Mortality in patients with chronic hepatitis B treated with tenofovir or entecavir: A multinational study.

BACKGROUND AND AIM: The benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)-related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear. METHODS: A total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all-cause, liver-related, and non-liver-related mortality between patients receiving ETV and those receiving TDF. RESULTS: The annual incidence of all-cause mortality in the entire cohort was 1.0/100 person-years (follow-up, 15 757.5 person-years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e-antigen seropositivity than those who received ETV. The factors associated with all-cause mortality were fibrosis-4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15-4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04-1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996-0.999, P = 0.003), and γ-glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001-1.003, P < 0.001). No significant difference in all-cause mortality was observed between the ETV and TDF groups (log-rank test, P = 0.69). After propensity score matching, no significant differences in all-cause, liver-related, or non-liver-related mortality were observed between the two groups. CONCLUSIONS: Long-term outcomes of all-cause mortality and liver-related and non-liver-related mortality did not differ between patients treated with ETV and those receiving TDF.

Harnessing Metabolic Indices as a Predictive Tool for Cardiovascular Disease in a Korean Population without Known Major Cardiovascular Event.

Background: This study evaluated the usefulness of indices for metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR), as predictive tools for cardiovascular disease in middle-aged Korean adults. Methods: The prospective data obtained from the Ansan-Ansung cohort database, excluding patients with major adverse cardiac and cerebrovascular events (MACCE). The primary outcome was the incidence of MACCE during the follow-up period. Results: A total of 9,337 patients were included in the analysis, of whom 1,130 (12.1%) experienced MACCE during a median follow-up period of 15.5 years. The metabolic syndrome severity Z-score, metabolic syndrome severity score, hepatic steatosis index, and NAFLD liver fat score were found to significantly predict MACCE at values above the cut-off point and in the second and third tertiles. Among these indices, the hazard ratios of the metabolic syndrome severity score and metabolic syndrome severity Z-score were the highest after adjusting for confounding factors. The area under the receiver operating characteristic curve (AUC) of the 10-year atherosclerotic cardiovascular disease (ASCVD) score for predicting MACCE was 0.716, and the metabolic syndrome severity Z-score had an AUC of 0.619. Conclusion: The metabolic syndrome severity score is a highly reliable indicator and was closely associated with the 10-year ASCVD risk score in predicting MACCE in the general population. Given the specific characteristics and limitations of metabolic syndrome severity scores as well as the indices of NAFLD and IR, a more practical scoring system that considers these factors is essential to achieve greater accuracy in forecasting cardiovascular outcomes.

Pretreatment gamma-glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs.

Elevated serum gamma-glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month-6) after initiating NAs were measured to explore their association with all-cause, liver-related, and non-liver-related mortality. The annual incidence of all-cause mortality was 0.9/100 person-years over a follow-up period of 17,436.3 person-years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month-6-GGT levels (62.1 vs. 38.4 U/L, p < 0.001). The factors associated with all-cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92-3.70, p < 0.001), pretreatment GGT levels (HR/CI: 1.004/1.003-1.006, p < 0.001), alanine aminotransferase level (HR/CI: 0.996/0.994-0.998, p = 0.001), and age (HR/CI: 1.06/1.04-1.07, p < 0.001). Regarding liver-related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79-6.89, p < 0.001), pretreatment GGT levels (HR/CI: 1.006/1.004-1.008, p < 0.001), alanine aminotransferase level (HR/CI: 0.993/0.990-0.997, p = 0.001), age (HR/CI: 1.03/1.01-1.05, p < 0.001), and fatty liver disease (HR/CI: 0.30/0.15-0.59, p = 0.001). Pretreatment GGT levels were also independently predictive of non-liver-related mortality (HR/CI: 1.003/1.000-1.005, p = 0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose-dependent manner of <25, 25-75, and >75 percentile of pretreatment GGT levels was observed with respect to the all-cause mortality (trend p < 0.001). Pretreatment serum GGT levels predicted all-cause, liver-related, and non-liver-related mortality in patients with CHB treated with NAs.

Increased spine bone density in patients with chronic hepatitis B switched to tenofovir alafenamide: A prospective, multinational study.

BACKGROUND: Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited. AIMS: To assess the treatment and renal/bone safety outcomes following the switch to TAF. METHODS: We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF. RESULTS: We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019). CONCLUSIONS: At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable.

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study.

BACKGROUND & AIMS: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. METHODS: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. RESULTS: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar. CONCLUSIONS: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

A survey on the awareness, current management, and barriers for non-alcoholic fatty liver disease among the general Korean population.

Non-alcoholic fatty liver disease (NAFLD) is often diagnosed incidentally during medical evaluation for diseases other than liver disease or during health checkups. This study aimed to investigate the awareness, current status, and barriers to the management of NAFLD in the general population. This cross-sectional study used an online survey, which consisted of 3-domain and 18-item questionnaires. The content validity index for each item of the questionnaire was rated above 0.80. Most respondents (72.8%) reported having heard of the term 'NAFLD', and a large proportion of the general population (85.7%) recognized the possibility of developing fatty liver without consuming alcohol. Awareness of the terminology of NAFLD and that NAFLD is a disease that needs to be managed is relatively high. However, the knowledge that NAFLD can progress to end-stage liver disease and new cardiovascular diseases is lacking. Only 25.7% of the general population is aware that NAFLD increases the incidence of heart and cerebrovascular diseases. Only 44.7% of those who were incidentally diagnosed during a health check-up were provided with any specific guidance on NAFLD, and more than half (55.3%) were not provided with education or guidance on NAFLD or did not remember it. Only 40.2% of people diagnosed with NAFLD incidentally visited a clinic. The reason for not visiting a clinic for the evaluation of NAFLD varied greatly depending on sex and age group. Only 40.2% of patients visited the clinic after being diagnosed with NAFLD. The reasons for not visiting the clinic after NAFLD diagnosis differed significantly according to sex and age.

Improved on-treatment fibrosis-4 during antiviral therapy and lower hepatocellular carcinoma risk in cirrhotic patients with hepatitis B.

Normalization of serum alanine aminotransferase (ALT) levels is one of the goals of hepatitis B treatment. However, ALT levels in cirrhosis patients might be normal or mildly elevated regardless of ongoing inflammation. Therefore, we examined whether on-treatment ALT and other potential on-treatment indicators could be clinical surrogates of antiviral therapy in HBV-related cirrhosis. A total of 911 patients with HBV-related liver cirrhosis who started treatment with entecavir or tenofovir were analyzed. At 1 year of antiviral therapy, we evaluated 'ALT normalization', 'undetectable serum HBV DNA', 'fibrosis-4 (FIB-4) index improvement', and 'serum HBeAg loss' as potential biomarkers for HCC development. During 6.6 (3.8-10.2) years of follow-up, 222 patients (24.3%) newly developed HCC. Undetectable HBV DNA levels at 1 year were observed in 667 patients (73.2%), and the HCC incidence was significantly lower in this population (adjusted hazard ratio (HR) 0.66, 95% CI 0.50-0.87). Improvement of the FIB-4 index (< 3.25) was associated with a lower risk of HCC in 478 patients with an elevated FIB-4 index (adjusted HR 0.59, 95% CI 0.55-0.82). However, there was no significant difference in HCC risk between those with and without normalization of ALT levels (p = 0.39) among those with elevated ALT levels or between those with and without HBeAg seroconversion (p = 0.55) among HBeAg-positive patients. Therefore, on-treatment FIB-4 levels at 1 year are clinically useful surrogates of antiviral therapy for HBV-related cirrhosis patients.

Personalized Antiviral Drug Selection in Patients With Chronic Hepatitis B Using a Machine Learning Model: A Multinational Study.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) for the prevention of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B; however, it has distinct long-term renal and bone toxicities. This study aimed to develop and validate a machine learning model (designated as Prediction of Liver cancer using Artificial intelligence-driven model for Network-antiviral Selection for hepatitis B [PLAN-S]) to predict an individualized risk of HCC during ETV or TDF therapy. METHODS: This multinational study included 13,970 patients with chronic hepatitis B. The derivation (n = 6,790), Korean validation (n = 4,543), and Hong Kong-Taiwan validation cohorts (n = 2,637) were established. Patients were classified as the TDF-superior group when a PLAN-S-predicted HCC risk under ETV treatment is greater than under TDF treatment, and the others were defined as the TDF-nonsuperior group. RESULTS: The PLAN-S model was derived using 8 variables and generated a c-index between 0.67 and 0.78 for each cohort. The TDF-superior group included a higher proportion of male patients and patients with cirrhosis than the TDF-nonsuperior group. In the derivation, Korean validation, and Hong Kong-Taiwan validation cohorts, 65.3%, 63.5%, and 76.4% of patients were classified as the TDF-superior group, respectively. In the TDF-superior group of each cohort, TDF was associated with a significantly lower risk of HCC than ETV (hazard ratio = 0.60-0.73, all P < 0.05). In the TDF-nonsuperior group, however, there was no significant difference between the 2 drugs (hazard ratio = 1.16-1.29, all P > 0.1). DISCUSSION: Considering the individual HCC risk predicted by PLAN-S and the potential TDF-related toxicities, TDF and ETV treatment may be recommended for the TDF-superior and TDF-nonsuperior groups, respectively.

Noninvasive serum biomarkers for liver steatosis in nonalcoholic fatty liver disease: Current and future developments.

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of the population worldwide and includes nonalcoholic fatty liver, nonalcoholic steatohepatitis (NASH), and cirrhosis. Since NAFLD-associated diseases begin with steatosis, the early diagnosis of steatosis helps to prevent the progression of NASH and fibrosis. In addition, more convenient and easily diagnosable serum biomarkers are becoming crucial in disease diagnosis. In this report, we summarize the known serum biomarkers for liver steatosis and provide guidance for their application in clinical practice.

Effect of exercise-based interventions in nonalcoholic fatty liver disease: A systematic review with meta-analysis.

BACKGROUND: The global burden of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing. AIMS: This study aimed to evaluate the effect of exercise on intrahepatic lipid (IHL), serum alanine aminotransferase (ALT), body mass index (BMI), and insulin resistance in NAFLD patients. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL, KMbase, and the Korean Studies Information Service System through April 2022. The included studies were randomised control trials (RCTs) of exercise, in which IHL was measured using magnetic resonance imaging in adult NAFLD patients. RESULTS: Eleven RCTs with 577 participants were included in this meta-analysis. Exercise was significantly associated with a reduction in IHL (mean difference (MD), -2.03; 95% CI, -3.26 to -0.79; P = 0.001) and a decrease in ALT (MD, -4.17; 95% CI, -6.60 to -1.73; P = 0.0008). Regarding the duration of exercise, maintaining exercise for more than 3 months significantly improved IHL (MD, -3.62; 95% CI, -5.76 to -1.48; P = 0.0009), while exercise for less than 3 months did not (MD, -1.23; 95% CI, -2.74 to 0.29; P = 0.11). BMI and insulin resistance did not improve significantly with exercise. CONCLUSIONS: We found that exercise improved IHL and ALT levels in NAFLD patients. The effect of exercise is particularly increased when one engages in exercises that last longer than 3 months.

Hepatocellular carcinoma incidence is decreasing in Korea but increasing in the very elderly.

BACKGROUND/AIMS: A comprehensive analysis of trends in the incidence of hepatocellular carcinoma (HCC) is important for planning public health initiatives. We aimed to analyze the trends in HCC incidence in South Korea over 10 years and to predict the incidence for the year 2028. METHODS: Data from patients with newly diagnosed HCC between 2008 and 2018 were obtained from Korean National Health Insurance Service database. Age-standardized incidence rates (ASRs) were calculated to compare HCC incidence. A poisson regression model was used to predict the future incidence of HCC. RESULTS: The average crude incidence rate (CR) was 22.4 per 100,000 person-years, and the average ASR was 17.6 per 100,000 person-years between 2008 and 2018. The CR (from 23.9 to 21.2 per 100,000 person-years) and ASR (from 21.9 to 14.3 per 100,000 person-years) of HCC incidence decreased during the past ten years in all age groups, except in the elderly. The ASR of patients aged ≥80 years increased significantly (from 70.0 to 160.2/100,000 person-years; average annual percent change, +9.00%; P<0.001). The estimated CR (17.9 per 100,000 person-years) and ASR (9.7 per 100,000 person-years) of HCC incidence in 2028 was declined, but the number of HCC patients aged ≥80 years in 2028 will be quadruple greater than the number of HCC patients in 2008 (from 521 to 2,055), comprising 21.3% of all HCC patients in 2028. CONCLUSION: The ASRs of HCC in Korea have gradually declined over the past 10 years, but the number, CR, and ASR are increasing in patients aged ≥80 years.

Regular Alpha-Fetoprotein Tests Boost Curative Treatment and Survival for Hepatocellular Carcinoma Patients in an Endemic Area.

Guidelines vary on alpha-fetoprotein (AFP) testing for hepatocellular carcinoma (HCC) screening. This study aims to reassess AFP's role in HCC surveillance, utilizing a comprehensive, recent, nationwide cohort. Utilizing the National Health Claims Database from the Korean National Health Insurance Service, this research included data from 185,316 HCC patients registered between 2008 and 2018. Specifically, 81,520 patients diagnosed with HCC from 2008 to 2014 were analyzed. The study focused primarily on mortality and, secondarily, on the status of curative treatments. Multivariate analysis revealed that frequent AFP testing significantly impacts overall survival in HCC patients. Specifically, each additional AFP test correlated with a 6% relative improvement in survival (hazard ratio = 0.94, 95% CI: 0.940-0.947, p < 0.001). Patients who underwent AFP testing three or more times within two years prior to HCC diagnosis showed improved survival rates, with 55.6% receiving liver transplantation or hepatectomy. This trend was particularly pronounced in hepatitis B patients undergoing antiviral treatment. The findings highlight the potential of regular AFP testing to enhance survival in HCC patients, especially those with hepatitis B. Integrating frequent AFP testing with ultrasonography could increase the likelihood of early detection and access to curative treatments.

Different Associations of Coffee Consumption with the Risk of Incident Metabolic Dysfunction-Associated Steatotic Liver Disease and Advanced Liver Fibrosis.

Although coffee has a potential hepatoprotective effect, evidence of the relationship between coffee consumption and metabolic dysfunction-associated steatotic liver disease (MASLD) remains conflicting. There is limited evidence regarding the most appropriate coffee intake to prevent advanced liver fibrosis (ALF) in patients with MASLD. We investigated the effect of coffee consumption on MASLD and ALF among 5266 participants without MASLD and 1326 with MASLD but without ALF. Participants were grouped by coffee intake: non-consumers, >0 and <1 cups/day, ≥1 and <2 cups/day, and ≥2 cups/day. Over a median follow-up of 11.6 years for MASLD and 15.7 years for ALF, coffee consumption did not significantly affect the incidence of MASLD, with 2298 new cases observed. However, a notable inverse association was found with ALF risk in patients with MASLD among those consuming coffee ≥2 cups/day (adjusted HR 0.57, 95% CI: 0.37-0.90, p = 0.014), especially among those consuming coffee ≥2 and <3 cups/day (adjusted HR 0.51, 95% CI: 0.30-0.89, p = 0.018). This suggests a potential hepatoprotective effect of coffee, especially in preventing the progression of liver fibrosis in patients with MASLD. These findings propose that coffee consumption could be a simple and effective approach to mitigate the risk of ALF in individuals with MASLD.

Direct-Acting Antivirals and the Risk of Hepatitis B Reactivation in Hepatitis B and C Co-Infected Patients: A Systematic Review and Meta-Analysis.

Hepatitis B (HBV) reactivation was observed to be more than 10% in patients receiving interferon-based therapy for hepatitis C (HCV) co-infection. At present, when direct-acting antiviral (DAA) has become the main treatment for HCV, there are few large-scale studies on the reactivation of HBV in these population. We studied HBV reactivation risk and prophylactic HBV treatment efficacy in HBV/HCV co-infected patients receiving DAA therapy. Relevant studies were selected from the Ovid-Medline, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, KoreaMed, KMbase, and RISS databases through 4 September 2020. Data pooling was carried out using the random-effects method. We identified 39 articles with 119,484 patients with chronic (n = 1673) or resolved (n = 13,497) HBV infection under DAA therapy. When the studies were pooled, the HBV reactivation rate was 12% (95% confidence interval (CI) 6-19, I2 = 87%), indicating that this population needs careful attention. When stratified by baseline HBV DNA, the undetectable HBV DNA group showed a significantly lower risk of reactivation than the detectable HBV DNA group (odds ratio (OR) 0.30, 95% CI 0.11-0.86, I2 = 0%). Prophylactic HBV therapy reduced HBV reactivation risk (OR 0.25, 95% CI 0.07-0.92, I2 = 0%). Patients with a resolved HBV infection showed a negligible rate (0.4%) of HBV reactivation. In conclusion, patients with detectable HBV DNA levels warrant careful monitoring for HBV reactivation and may benefit from preventive anti-HBV treatment.

Direct-Acting Antivirals for HCV Treatment in Decompensated Liver Cirrhosis Patients: A Systematic Review and Meta-Analysis.

DAA therapy is known to clear hepatitis C virus infection in patients with decompensated cirrhosis (DC). However, the safety and benefits of DAA in DC remain unclear, especially with the use of protease inhibitors (PI). Therefore, we evaluated the efficacy and clinical safety of DAA in DC patients and observed whether there was a discrepancy between PI-based and non-PI-based treatment. We searched Ovid-Medline, Ovid-EMBASE, Cochrane Library, and three local medical databases through October 2021 to identify relevant studies on the clinical safety and effectiveness of DAA in DC patients. The outcomes were sustained virologic response (SVR), overall mortality, the incidence rate of hepatocellular carcinoma (HCC), adverse events, improvement or deterioration of liver function, and delisting from liver transplantation (LT). Two independent reviewers extracted the data from each study using a standardized form. The pooled event rate in DC patients and relative effect (odds ratio (OR)) of PI-treated versus non-PI-based DAA in DC patients were calculated using a random-effects model. In patients with DC, the SVR rate was 86% (95% CI 83-88%), the development of HCC 7% (95% CI 5-9%), and mortality 6% (95% CI 4-8%). Improvement in liver function was observed in 51% (95% CI 44-58%) of patients, and 16% (95% CI 5-40%) were delisted from LT. PI-based treatment showed a similar rate of serious adverse events (23% vs. 18%), HCC occurrence (5% vs. 7%), and mortality (5% vs. 6%) to that of non-PI-based DAA treatment in DC patients. HCC occurrence and mortality rates were low in patients with DC following DAA treatment. PI-based treatment in DC patients was relatively safe when compared to non-PI-based treatment. Overall, DAA improved liver function, which may have allowed for delisting from LT.

Effectiveness of entecavir vs tenofovir disoproxil fumarate for functional cure of chronic hepatitis B in an international cohort.

INTRODUCTION: Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line therapies for chronic hepatitis B (CHB), but their comparative effectiveness with regards to hepatitis B surface antigen (HBsAg) seroclearance remains unclear. METHODS: This international multicenter cohort study enrolled 7697 treatment-naïve CHB patients (median age 50 years; male 66.75%) initiated on either ETV (n = 5430) or TDF (n = 2267) without baseline malignancy or immunosuppression from 23 centers across 10 countries or regions. Patients were observed for HBsAg seroclearance until death, loss to follow-up, or treatment discontinuation or switching. The incidences of HBsAg seroclearance were adjusted for competing mortality and compared between ETV and TDF cohorts with inverse probability of treatment weighting (IPTW) and also by multivariable regression analysis. RESULTS: The study population was followed up for a median duration of 56.1 months with 36,929 11 person-years of observation. HBsAg seroclearance occurred in 70 ETV-treated and 21 TDF-treated patients, yielding 8-year cumulative incidence of 1.69% (95% confidence interval [CI] 1.32-2.17) for ETV and 1.34% (95% CI 0.85-2.10%), for TDF (p = 0.58). In the IPTW analysis with the two study cohorts more balanced in background covariates, the age-adjusted hazard ratio (HR) of TDF versus ETV for HBsAg seroclearance was 0.91 (95% CI 0.50-1.64; p = 0.75). Furthermore, there was no significant difference between the two medications in the multivariable competing risk regression model (adjusted sub-distributional HR 0.92 for TDF vs. ETV; 95% CI 0.56-1.53; p = 0.76). CONCLUSIONS: ETV and TDF did not differ significantly in the incidence of HBsAg seroclearance, which rarely occurred with either regimen.

Metabolic Score for Insulin Resistance Is Inversely Related to Incident Advanced Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

We determined the relationships between metabolic score for IR (METS-IR), triglyceride-glucose (TyG) index, and homeostatic model assessment for IR (HOMA-IR) and incident advanced liver fibrosis (ALF) and assessed the abilities of the three IR indicators to predict ALF in patients with non-alcoholic fatty liver disease (NAFLD) in adults with NAFLD who were aged 40-69 years old. Among 2218 participants with NAFLD at baseline, the areas under the receiver operating characteristic curve for predicting ALF of the METS-IR was 0.744 (0.679-0.810), significantly higher than that of TyG index (0.644 (0.569-0.720)) or that of HOMA-IR (0.633 (0.556-0.710)). Among 1368 patients with NAFLD and without ALF at baseline, 260 (19.0%) patients with NAFLD progressed to ALF during the 16-year follow-up period. Multivariable Cox proportional hazard regression analysis revealed that the adjusted hazard ratio (95% confidence interval) for incident ALF in the highest tertiles of METS-IR, TyG index, and HOMA-IR compared with the lowest tertile of each IR indicator were 0.5 (0.36-0.91), 0.7 (0.49-1.00), and 1.01 (0.71-1.42), respectively. METS-IR was inversely associated with ALF in patients with NAFLD, which cautiously suggests that the risk of ALF may need to be evaluated when metabolic parameters improve in individuals with NAFLD.

The usefulness of metabolic score for insulin resistance for the prediction of incident non-alcoholic fatty liver disease in Korean adults.

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). CONCLUSION: 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.