Trajectories of hepatic steatosis and incidence of cardiovascular disease over a 29-year follow-up.

AIM: To examine the dynamic change in hepatic steatosis status during repeated assessments over time, and its potential impact on the risk of developing cardiovascular disease (CVD). METHODS: We assessed trajectories of hepatic steatosis and other metabolic disorders in 3134 middle-aged adults undergoing longitudinal assessment of ultrasonography during a pre-baseline period (1993-2009) in a population-based cohort study of liver health. Subsequently, we determined the association of hepatic steatosis trajectories with the incidence of CVD among 2185 CVD-free individuals, followed until 2021. Metabolic risk factors and cardiovascular events (including coronary heart disease and stroke) were determined through medical examination and linkage with nationwide health databases. RESULTS: We identified three discrete trajectories of hepatic steatosis according to changing pattern over time through group-based trajectory modeling: "stable, non-steatosis" (n = 1298), "intermittent" (n = 921), and "persistent steatosis" (n = 915). During the pre-baseline period, hepatic steatosis trajectories were associated with trajectories of developing diabetes and hypertension, and persistent steatosis (vs. other trajectories) was associated with higher risks and rapidly progressive disease patterns. At a median 13.6 years of follow-up, 629 CVD events occurred. A persistent (vs. non-steatosis: HR 1.44, 95% CI 1.17-1.76), but not intermittent, steatosis pattern predicted the future risk of CVD, after adjustment for age, sex, smoking, and obesity. This association was independent of genetic background, and remained after accounting for pre-baseline body-mass index, other cardiometabolic risk factors, Framingham risk score, medications, and hepatic fibrosis score. CONCLUSIONS: The persistence of hepatic steatosis is associated with trajectories of metabolic disorder development and increased risk of CVD. These data have important implications for practice and further research.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

Dynamic change of metabolic dysfunction-associated steatotic liver disease in patients with hepatitis C virus infection after achieving sustained virologic response with direct-acting antivirals.

BACKGROUND: Information on the dynamics of metabolic dysfunction-associated steatotic liver disease (MASLD) among hepatitis C virus patients achieving sustained virologic response (SVR12) with direct-acting antivirals (DAAs) is limited. METHODS: We enrolled 1512 eligible participants in this prospective study. MASLD was defined by a controlled attenuation parameter (CAP) of ≥248 dB/m utilizing vibration-controlled transient elastography in conjunction with presence of ≥1 cardiometabolic risk factor. The distribution of MASLD and the changes in CAP were evaluated before treatment and at SVR12. Forward stepwise logistic regression analyses were performed to determine factors significantly associated with the regression or emergence of MASLD. RESULTS: The prevalence of MASLD decreased from 45.0% before treatment to 36.1% at SVR12. Among 681 participants with MASLD before treatment, 144 (21%) exhibited MASLD regression at SVR12. Conversely, among 831 participants without MASLD before treatment, 9 (1.1%) developed MASLD at SVR12. Absence of type 2 diabetes (T2D) [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.13-2.65, p = 0.011], age > 50 years (OR: 1.73, 95% CI: 1.11-2.68, p = 0.015), and alanine transaminase (ALT) ≤ 2 times the upper limit of normal (ULN) (OR: 1.56; 95% CI: 1.03-2.37, p = 0.035) were associated with the regression of MASLD. Presence of T2D was associated with the emergence of MASLD (OR: 5.83, 95% CI: 1.51-22.56, p = 0.011). CONCLUSIONS: The prevalence of MASLD decreased after achieving SVR12 with DAAs. Patients with pre-existing T2D showed a diminished probability of MASLD regression and a heightened risk of MASLD emergence post-SVR12.

Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan.

BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program.

BACKGROUND/AIMS: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Taiwan Association for the Study of the Liver-Taiwan Society of Cardiology Taiwan position statement for the management of metabolic dysfunction- associated fatty liver disease and cardiovascular diseases.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Lifetime risk of liver-related outcomes and determinants in male inactive carriers of chronic hepatitis B.

The full spectrum of risks for the life course of inactive hepatitis B virus (HBV) carriers remains unclear. In this study, 995 untreated HBV carriers (median age: 42.8 years; median follow-up: 30.2 years) were included. Their data were sourced from a population-based cohort study of male civil servants recruited in 1989-1992. Outcomes were identified by active follow-up examinations and linkage with national health insurance research database. At baseline, 483 subjects were inactive carriers, 385 with indeterminate phase, and 127 with other phases. The joint lifetime risk for incident cirrhosis, decompensation, hepatocellular carcinoma, and liver-related deaths was lower for inactive carriers compared to subjects in other phases (p < 0.0001). There was a trend of increase in incidence among inactive carriers; the 5-, 10-, and 20-year cumulative incidences were 1.86%, 6.03%, and 10.07%, respectively. Of the inactive carriers, 37.7% cleared HBsAg and 36.6% had biochemical relapse during the study. Biochemical relapse, obesity, and advanced age were predictors for disease progression in inactive carriers. Virological relapse was the predominant cause of biochemical relapse. Higher HBV-DNA levels (≥1000 copies/mL or 200 IU/mL) and HBV genotype B (vs. C) were associated with higher virological relapse rate. After 30 years, we found that one-time measure of inactive carrier state continued to have the lowest risk compared with other infection phases. Despite a more favorable prognosis, inactive carriers had a non-negligible risk. Our findings of lifetime risk may provide important clues for the management of such patients and consideration of therapeutic strategies aiming to achieve functional cure.

Effectiveness and safety of 8-week glecaprevir/pibrentasvir in HCV treatment-naïve patients with compensated cirrhosis: real-world experience from Taiwan nationwide HCV registry.

BACKGROUND: Large-scale real-world data of the 8-week glecaprevir/pibrentasvir (GLE/PIB) therapy for treatment-naïve patients of chronic hepatitis C virus (HCV) infection with compensated cirrhosis is scarce. METHODS: The TASL HCV Registry (TACR) is an ongoing nationwide registry program that aims to set up a database and biobank of patients with chronic HCV infection in Taiwan. In this study, data were analyzed as of 31 October 2021 for treatment-naïve HCV patients with compensated cirrhosis receiving 8-week GLE/PIB therapy. Effectiveness reported as sustained virologic response at off-therapy week 12 (SVR12) and safety profiles were assessed. Patient characteristics potentially related to SVR12 were also evaluated. RESULTS: Of the 301 patients enrolled, 275 had available SVR12 data. The SVR12 rate was 98.2% (270/275) in the modified intention-to-treat (mITT) population and 89.7% (270/301) in the ITT population. For those mITT patients with genotype 3, FibroScan > 20 kPa, platelet < 150,000/µl, and FibroScan > 20 kPa and platelet < 150,000/µl, the SVR12 rates were 100% (6/6), 100% (12/12), 98.0% (144/147), 100% (7/7), respectively. Overall, 24.9% (75/301) patients experienced adverse events (AEs). The most frequent AEs (> 5%) included fatigue (9.0%) and pruritus (7.0%). Seven (2.3%) patients experienced serious AEs and two (0.7%) resulted in permanent drug discontinuation. None of them were considered as GLE/PIB-related. CONCLUSIONS: In this large-scale real-world Taiwanese cohort, 8-week GLE/PIB therapy was efficacious and well tolerated for treatment-naïve compensated cirrhosis patients. SVR12 rates were similarly high as in the clinical trials, including those with characteristics of advanced liver disease.

Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) is responsible for more than 50% of hepatocellular carcinoma (HCC) in HBV hyperendemic areas, such as the Asia-Pacific region. Several hepatitis B viral factors are involved in HBV-related hepatocarcinogenesis. Hepatitis B viral load is the most important risk factor of HCC development. In addition, HBV integration, HBV genotype C, and core-promoter mutations are also associated with a risk of HCC development. For untreated chronic hepatitis B (CHB) patients, the estimated HCC incidence rates per 100 patient-years were 0.03-0.17 in inactive carriers, 0.07-0.42 in asymptomatic carriers, 0.12-0.49 in chronic hepatitis, and 2.03-3.37 in cirrhosis. Complementary to HBV DNA, serum levels of the hepatitis B surface antigen and hepatitis B core-related antigen (HBcrAg) can predict the occurrence of HCC for untreated patients with low and intermediate viral loads, respectively. For patients receiving antiviral therapy, the risks of HCC occurrence 40-60% lower than those for untreated patients. Patients treated with residual detectable HBV DNA or intrahepatic cccDNA still have a risk of HCC. Serum levels of HBcrAg, M2BPGi and fibrosis-4 are predictive of the risk of HCC development in treated patients. Several well-developed HCC risk scores can help clinicians identify high-risk CHB patients for HCC surveillance, regardless of treatment status. These strategies can help minimize the threat of HCC and prolong survival in CHB patients.

Acute cytomegalovirus hepatitis in an immunocompetent patient: A case report.

BACKGROUND: Cytomegalovirus (CMV) infection is usually subclinical and asymptomatic in the healthy population, whereas severe complications occur in immunocompromised patients. CASE SUMMARY: In this case report, we described a rare case of acute CMV hepatitis in a 35-year-old male immunocompetent patient who presented with a history of week-long intermittent fever with nonspecific constitutional symptoms. Acute hepatitis was suspected according to the initial serological tests. After ruling out other etiologies, including viral hepatitis A, B, C, drug, alcohol, autoimmune, and Wilson disease, acute CMV hepatitis was diagnosed based on positive CMV IgM and DNA quantitative tests. Because there was no any local acute hepatitis E reported in Taiwan, so hepatitis E was not checked. The patient recovered both clinically and serologically with symptomatic management and without antiviral therapy within 12 days from the onset of symptom. CONCLUSION: In conclusion, a diagnosis of CMV infection should be considered when nonspecific prodromal symptoms occur in acute hepatitis with an uncertain etiology. Antiviral therapy should not be used in immunocompetent patient who had no decompensation of the liver, such as this patient. Widely available noninvasive tests for CMV can facilitate early diagnosis if used appropriately. Harm-benefit analysis is essential before using antiviral therapy in immunocompetent patients.

Metabolic-Associated Fatty Liver Disease, Hepatitis B Surface Antigen Seroclearance, and Long-Term Risk of Hepatocellular Carcinoma in Chronic Hepatitis B.

The value of metabolic-associated fatty liver disease (MAFLD) and its ability to assess hepatocellular carcinoma (HCC) risk remains uncertain for chronic hepatitis B (CHB). We evaluated the impacts of MAFLD and its coincidental metabolic abnormalities and related genetic predisposition on HCC incidence and mortality outcomes in CHB. We analyzed data from 1453 HBsAg-positive men (median age = 49.2 years at baseline) from a cohort of civil servants recruited from 1989−1992. MAFLD was defined as hepatic steatosis on ultrasound with obesity, diabetes, or metabolic dysfunction at baseline. During follow-up (median = 19.3 years), 105 HCC events occurred. MAFLD was not associated with HCC (adjusted hazard ratio (aHR) = 1.02) but was associated with a higher HBsAg seroclearance rate (aHR = 1.43). In mediation analysis, HBsAg seroclearance driven by hepatic steatosis explained 31.6% of the association between MAFLD and HCC. Antiviral treatment or fatty liver disease-associated genetic variants did not influence the MAFLD−HCC association. In contrast, even after adjustment for MAFLD and the other metabolic abnormalities, diabetes (aHR = 2.28), obesity (aHR = 1.72), and metabolic dysfunction (aHR = 3.30) increased the risk of HCC (all p < 0.030). The risk of HCC increased with the number of metabolic abnormalities (vs 0: aHR = 2.05 and 5.72 for 2 and ≥ 3 metabolic abnormalities, respectively), and the cumulative effect of metabolic abnormalities was found across subgroups categorized by hepatic steatosis as well as in participants both with and without HBsAg seroclearance. In conclusion, MAFLD was not associated with increased HCC incidence in CHB. A more informative assessment of HCC risk can be obtained by taking into account the number of metabolic abnormalities.

Hepatitis C Virus Reinfection in People With HIV in Taiwan After Achieving Sustained Virologic Response With Antiviral Treatment: The RECUR Study.

Background: Data on hepatitis C virus (HCV) reinfection in East Asian people with HIV after treatment-induced sustained virologic response (SVR) are limited. Methods: HIV/HCV-coinfected patients in Taiwan who achieved SVR12 with interferon (IFN) or direct-acting antivirals (DAAs) between 2005 and 2021 underwent HCV RNA measurements at SVR24 and then biannually. HCV reinfection was defined as the detection of different HCV strains beyond SVR12. HIV-negative, low-risk individuals with SVR12 served as reference patients. Crude reinfection rates and secular trends were assessed. Multivariate Cox regression analysis was performed to identify baseline factors associated with HCV reinfection. Results: A total of 216 HIV-positive and 1589 reference patients were recruited, with median follow-up durations of 3.0 and 6.0 years, respectively. During a total of 772 person-years of follow-up (PYFU), the HCV reinfection rate in HIV-positive patients was 4.02 per 100 PYFU (95% CI, 2.85-5.65), while the HCV reinfection rate in reference patients was 0.14 per 100 PYFU (95% CI, 0.09-0.23) during 10 862 PYFU. HIV-positive patients had a higher risk of HCV reinfection than reference patients (hazard ratio [HR], 17.63; 95% CI, 7.10-43.80; P < .001). No baseline factors were predictive of HCV reinfection in HIV-positive patients. The incidence of HCV reinfection in HIV-positive patients increased after 2015, when DAAs were made available in Taiwan. Conclusions: The risk of HCV reinfection remains high in HIV/HCV-coinfected patients with treatment-induced SVR12. In addition to mass screening and treatment scale-up, strategies to reduce reinfection are needed for HCV microelimination in HIV-positive patients in Taiwan.

The impact of body mass index on clinicopathological features of nonalcoholic fatty liver disease in Taiwan.

BACKGROUND AND AIM: The aim of this study was to assess the impact of body mass index (BMI) on the clinical and histological characteristics of patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Patients with clinically diagnosed NAFLD who received liver biopsy were retrospectively enrolled from 2007 to 2019. For comparison, all of the patients were divided into lean body mass (< 23 kg/m2 ), overweight (23-24.9 kg/m2 ), and obesity (BMI â‰§ 25 kg/m2 ). RESULTS: A total of 572 patients with histologically confirmed NAFLD, including 40 (6.99%) lean body mass, 54 (9.44%) overweight, and 478 (83.57%) obese patients, were recruited. Obese NAFLD patients had significantly higher grade of steatosis (grade 3: 29.92% vs 22.22% vs 12.5%, P < 0.0001) and hepatocyte ballooning (grade 2: 14.85% vs 12.96% vs 12.5%, P < 0.0001) than overweight and lean NAFLD patients. The prevalence of nonalcoholic steatohepatitis (NASH) was 22.5%, 25.93%, and 36.19% in lean, overweight, and obese NAFLD patients, respectively. Obesity was significantly associated with fibrosis severity (P = 0.03). The fibrosis index based on four factors (FIB-4) score can identify NAFLD patients without significant fibrosis or with cirrhosis. The areas under the receiver-operating characteristic curve of FIB-4 score to identify patients without significant fibrosis or with cirrhosis were 0.82 (95% confidence interval [CI]: 0.69-0.96) and 0.87 (95% CI: 0.76-0.99) in lean patients; 0.77 (95% CI: 0.61-0.93) and 0.81 (95% CI: 0.59-1.0) in overweight patients; and 0.77 (95% CI: 0.72-0.82) and 0.89 (95% CI: 0.85-0.92) in obese patients. CONCLUSIONS: The majority of NAFLD patients are obese, as defined by BMI. Obesity was significantly associated with NASH and hepatic fibrosis severity in patients with NAFLD.

Impact of PNPLA3 p.I148M and Hepatic Steatosis on Long-Term Outcomes for Hepatocellular Carcinoma and HBsAg Seroclearance in Chronic Hepatitis B.

Background: Coexistence of hepatitis B and nonalcoholic fatty liver disease is common; however, little is known about the impact of hepatic steatosis and its major genetic determinants on the natural history of HBV infection. We aimed to study the effects of hepatic steatosis and PNPLA3 variant p.I148M on the risk of hepatocellular carcinoma (HCC) and the lifetime probability of HBsAg seroclearance, which is associated with functional remission and improved long-term outcome of HBV infection. Methods: We conducted a cohort study of 2385 male, HBsAg-positive Taiwanese civil servants recruited in 1989-1992, and followed up until 2019. Cox regression with competing-risk models was used to estimate sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs). Results: Of 2385 participants, 628 experienced HBsAg seroclearance and 217 developed HCC. Hepatic steatosis, excess body-mass index, and the PNPLA3-148M variant were significantly associated with higher HBsAg seroclearance rate. However, multivariate analyses accounting for HBsAg seroclearance and various HCC risk factors showed that, while steatosis was associated with decreased HCC risk (sHR [95% CI]: 0.49 [0.36-0.66]), carriage of the PNPLA3-148M variant allele (vs II homozygotes: 1.64 [1.20-2.25] for MI heterozygotes; 1.83 [1.20-2.78] for MM homozygotes) and obesity (1.51 [1.07-2.13]) were associated with increased risk. The inverse hepatic steatosis-HCC association persisted after additional adjustment for other viral factors or using different follow-up time cut-offs to account for reverse causality. Moreover, the PNPLA3 MM genotype was positively associated with elevations of ALT and AST and liver cirrhosis, while hepatic steatosis was positively associated with ALT but inversely associated with AST and liver cirrhosis. Conclusion: Hepatic steatosis and PNPLA3-148M variant appeared to have distinct impacts on the development of HBV-related progressive liver disease and HCC. PNPLA3 p.I148M, but not a diagnosis of hepatic steatosis, can help to identify HBV carriers with high-risk fatty liver disease in the progression to HCC.

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.