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.

Chronic Hepatitis C Related Steatotic Liver Disease Is More Than "Miscellaneous Steatotic Liver Disease".

The terminology and definition of fatty liver disease has evolved significantly. Recently, the overarching term of steatotic liver disease (SLD) has been endorsed by international societies.1,2 SLD further encompasses individuals with cardiometabolic risk factors (CMRFs), namely, metabolic dysfunction-associated steatotic liver disease (MASLD).

Chronic Viral Hepatitis B and C Outweigh MASLD in the Associated Risk of Cirrhosis and HCC.

BACKGROUND & AIMS: The impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the development of cirrhosis and hepatocellular carcinoma (HCC) by chronic hepatitis B (CHB) or C infection and antiviral treatment statuses is not well-known. METHODS: A total of 336,866 adults aged ≥30 years were prospectively enrolled in a health screening program between 1997-2013. MASLD was identified by abdominal ultrasonography and cardiometabolic profiles. Data linkage was performed using 3 nationwide databases-National Health Insurance, Cancer Registry, and Death Certification System-to obtain information on antiviral treatment, vital status, and newly diagnosed cirrhosis and HCC. Follow-up was conducted until December 31, 2019. RESULTS: In the total population, 122,669 (36.4%) had MASLD. Over a mean follow-up of 15 years, 5562 new cases of cirrhosis and 2273 new cases of HCC were diagnosed. Although MASLD significantly increased the cumulative risks of cirrhosis or HCC (P < .0001), the associated risk was more pronounced when comparing CHB or C infection with the presence of MASLD. Stratifying the participants based on their MASLD and CHB or C statuses, hazard ratios (HRadj) with 95% confidence intervals for HCC were 8.81 (7.83-9.92) for non-steatotic liver disease (SLD) with CHB or C, 1.52 (1.32-1.74) for MASLD without CHB or C, and 8.86 (7.76-10.12) for MASLD with CHB or C, compared with non-SLD without CHB or C (all P < .0001). Among CHB or C patients who received antivirals during follow-up, MASLD was associated with increased risks of cirrhosis and HCC, with HRadj of 1.23 (1.01-1.49) and 1.32 (1.05-1.65), respectively. CONCLUSIONS: These findings underscore the need to prioritize treatment of chronic viral hepatitis before addressing MASLD.

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.

Long-term Risks of Cirrhosis and Hepatocellular Carcinoma Across Steatotic Liver Disease Subtypes.

INTRODUCTION: The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD). METHODS: We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC. RESULTS: After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95% CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference. DISCUSSION: This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention.

Antiviral therapy substantially reduces HCC risk in patients with chronic hepatitis B infection in the indeterminate phase.

BACKGROUND AND AIMS: HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase. APPROACH AND RESULTS: We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52) U/L, the mean HBV DNA was 4.5±2.1 log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000 IU/mL, and alanine transaminase

The interplay of metabolic dysfunction-associated fatty liver disease and viral hepatitis on liver disease severity: A large community-based study in a viral endemic area.

BACKGROUND AND AIM: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its interplay with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of liver disease severity is elusive. METHODS: A mass surveillance program was conducted in a viral hepatitis endemic area. The objective was to identify MAFLD/non-MAFLD subjects with advanced liver disease. RESULTS: Two thousand two hundred and forty-two (41.7%) of the 5378 subjects were identified as having MAFLD, and 375 (7.0%) had advanced liver disease. The proportions of anti-HCV and HBsAg seropositivity were 19.3% and 9.7%, respectively. The proportions of advanced fibrosis in subjects with non-viral hepatitis (NBNC), HBV and HCV infection were 2.8%, 5.7% and 23.4%, respectively. Subjects with MAFLD had a significantly higher proportion of advanced fibrosis (8.7% vs 5.7%, P < 0.001). Factors associated with advanced fibrosis included age (odds ratio [OR]/95% confidence interval [CI]: 4.8/3.7-6.0, P < 0.001), male sex (OR/CI: 1.3/1.0-1.7, P = 0.019), anti-HCV seropositivity (OR/CI: 5.9/4.6-7.5, P = 0.019), MAFLD-lean metabolic dysregulation (MS) (OR/CI: 2.6/1.3-5.2, P = 0.005; compared with the non-MAFLD group) and MAFLD-diabetes (OR/CI: 1.5/1.1-2.1, P = 0.008; compared with the non-MAFLD group). MAFLD did not aggravate liver disease severity in patients with viral hepatitis. However, among NBNC subjects, factors associated with advanced liver disease included MAFLD-lean MS group (OR/CI: 9.1/2.4-34.6, P = 0.001; compared with non-MAFLD group) and MAFLD-DM group (OR/CI: 2.0/1.2-3.2, P = 0.004; compared with non-MAFLD group). CONCLUSIONS: MAFLD patients with diabetes and metabolic dysregulation had a higher risk of advanced liver disease. The effect was more significant in non-viral hepatitis subjects in a community level.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIM: This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. METHODS: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. RESULTS: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend < 0.001). DISCUSSION: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

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.

Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan.

BACKGROUND & AIMS: Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). We aimed to evaluate whether metformin reduces HCC risk among individuals with DM and CHC after successful antiviral therapy. METHODS: Individuals with CHC who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). Cases of HCC at least 1 year after SVR were identified through linkage to the catastrophic illness and cancer registry databases. RESULTS: Of 7,249 individuals with CHC enrolled in the study, 781 (10.8%) had diabetes and 647 (82.8%) were metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence was 10.9% in non-metformin users and 2.6% in metformin users, compared to 3.0% in individuals without DM (adjusted hazard ratio [aHR] 2.83; 95% CI 1.57-5.08 and aHR 1.46; 95% CI 0.98-2.19, respectively). Cirrhosis was the most important factor significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male sex, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Using the two most crucial risk factors, cirrhosis and DM non-metformin use, we constructed a simple risk model that could predict HCC risk among individuals with CHC after SVR. Metformin use was shown to reduce the risk of all liver-related complications. CONCLUSIONS: Metformin use greatly reduced HCC risk after successful antiviral therapy in individuals with diabetes and CHC. A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after SVR. IMPACT AND IMPLICATIONS: The current study provides evidence that metformin could reduce hepatocellular carcinoma (HCC) incidence after successful antiviral therapy among those with diabetes and chronic hepatitis C in a large-scale nationwide cohort study. Although successful antiviral therapy greatly reduces HCC risk in individuals with chronic hepatitis C, those with cirrhosis, diabetes, obesity, and the elderly remain at high risk of HCC development. We demonstrated that a simple risk model composed of two crucial unfavorable factors, cirrhosis and diabetes without metformin use, predicts the risk of HCC and major liver-related complications after successful antiviral therapy in individuals with chronic hepatitis C. Metformin use is highly recommended for individuals with diabetes and chronic hepatitis C after viral eradication to reduce the risk of HCC.

Poor Diagnostic Efficacy of Noninvasive Tests for Advanced Fibrosis in Obese or Younger Than 60 Diabetic NAFLD patients.

BACKGROUND & AIMS: Serum-based noninvasive tests (NITs) have been widely used to assess liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). However, the diagnostic efficacy of NITs across ranges of age, body mass index (BMI), and presence of type 2 diabetes (T2DM) may vary and have not been well-characterized. METHODS: We analyzed 1489 patients with biopsy-proven NAFLD from 6 centers in Japan, Taiwan, and Korea. Using histology as the gold standard, we compared the areas under the receiver operating characteristic (AUROCs) of Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and the new Hepamet fibrosis score (HFS), with a focus on performance in subgroups as stratified by age, BMI, and the presence of T2DM. RESULTS: By histology, 44.0% of the overall cohort (655/1489) had F2-4, and 20.6% (307/1489) had F3-4 fibrosis. FIB-4 had the highest AUROCs for both F2-4 (0.701 vs NFS 0.676 and HFS 0.682, P = .001) and F3-4 (0.767 vs NFS 0.736 and HFS 0.752, P = .002). However, for F3-4 fibrosis, the AUROCs of all 3 NITs were generally higher in older (>60 years), nonobese (BMI <25 kg/m2), and non-diabetic patients, although overall the best performance was observed with FIB-4 among nonobese (BMI<25) diabetic patients (AUROC, 0.92). The worst performance was observed in younger patients with T2DM for all NITs including FIB-4 (AUROC, 0.63-0.66). CONCLUSIONS: FIB-4 had higher diagnostic efficacy for F3-4 than NFS or HFS, but this varied greatly by age, BMI, and T2DM, with better performance in older, nonobese, and nondiabetic patients. However, all NITs including FIB-4 had unacceptably poor performance in young or obese diabetic patients.

Impact of comorbidities on the serological response to COVID-19 vaccination in a Taiwanese cohort.

BACKGROUND/AIMS: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive. METHODS: Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities. RESULTS: A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0-1, 2-3 and > 4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥ 4160 AU/mL) included age ≥ 60 years (odds ratio [OR]/95% confidence interval [CI]: 0.50/0.34-0.72, P < 0.001), female sex (OR/CI: 1.85/1.30-2.63, P = 0.001), Moderna-Moderna-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 6.49/3.90-10.83, P < 0.001), BNT-BNT-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 7.91/1.82-34.3, P = 0.006) and a CCI score ≥ 4 (OR/CI: 0.53/0.34-0.82, P = 0.004). There was a decreasing trend in antibody titers with increasing CCI scores (trend P < 0.001). Linear regression analysis revealed that higher CCI scores (ß: - 0.083; 95% CI: - 0.094-0.011, P = 0.014) independently correlated with low IgG spike antibody levels. CONCLUSIONS: Subjects with more comorbidities had a poor serological response to 3 doses of COVID-19 vaccination.

Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine.

BACKGROUND & AIMS: Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. METHODS: We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. RESULTS: The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. CONCLUSION: There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.

Impact of Sofosbuvir-Based Direct-Acting Antivirals on Renal Function in Chronic Hepatitis C Patients With Impaired Renal Function: A Large Cohort Study From the Nationwide HCV Registry Program (TACR).

BACKGROUND & AIMS: Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. METHODS: The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non-sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). RESULTS: The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P < .001) and substantially recovered at EOF (88.8 mL/min/1.73 m2) but did not return to pretreatment levels (P < .001). Notably, a significant decrease in eGFR was observed only in patients with baseline eGFR ≥90 mL/min/1.73 m2 (from 112.9 to 106.4 mL/min/1.73 m2; P < .001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m2 (from 70.0 to 71.5 mL/min/1.73 m2; P < .001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR >90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 mL/min/1.73 m2; 95% confidence interval, -2.24 to -1.72; P < .001). The use of sofosbuvir was not an independent factor associated with eGFR change. CONCLUSIONS: Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.

Body weight changes in treated hepatitis B patients switching to tenofovir alafenamide☆.

BACKGROUND/PURPOSE: Switching to a tenofovir alafenamide (TAF)-containing regimen has been reported to be associated with body weight gain in human immunodeficiency virus-infected subjects. We aimed to investigate the body weight change and virological, hepatic, and renal outcomes of TAF switching among chronic hepatitis B (CHB) patients. METHODS: This retrospective study included 121 CHB patients who were switched to TAF after >12 months of treatment with another nucleot(s)ide analog (NUC). All patients were monitored for 12 months. RESULTS: The cohort was mostly Asian (96.7%) with a mean age of 55 years, 72% male, 14% cirrhosis, 21% HBeAg positive, and 75% with prior use of tenofovir disoproxil fumarate. At 12 months after TAF switching, their body weight significantly increased from 66.4 ± 11.8 to 67.8 ± 12.3 kg (p < 0.001), and 21.1% of the subjects had a ≥5% weight gain. Patients without diabetes or hypertension were more likely to have a body weight gain. Meanwhile, the complete viral suppression rate increased significantly from 89.3% to 96.2% (p = 0.016). The rate of alanine aminotransferase normalization also increased significantly from 71.1% to 87.6% (p < 0.001) by local criteria and from 58.7% to 70.2% (p = 0.029) by AASLD criteria. The mean eGFR (mL/min/1.73 m2) did not change (88.2 ± 18.8 vs. 87.2 ± 17.5, p = 0.28). However, for the subgroup with GFR <90 at TAF switching, there was a significant improvement in eGFR (72.9 ± 12.0 vs. 75.7 ± 14.2, p = 0.027). CONCLUSION: In real-world NUC-experienced CHB patients, unexpected body weight gain was observed after TAF switching. The mechanism needs to be investigated in the future.

Ledipasvir/sofosbuvir for HCV genotype 1, 2, 4-6 infection: Real-world evidence from a nationwide registry in Taiwan.

BACKGROUND/PURPOSE: The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. METHODS: Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). RESULTS: 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P < 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common. CONCLUSION: LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.

Development and Validation of a Risk Score for Liver Cirrhosis Prediction in Untreated and Treated Chronic Hepatitis B.

BACKGROUND: Chronic hepatitis B (CHB) can progress to cirrhosis, but there are limited noninvasive tools available to estimate cirrhosis risk, including in patients receiving antiviral therapy. This study developed and validated a simple model to assess risk in CHB patients. METHODS: The derivation cohort included 3000 CHB patients from 6 centers in the United States, with 52.60% receiving antiviral therapy. External validation was performed for 4552 CHB individuals from similar cohorts in Taiwan, with 21.27% receiving therapy. Cox proportional hazards regression analyses were used to screen predictors and develop the risk score for cirrhosis. Areas under receiver operating characteristic curves (AUROCs) were calculated for predictive value. RESULTS: Sex, age, diabetes, antiviral treatment status/duration, hepatitis B e-antigen, and baseline alanine aminotransferase/aspartate aminotransferase levels were significantly associated with increased cirrhosis risk. A 13-point risk score was developed based on these predictors. The AUROCs for predicting cirrhosis risk were 0.82 at 3 years, 0.85 at 5 years, and 0.89 at 10 years in the derivation cohort, and 0.82, 0.79, and 0.77 in the validation cohort, respectively. CONCLUSIONS: We developed and validated a simple cirrhosis prediction model with an independent external cohort that can be applied to both treatment-naive and treatment-experienced CHB patients in diverse settings and locations.

Association Between Fatty Liver and Cirrhosis, Hepatocellular Carcinoma, and Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B.

BACKGROUND: Chronic hepatitis B (CHB) and fatty liver (FL) are common, natural history data on concurrent FL and CHB (FL-CHB) are limited. This study aimed to evaluate the effect of FL on cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance incidence in CHB patients. METHODS: In a retrospective cohort study of 6786 adult CHB patients, we used propensity score matching (PSM) to balance the FL-CHB and non-FL CHB groups. Kaplan-Meier methods were used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups. RESULTS: Before PSM, compared to non-FL CHB, FL-CHB patients had lower 10-year cumulative rates of cirrhosis, HCC, and a higher HBsAg seroclearance rate. Similar results were found in the matched FL-CHB and non-FL CHB patients, as well as in the antiviral-treated PSM cohort. Cox proportional hazards model indicated FL to remain significantly and strongly associated with lower risk of cirrhosis and HCC (hazard ratio [HR], 0.19 [95% confidence interval {CI}, .12-.33], P < .001 and HR, 0.21 [95% CI, .09-.51], P = .001, respectively) in antiviral-treated patients but not in untreated patients. CONCLUSIONS: FL was significantly associated with lower cirrhosis and HCC risk and higher HBsAg seroclearance. Further studies are needed to confirm our funding and investigate the mechanisms underlying the impact of FL on CHB.

Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B.

BACKGROUND: Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood. METHODS: This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression. RESULTS: The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%-2.88%) and an annual rate of 0.22% (.17%-.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 [95% confidence interval, 1.80-5.49]), elevated serum alanine aminotransferase >200 U/L (3.68 [2.07-6.53]), serum bilirubin (1.11 per mg/dL; [1.06-1.17 mg/dL]), and fatty liver (1.84 [1.03-3.29]). CONCLUSION: HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.

Establishment of an outreach, grouping healthcare system to achieve microelimination of HCV for uremic patients in haemodialysis centres (ERASE-C).

OBJECTIVE: HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme. DESIGN: The ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up). RESULTS: At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively. CONCLUSION: Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population. CLINICALTRIALSGOV IDENTIFIER: NCT03803410 and NCT03891550.