Steatotic liver disease (SLD) is a leading cause of disease globally and demands new therapeutic approaches to mitigate underlying metabolic dysregulation. Incretin-based therapies are emerging as a viable prospect to fulfil this unmet niche. A literature review to inform the evidence base for incretin focussed pharmacology in the metabolic liver diseases space and an informed commentary on unmet areas of need. Incretin-based therapeutics demonstrate multifarious benefits across the chronic metabolic disease spectrum with promising data across the continuum of pathology.
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Pojsakorn Danpanichkul, Luis Antonio Díaz, Kanokphong Suparan, Primrose Tothanarungroj, Supapitch Sirimangklanurak, Thanida Auttapracha, Hanna L. Blaney, Banthoon Sukphutanan, Yanfang Pang, Siwanart Kongarin, Francisco Idalsoaga, Eduardo Fuentes-López, Lorenzo Leggio, Mazen Noureddin, Trenton M. White, Alexandre Louvet, Philippe Mathurin, Rohit Loomba, Patrick S. Kamath, Jürgen Rehm, Jeffrey V. Lazarus, Karn Wijarnpreecha, Juan Pablo Arab
Clin Mol Hepatol 2025;31(2):525-547. Published online January 9, 2025
Background/Aims Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000–2021.
Methods We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database. We estimated the annual percent change (APC) and its 95% confidence interval (CI) to assess changes in age-standardized rates over time.
Results In 2021, there were 111.12 million cases of AUD, 3.02 million cases of ALD, and 132,030 cases of alcohol-attributable primary liver cancer. Between 2000 and 2021, there was a 14.66% increase in AUD, a 38.68% increase in ALD, and a 94.12% increase in alcohol-attributable primary liver cancer prevalence. While the age-standardized prevalence rate for liver cancer from alcohol increased (APC 0.59%; 95% confidence interval [CI] 0.52 to 0.67%) over these years, it decreased for ALD (APC –0.71%; 95% CI –0.75 to –0.67%) and AUD (APC –0.90%; 95% CI –0.94 to –0.86%). There was significant variation by region, socioeconomic development level, and sex. During the last years (2019–2021), the prevalence, incidence, and death of ALD increased to a greater extent in females.
Conclusions Given the high burden of AUD, ALD, and alcohol-attributable primary liver cancer, urgent measures are needed to prevent them at both global and national levels.
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Background/Aims Multi-society experts proposed the adoption of new terminology, metabolic dysfunctionassociated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US.
Methods Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature.
Results The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI] 33.4–36.7). Within this category, the age-adjusted prevalence for MASLD was 31.9% (95% CI 30.4–33.4), MetALD 2.2% (95% CI 1.8–2.6), and ALD 0.8% (95% CI 0.6–1.1). The prevalence of SLD and MASLD showed a statistically insignificant decrease during COVID-19, while ALD increased without significance. In contrast, the prevalence of advanced fibrosis in SLD was significantly higher during the COVID-19 era, at 9.8% for 285 dB/m and 7.8% for 263 dB/m, compared to 7.4% (P=0.039) and 6% (P=0.041) in the pre-COVID-19 era. The proportion of advanced fibrosis and cirrhosis in individuals with ALD was two-fold higher than MASLD and MetALD, largely due to increases during the COVID-19 era.
Conclusions While the prevalence of SLD and its subcategories remained stable, there was a significant increase in advanced fibrosis among SLD individuals during the COVID-19 era, with ALD having a proportion of advanced fibrosis and cirrhosis that was twice as high as MASLD and MetALD.
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Darren Jun Hao Tan, Sabrina Xin Zi Quek, Jie Ning Yong, Adithya Suresh, Kaiser Xuan Ming Koh, Wen Hui Lim, Jingxuan Quek, Ansel Tang, Caitlyn Tan, Benjamin Nah, Eunice Tan, Taisei Keitoku, Mark D. Muthiah, Nicholas Syn, Cheng Han Ng, Beom Kyung Kim, Nobuharu Tamaki, Cyrus Su Hui Ho, Rohit Loomba, Daniel Q. Huang
Clin Mol Hepatol 2022;28(4):864-875. Published online July 25, 2022
Background/Aims Depression and anxiety are associated with poorer outcomes in patients with hepatocellular carcinoma (HCC). However, the prevalence of depression and anxiety in HCC are unclear. We aimed to establish the prevalence of depression and anxiety in patients with HCC.
Methods MEDLINE and Embase were searched and original articles reporting prevalence of anxiety or depression in patients with HCC were included. A generalized linear mixed model with Clopper-Pearson intervals was used to obtain the pooled prevalence of depression and anxiety in patients with HCC. Risk factors were analyzed via a fractional-logistic regression model.
Results Seventeen articles involving 64,247 patients with HCC were included. The pooled prevalence of depression and anxiety in patients with HCC was 24.04% (95% confidence interval [CI], 13.99–38.11%) and 22.20% (95% CI, 10.07–42.09%) respectively. Subgroup analysis determined that the prevalence of depression was lowest in studies where depression was diagnosed via clinician-administered scales (16.07%;95% CI, 4.42–44.20%) and highest in self-reported scales (30.03%; 95% CI, 17.19–47.01%). Depression in patients with HCC was lowest in the Americas (16.44%; 95% CI, 6.37–36.27%) and highest in South-East Asia (66.67%; 95% CI, 56.68–75.35%). Alcohol consumption, cirrhosis, and college education significantly increased risk of depression in patients with HCC.
Conclusions One in four patients with HCC have depression, while one in five have anxiety. Further studies are required to validate these findings, as seen from the wide CIs in certain subgroup analyses. Screening strategies for depression and anxiety should also be developed for patients with HCC.
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