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Understanding the barriers and tackling the hurdles of hepatitis C virus (HCV) care cascades is key to HCV elimination. The current study aimed to investigate the rates of disease awareness, link‐to‐care, and treatment uptake of HCV in a hyperendemic area in Taiwan. Tzukuan residents from 2000 to 2018 were invited to participate in the questionnaire‐based interviews for HCV. The rates of disease awareness, accessibility, and anti‐HCV therapy were evaluated in anti‐HCV‐seropositive participants. Among 10,348 residents, 1789 (17.3%) were anti‐HCV seropositive. Of these 1789 anti‐HCV‐seropositive participants, data of 594 participants from questionnaire‐based interviews in 2005–2018 were analyzed for HCV care cascades. Overall, 24.9% of anti‐HCV‐seropositive HCV participants had disease awareness, 53.9% of aware participants had accessibility, and 79.8% of assessed participants had received HCV treatment, with a community effectiveness of 10.7%. HCV prevalence decreased over time, from 21.2% in the early cohort to 9.3% in the recent cohort. Disease awareness increased over time, from 15.6% to 41.7%, with the community effectiveness increasing from 1.3% to 28.8%. Lower education levels and normal liver biochemistry were associated with a lower rate of disease awareness. Notably, 68% of participants with abnormal liver biochemistry and 69% of those with advanced fibrosis (FIB‐4 > 3.25) were unaware of their HCV disease. We demonstrated huge gaps in disease awareness, link‐to‐care, and treatment uptake in the HCV care cascade in an HCV‐hyperendemic area, even in the initial era of direct‐acting antiviral agents. There is an urgent need to overcome these hurdles to achieve HCV elimination. [ABSTRACT FROM AUTHOR]

Whether patients with advanced hepatocellular carcinoma (aHCC) benefit from hepatitis C virus (HCV) eradication is uncertain. We aimed to investigate whether a survival benefit was conferred by HCV eradication in aHCC patients. This retrospective cohort study enrolled 168 HCV‐infected aHCC patients from April 2013 to January 2019. All patients were treated with sorafenib. Endpoints included overall survival (OS), progression free survival (PFS), and time to liver decompensation. Patients with undetectable HCV RNA exhibited reduced aspartate aminotransferase and alpha fetoprotein levels, as well as an attenuated proportion of aHCC at initial diagnosis but increased albumin and mean sorafenib daily dosing. Patients with undetectable HCV RNA exhibited significantly longer OS compared to patients with detectable or unknown HCV RNA, which was an independent factor of OS (HR: 0.56, 95% CI: 0.350‐0.903, P =.017). Patients with undetectable HCV RNA also presented a trend for longer PFS (HR 0.68, 95% CI: 0.46‐1.00, P =.053). The survival benefit was considered with respect to the significantly prolonged time to Child‐Pugh B scores in patients with undetectable HCV RNA (HR 0.59, 95% CI: 0.38‐0.92, P =.020). Patients with detectable HCV RNA at sorafenib initiation who further received direct acting antiviral therapy also had significantly longer OS (HR 0.11, 95% CI: 0.02‐0.81, P =.030) and PFS (HR 0.23, 95% CI: 0.06‐0.99, P =.048). In conclusion, abolishing HCV viremia preserves liver function and confers a survival benefit in advanced HCC patients on sorafenib treatment. [ABSTRACT FROM AUTHOR]

Background and aims: Hepatitis C virus (HCV) genotyping is a pivotal tool for epidemiological investigation, guiding management and antiviral treatment. Challenge existed in identifying subtypes of genotype-1 (G-1) and genotype (GT) of indeterminate. Recently, the Abbott HCV RealTime Genotype Plus RUO assay (HCV GT Plus) has been developed aiming to overcome the limitations. We aimed to evaluate the performance of the assay compared with 5' UTR sequencing in clinical samples. Materials and methods: Eligible individuals were treatment chronic hepatitis C patients that were enrolled consecutively in a medical center and two core regional hospitals in southern Taiwan from Oct 2017 through Aug 2018. The patient with genotype 1 without subtype and indeterminate previously genotyped by Abbott RealTime HCV GT II will further determinate by Abbott HCV RealTime HCV GT Plus. All of the genotype results were validated by 5' UTR sequencing as a reference standard. Results: A total of 100 viremic CHC patients were recruited, including 63 G-1 patients (male: 28), and 37 patients (male: 15) of indeterminate genotyped by Abbott RealTime HCV GT II assay (HCV GT II), respectively. The detection rate of 63 GT1 samples without subtype were 93.7% (59/63), 37 indeterminate samples without genotype were 62.2 (23/37) by HCV GT Plus. 5' UTR sequencing confirmed HCV GT Plus characterized results for 84.7% (50/59) of type1, with 100% (4/4), 82.8 (24/29) and 84.6% (22/26) for 1a, 1b and type6; 65.2% (15/23) of indeterminate with 100% (3/3) and 60% (12/20) for 1b and type 6 samples, respectively. Conclusions: The Abbott RealTime HCV GT Plus RUO assay provides additional performance in GT detection. [ABSTRACT FROM AUTHOR]

Both dengue virus (DENV) and hepatitis C virus (HCV) belong to the Flaviviridae family and could induce hepatitis. We aimed to investigate the interference between them. In total, 515 patients confirmed with dengue fever (DF) were enrolled. Thirty-two patients (6.21%) were seropositive for anti-HCV; 12 of 32 anti-HCV-positive patients had detectable HCV-RNA at presentation of DF. The proportion of dengue hemorrhagic fever was comparable between patients with or without anti-HCV and between those with or without HCV-RNA. Eleven of 32 patients received HCV-RNA testing during a median interval of 23 months after DF, which revealed significantly increased HCV-RNA levels (5.43 ± 0.77 vs 3.09 ± 1.24 log IU/mL, follow-up vs acute-DF phase; P  = .003). Four of 11 patients with baseline HCV-RNA values before DF demonstrated a nadir viremia during acute DF. We also included age-, sex-, and follow-up duration–matched HCV-monoinfected patients as controls; higher delta HCV-RNA changes were demonstrated in patients with DF than in controls during the follow-up period (2.34 ± 1.15 vs –0.27 ± 0.76 log IU/mL; P  < .001). Further in vitro experiments showed that HCV nonstructural protein 5A was downregulated in Con1 HCV replicon cells infected by DENV1. These clinical and experimental findings suggested possible viral interference in DENV/HCV. However, HCV viremia did not affect the disease outcomes of DF. [ABSTRACT FROM AUTHOR]

Background: The features and risk analysis of non-alcoholic fatty liver disease (NAFLD) in a community-based setting remain elusive. The predictors between obese and lean subjects need further clarification. We aimed to assess the characteristics of NAFLD during a community screening. The associated metabolic abnormalities and cardiovascular risk assessment were also analyzed.Methods: A total of 2483 subjects receiving multi-purpose health screening at 10 primary care centers were recruited. They received clinical assessment, including demographic data, laboratory examination, and abdominal sonography.Results: The prevalence of NAFLD and metabolic syndrome were 44.5%, and 15.8%, respectively. Among those NAFLD subjects, 1212 (48.8%) subjects were obese (BMI≥ 24 kg/m2). There was an increasing trend of NAFLD according to age, ranging from 25.8% of those aged <30 years to 54.4% of those aged 50-70 years (P for trend< 0.0001). High insulin resistance (IR) was the significant predictive factor for NAFLD in both obese (odds ratio [OR] = 3.85, 95% confidence interval [CI] = 1.87-8.36, P = 0.0002) and lean subjects (OR = 2.52, 95% CI = 1.13-5.54, p = 0.02). The prevalence of high Framingham Risk Score (≥7.5%) was 56.7% (211/372) among the male subjects, which was significantly higher than that (26%, 191/734) of the females (P < 0.001). There was a significant increase of high Framingham Risk Score according to BMI, ranging from 23.1% of BMI<24 kg/m2 to 45% of BMI>27 kg/m2 (P for trend< 0.0001).Conclusion: IR is predictive of NAFLD irrespective of BMI. The cardiovascular risk may exist in lean NAFLD subjects. [ABSTRACT FROM AUTHOR]

Sorafenib is currently the first‐line therapy for advanced hepatocellular carcinoma (aHCC) patients. However, the outcomes and prognostic factors of sorafenib therapy have not been well investigated. We aimed to investigate the pretreatment factors and outcomes among Taiwanese aHCC patients receiving sorafenib treatment. A total of 347 patients with aHCC and well‐compensated liver cirrhosis (Child‐Pugh A) status receiving sorafenib were consecutively enrolled from March 2013 through December 2016. Pre‐treatment clinical data and viral hepatitis markers were collected and analyzed with their outcomes. The primary endpoint of the study was overall survival. The factors associated with overall survival were also investigated. The median overall survival of all the patients was 238 days (range, 9‐1504 days) with a 1‐year overall survival of 43.2%. Positive hepatitis B surface antigen and absence of portal vein thrombosis (PVT) were independent factors associated with better overall survival. The median duration of sorafenib therapy was 93.0 days (range, 4‐1504 days). After stopping sorafenib, the median survival was 93.0 days (range, 1‐1254 days). The 1‐year survival after stopping sorafenib was 21.2%. In chronic hepatitis B patients, total bilirubin level was the only factor associated with overall survival. Hepatitis C antibody RNA negativity, tumor size, PVT, and white blood cell count were the independent factors associated with survival among those chronic hepatitis C patients. There were different prognostic factors stratified by viral etiologies in aHCC patients receiving sorafenib. Viral eradication increased survival in chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

Background: Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) was a novel marker of liver fibrosis. We aimed to investigate WFA+-M2BP level in assessing liver fibrosis in patients with chronic hepatitis B (CHB) infection. Methods: A total of 160 CHB patients, who received a liver biopsy, were consecutively recruited. Serum WFA+-M2BP level was quantified at the time point of biopsy. The results were compared with histopathological manifestations and clinical characteristics of the patients. Results: The median WFA+-M2BP level, aspartate aminotransferase-to-platelet ratio (APRI) and Fibrosis-4 (FIB-4) index were 1.20 COI, 1.19, and 1.63, respectively. Fifty-one (31.9%) patients had advanced fibrosis. There was a significant increase of WFA+-M2BP levels in parallel to necroinflammation/fibrosis stages. The areas under the receiver operating characteristic curve (AUROC) of WFA+-M2BP level for predicting fibrosis stages were 0.780 of F2, 0.785 of F3, and 0.769 of F4, respectively (all p <0.001). The multivariate analysis identified age (Odds ratio [OR] 1.05, 95% confidence interval [CI]: 1.010–1.092, p = 0.014), platelet (OR: 0.99, 95%CI: 0.980–0.998, p = 0.013), and WFA+-M2BP level (OR: 1.97, 95% CI: 1.299–2.984, p = 0.001) as independent factors associated with advanced fibrosis. Combination of age, platelet and WFA+-M2BP level achieved a better diagnostic performance for advanced fibrosis (AUROC: 0.732, accuracy: 81.3%) than APRI (AUROC: 0.577, accuracy: 63.8%) or FIB-4 index (AUROC: 0.691, accuracy: 75.6%). Conclusion: WFA+-M2BP had a good performance indistinguishing liver fibrosis in CHB patients. The combination of age, platelet, and WFA+-M2BPaddressed more accuracy in identifying patients with advanced fibrosis. [ABSTRACT FROM AUTHOR]

Background & aims: Identification of disease severity remains a challenge in the management of non-alcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18), is a recently developed non-invasive biomarker for NASH. We aimed to assess the performance of CK18 in disease severity prediction among Taiwanese NASH patients. Methods: A total of 76 biopsy-proven NASH patients (54 males, age = 41.0 ± 13.5 years) were consecutively recruited. The optimal cutoff values of CK18 for each stage of fibrosis were correlated with their histopathological manifestations. Results: There were 23 (30.3%) patients of Metavir fibrosis stage 0 (F0), 32 (42.1%) patients of F1, 14 (18.4%) patients of F2, and 7 (9.2%) patients of F3-4, respectively. The CK18 levels among those patients of F0, F1, F2, F3-4 were 86.7 ± 75.6 U/L, 122.4 ± 123.8 U/L, 160.7 ± 120.4 U/L, and 507.3 ± 343 U/L, respectively (trend for P<0.001). The adjusted optimal cutoff value for F2 prediction was 312.5 U/L, yielding the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy of 96.4%, 28.6%, 77.9%, 75%, and 77.6%, respectively (P = 0.009). For the prediction of advanced fibrosis (F3-4), the adjusted optimal cutoff value was 374.5 U/L, yielding the sensitivity, specificity, PPV, NPV, and the accuracy of 97.1%, 54.1%, 95.7%, 66.7%, and 77.6%, respectively (P = 0.003). Among those patients without hyperuricemia, the PPV, NPV, and accuracy of CK18 reached 100%, 95.8%, and 96%, respectively (P<0.001). Conclusions: CK18 combined with uric acid measurement is a promising non-invasive biomarker for prediction of disease severity in NASH patients. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background & Aims: Asians are more susceptible to non-alcoholic steatohepatitis (NASH) as well as metabolic disorder than other ethnicities. We aimed to assess the interaction between metabolic factors and fibrosis in Taiwanese NASH patients. Methods: A total of 130 biopsy-proven Taiwanese NASH patients (94 males, age = 43.0 ± 13.0 years) were consecutively enrolled. Their demographic, metabolic profiles and histopathological manifestations were analyzed. Results: Twenty-four (18.5%) NASH patients were non-obese. Thirty-three (25.4%) patients had significant fibrosis (F2) or more: 22 (16.9%) patients were of F2, whilst 11 (8.5%) patients were of advanced fibrosis (F3-4). The prevalence of metabolic syndrome, diabetes and hypertension were 60.8%, 39.4%, and 61.5%, respectively. There was a significant inverse correlation between hyperuricemia and fibrosis stages, ranging from 48.4% of F0-1, 33.3% of F2, and 9.1% of F3-4, respectively (P = 0.01, linear trend). Multivariate logistic regression analysis showed that a decreased serum albumin level (OR = 40.0, 95% CI = 4.5–300, P = 0.001) and normal uric acid level (OR = 5.6, 95% CI = 1.5–21.7, P = 0.01) were the significant factors associated with significant fibrosis. Conclusions: Hyperuricemia inversely predicts fibrosis stages. Females might carry a more disease severity than males in Taiwanese NASH patients. [ABSTRACT FROM AUTHOR]

Detection and quantification for hepatitis B virus (HBV) DNA has been an essential tool in the clinical setting. We aimed to assess clinical performance of the RealArt HBV TM PCR (RealArt) assay and the COBAS TaqMan HBV (COBAS) assay. Serum levels of HBV DNA in 146 treatment-naive chronic HBV (CHB) Taiwanese patients (118 males, 47 HBeAg + ; mean age, 34.7±13.0 y) were determined by both assays. The detection rate by the RealArt assay was 85.6% (125/146), which was not significantly different from the COBAS assay (89.7%, 131/146). The detection rate was also not significantly different between both assays irrespective of HBeAg seropositivity. The 2 assays were also comparable regarding quantification rate (92.8%, 116/125 vs 93.1%, 122/131). There was a positive correlation in the 109 specimens measurable by both assays (r=0.94, p<0.001). The mean HBV DNA level measured by the COBAS assay was significantly higher than the RealArt assay (5.24±1.83 vs 4.79±2.09 log IU/ml, p<0.001). This study demonstrated that both RealArt and COBAS assays were comparable regarding clinical performance in HBV DNA measurement. [ABSTRACT FROM AUTHOR]

Background/Aims: Insulin resistance (IR) might be associated with hepatitis C virus (HCV) infection. This study aimed to elucidate impact of IR and beta-cell function on the response to peginterferon-alpha (PEG-IFN)/ribavirin combination therapy in chronic hepatitis C (CHC) patients. Methods: Three hundred and thirty patients without overt diabetes were treated with combination therapy with (PEG-IFN)/ribavirin for 24 weeks. The IR and beta-cell function were evaluated by homeostasis model assessment of IR (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-beta) before treatment. Results: HCV genotype, pretreatment HCV RNA level and pretreatment HOMA-IR, but not HOMA-beta, were independent factors associated with sustained virologic response (SVR). In 150 patients with genotype 1b infection, pretreatment HCV RNA level, HOMA-IR and age were independent predictors for SVR. The significantly lower SVR rate in high HOMA-IR patients was observed in 76 patients with high HCV RNA levels (⩾400,000IU/mL) who were defined as ‘difficult-to-treat’ patients. The mean HOMA-IR of ‘difficult-to-treat’ patients was significantly lower in 42 sustained responders than in 34 non-responders. Conclusions: IR was associated with SVR to (PEG-IFN)/ribavirin therapy for CHC, especially among ‘difficult-to-treat’ patients. These findings suggested clinical application of pretreatment HOMA-IR could enable treatment outcome to be predicted and treatment regimens to be determined. [Copyright &y& Elsevier]

Background/Aims: Hepatitis C virus (HCV) infection carries a significant risk for development of insulin resistance (IR) and/or diabetes mellitus. Recently, retinol-binding protein 4 (RBP4) has been reported as a protein contributing to IR. This study aimed to assess the correlation between RBP4 and disease severity of chronic HCV infection (CHC). Methods: Serum RBP4 was measured in 105 treatment-naı¨ve CHC patients and its correlation with the homeostasis model assessment of insulin resistance index (HOMA-IR), liver histology, virology and metabolic factors was investigated. Patients were stratified into different stages of glucose tolerance by oral glucose tolerance test. Results: There was a significant decreasing linear trend of RBP4 dependent on both histological grading (from 35.8±16.5μg/mL of minimal to 19.2±12.5μg/mL of severe, P =0.002) and staging (from 34.2±10.0μg/mL of F0 to 22.2±11.9μg/mL of F3-4, P =0.02) progression, whilst a significant increment of HOMA-IR was found. Multivariate regression analysis showed BMI (1.1, 95% CI 0.44∼1.77, P =0.001), HDL-C (−0.40, 95% CI −0.73∼−0.06, P =0.02), and LDL-C (0.31, 95% CI 0.02∼0.61, P =0.04) were the significant variables for prediction of RBP4. Conclusions: Disease severity may limit the role of RBP4 as a predictor of IR in CHC. [Copyright &y& Elsevier]

Objectives: Hepatitis C virus (HCV) infection is the leading cause of cirrhosis and hepatocellular carcinoma worldwide. Tzukuan, located in the southwestern area of Taiwan, is an HCV hyperendemic area (>30%). This study aimed to assess the changing epidemiological characteristics of HCV infection and to evaluate the long-term outcomes after the implementation of public health strategies for two decades., Design: A population-based retrospective cohort study., Setting: A comprehensive care programme was implemented, namely COMPACT Study, in Tzukuan since 1997., Participants: A total of 10 714 residents participated the screening., Outcome Measures: The HCV status, demographic and clinical profiles of the participants were recorded and validated annually from 2000 through 2019., Results: The HCV infection prevalence rates were 21.1% (1076/5099) in 2000-2004, 18.8% (239/1269) in 2005-2009, 14.1% (292/2071) in 2010-2014 and 10.3% (234/2275) in 2015-2019 (p for trend test <0.0001). Among them, 1614 underwent repeated tests during the follow-up period. The annual incidence rates were 0.54% in 2005-2009, 0.4% in 2010-2014 and 0.22% in 2015-2019, respectively (p=0.01). In addition to old age, lower education level was a major risk factor for HCV infection across different periods. HCV infection prevalence rate among those illiterates reached 40.9%, followed by 28.5% in those with elementary school level, and <10% in those with high school or higher levels. The major risk factor has shifted from iatrogenic exposure in 2000-2009 to household transmission after 2010., Conclusions: HCV infection has been decreasing and the epidemiological features are changing in the hyperendemic area by continuing education, prevention and treatment strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Direct-acting antiviral agents (DAAs) have been widely used for chronic hepatitis C (CHC) treatment recently. The characteristics of glucose abnormalities after DAAs therapy however, remain elusive. We aimed to elucidate the mutual impact between treatment response and parameters of glucose abnormalities after DAAs therapy in CHC patients. CHC patients who received DAAs therapy were recruited. The primary outcome measurements were their insulin resistance (IR) and beta-cell function assessed by the homeostasis model assessment (HOMA) method before treatment and at end-of-follow-up (EOF). Sixty-five CHC patients (19 males, mean age = 59.8 ± 10.3 years) were consecutively enrolled. They included 47 (72.3%) patients of genotype-1 infection. The treatment regimens among patients were sofosbuvir in 30 patients, paritaprevir-ritonavir/ombitasvir/dasabuvir in 23 patients, and asunaprevir/daclatasvir in 12 patients respectively. The overall sustained virological response rate was 98.5%. The mean IR at EOF was 2.6 ± 1.8, which was not significantly different from baseline level (2.7 ± 2.9, P = 0.75). There was a significant improvement of beta-cell function at EOF compared to baseline (107.7 ± 86.8 to 86.7 ± 44.5, P = 0.05). The amelioration of beta-cell function at EOF was significantly observed among 23 patients of high baseline IR (166.7 ± 111.3 of baseline vs 105.7 ± 48.2 of EOF, P = 0.04). Six (60%) of the 10 pre-diabetic patients at baseline achieved a normoglycemic state at EOF. Successful eradication of HCV by DAAs might improve glucose abnormalities in CHC patients, particularly among those who had high IR., (Copyright © 2017. Published by Elsevier Taiwan.)

This case-control study was aimed to assess the effect of genetic variants of tumor necrosis factor (TNF) α-308 and lymphotoxin (LT) α+252 on development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Their gene-gene interaction was also investigated. We enrolled 200 pairs of age- and sex-matched patients with cirrhotic HBV-HCC and unrelated patients with HBV-cirrhosis alone. Polymorphisms of TNFα-308 and LTα+252 were genotyped. Synergy index was used to calculate interaction between the variant genotypes. The results indicated that the frequency distribution of the variant genotypes (TNFα-308 G/A and LTα+252 G/G) in patients with HCC were significantly higher than those in patients with cirrhosis alone. Multivariate analysis indicated that TNFα-308 G/A (odds ratio [OR], 2.34) and LTα+252 G/G (OR, 2.04) were independent risk factors for HCC. By the clinical characteristics of study population, multivariate analysis demonstrated that independent factors associated with harboring the variant genotypes included cirrhosis with Child-Pugh C (OR = 6.47 in cases and OR = 11.56 in controls) and thrombocytopenia (OR = 8.86 in cases and OR = 7.74 in controls). Calculation of synergy index (SI) indicated that there are additive interaction between TNFα-308 G/A and LTα+252 G/G on risk of HCC (SI = 1.29)., In Conclusion: There are independent and additive interactions between TNFα-308 G/A and LTα+252 G/G on risk for HBV-HCC. They correlated with advanced hepatic fibrosis and severe liver damage, which might contribute to a higher risk for HCC., (Copyright © 2017 Kaohsiung Medical University. Published by Elsevier Taiwan. All rights reserved.)

This case-control study aimed to assess the interactive effect between polymorphisms of lymphotoxin (LT) α +252 and habitual substance use on risk of hepatocellular carcinoma (HCC). We enrolled 150 pairs of sex- and age-matched HCC patients and unrelated healthy controls. LTα genotypes were detected with polymerase-chain reaction and restrictive fragment length polymorphisms. Information about habits of substance use was obtained through personal interview. Multivariate analysis indicated that LTα +252 G/G genotypes [odds ratio (OR) = 3.36], Hepatitis B surface antigen (OR = 16.68), antibodies to hepatitis C virus (OR = 34.88) and having at least two habits of substance use (OR = 2.50) were independent risk factors for HCC. There were additive interactions among LTα +252 G/G genotype, chronic viral hepatitis, and habit of each substance use., In Conclusion: There are independent and additive interactions between LTα +252 G/G genotype, chronic viral hepatitis, and habits of substance use on risk of HCC., (Copyright © 2017. Published by Elsevier Taiwan.)

The subsequent maintenance therapy in chronic hepatitis B (CHB) patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM) maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV) DNA after 3 years of entecavir (ETV) therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL). A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p<0.001). However, none of the 48 historical control patients developed relapse of HBV, which was significantly lower than the rate in LAM switch group (p < 0.001). LAM switch was the only factor associated with HBV DNA relapse. In conclusion, continuous long-term potent nucleot(s)ide analogue therapy is mandatory for prevention of viral relapse in CHB patients., (Copyright © 2016 Kaohsiung Medical University. Published by Elsevier Taiwan.. All rights reserved.)

To assess the contribution of tumor necrosis factor (TNF)β +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. TNFβ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that TNFβ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between TNFβ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with TNFβ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum α-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with TNFβ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that TNFβ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between TNFβ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), α-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29- 8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ- related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

Hepatitis C virus (HCV) infection has been associated with hepatic steatosis. However, the role of hepatic steatosis in the pathogenesis of HCV infection remains controversial. In our study, 425 consecutive HCV-viremic patients with biopsy-proven chronic hepatitis C (male, 264; mean age, 49.0 years) were enrolled. Scoring of hepatic steatosis was based on the method described by Kleiner and on histopathology performed using the Knodell and Scheuer systems. HCV RNA level and genotypes were determined at the time of biopsy. Hepatic steatosis was observed in 30.8% of patients, including 113 mild, 16 moderate, and 3 with severe hepatic steatosis. Patients with a body mass index (BMI) <23 kg/m(2) had a significantly lower rate (18.9%) of hepatic steatosis (P<0.001). Hepatic steatosis did not correlate with the hepatic necroinflammatory activity, but was related to hepatic fibrosis (P=0.035). Hepatic steatosis was also not associated with HCV RNA level, and the distribution was similar between patients with HCV genotype 1 and genotype 2 infection. According to multivariate analysis, BMI is the strongest risk factor associated with hepatic steatosis, followed by hepatic fibrosis and triglyceride level with odds ratios (95% confidence intervals) of 2.51 (1.49-4.23), 2.06 (1.14-3.70), and 1.02 (1.01-1.03), respectively. Hepatic steatosis was associated with being overweight, hepatic fibrosis, and triglyceride level in chronic hepatitis C.

To identify areas endemic for hepatitis C virus (HCV), we attempted to predict the prevalence of antibody to HCV (anti-HCV) in a community by the prevalence of elevated levels of alanine aminotransferase (ALT). The results of health examinations of 2,273 women > or = 40 years old in five townships in central Taiwan were analyzed. The overall prevalence of elevated ALT levels was 11.6%. A township (20.3%) and 10 villages were identified as having a high prevalence (17.9-40.0%) of elevated ALT levels. Five communities with variant rates of elevated ALT levels, which ranged from 8.0% to 27.3%, were selected for correlation with the prevalence of anti-HCV among adults (> or = 40 years old). The prevalence of anti-HCV, which ranged from 10.1% to 72.1%, were obtained by community screenings and/or hospital-based studies. The correlation equation used was the prevalence of anti-HCV (%) = 3.33 x (prevalence of elevated ALT levels (%) - 5.7%) (r2 = 0.94, P < 0.01). Using this method, areas endemic for HCV can be identified by determining the community prevalence of elevated ALT levels.