special Review

Steatotic liver disease

Critical appraisal of metabolic dysfunction-associated steatotic liver disease: Implication of Janus-faced modernity: Gi-Ae Kim, Joon Ho Moon, Won Kim; Clin Mol Hepatol 2023;29(4):831-843.
Published online August 25, 2023; DOI: https://doi.org/10.3350/cmh.2023.0277

Abstract
PDF

The existing term non-alcoholic fatty liver disease (NAFLD) has raised substantial concerns due to its inherent disadvantages of using exclusionary diagnostic criteria and the stigmatizing word ‘fatty.’ Three pan-national liver associations set out to explore a new nomenclature to replace both NAFLD and its suggested alternative, metabolic (dysfunction)-associated fatty liver disease (MAFLD). They surveyed if a change in nomenclature and/or definition is favored and which nomenclature best communicates disease characteristics and increases awareness. In lieu of NAFLD/MAFLD, metabolic dysfunction-associated steatotic liver disease (MASLD) has been chosen, and an umbrella term, steatotic liver disease (SLD), encompassing the whole spectrum of liver disease, has been proposed. It has been suggested that cardiometabolic risk factors should be considered when categorizing SLD patients. Furthermore, a new subcategory, MASLD with increased alcohol intake (MetALD), casts light on a neglected group of patients with moderate or more alcohol consumption. The importance of metabolic dysfunction was acknowledged in this new nomenclature, but the precise contribution of metabolic dysfunction and alcohol consumption to the development and progression of SLD remains unclear. Herein, we review hepatologists’ and endocrinologists’ perspectives on the new nomenclature, along with its possible impact on clinical practice. Although it is premature to predict the settlement of the new nomenclature, this review may help build more evidence for a soft landing of it in the future.

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Original Article

Steatotic liver disease

Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity: Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe; Clin Mol Hepatol 2023;29(4):987-1001.
Published online July 5, 2023; DOI: https://doi.org/10.3350/cmh.2023.0035

Background/Aims
To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis.
Methods
This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3^rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography.
Results
Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors.
Conclusions
In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.

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Correspondence

Steatotic liver disease

Correspondence on Letter regarding “Non-alcoholic fatty liver disease: Definition and subtypes”: Seul Ki Han, Soon Koo Baik, Moon Young Kim; Clin Mol Hepatol 2023;29(3):817-819.
Published online May 17, 2023; DOI: https://doi.org/10.3350/cmh.2023.0155

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Letter to the Editor

Steatotic liver disease

Letter regarding “Non-alcoholic fatty liver disease: Definition and subtypes”: Seogsong Jeong, Yohwan Lim, Su Kyoung Lee, Hyun Wook Han; Clin Mol Hepatol 2023;29(3):810-811.
Published online May 8, 2023; DOI: https://doi.org/10.3350/cmh.2023.0129

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Original Article

Viral hepatitis

Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis: Yu Jun Wong, Vy H. Nguyen, Hwai-I Yang, Jie Li, Michael Huan Le, Wan-Jung Wu, Nicole Xinrong Han, Khi Yung Fong, Elizebeth Chen, Connie Wong, Fajuan Rui, Xiaoming Xu, Qi Xue, Xin Yu Hu, Wei Qiang Leow, George Boon-Bee Goh, Ramsey Cheung, Grace Wong, Vincent Wai-Sun Wong, Ming-Whei Yu, Mindie H. Nguyen; Clin Mol Hepatol 2023;29(3):705-720.
Published online May 8, 2023; DOI: https://doi.org/10.3350/cmh.2023.0004

Background/Aims
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
Methods
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
Results
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
Conclusions
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

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Changing the nomenclature from nonalcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease is more than a change in terminology: Eileen Laurel Yoon, Dae Won Jun; Clin Mol Hepatol 2023;29(2):371-373.
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Steatotic liver disease

Implications of comorbidities in nonalcoholic fatty liver disease: Sherlot Juan Song, Vincent Wai-Sun Wong; Clin Mol Hepatol 2023;29(2):384-389.
Published online March 14, 2023; DOI: https://doi.org/10.3350/cmh.2023.0066

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Steatotic liver disease

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Published online March 9, 2023; DOI: https://doi.org/10.3350/cmh.2023.0088

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Steatotic liver disease

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Reviews

Chronic hepatitis B with concurrent metabolic dysfunction-associated fatty liver disease: Challenges and perspectives: Shang-Chin Huang, Chun-Jen Liu; Clin Mol Hepatol 2023;29(2):320-331.
Published online February 1, 2023; DOI: https://doi.org/10.3350/cmh.2022.0422

Abstract
PDF

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has increased among the general population and chronic hepatitis B (CHB) patients worldwide. Although fatty liver disease is a well-known risk factor for adverse liver outcomes like cirrhosis and hepatocellular carcinoma, its interactions with the hepatitis B virus (HBV) and clinical impacts seem complex. The presence of hepatic steatosis may suppress HBV viral activity, potentially leading to attenuated liver injury. In contrast, the associated co-morbidities like diabetes mellitus or obesity may increase the risk of developing adverse liver outcomes. These findings implicate that components of MAFLD may have diverse effects on the clinical manifestations of CHB. To this end, a clinical strategy is proposed for managing patients with concurrent CHB and MAFLD. This review article discusses the updated evidence regarding disease prevalence, interactions between steatosis and HBV, clinical impacts, and management strategies, aiming at optimizing holistic health care in the CHB population.

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Steatotic liver disease

Non-alcoholic fatty liver disease: Definition and subtypes: Seul Ki Han, Soon Koo Baik, Moon Young Kim; Clin Mol Hepatol 2023;29(suppl):S5-S16.
Published online December 28, 2022; DOI: https://doi.org/10.3350/cmh.2022.0424

Abstract
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Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, with a global prevalence of approximately 30%. However, the prevalence of NAFLD has been variously reported depending on the comorbidities. The rising prevalence of obesity in both the adult and pediatric populations is projected to consequently continue increasing NAFLD prevalence. It is a major cause of chronic liver disease worldwide, including cirrhosis and hepatocellular carcinoma (HCC). NAFLD has a variety of clinical phenotypes and heterogeneity due to the complexity of pathogenesis and clinical conditions of its occurrence, resulting in various clinical prognoses. In this article, we briefly described the basic definition of NAFLD and classified the subtypes based on current knowledge in this field.

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Original Article

Steatotic liver disease

The independent effect of exercise on biopsy-proven non-alcoholic fatty liver disease: A systematic review: George Chen, Bubu Banini, Albert Do, Joseph K. Lim; Clin Mol Hepatol 2023;29(Suppl):S319-S332.
Published online December 14, 2022; DOI: https://doi.org/10.3350/cmh.2022.0366

Abstract
PDF

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Although previous studies have demonstrated that exercise independently reduces hepatic steatosis measured by imaging modalities in NAFLD, the effect of exercise on histological endpoints remains unclear. We aimed to conduct a systematic review of the independent effect of exercise on hepatic steatosis, steatohepatitis, and liver fibrosis as measured by histological assessment or non-invasive tests (NITs) in biopsy-proven NAFLD. A systematic literature search of PubMed, Embase, and Web of Science databases was performed using keywords related to exercise, NAFLD, and biopsy. Articles were selected based on the following inclusion criteria: (1) involved human subjects with biopsy-proven NAFLD, (2) analyzed the independent effect of exercise, (3) assessed changes in hepatic steatosis, steatohepatitis, or liver fibrosis via either histological evaluation or NITs, and (4) were original research studies. We identified a total of six studies that analyzed the independent effect of exercise on histological endpoints in biopsy-proven NAFLD. Two randomized controlled trials (RCTs) did not detect significant histological improvement following exercise interventions, while other non-randomized interventional studies showed that exercise reduces hepatocyte ballooning and liver fibrosis. In addition, five studies assessed NIT outcomes, collectively demonstrating that exercise improves hepatic steatosis measured by magnetic resonance imaging-based techniques but not serum biomarkers for steatohepatitis and liver fibrosis. Additional large RCTs and meta-analyses are warranted to investigate the independent effect of exercise on histological and clinical outcome endpoints in NAFLD.

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Reviews in Cardiovascular Medicine.2023;[Epub] CrossRef

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Reviews

Steatotic liver disease

Non-invasive imaging biomarkers for liver steatosis in non-alcoholic fatty liver disease: present and future: Asako Nogami, Masato Yoneda, Michihiro Iwaki, Takashi Kobayashi, Yasushi Honda, Yuji Ogawa, Kento Imajo, Satoru Saito, Atsushi Nakajima; Clin Mol Hepatol 2023;29(Suppl):S123-S135.
Published online December 12, 2022; DOI: https://doi.org/10.3350/cmh.2022.0357

Abstract
PDF

Non-alcoholic fatty liver disease is currently the most common chronic liver disease, affecting up to 25% of the global population. Simple fatty liver, in which fat is deposited in the liver without fibrosis, has been regarded as a benign disease in the past, but it is now known to be prognostic. In the future, more emphasis should be placed on the quantification of liver fat. Traditionally, fatty liver has been assessed by histological evaluation, which requires an invasive examination; however, technological innovations have made it possible to evaluate fatty liver by non-invasive imaging methods, such as ultrasonography, computed tomography, and magnetic resonance imaging. In addition, quantitative as well as qualitative measurements for the detection of fatty liver have become available. In this review, we summarize the currently used qualitative evaluations of fatty liver and discuss quantitative evaluations that are expected to further develop in the future.

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Steatotic liver disease

Identification of high-risk subjects in nonalcoholic fatty liver disease: Christiane Stern, Laurent Castera; Clin Mol Hepatol 2023;29(Suppl):S196-S206.
Published online December 5, 2022; DOI: https://doi.org/10.3350/cmh.2022.0431

Abstract
PDF

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease worldwide, and its burden is expected to increase due to the growing epidemic of obesity and diabetes. The key challenge among NAFLD patients is to identify those with advanced fibrosis (F3F4), who are at high risk of developing complications and will benefit from specialized management and treatment with new pharmacotherapies when they are approved. Liver biopsy appears unrealistic and unsuitable in practice, given the large number of high-risk patients and its well-known limitations. Non-invasive sequential algorithms using fibrosis-4 index as first-line test, followed by vibration-controlled transient elastography or patented blood test, are the best strategy for case finding of high-risk subjects. In fact, they are now recommended by several international guidelines, and should be used and disseminated to increase awareness among physicians beyond liver clinics where most NAFLD patients are seen.

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Letter to the Editor

Steatotic liver disease

Correspondence on Letter regarding “The usefulness of metabolic score for insulin resistance for the prediction of incident non-alcoholic fatty liver disease in Korean adults”: Jun-Hyuk Lee, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn; Clin Mol Hepatol 2023;29(1):179-181.
Published online November 22, 2022; DOI: https://doi.org/10.3350/cmh.2022.0409

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Impact of smoking cessation on non-alcoholic fatty liver disease prevalence: a systematic review and meta-analysis
Shengan Zhang, Zhidong Liu, Qinghua Yang, Zichun Hu, Wenjun Zhou, Guang Ji, Yanqi Dang
BMJ Open.2023; 13(12): e074216. CrossRef

5,707 View
54 Download
1 Web of Science
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Reviews

Steatotic liver disease

Causes and risk profiles of mortality among individuals with nonalcoholic fatty liver disease: Peter Konyn, Aijaz Ahmed, Donghee Kim; Clin Mol Hepatol 2023;29(Suppl):S43-S57.
Published online November 22, 2022; DOI: https://doi.org/10.3350/cmh.2022.0351

Abstract
PDF

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and worldwide. Though nonalcoholic fatty liver per se may not be independently associated with an increased risk for all-cause mortality, it is associated with a number of harmful metabolic risk factors, such as type 2 diabetes mellitus, hyperlipidemia, obesity, a sedentary lifestyle, and an unhealthy diet. The fibrosis stage is a predictor of all-cause mortality in NAFLD. Mortality in individuals with NAFLD has been steadily increasing, and the most common cause-specific mortality for NAFLD is cardiovascular disease, followed by extra-hepatic cancer, liver-related mortality, and diabetes. High-risk profiles for mortality in NAFLD include PNPLA3 I148M polymorphism, low thyroid function and hypothyroidism, and sarcopenia. Achieving weight loss through adherence to a high-quality diet and sufficient physical activity is the most important predictor of improvement in NAFLD severity and the benefit of survival. Given the increasing health burden of NAFLD, future studies with more long-term mortality data may demonstrate an independent association between NAFLD and mortality.

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Steatotic liver disease

Non-alcoholic fatty liver disease: the pathologist’s perspective: Wei-Qiang Leow, Anthony Wing-Hung Chan, Paulo Giovanni L. Mendoza, Regina Lo, Kihan Yap, Haeryoung Kim; Clin Mol Hepatol 2023;29(Suppl):S302-S318.
Published online November 15, 2022; DOI: https://doi.org/10.3350/cmh.2022.0329

Abstract
PDF

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases characterized by fatty accumulation in hepatocytes, ranging from steatosis, non-alcoholic steatohepatitis, to cirrhosis. While histopathological evaluation of liver biopsies plays a central role in the diagnosis of NAFLD, limitations such as the problem of interobserver variability still exist and active research is underway to improve the diagnostic utility of liver biopsies. In this article, we provide a comprehensive overview of the histopathological features of NAFLD, the current grading and staging systems, and discuss the present and future roles of liver biopsies in the diagnosis and prognostication of NAFLD.

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Letters to the Editor

Steatotic liver disease

Letter regarding “The usefulness of metabolic score for insulin resistance for the prediction of incident non-alcoholic fatty liver disease in Korean adults”: Hye Won Lee; Clin Mol Hepatol 2023;29(1):169-170.
Published online November 10, 2022; DOI: https://doi.org/10.3350/cmh.2022.0384

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Correspondence on Letter regarding “The usefulness of metabolic score for insulin resistance for the prediction of incident non-alcoholic fatty liver disease in Korean adults”
Jun-Hyuk Lee, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn
Clinical and Molecular Hepatology.2023; 29(1): 179. CrossRef

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Steatotic liver disease

Correspondence on Letter regarding “Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF-κB signaling pathways”: Seung Min Lee, Dae Won Jun; Clin Mol Hepatol 2023;29(1):171-172.
Published online November 10, 2022; DOI: https://doi.org/10.3350/cmh.2022.0381

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COVID-19

Correspondence on Letter regarding “COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: A meta-analysis”: Ka Shing Cheung, Chiu Hang Mok, Wai Kay Seto, Man Fung Yuen; Clin Mol Hepatol 2023;29(1):176-178.
Published online November 10, 2022; DOI: https://doi.org/10.3350/cmh.2022.0377

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Correspondence

Steatotic liver disease

Correspondence on Editorial regarding “Screening and prediction of nonalcoholic fatty liver disease using a peripheral insulin resistance index: Potential benefits and limitations”: Jun-Hyuk Lee, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn; Clin Mol Hepatol 2023;29(1):185-187.
Published online November 10, 2022; DOI: https://doi.org/10.3350/cmh.2022.0375

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Letters to the Editor

Steatotic liver disease

Letter regarding “Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF-κB signaling pathways”: Yuanbin Liu, Mingkai Chen; Clin Mol Hepatol 2023;29(1):163-164.
Published online October 27, 2022; DOI: https://doi.org/10.3350/cmh.2022.0326

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Correspondence on Letter regarding “Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF-κB signaling pathways”
Seung Min Lee, Dae Won Jun
Clinical and Molecular Hepatology.2023; 29(1): 171. CrossRef

6,440 View
70 Download
1 Web of Science
Crossref

Non-alcoholic fatty liver disease and risk of dementia: Unmet need for a pooled analysis of cohort studies: Seogsong Jeong, Won Kim, Sang Min Park; Clin Mol Hepatol 2022;28(4):933-934.
Published online September 14, 2022; DOI: https://doi.org/10.3350/cmh.2022.0267

Citations

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Lean Metabolic Dysfunction-Associated Steatotic Liver Disease and Dementia Risk: A High-Risk Phenotype beyond Body Mass Index
Seogsong Jeong
Gut and Liver.2026; 20(1): 3. CrossRef
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Paige N Braden-Kuhle, Vivienne A Lacy, Kelly N Brice, Morgan E Bertrand, Hatice Buse Uras, Catherine Shoffner, Bridgette E Fischer, Ashish Rana, Jada L Willis, Gary W Boehm, Michael J Chumley
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Review

Hepatic neoplasm

Hepatocellular carcinoma surveillance in patients with non-alcoholic fatty liver disease: Karim Seif El Dahan, Darine Daher, Amit G. Singal; Clin Mol Hepatol 2023;29(Suppl):S207-S219.
Published online September 14, 2022; DOI: https://doi.org/10.3350/cmh.2022.0247

Abstract
PDF

Non-alcoholic fatty liver disease (NAFLD) may progress to cirrhotic or non-cirrhotic hepatocellular carcinoma (HCC), and is currently recognized as the fastest growing cause of HCC worldwide. Accordingly, professional society guidelines recommend HCC surveillance in patients with cirrhosis from any etiology, and some may consider it beneficial in subgroups with non-cirrhotic NAFLD at higher risk for HCC. Notably, patients with NAFLD-related HCC are more likely to have HCC diagnosed at more advanced stages and have poorer outcomes when compared to other etiologies, and suboptimal effectiveness of HCC surveillance programs is a major culprit. In this review, we summarize the current guidelines for HCC surveillance and discuss its benefits versus potential harms for NAFLD patients. We also address the unique challenges of HCC surveillance in NAFLD, including higher proportion of NAFLD-related HCC without cirrhosis, poor recognition of at-risk patients, lack of consensus regarding the value of surveillance in non-cirrhotic NAFLD, subpar effectiveness of surveillance tools related to NAFLD phenotype, and preponderant surveillance underuse among NAFLD patients. Finally, we examine the effectiveness of currently used surveillance tools (i.e., ultrasound and alpha fetoprotein) and outline future perspectives including emerging risk stratification tools, imaging surveillance strategies (e.g., abbreviated magnetic resonance imaging protocols), blood-based biomarkers (e.g., GALAD and circulating tumor DNA panels), and interventions to improve surveillance adherence.

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Yang Ma, Jinguo Wang, Wenping Xiao, Xiaoming Fan
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Letter to the Editor

Non-alcoholic fatty liver disease and the risk of dementia: A meta-analysis of cohort studies: Li-Yu Lu, Min-You Wu, Yung-Shuo Kao, Cheng-Hsien Hung; Clin Mol Hepatol 2022;28(4):931-932.
Published online September 5, 2022; DOI: https://doi.org/10.3350/cmh.2022.0259

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Review

Hepatic neoplasm

Development and prognosis of hepatocellular carcinoma in patients with diabetes: Takuma Nakatsuka, Ryosuke Tateishi; Clin Mol Hepatol 2023;29(1):51-64.
Published online July 29, 2022; DOI: https://doi.org/10.3350/cmh.2022.0095

Abstract
PDF

The incidence of diabetes mellitus and hepatocellular carcinoma (HCC) has been increasing worldwide during the last few decades, in the context of an increasing prevalence of obesity and non-alcoholic fatty liver disease (NAFLD). Epidemiologic studies have revealed that patients with diabetes have a 2- to 3-fold increased risk of developing HCC, independent of the severity and cause of the underlying liver disease. A bidirectional relationship exists between diabetes and liver disease: advanced liver disease promotes the onset of diabetes, and HCC is an important cause of death in patients with diabetes; conversely, diabetes is a risk factor for liver fibrosis progression and HCC development, and may worsen the long-term prognosis of patients with HCC. The existence of close interconnections among diabetes, obesity, and NAFLD causes insulin resistance-related hyperinsulinemia, increased oxidative stress, and chronic inflammation, which are assumed to be the underlying causes of hepatocarcinogenesis in patients with diabetes. No appropriate surveillance methods for HCC development in patients with diabetes have been established, and liver diseases, including HCC, are often overlooked as complications of diabetes. Although some antidiabetic drugs are expected to prevent HCC development, further research on the optimal use of antidiabetic drugs aimed at hepatoprotection is warranted. Given the increasing medical and socioeconomic impact of diabetes on HCC development, diabetologists and hepatologists need to work together to develop strategies to address this emerging health issue. This article reviews the current knowledge on the impact of diabetes on the development and progression of HCC.

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Original Articles

The usefulness of metabolic score for insulin resistance for the prediction of incident non-alcoholic fatty liver disease in Korean adults: Jun-Hyuk Lee, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn; Clin Mol Hepatol 2022;28(4):814-826.
Published online June 9, 2022; DOI: https://doi.org/10.3350/cmh.2022.0099

Abstract
PDF

Background/Aims
The early detection and prevention of non-alcoholic fatty liver disease (NAFLD) has been emphasized considering the burden of this disease. Both hepatic and peripheral insulin resistances are strongly associated with NAFLD. We aimed to compare the predictive powers of a hepatic insulin resistance index, the homeostatic model assessment for insulin resistance (HOMA-IR), and a novel peripheral insulin resistance index, the metabolic score for insulin resistance (METS-IR), for the prediction of prevalent and incident NAFLD.
Methods
Data from 8,360 adults aged 40–69 years at baseline and 5,438 adults without NAFLD who were followed-up at least once after the baseline survey in the Korean Genome and Epidemiology Study were analyzed. The survey was performed biennially, up to the eighth follow-up.
Results
The predictive powers of the METS-IR and HOMA-IR for prevalent NAFLD were not significantly different (area under the receiver operating characteristic [ROC] curve [95% confidence interval]: METS-IR, 0.824 [0.814–0.834]; HOMAIR, 0.831 [0.821–0.842]; P=0.276). The area under the time-dependent ROC curve (Heagerty’s integrated area under the curve) of the METS-IR for incident NAFLD was 0.683 (0.671–0.695), significantly higher than that of the HOMA-IR (0.551 [0.539–0.563], P<0.001).
Conclusions
The METS-IR is superior to the HOMA-IR for the prediction of incident NAFLD and is not inferior to the HOMA-IR for the prediction of prevalent NAFLD. This suggests that the METS-IR can be a more useful insulin resistance index than the HOMA-IR for the early detection and prevention of NAFLD in Korean population.

Citations

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COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: A meta-analysis: Ka Shing Cheung, Chiu Hang Mok, Xianhua Mao, Ruiqi Zhang, Ivan FN Hung, Wai Kay Seto, Man Fung Yuen; Clin Mol Hepatol 2022;28(4):890-911.
Published online June 3, 2022; DOI: https://doi.org/10.3350/cmh.2022.0087

Background/Aims
Data of coronavirus disease 2019 (COVID-19) vaccine immunogenicity among chronic liver disease (CLD) and liver transplant (LT) patients are conflicting. We performed meta-analysis to examine vaccine immunogenicity regarding etiology, cirrhosis status, vaccine platform and type of antibody.
Methods
We collected data via three databases from inception to February 16, 2022, and reported pooled seroconversion rate, T cell response and safety data after two vaccine doses.
Results
Twenty-eight (CLD only: 5; LT only: 18; both: 2; LT with third dose: 3) observational studies of 3,945 patients were included. For CLD patients, seroconversion rate ranged between 84% (95% confidence interval [CI], 76–90%) and 91% (95% CI, 83–95%), based predominantly on neutralizing antibody and anti-spike antibody, respectively. Seroconversion rate was 81% (95% CI, 76–86%) in chronic hepatitis B, 96% (95% CI, 93–97%) in non-alcoholic fatty liver disease, 85% (95% CI, 75–91%) in cirrhosis and 85% (95% CI, 78–90%) in non-cirrhosis, 86% (95% CI, 78–92%) for inactivated vaccine and 89% (95% CI, 71–96%) for mRNA vaccine. The pooled seroconversion rate of anti-spike antibody was 66% (95% CI, 55–75%) after two doses of mRNA vaccines and 88% (95% CI, 58–98%) after third dose among LT recipients. T cell response rate was 65% (95% CI, 30–89%). Prevalence of adverse events was 27% (95% CI, 18–38%) and 63% (95% CI, 39–82%) among CLD and LT groups, respectively.
Conclusions
CLD patients had good humoral response to COVID-19 vaccine, while LT recipients had lower response.

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The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease: Cheng Han Ng, Kai En Chan, Yip Han Chin, Rebecca Wenling Zeng, Pei Chen Tsai, Wen Hui Lim, Darren Jun Hao Tan, Chin Meng Khoo, Lay Hoon Goh, Zheng Jye Ling, Anand Kulkarni, Lung-Yi Loey Mak, Daniel Q Huang, Mark Chan, Nicholas WS Chew, Mohammad Shadab Siddiqui, Arun J. Sanyal, Mark Muthiah; Clin Mol Hepatol 2022;28(3):565-574.
Published online May 19, 2022; DOI: https://doi.org/10.3350/cmh.2022.0096

Abstract
PDF

Background/Aims
Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals.
Methods
Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk.
Results
Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality.
Conclusions
Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.

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Editorial

Association of nonalcoholic fatty liver disease with incident dementia later in life among elderly adults: Byoung Seok Ye; Clin Mol Hepatol 2022;28(3):481-482.
Published online May 16, 2022; DOI: https://doi.org/10.3350/cmh.2022.0097

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Seul Ki Han, Soon Koo Baik, Moon Young Kim
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Original Article

Effect of moderate-to-severe hepatic steatosis on neutralising antibody response among BNT162b2 and CoronaVac recipients: Ka Shing Cheung, Lok Ka Lam, Rex Wan Hin Hui, Xianhua Mao, Ruiqi R Zhang, Kwok Hung Chan, Ivan FN Hung, Wai Kay Seto, Man-Fung Yuen; Clin Mol Hepatol 2022;28(3):553-564.
Published online May 11, 2022; DOI: https://doi.org/10.3350/cmh.2022.0082

Background/Aims
Studies of hepatic steatosis (HS) effect on COVID-19 vaccine immunogenicity are lacking. We aimed to compare immunogenicity of BNT162b2 and CoronaVac among moderate/severe HS and control subjects.
Methods
Two hundred ninety-five subjects who received BNT162b2 or CoronaVac vaccines from five vaccination centers were categorized into moderate/severe HS (controlled attenuation parameter ≥268 dB/m on transient elastography) (n=74) or control (n=221) groups. Primary outcomes were seroconversion rates of neutralising antibody by live virus Microneutralization (vMN) assay (titer ≥10) at day21 (BNT162b2) or day28 (CoronaVac) and day56 (both). Secondary outcome was highest-tier titer response (top 25% of vMN titer; cutoff: 160 [BNT162b2] and 20 [CoronaVac]) at day 56.
Results
For BNT162b2 (n=228, 77.3%), there was no statistical differences in seroconversion rates (day21: 71.7% vs. 76.6%; day56: 100% vs. 100%) or vMN geometric mean titer (GMT) (day21: 13.2 vs. 13.3; day56: 91.9 vs. 101.4) among moderate/severe HS and control groups respectively. However, lower proportion of moderate/severe HS patients had highest-tier response (day56: 5.0% vs. 15.5%; P=0.037). For CoronaVac (n=67, 22.7%), there was no statistical differences in seroconversion rates (day21: 7.1% vs. 15.1%; day56: 64.3% vs. 83.0%) or vMN GMT (5.3 vs. 5.8,) at day28. However, moderate/severe HS patients had lower vMN GMT (9.1 vs. 14.8, P=0.021) at day 56 with lower proportion having highest-tier response (21.4% vs. 52.8%, P=0.036).
Conclusions
While there was no difference in seroconversion rate between moderate/severe HS and control groups after two doses of vaccine, a lower proportion of moderate/severe HS patients achieved highest-tier response for either BNT162b2 or CoronaVac.

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