Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions.

Globally, nearly half of deaths from cirrhosis and chronic liver diseases (CLD) and three-quarters of deaths from hepatocellular carcinoma (HCC) occur in the Asia-Pacific region. Chronic hepatitis B is responsible for the vast majority of liver-related deaths in the region. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of CLD, affecting an estimated 30% of the adult population. Compared with people of European descent, people from the Asia-Pacific region carry more genetic variants associated with MASLD and its progression. Alcohol is a fast-growing cause of CLD and HCC in Asia as a result of the rising per-capita consumption of alcohol. Drug-induced liver injury is under-recognized and probably has a high prevalence in this region. The epidemiological and outcome data of acute-on-chronic liver failure are heterogeneous, and non-unified definitions across regions contribute to this heterogeneity. CLDs are severely underdiagnosed, and effective treatments and vaccinations are underutilized. In this Review, we highlight trends in the burden of CLD and HCC in the Asia-Pacific region and discuss the rapidly changing aetiologies of liver disease. We examine the multiple gaps in the care cascade and propose mitigating strategies and future directions.

Liver stiffness progression in biopsy-proven metabolic dysfunction-associated steatotic disease among people with diabetes versus people without diabetes: A prospective multicenter study.

BACKGROUND AND AIMS: There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes mellitus (T2DM) versus those without T2DM in biopsy-proven metabolic dysfunction-associated steatotic liver disease. We examined LSM progression in participants with T2DM versus those without T2DM in a large, prospective, multicenter cohort study. APPROACH AND RESULTS: This study included 1231 adult participants (62% female) with biopsy-proven metabolic dysfunction-associated steatotic liver disease who had VCTEs at least 1 year apart. LSM progression and regression were defined by a ≥20% increase and an upward or downward change, respectively, in the LSM category in the Baveno VII categories for compensated advanced chronic liver disease, compared between participants with T2DM (n = 680) versus no T2DM (n = 551) at baseline. The mean (±SD) age and body mass index were 51.8 (±12.0) years and 34.0 (±6.5) kg/m 2 , respectively. The median (IQR) time between the first and last VCTE measurements was 4.1 (2.5-6.5) years. Participants with T2DM had higher LSM progression at 4 years (12% vs. 10%), 6 years (23% vs. 16%), and 8 years (50% vs. 39%), p = 0.04. Using a multivariable Cox proportional hazards model adjusted for multiple confounders, the presence of T2DM remained an independent predictor of LSM progression (adjusted HR: 1.35, 95% CI: 1.01-1.81, p = 0.04). T2DM was not associated with LSM regression ( p = 0.71). Mean HbA1c was significantly associated with LSM progression ( p = 0.003) and regression ( p = 0.02). CONCLUSIONS: Using serial VCTE data from a multicenter study of participants with biopsy-proven metabolic dysfunction-associated steatotic liver disease, we demonstrate that T2DM and HbA1c are associated with LSM progression.

Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study.

Background and Aims: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. Methods: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. Results: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. Conclusions: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

Global Prevalence, Clinical Characteristics, Surveillance, Treatment Allocation, and Outcomes of Alcohol-Associated Hepatocellular Carcinoma.

BACKGROUND: Although the burden of alcohol-associated hepatocellular carcinoma (HCC) is increasing with rising alcohol consumption, clinical presentation and outcomes of alcohol-associated HCC have not been systematically assessed. We aimed to determine the prevalence, clinical characteristics, surveillance rates, treatment allocation, and outcomes of alcohol-associated HCC. METHODS: Medline and Embase were searched from inception to January 2023. Proportional data were analyzed using a generalized linear mixed model. The odds ratio (OR) or mean difference comparing alcohol-associated HCC and other causes was obtained with pairwise meta-analysis. Survival outcomes were evaluated using a pooled analysis of hazard ratios. RESULTS: Of 4824 records identified, 55 articles (86,345 patients) were included. Overall, 30.4% (95% confidence interval [CI], 24.0%-37.7%) of HCC was alcohol associated, with the highest proportion in Europe and the lowest in the Americas. People with alcohol-associated HCC were more likely male but were similar in age and comorbidities compared with other causes. A total of 20.8% (95% CI, 11.4%-34.9%) of people with alcohol-associated HCC underwent surveillance compared with 35.0%, 31.6%, and 21.4% in hepatitis B virus, hepatitis C virus, and metabolic dysfunction-associated HCC, respectively (all P < .05). Alcohol-associated HCC had a lower likelihood of Barcelona Clínic Liver Cancer C stage (0/A) (OR, 0.7; 95% CI, 0.6-0.9; P = .018) and curative therapy (24.5% vs 33.9%; OR, 0.7; 95% CI, 0.5-0.9; P = .003), and higher mortality (HR, 1.3; 95% CI, 1.1-1.5; P = .012) when compared with other causes. CONCLUSIONS: Alcohol-associated HCC is associated with lower surveillance rates, more advanced BCLC stage, lower likelihood of receiving curative therapy, and poorer survival. These data call for measures to reduce heavy alcohol consumption and improve strategies for effective HCC surveillance in high-risk individuals.

Comparative efficacy of pharmacologic therapies for MASH in reducing liver fat content: Systematic review and network meta-analysis.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. Dynamic changes in MRI proton-density-fat fraction (PDFF) are associated with MASH resolution. We aimed to determine the relative efficacy of therapeutic agents for reducing hepatic fat, assessed by MRI-PDFF. APPROACH AND RESULTS: In this systematic review and network meta-analysis, we searched MEDLINE and Embase from inception until December 26, 2023, for published randomized controlled trials comparing pharmacological interventions in patients with MASH that assessed changes in MRI-PDFF. The primary outcome was the absolute change in MRI-PDFF. The secondary outcome was a ≥30% decline in MRI-PDFF. A surface under-the-curve cumulative ranking probabilities (SUCRA) analysis was performed. Of 1550 records, a total of 39 randomized controlled trials (3311 participants) met the inclusion criteria. For MRI-PDFF decline at 24 weeks, aldafermin (SUCRA: 83.65), pegozafermin (SUCRA: 83.46), and pioglitazone (SUCRA: 71.67) were ranked the most effective interventions. At 24 weeks, efinopegdutide (SUCRA: 67.02), semaglutide + firsocostat (SUCRA: 62.43), and pegbelfermin (SUCRA: 61.68) were ranked the most effective interventions for achieving a ≥30% decline in MRI-PDFF. CONCLUSIONS: This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat. These data may help inform the design and sample size calculation of future clinical trials and assist in the selection of combination therapy.

Repeatability of vibration-controlled transient elastography versus magnetic resonance elastography in patients with cirrhosis: A prospective study.

BACKGROUND AND AIMS: Magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE) have the potential to assess disease progression; however, repeatability data in people with cirrhosis are lacking. We aimed to assess the effect of disease severity on measurement variability and contribute to the evidentiary basis for the qualification of repeating liver stiffness measurements (LSM) in practice and research. METHODS: This prospective study included 49 adult participants (58.3% female) with cirrhosis who underwent same-day repeat LSM examinations. The primary outcome was the same-day, same-operator repeatability coefficient% (RC%) and the within-case coefficient of variation (wCV) for each modality. Secondary outcomes include the intra-class correlation coefficient (ICC). The relationship between measurement variability (interquartile for VCTE, standard deviation for MRE) and disease severity (mean liver stiffness) was evaluated by linear regression with the coefficient of determination R2 reported. RESULTS: Same-day repeat MRE and VCTE exams were prospectively conducted in 33 and 45 participants, respectively. The RC% appeared 82% higher for VCTE versus MRE (38% vs. 21%), with consistent findings in head-to-head analyses. The wCV for VCTE and MRE was 14% and 8% respectively, indicating VCTE has 75% higher within-subject measurement variation than MRE. ICC was excellent for LSM by VCTE (0.92) and MRE (0.96). Measurement variability increased with mean liver stiffness for VCTE (R2 = 0.78) and MRE (R2 = 0.93). CONCLUSION: Both VCTE and MRE demonstrated increased measurement variability with disease severity. However, MRE outperformed VCTE in terms of technical repeatability in patients with cirrhosis. These repeatability estimates may improve the qualification of NITs in practice.

Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.

BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium. METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses. RESULTS: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001). CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed. IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.

The Burden of Overweight and Obesity-Associated Gastrointestinal Cancers in Low and Lower-Middle-Income Countries: A Global Burden of Disease 2019 Analysis.

INTRODUCTION: Obesity is associated with cancer, including gastrointestinal (GI). Data from low (LICs) and lower-middle-income countries (MICs) are limited. METHODS: We utilized data from the Global Burden of Disease Study 2019 to determine the mortality from GI cancer risk of high body mass index (BMI) in these countries. RESULTS: Mortality rates of GI cancers from high BMI increased in LICs and lower MICs, while burdens decreased or remained stable in high and middle-income countries. DISCUSSION: The GI cancer-related burden from high BMI increased in LICs and lower MICs, necessitating a concerted effort to tackle the obesity pandemic.

Sex-based Disparities in Liver Transplantation for Hepatocellular Carcinoma and the Impact of the Growing Burden of NASH.

Background: The cause of liver disease is changing, but its impact on liver transplantation (LT) for hepatocellular carcinoma (HCC) in women and men is unclear. We performed a nationwide study to assess the prevalence and posttransplant survival outcomes of the various causes of liver disease in women and men with HCC. Methods: Data were obtained from the United Network for Organ Sharing database from 2000 to 2022. Data related to the listing, transplant, waitlist mortality, and posttransplant mortality for HCC were extracted. The proportion of HCC related to the various causes of liver disease among LT candidates and recipients and posttransplant survival were compared between women and men. Results: A total of 51 721 individuals (39 465 men, 12 256 women) with HCC were included. From 2000 to 2022, nonalcoholic steatohepatitis (NASH) was the fastest-growing cause of liver disease among female LT candidates with HCC (P < 0.01), followed by alcohol-associated liver disease. NASH overtook chronic hepatitis C as the leading cause of liver disease in 2020 and 2022 among waitlisted women and men with HCC, respectively. Female patients with HCC spent a significantly longer time on the LT waitlist compared with male patients (ß: 8.73; 95% confidence interval [CI], 2.91-14.54). Female patients with HCC from alcohol-associated liver disease also have a lower probability of receiving LT (subdistribution hazard ratio: 0.90; 95% CI, 0.82-0.99). Among transplant recipients with NASH HCC, female sex was associated with lower posttransplant mortality compared with male sex (hazard ratio: 0.79; 95% CI, 0.70-0.89; P < 0.01). Conclusions: Women have a significantly longer waitlist duration compared with men. NASH is now the leading cause of liver disease among both female and male LT candidates and recipients with HCC.

The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

AIM: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. METHODS: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. RESULTS: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002). CONCLUSION: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.

Socio-economic association of alcohol use disorder and cardiovascular and alcohol-associated liver disease from 2010 to 2019.

BACKGROUNDS AND AIMS: Alcohol use leads to disabilities and deaths worldwide. It not only harms the liver but also causes alcohol use disorder (AUD) and heart disease. Additionally, alcohol consumption contributes to health disparities among different socio-economic groups. METHODS: We estimated global and regional trends in the burden of AUD, liver disease, and cardiovascular disease from alcohol using the methodology of the Global Burden of Disease study. RESULTS: In 2019, the highest disability-adjusted life years rate per 100,000 population was due to AUD (207.31 [95% Uncertainty interval (UI) 163.71-261.66]), followed by alcohol-associated liver disease (ALD) (133.31 [95% UI 112.68-156.17]). The prevalence rate decreased for AUD (APC [annual percentage change] -0.38%) and alcohol-induced cardiomyopathy (APC -1.85%) but increased for ALD (APC 0.44%) and liver cancer (APC 0.53%). Although the mortality rate for liver cancer from alcohol increased (APC 0.30%), mortality rates from other diseases decreased. Between 2010 and 2019, the burden of alcohol-associated complications increased in countries with low and low-middle sociodemographic index (SDI), contributing more significantly to the global burden. CONCLUSION: The global burden of AUD, liver, and cardiovascular disease has been high and increasing over the past decade, particularly for liver complications. Lower SDI countries are contributing more to this global burden. There is a pressing need for effective strategies to address this escalating burden.

Quantitative HBeAg is a strong predictor of HBeAg loss among patients receiving pegylated interferon.

BACKGROUND: HBeAg loss is an important endpoint for antiviral therapy in chronic hepatitis B (CHB), however there are no reliable biomarkers to identify patients who will respond to the addition of pegylated interferon to nucleos(t)ide analogue (NA) therapy. AIM: To evaluate the use of serum biomarkers to predict HBeAg loss. METHODS: HBeAg positive CHB participants on NAs who switched-to or added-on 48 weeks pegylated interferon alpha2b (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBeAg loss. The predictive ability of qHBeAg, qHBsAg, HBV RNA and clinical variables for HBeAg loss were investigated. RESULTS: HBeAg loss occurred in 15/55 (27.3%) participants who completed 48 weeks of pegylated interferon. There was a lower baseline qHBeAg (1.18 IU/mL [2.27] versus 10.04 IU/mL [24.87], P = 0.007) among participants who lost HBeAg. Baseline qHBeAg (OR = 0.15, 95% CI 0.03-0.66, P = 0.01) and detectable HBV DNA at baseline (OR = 25.00, 95% CI 1.67-374.70, P = 0.02) were independent predictors of HBeAg loss. In addition, on-treatment qHBeAg was also a strong predictor of HBeAg loss (OR = 0.39, 95% CI 0.18-0.81, P = 0.012). The models combining detectable baseline HBV DNA with baseline (C-statistic 0.82) and on-treatment (C-statistic 0.83) had good accuracy for predicting HBeAg loss. A rise in qHBeAg ≥ 10 IU/ml was a predictor of flare (ALT ≥ 120 U/ml) on univariable analysis but not after adjustment for treatment arm. CONCLUSIONS: Baseline and on-treatment qHBeAg is a useful biomarker that can identify participants on NA therapy who may benefit from adding or switching to pegylated interferon.

Changing global epidemiology of chronic hepatitis C virus-related outcomes from 2010 to 2019: cirrhosis is the growing burden of hepatitis C virus-related disease.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) has a long-term impact on hepatic consequences. A comprehensive evaluation of the global burden of HCV-related health outcomes can help to develop a global HCV prevention and treatment program. METHODS: We used the 2019 Global Burden of Disease (GBD) Study to comprehensively investigate burden and temporal trends in incidence, mortality and disability-adjusted life-years (DALYs) of HCV-related diseases, including liver cancer and cirrhosis and other liver diseases across 264 countries and territories from 2010 to 2019. RESULTS: Globally, there were 152 225 incident cases, 141 811 deaths and approximately 2.9 million DALYs because of HCV-related liver cancer, and 551 668 incident cases, 395 022 deaths and about 12.2 million DALYs because of HCV-related cirrhosis in 2019. Worldwide, during the 2010-2019 period, liver cancer incidence declined, however, there was a 62% increase in cirrhosis incidence. In 2019, the Eastern Mediterranean was the region with the highest rates of incidence and mortality of both liver cancer and cirrhosis. Africa was the region with the fastest-growing trend of incidence of cirrhosis in the 2010-2019 period [annual percentage change (APC) = 2.09, 95% confidence interval (CI): 1.93-2.25], followed by the Western Pacific region (APC = 1.17, 95% CI: 1.09-1.22). Americas were the only region observing increased trends in liver cancer and cirrhosis mortality (APC = 0.70 and 0.12, respectively). We identified three patterns of temporal trends of mortality rates of liver cancer and cirrhosis in countries that reported HCV treatment rates. CONCLUSION: Urgent measures are required for diagnosis, treatment and research on HCV-related cirrhosis at global, regional and country levels, particularly in Africa, the Western Pacific and the Eastern Mediterranean.

Hepatocellular Carcinoma Screening in a Contemporary Cohort of At-Risk Patients.

Importance: Cohort studies demonstrating an association of hepatocellular carcinoma (HCC) screening with reduced mortality are prone to lead-time and length-time biases. Objective: To characterize the clinical benefits of HCC screening, adjusting for lead-time and length-time biases, in a diverse, contemporary cohort of at-risk patients. Design, Setting, and Participants: This retrospective cohort study of patients with HCC was conducted between January 2008 and December 2022 at 2 large US health systems. Data analysis was performed from September to November 2023. Main Outcomes and Measures: The primary outcome was screen-detected HCC, defined by abnormal screening-intent abdominal imaging or α-fetoprotein level within 6 months before diagnosis. Cox regression analysis was used to characterize differences in overall survival between patients with screen-detected and non-screen-detected HCC; lead-time and length-time adjustments were calculated using the Duffy parametric formula. Results: Among 1313 patients with HCC (mean [SD] age, 61.7 [9.6] years; 993 male [75.6%]; 739 [56.3%] with Barcelona Clinic Liver Cancer stage 0/A disease), HCC was screen-detected in 556 (42.3%) and non-screen detected in 757 (57.7%). Patients with screen-detected HCC had higher proportions of early-stage HCC (393 patients [70.7%] vs 346 patients [45.7%]; risk ratio [RR], 1.54; 95% CI, 1.41-1.70) and curative treatment receipt (283 patients [51.1%] vs 252 patients [33.5%]; RR, 1.52; 95% CI, 1.34-1.74) compared with patients with non-screen-detected HCC. The screen-detected group had significantly lower mortality, which persisted after correcting for lead-time bias (hazard ratio, 0.75; 95% CI, 0.65-0.87) in fully adjusted models. Both groups had similar tumor doubling times (median [IQR], 3.8 [2.2-10.7] vs 5.6 [1.7-11.4] months) and proportions of indolent tumors (28 patients [35.4%] vs 24 patients [38.1%]; RR, 0.93; 95% CI, 0.60-1.43). Adjustment for length-time bias decreased survival estimates, although 3-year and 5-year survival for patients with screen-detected HCC remained longer than that for patients with non-screen-detected HCC. Conclusions and Relevance: The findings of this cohort study suggest that HCC screening is associated with reduced mortality even after accounting for lead-time and length-time biases. However, these biases should be considered in future studies.

Natural history of clinical outcomes and hepatic decompensation in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: The natural progression of hepatic decompensation in metabolic dysfunction-associated steatotic liver disease (MASLD) is not well-characterised. We aimed to describe it by conducting a retrospective analysis. METHODS: This longitudinal, retrospective analysis of well-characterised MASLD cohorts followed for hepatic decompensation and death. The sequence of liver-related events was evaluated, and the median time between hepatic decompensation episodes and death versus. transplantation was measured. RESULTS: Of the 2016 patients identified, 220 (11%) developed at least one episode of hepatic decompensation during a median follow-up of 3.2 years. Ascites was the most common first liver-related event [153 (69.5%)], followed by hepatic encephalopathy (HE) [55 (25%)] and variceal haemorrhage (VH) [30 (13.6%)]. Eighteen out of the 220 (8.1%) patients had more than one liver-related event as their first hepatic decompensation. Among the patients who had the first episode, 87 (39.5%) had a second episode [44 (50.5%) HE, 31 (35.6%) ascites, and 12 (13.7%) VH]. Eighteen out of 220 (8.1%) had a third episode [10 (55.5%) HE, 6 (33.3%) VH, and 2 (11.1%) ascites]. Seventy-three out of 220 (33.1%) died, and 31 (14%) received liver transplantation. The median time from the first episode to the second was 0.7 years and 1.3 years from the second episode to the third. The median survival time from the first episode to death or transplantation was 2.0 years. CONCLUSION: The most common first liver-related event in MASLD patients is ascites. The median survival from the first hepatic decompensation to either death or transplantation is 2 years.