Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: Both metabolic dysfunction and alcohol consumption cause steatotic liver disease (SLD). The distinction between metabolic dysfunction-associated SLD (MASLD) and MetALD categories is based on arbitrary thresholds of alcohol intake. Thus, we assessed the impact of different levels of alcohol consumption on SLD severity and their interaction with metabolic comorbidities. METHODS: We performed a population-based study with transient elastography (FibroScan®) data from participants in Spain (derivation cohort) and the US (validation cohort). A controlled attenuation parameter ≥275 dB/m was used to define SLD. At least one cardiometabolic risk factor was required to define MASLD. Among patients with MASLD, low alcohol consumption was defined as an average of 5-9 drinks/week, moderate consumption as 10-13 drinks/week for females and 10-20 drinks/week for males, and increased alcohol intake (MetALD) as 14-35 drinks/week for females and 21-42 drinks/week for males. Significant fibrosis was defined as a liver stiffness measurement ≥8 kPa and at-risk metabolic dysfunction-associated steatohepatitis (MASH) as a FAST score ≥0.35. RESULTS: The derivation cohort included 2,227 individuals with MASLD (9% reported low, 14% moderate alcohol consumption) and 76 cases with MetALD. Overall prevalences of significant fibrosis and at-risk MASH were 7.6% and 14.8%, respectively. In the multivariable analysis, alcohol consumption was independently associated with significant fibrosis and at-risk MASH. A dose-dependent increase in the prevalence of significant fibrosis and at-risk MASH was observed between the number of drinks/week and the number of cardiometabolic factors. The validation cohort included 1,732 participants with MASLD, of whom 17% had significant fibrosis and 13% at-risk MASH. This cohort validated the association between moderate intake and MASLD at risk of progression (odds ratio 1.69, 95% CI 1.06-2.71). CONCLUSIONS: Moderate alcohol intake is commonly seen in MASLD and increases the risk of advanced disease to a level similar to that observed in MetALD. IMPACT AND IMPLICATIONS: Metabolic risk factors such as overweight, diabetes or dyslipidemia, and alcohol consumption can cause liver disease. These factors frequently coexist, but their joint effects on liver fibrosis remain uncertain. In this study, we have analyzed individuals from the general population with MASLD (metabolic dysfunction-associated steatotic liver disease) enrolled in Spain and the US. We show that moderate alcohol consumption has a supra-additive effect with metabolic risk factors, exponentially increasing the risk of liver fibrosis. These results suggest that there are no safe limits of daily alcohol intake in patients with unhealthy metabolic status and MASLD.

Epidemiology of hepatitis C virus infection in a country with universal access to direct-acting antiviral agents: Data for designing a cost-effective elimination policy in Spain.

Accurate HCV prevalence estimates are necessary for guiding elimination policies. Our aim was to determine the HCV prevalence and assess the cost-effectiveness of a screen-and-treat strategy in the Spanish population. A population-based, cross-sectional study (PREVHEP-ETHON Cohort, Epidemiological sTudy of Hepatic infectiONs; NCT02749864) was performed from July 2015-April 2017. Participants from three Spanish regions were selected using two-stage conglomerate sampling, and stratified by age, with randomized subject selection. Anthropometric and demographic data were collected, and blood samples were taken to detect anti-HCV antibodies/quantify HCV RNA. The cost-effectiveness of the screening strategies and treatment were analysed using a Markov model. Among 12 246 participants aged 20-74 (58.4% females), the overall anti-HCV prevalence was 1.2% (95% CI 1.0-1.4), whereas the detectable HCV-RNA prevalence was 0.3% (0.2-0.4). Infection rates were highest in subjects aged 50-74 years [anti-HCV 1.6% (1.3-1.9), HCV RNA 0.4% (0.3-0.6]. Among the 147 anti-HCV + subjects, 38 (25.9%) had active infections while 109 (74.1%) had been cleared of infection; 44 (40.4%) had cleared after antiviral treatment, whereas 65 (59.6%) had cleared spontaneously. Overall, 59.8% of the anti-HCV + participants were aware of their serological status. Considering a cost of treatment of €7000/patient, implementing screening programmes is cost-effective across all age cohorts, particularly in patients aged 50-54 (negative incremental cost-effectiveness ratio which indicates a cost-saving strategy). The current HCV burden is lower than previously estimated, with approximately 25% of anti-HCV + individuals having an active infection. A strategy of screening and treatment at current treatment prices in Spain is cost-effective across all age cohorts.

Update on epidemiology of hepatitis B in a low-endemic European country: There is still much to do.

The latest epidemiological data in Spain were obtained a decade ago and revealed a prevalence of hepatitis B surface antigen (HBsAg) of 0.7%; hence, updated epidemiological data are necessary. Our aim was to determine the prevalence of hepatitis B virus (HBV) infection, and to analyse associated factors and characterize chronic infection. A population-based, cross-sectional study was performed in Spain between July 2015 and April 2017. Participants from three regions were selected using two-stage conglomerate sampling and stratified by age. Anthropometric and demographic data were collected, and blood samples were taken to detect serological markers of HBV infection and to quantify HBV-DNA. The characterization of chronic HBV infection was based on ALT (alanine aminotransferase) values, HBV-DNA levels, and results of transient elastography. The overall prevalence rates of HBsAg and antibody to hepatitis B core antigen (anti-HBc) among 12 246 participants aged 20-74 years (58.4% females) were 0.6% (95% CI [0.4-0.7]) and 8.2% (7.7-8.7), respectively. The risk factors for HBV infection identified in the multivariate analysis were age, nosocomial risk, and non-Spanish nationality. Moreover, most patients HBsAg positive (76.6%) presented as hepatitis B e antigen (HBeAg)-negative chronic infection (formerly 'inactive carriers') and only 6 (9.4%) HBsAg carriers fulfilled current criteria for treatment. The current HBV burden in Spain remains low but virtually unchanged over the past 15 years. Increased efforts are still needed to reach the goal set forth by the World Health Organization (WHO) for HBV elimination by 2030.

High liver stiffness values by transient elastography related to metabolic syndrome and harmful alcohol use in a large Spanish cohort.

BACKGROUND AND AIMS: Transient elastography (TE) to estimate liver stiffness has proved to be very useful in the diagnosis of chronic liver disease. Here, we intend to evaluate its use in a large Spanish cohort. METHOD: Nested study within the PREVHEP-ETHON (Epidemiological sTudy of Hepatic infectiONs; NCT02749864) population-based, cross-sectional study performed between July 2015 and April 2017. An epidemiological questionnaire, laboratory tests and TE and anthropometric measurements were obtained. RESULTS: Data from 11,440 subjects were analyzed. Mean age was 50.3 (SD 12.4), of which 58.1% were women. 15.4% showed metabolic syndrome (NCEP ATP-III), 1.3% were positive for hepatitis C antibodies, 0.8% positive for HBsAg, 9.1% reported harmful use of alcohol. The prevalence of significant fibrosis (LSM > 8 kPa), suggestive compensated advanced chronic liver disease (cACLD) (LSM ≥ 10 kPa) and highly suggestive cACLD (LSM > 15 kPa) was 5.6%, 2.9%, and 1.2% respectively. Risk factors associated with significant fibrosis were age (OR 1.03 [1.02-1.04; p < 0.001]), sex (OR 0.8 [0.6-0.95; p = 0.02]), AST (OR 1.01 [1.01-1.02; p < 0.001]), GGT (OR 1.005 [1.003-1.006; p < 0.001]) and metabolic syndrome (OR 2.1 [1.7-2.6; p < 0.001]); risk factors associated with suggestive cACLD were age (OR 1.04 [1.02-1.05; p < 0.001]), AST (OR 1.01 [1.01-1.02; p < 0.001]), GGT (OR 1.006 [1.004-1.008; p < 0.001]), low platelets (OR 0.997 [0.994-0.999; p = 0.02]) and metabolic syndrome (OR 2.2 [1.6-2.9; p < 0.001]); and risk factors associated with highly suggestive cACLD were age (OR 1.04 [1.02-1.06; p = 0.001]), AST (OR 1.02 [1.01-1.03; p < 0.001]), GGT (OR 1.005 [1.003-1.007; p < 0.001]), low platelets (OR 0.993 [0.989-0.997; p < 0.001]), metabolic syndrome (OR 2.1 [1.4-3.3; p = 0.001]) and alcohol consumption (OR 1.8 [1.05-3.1; p = 0.03]). A non-negligible proportion of patients with normal transaminase levels, even with healthy transaminase levels, showed significant fibrosis and suggestive and highly suggestive cACLD 4.6% (95% CI 2.4-3.0), 2.1% (95% CI 1.9-2.5) and 1% (95% CI 0.7-1.1), respectively. CONCLUSION: We found high proportion of significant fibrosis and cACLD measured by TE. The most relevant factor associated with significant fibrosis was metabolic syndrome, however TE is still an imperfect method since it overestimated the fibrosis stage in 50% of the histologically analyzed subjects.