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Hepatitis C virus (HCV) eradication through antivirals ameliorates metabolic profiles. The changes in 2-h plasma glucose (2HPG) levels by oral glucose tolerance test (OGTT), in chronic hepatitis C (CHC) patients who receive directly acting antivirals (DAAs) was elusive. Five hundred and thirty-three CHC patients who achieved sustained virological response (SVR, undetectable HCV RNA throughout 3 months after the end-of-treatment) by DAAs were consecutively enrolled. Pre- and posttreatment 2HPG levels and glucose status were compared. The proportion of patients with improved, worsened, and stable 2HPG was 14.4% (n = 77), 18.6% (n = 99), and 67.0% (n = 357), respectively. Compared with patients with worsening 2HPG, those with improved 2HPG had a higher proportion of cirrhosis (45.5% vs. 24.2%, p = 0.004) and higher pretreatment 2HPG levels (175.3 vs. 129.5 mg/dl, p 0.001). High baseline 2HPG was independently associated with improved 2HPG in multivariate analysis (odds ratio [OR]/CI: 1.05/1.03-1.06, p 0.001). When baseline 2HPG was not taken into account, cirrhosis was the only factor independently associated with improved 2HPG status (OR/CI: 2.58/1.29-5.15, p = 0.007). Linear regression analysis revealed that factors independently correlated to changes in 2HPG levels were female sex (β: 8.78; 95% CI:2.34, 15.22; p = 0.01), diabetes (β: -27.72; 95% CI: -50.16, -5.28; p = 0.02), liver cirrhosis (β: -8.91; 95% CI: -16.75, -2.20; p = 0.01), and genotype 1 of HCV (β: -0.12; 95% CI: -15.19, -2.43; p = 0.01). 2HPG improved after HCV eradication by DAAs, particularly in cirrhotic patients.

The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10–0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13–0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04–40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.

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.

Hepatitis C virus (HCV) eradication deteriorates lipid profiles. Although HCV eradication may reduce the risk of vascular events as a whole, whether deteriorated lipid profiles increases the risk of cardio‐cerebral disease in certain patients is elusive. Serial lipid profiles were measured before, during, at and 3 months after the end of direct‐acting antivirals (DAAs) therapy, and annually thereafter in chronic hepatitis C patients who achieved a sustained virological response (SVR, undetectable HCV RNA at posttreatment week 12). The primary end‐point was the occurrence of the events. A total of 617 patients were included, with a mean follow‐up period of 26.8 months (range: 1‐65 months). The total cholesterol and low‐density lipoprotein cholesterol (LDL‐C) levels increased significantly from treatment week 4 to 2 years after treatment. Logistic regression analysis revealed that the factors independently associated with a significant cholesterol increase included age (odds ratio [OR]/95% confidence intervals [CIs]:1.02/1.006‐1.039, P = .007) and smoking (OR/CI:3.21/1.14‐9.02, P = .027). Five patients developed cardio‐cerebral diseases during 1376 person‐years follow‐up period. Compared to patients without vascular events, a significantly higher proportion of those with vascular events experienced an LDL‐C surge >40% (80% vs 19.9%, P = .001). Cox‐regression analysis revealed that an LDL‐C surge >40% was the only factor predictive of vascular events (HR/CI: 15.44/1.73‐138.20, P = .014). Dyslipidemia occurred after HCV eradication, and it was associated with the risk of cardio‐cerebrovascular diseases. Attention should also be paid to the extrahepatic consequence beyond liver‐related complications in the post‐SVR era.

Background During autophagy defense against invading microbes, certain lipid types are indispensable for generating specialized membrane-bound organelles. The lipid composition of autophagosomes remains obscure, as does the issue of how specific lipids and lipid-associated enzymes participate in autophagosome formation and maturation. Helicobacter pylori is auxotrophic for cholesterol and converts cholesterol to cholesteryl glucoside derivatives, including cholesteryl 6ʹ-O-acyl-α-d-glucoside (CAG). We investigated how CAG and its biosynthetic acyltransferase assist H. pylori to escape host-cell autophagy. Methods We applied a metabolite-tagging method to obtain fluorophore-containing cholesteryl glucosides that were utilized to understand their intracellular locations. H. pylori 26695 and a cholesteryl glucosyltransferase (CGT)-deletion mutant (ΔCGT) were used as the standard strain and the negative control that contains no cholesterol-derived metabolites, respectively. Bacterial internalization and several autophagy-related assays were conducted to unravel the possible mechanism that H. pylori develops to hijack the host-cell autophagy response. Subcellular fractions of H. pylori-infected AGS cells were obtained and measured for the acyltransferase activity. Results The imaging studies of fluorophore-labeled cholesteryl glucosides pinpointed their intracellular localization in AGS cells. The result indicated that CAG enhances the internalization of H. pylori in AGS cells. Particularly, CAG, instead of CG and CPG, is able to augment the autophagy response induced by H. pylori. How CAG participates in the autophagy process is multifaceted. CAG was found to intervene in the degradation of autophagosomes and reduce lysosomal biogenesis, supporting the idea that intracellular H. pylori is harbored by autophago-lysosomes in favor of the bacterial survival. Furthermore, we performed the enzyme activity assay of subcellular fractions of H. pylori-infected AGS cells. The analysis showed that the acyltransferase is mainly distributed in autophago-lysosomal compartments. Conclusions Our results support the idea that the acyltransferase is mainly distributed in the subcellular compartment consisting of autophagosomes, late endosomes, and lysosomes, in which the acidic environment is beneficial for the maximal acyltransferase activity. The resulting elevated level of CAG can facilitate bacterial internalization, interfere with the autophagy flux, and causes reduced lysosomal biogenesis.

Hepatitis C virus eradication via the use of antivirals ameliorates metabolic profiles. The changes in serum uric acid (SUA) levels in chronic hepatitis C patients who receive antivirals are not well understood. We aimed to address this issue by comparing the SUA changes before and after the achievement of a sustained virological response (which is defined as hepatitis C virus RNA seronegativity at 12 weeks after the end of treatment).Two hundred and thirteen sustained virological response patients who were treated by directly acting antivirals were consecutively enrolled. Pretreatment and post-treatment SUA levels were compared. Hyperuricemia was defined as a uric acid level 7.0 mg/dL in men and 6.0 mg/dL in women.The SUA levels significantly decreased after treatment, as compared to the pretreatment levels (5.6 ± 1.5 vs 6.0 ± 1.7 mg/dL, respectively; P 0.001). The proportion of hyperuricemia incidences significantly decreased after treatment (25.8% vs 35.7%, respectively; P = 0.001). The improvement was only observed in patients with a fibrosis-4 index (FIB-4) 6.5 (25.7% vs 37.1%, P = 0.001) but not in those patients with a FIB-4 ≧ 6.5 (26.3% vs 28.9%, P = 1.00). A multivariate analysis revealed that the factor that was associated with significantly decreased SUA levels was FIB-4 6.5 (odds ratio [OR]/95% confidence interval [CI]: 3.22/1.04-9.95, P = 0.04) and estimated glomerular filtration rate 60 mL/min/1.73 mSUA levels were significantly decreased in chronic hepatitis C patients after viral eradication. The improvement was particularly enhanced in patients with mild liver disease.

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.

Background: The efficacy and safety of insulin sensitizer in Asians with non-alcoholic steatohepatitis (NASH) remain elusive. Aims: The double-blind, randomized, placebo-controlled trial was conducted aiming to investigate the efficacy and safety of pioglitazone in NASH patients. Methods: A total of 90 NASH patients (66 males, age= 44.1 ± 12.7 years) were prospectively randomized into oral pioglitazone 30 mg/day (Arm A) or placebo (Arm B) for 24 weeks. The primary endpoint was the efficacy of pioglitazone in reducing inflammation and liver fat at end-of-treatment (EOT). NASH resolution/improvement without fibrosis worsening were also evaluated.Results: At EOT, there was a significantly decline of alanine aminotransferase (86.9 ± 34.3 to 45.7 ± 35.8 IU/L, P=0.003) level in Arm A patients. In intention-to-treat analysis among 66 patients who completed paired biopsies, The NAFLD activity score (NAS) of 30 Arm A patients significantly decreased from 4.27 ± 1.14 at baseline to 2.53 ± 1.63 at EOT (P< 0.0001), whereas there was no significant change in patients of Arm B (3.94 ± 1.41 vs 3.94 ± 1.51, P= 1.0). NASH improvement without worsening of fibrosis was achieved in 46.7% (14/30) patients in Arm A, compared to 11.1% (4/36) patients in Arm B (P= 0.002). Liver fat content reduced (20.2 ± 9.0 to 14.3 ± 6.9%, PConclusions: A 24-weeks pioglitazone treatment was well-tolerated and effective in improving liver histology and reducing liver steatosis in Asian NASH patients. (ClinicalTrials.gov number: NCT01068444)

The prevalence of mixed cryoglobulinemia is 15-50% in chronic hepatitis C (CHC) patients, and these patients are in an increased risk of liver fibrosis and cirrhosis, but it is controversial. This study aimed to reveal the prevalence of mixed cryoglobulinemia in Asian population and to determine the relationship between presence of serum cryoglobulinemia and liver fibrosis in CHC patients with or without liver biopsy.In total, 2255 treatment-naïve patients retrospectively enrolled in our study. Serum cryoglobulinemia precipitation, liver biopsy, and four indexes of fibrosis (FIB4) were assessed to detect the associated factors.Three hundred sixty-four (32%) out of 1135 liver biopsy patients and 341 (30.4%) out of 1120 non-biopsy patients were positive for serum cryoglobulinemia. Multivariate analysis revealed that male gender, hepatitis C virus RNA, platelet and advanced fibrosis (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.05-1.87, P = 0.021) were significantly associated with the presence of cryoglobulinemia in the liver biopsy proven patients. The presence of serum cryoglobulinemia (OR 1.43, 95% CI 1.04-1.96, P = 0.026) was associated with advanced liver fibrosis (F3 and F4) by multivariate logistic regression analysis. In patients without liver biopsy, FIB4 (OR 1.72, 95% CI 1.30-2.27, P = 0.0001) was associated with the presence of serum cryoglobulinemia, and also cryoglobulinemia (OR 1.74, 95% CI 1.32-2.30, P = 0.0001) was associated with high FIB4 (≥ 3.25) patients.The prevalence of the presence of serum cryoglobulinemia is 30.4-32% in CHC patients and associated with advanced fibrosis in liver biopsy proven patients and high-FIB4 (≥ 3.25) patients without liver biopsy.

Background & Aims Genetic variants of patatin-like phospholipase domain-containing 3 ( PNPLA3 ) and diabetes are associated with liver disease severity, in patients with chronic hepatitis C (CHC) infection. We aimed at exploring their interaction in determining hepatitis C virus (HCV)-related liver fibrosis. Methods The PNPLA3 genetic polymorphism at rs738409 was verified in 1077 biopsy-proven CHC patients. Other clinical variables, including diabetes status, were analysed for factors associated with bridging fibrosis. Results Patients with advanced liver fibrosis had higher proportions of the GG genotype (14.5% vs. 10.4%, p= 0.06 in recessive model) and GG/GC genotype carriage (64.0% vs. 56.8%, p= 0.03 in dominant model). Stepwise logistic regression analysis revealed that factors predictive of advanced liver fibrosis included age (odds ratio [OR]: 1.02, 95% confidence intervals [CI]: 1.008–1.037, p= 0.002), diabetes (OR: 1.81, CI: 1.236–2.653, p= 0.002), α-fetoprotein (OR: 1.006, CI: 1.001–1.01, p= 0.01), platelet counts (OR: 1.009, CI: 1.006–1.012, p 0.001), and PNPLA3 rs738409 CG/GG genotype (OR: 1.34, CI: 1.006–1.785, p= 0.046). When patients were grouped according to their diabetes status, the PNPLA3 genetic variants were associated with advanced liver fibrosis in diabetic patients only, but not in non-diabetic patients. The PNPLA3 gene was the most important predictive factor of bridging fibrosis in diabetic patients, using the recessive model (OR: 4.53, CI: 1.356–15.106, p= 0.014) or the dominant model (OR: 2.20, CI: 1.026–4.734, p= 0.04). Compared to non-diabetic patients, patients with the diabetes/GG genotype were more likely to have advanced liver fibrosis (OR: 8.79, CI: 2.889–26.719, p 0.001), followed by those with diabetes/non-GG genotype (OR: 1.55, CI: 1.048–2.286, p= 0.03). Conclusions The effect of PNPLA3 genetic variants in HCV-related advanced liver fibrosis was enhanced in diabetic patients. The strong genetic–environmental interaction contributed to the high risk of advanced liver disease in CHC patients.

Background & Aims: Hepatitis C virus (HCV)-infected patients with cirrhosis remain at risk of hepatocellular carcinoma (HCC) even after achieving sustained virological response (SVR). The aim of the study was to explore the incidence and risk for HCC among non-cirrhotic patients with an SVR. Methods: A total of 642 patients with an SVR after peginterferon/ ribavirin therapy were enrolled with a median follow-up period of 53.0 months (range: 6–133 months). Results: Thirty-three of the 642 (5.1%) patients developed HCC over 2324.8 person-years of follow-up. Cox regression analysis revealed that the strongest predictive factor of HCC occurrence was liver cirrhosis (HR 4.98, 95% CI 2.32–10.71, p

Chronic hepatitis C virus (HCV) infection had been associated with cytokine imbalance. Cytokine dynamics in response to peginterferon/ribavirin therapy have an impact on the treatment efficacy for HCV patients. Ninety-two treatment-naive chronic hepatitis C patients were treated with 24 or 48 weeks of peginterferon/ribavirin therapy according to their viral genotypes. Sustained virologic response (SVR) is defined as undetectable HCV RNA throughout a 24-week post-treatment follow-up period. Dynamic serum levels of the following cytokines: (1) Th1-mediated cytokines: IFN-γ, interleukin-2, and TNF-alpha; (2)Th2-mediated cytokines: interleukin-4, interleukin-5, interleukin-6, and interleukin-10 and (3)immuno-modulatory cytokines: interleukin-1β, interleukin-8, and interleukin-12 were determined by Fluorescent Bead immunoassay. Serial dynamic cytokine expression demonstrated that not only elevated IFN-γ concentrations at specific time points but also the total IFN-γ amount was strongly linked to non-response in peginterferon/ribavirin therapy. IFN-γ levels could serve as an independent predictor for SVR analyzed by multivariate logistic regression test. The accuracy of discriminating responders from non-responders was acceptable when IFN-γ cut-off levels were set at 180, 120, and 40 pg/ml at the 4th week, 12th week, and end-of-treatment of therapy, respectively. Elevated on-treatment IFN-γ concentration was significantly associated with treatment failure among interleukin-28B rs8099917TT carriers and those patients failed to achieve rapid virologic response.

A substantial proportion of hepatitis C virus genotype 1 (HCV-1) patients achieved a sustained virological response (SVR, HCV RNA seronegative throughout 24 weeks of post-treatment follow-up) after 24 weeks peginterferon/ribavirin therapy. We explored the role of interleukin-28B genotype in identifying patients who responded to the regimen.Interleukin-28B rs8099917 genotype was determined in 226 HCV-1 patients with 24 weeks peginterferon/ribavirin.Compared to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly higher rapid virological response (RVR, HCV RNA seronegative at treatment week 4, 54.0% vs. 17.9%, p0.001) and SVR (64.7% vs. 25.6%, p0.001) rates, and lower relapse rate (28.0% vs. 54.5%, p=0.01). Logistic regression analysis revealed that the strongest factor predictive of a RVR was the carriage of rs8099917 TT genotype (odds ratio/ 95% confidence intervals [OR/CI]: 6.24/2.34-16.63), followed by lower viral loads (OR/CI: 5.29/2.81-9.93) and age (OR/CI:0.94/0.91-9.97). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 22.23/9.22-53.58), followed by the carriage of rs8099917 TT genotype (OR/CI: 3.38/1.18-9.65), lower viral loads (OR/CI: 2.23/1.00-4.93) and ribavirin exposure dose (OR/CI: 1.17/1.06-1.30). The determinant power of rs8099917 genotype on SVR was mainly restricted to non-RVR patients, particularly those with higher baseline viral loads. Combination of the two pretreatment predictors, interleukin-28B genotype and baseline viral loads, could predict treatment efficacy with a positive predictive value of 80% and a negative predictive value of 91%.Interleukin-28B genotype could help identifying patients who are or are not candidates for an abbreviated regimen before treatment.

Background & Aims Evidence on the efficacy of antiviral treatment in chronic hepatitis C (CHC) patients with hepatocellular carcinoma (HCC) after curative treatment is scarce. We aimed to evaluate the efficacy and safety of pegylated interferon-alpha plus ribavirin (pegIFN/RBV) combination therapy in these patients, compared to cirrhotic patients. Methods This prospective, multicenter, case–control study recruited 82 consecutive CHC patients with HCC after curative management and 87 sex/age-matched cirrhotic patients. All patients received pegIFN-alpha-2a and weight-based RBV according to current treatment recommendations. The primary outcome measurement was sustained virological response (SVR, seronegative of hepatitis C virus RNA throughout the 6-month post-treatment follow-up period). Results The SVR rate was significantly lower in the HCC group compared to the cirrhosis group (48.8% vs 64.4%, p =0.04). However, the significantly lower rate of SVR in the HCC group was observed among genotype-1 patients (33.3% vs 60.7%, p =0.005) but not among genotype-2/3 patients (70.6% vs 71.0%, p =0.88). In patients who achieved 80/80/80 adherence, there was no significant difference of SVR rate between groups (50.7% vs 64.2%, p =0.12) Multivariate logistic regression analysis demonstrated that rapid virological response (viral clearance during the first 4weeks of treatment, odds ratio=22.1, p p =0.05) were predictive factors associated with SVR, whilst previous occurrence of HCC was not associated with SVR (Odds ratio=0.4, p =0.09). The incidence of severe adverse events did not differ between the two groups. Conclusions The study proved the feasibility of pegIFN/RBV therapy with current treatment guidelines in CHC patients after successful eradication of HCC, with careful monitoring.

Hepatitis C virus (HCV) infection has been shown to be associated with a low platelet count. This study aimed to elucidate the association between virologic status and platelet count in individuals with HCV infection.A large-scale survey, enrolling 11,239 residents, was conducted in the Kaohsiung area of Taiwan. Serum HCV RNA and non-invasive markers of fibrosis (FibroTest) were tested for antibody to HCV (anti-HCV)-positive subjects. The platelet counts of age- and sex-matched, biopsy-proven, hospital-based patients and community-based patients with minimal fibrosis were compared.Anti-HCV was positive in 703 (6.2%) subjects and was significantly associated with older age, female sex, abnormal alanine aminotransferase (ALT) value and low platelet count (150,000/microl). The independent factors significantly associated with low platelet count were abnormal ALT value (odds ratio [OR]: 3.70, 95% confidence intervals [CI]: 2.18-6.28) and positive HCV RNA (OR: 2.00, 95% CI: 1.01-3.97). After adjustment for the fibrosis, HCV RNA remained significantly associated with platelet counts.Our results evaluating the association between platelet count and HCV viremia and taking the influences of fibrosis into consideration implicate that platelets may be affected directly by HCV.

The production of transforming growth factor beta 1 (TGF-beta1) has been reported as being significantly associated with the gene polymorphism in the leader sequence at positions +29. The current study aimed to evaluate the associations between the polymorphism and the clinical characteristics of chronic hepatitis C (CHC). A total of 422 (252 men; mean age: 49.7 +/- 11.2 years) Taiwanese CHC patients with liver biopsies were enrolled. The TGF-beta1 gene polymorphism at position +29 (T or C), hepatitis C virus (HCV) RNA genotypes, and serum HCV RNA levels of these patients were determined. Of the 422 patients, the frequency of the T allele was 45.4%. Based on univariate analyses, a significantly lesser proportion of patients with allele T had high viral loads than those who were without allele T (P = 0.026). The lesser HCV RNA levels and HCV genotype 1b infection were significantly associated with the inheritance of the T allele in female patients based on univariate (P = 0.012 and 0.007, respectively) and multivariate regression (odds ratio/95% confidence interval: 0.434/0.219-0.859 and 0.468/0.237-0.927, respectively) analyses. In male patients with or without inheritance of the T allele, the clinical characteristics were similar. In conclusion, the association between TGF-beta1 polymorphism and virologic characteristics of chronic HCV infection implicated a significant role of host genetic factors on the clinical features of CHC. Female patients who carry T allele at position +29 were predisposed to be associated with HCV genotype non-1b infection and lesser HCV viral load, which revealed the gender effect.

Tzukuan Township in Taiwan has been reported to be an endemic area for hepatitis C virus (HCV) infection both in adults and adolescents. The maritime part of the township carries a higher prevalence than the non-maritime part and, as a consequence, several public education strategies have been introduced during the past decade. The current follow-up study aimed to clarify the changing prevalence of HCV infection among teenagers in the endemic maritime part of Tzukuan. In addition to viral hepatitis markers and biochemical profiles, we compared the epidemiological characteristics of 887 and 394 teenagers (aged 13-16 years) from the maritime part enrolled in 1995 and 2005, respectively. Compared with the results of surveillance in 1995, the prevalence of anti-HCV seropositivity (1.0% vs. 2.8%; P=0.045) and HCV RNA (0.5% vs. 2.3%; P=0.026) had decreased significantly by 2005. Transfusions and anti-HCV-positive families were the main risk factors amongst the 25 anti-HCV-positive teenagers in 1995, and became non-significant amongst the four anti-HCV-positive teenagers in 2005. In conclusion, the seroprevalence of HCV infection has significantly decreased after one decade of intervention among the teenage population in this endemic area.

Background/Aims To evaluate the association of virologic status with serum cholesterol and triglyceride levels in individuals with hepatitis C virus (HCV) infection. Methods We conducted a large scale community-based study enrolling 11,239 residents in an area endemic for hepatitis B virus (HBV) and HCV infection in southern Taiwan. Overall, 703 (6.3%), 1,536 (13.7%), 84 (0.7%) and 9,084 (80.8%) subjects were sero-positive for anti-HCV antibody (anti-HCV), hepatitis B surface antigen (HBsAg), and both anti-HCV and HBsAg, and negative for anti-HCV and HBsAg, respectively. Results By multivariate logistic analyses, the independent factors significantly associated with elevated serum cholesterol level were older age, female, negative for diabetes, anti-HCV or HBsAg and elevated triglyceride levels. The independent factors significantly associated with elevated serum triglyceride level were male, positive for diabetes, negative for anti-HCV or HBsAg, higher body mass index (BMI) and elevated cholesterol levels. Of 642 anti-HCV-positive subjects that have HCV RNA tested by standardized automated qualitative PCR assay, 478 (74.5%) were positive for HCV RNA. By multivariate logistic analyses, the independent factors associated with elevated serum cholesterol level were female, elevated serum triglyceride levels, negative for diabetes or HCV RNA. The independent factors associated with elevated serum triglyceride levels were elevated serum cholesterol levels, positive for diabetes, higher BMI and negative for HCV RNA. Diabetes, lower cholesterol and triglyceride levels were independent factors associated with positive HCV RNA. Conclusions Based on the result of this large scale community study, HCV viremia appears to be associated with lower serum cholesterol and triglyceride levels which implies that HCV itself might play a significant role on serum lipid profile of patients with chronic HCV infection.

Recommended treatment for hepatitis C virus genotype 1 (HCV-1) patients is peginterferon plus ribavirin for 48 weeks. We assessed whether treatment duration of 24 weeks is as effective as standard treatment in HCV-1 patients with a rapid virological response (RVR; seronegative for hepatitis C virus [HCV] RNA at 4 weeks). Two hundred HCV-1 patients were randomized (1:1) to either 24 or 48 weeks of peginterferon-alpha-2a (180 microg/week) and ribavirin (1000-1200 mg/day) with a 24-week follow-up. The primary endpoint was a sustained virological response (SVR; seronegative for HCV RNA at 24-week follow-up). Overall, the 48-week arm had a significantly higher SVR rate (79%) than the 24-week arm (59%, P = 0.002). For 87 (43.5%) patients with an RVR, the 24-week arm had a lower SVR rate [88.9%; 95% confidence interval (CI): 80%-98%] than the 48-week arm (100%, P = 0.056). For 52 patients with low baseline viremia (400,000 IU/mL) and an RVR, the 24-week arm had rates (CI) of relapse and SVR of 3.6% (-3%-11%) and 96.4% (89%-103%), respectively, which were comparable to those of the 48-week arm (0% and 100%) with difference (CI) of 3.6% (-7.2%-6.6%) and -3.6% (-14.3% to -0.6%), respectively. Multivariate analysis in all patients showed that RVR was the strongest independent factor associated with an SVR, followed by treatment duration, mean weight-based exposure of ribavirin, and baseline viral load.HCV-1 patients derive a significantly better SVR from 48 weeks versus 24 weeks of peginterferon/ribavirin even if they attain an RVR. Both 24 and 48 weeks of therapy can achieve high SVR rates (96%) in HCV-1 patients with low viral loads and an RVR.

Background: SouthernTaiwan is a hepatitis B and C viruses (HBV, HCV) endemic area. SEN virus (SENV) infection has been suggested as transfusion-related hepatitis. Two variants of SENV (SENV-D and SENV-H) have been studied in non-transfused children and transfusion-dependent thalassemia patients. Methods: Sera of 67 non-transfused children and 55 pediatric thalassemia patients with multiple transfusions were tested for SENV-D and SENV-H DNAs, liver function, iron status, HBV and HCV markers. Results: The prevalence of SENV (D or H), SENV-D, SENV-H infection, and SENV-D/H coinfection was significantly lower in nontransfused children than in thalassemia patients (22.4, 20.9, 5.0 and 1.5%, respectively, versus 67.3, 52.7, 40.0 and 25.5%, respectively, p < 0.001). The serum alanine aminotransferase (ALT) levels in thalassemia patients with SENV infection alone were significantly lower than levels in patients with SENV/HCV co-infection (p < 0.05), but not different when compared with those without SENV/HCV infection. SENV viremia was not associated with elevated ALT levels in thalassemia patients. SENV viremia did not increase the risk of HCV infection in thalassemia patients. Conclusions: SENV infection is high among non-transfused controls in Taiwan. Transfusion significantly increases the relevance of SENV infection. SENV viremia was not associated with the ALT levels in thalassemia patients.

The prevalence and clinical significance of two SEN virus (SENV) strains, SENV-D and SENV-H, was investigated among patients on maintenance hemodialysis in southern Taiwan.Sera from 99 uremic patients were tested for alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), and SENV-D and -H DNA. Sera from 120 healthy blood donors were tested as a control group.Of the 99 patients, 24.2 and 7.1% were positive for anti-HCV and HBsAg, respectively, and the prevalence of SENV-D and/or -H (SENV-D/H), SENV-D and SENV-H DNA was 61.6, 46.5 and 27.3%, which was significantly higher than for donors (23.3, 18.3, and 5.8%, respectively; all P0.0001). Patients with SENV-D DNA had significantly higher mean age among both patients (P=0.019) and donors (P=0.015). Mean serum ALT levels were significantly higher among patients with anti-HCV (P=0.003) and patients with SENV-D and -H concurrent infection (P=0.034). By multivariate analyses, the presence of serum anti-HCV and concurrent SENV-D and -H infection were independent factors associated with increased ALT level.The prevalence of SENV-D/H infection is high among Taiwanese patients on maintenance hemodialysis with SENV-D more prevalent than SENV-H. The ALT level was associated with not only positive anti-HCV but also concomitant viremia of both SENV-D and SENV-H.

Background: The aim of the present study was to compare the histological characteristics of livers between chronic hepatitis C (CHC) patients with and without hepatitis B virus (HBV) coinfection. Methods: A total of 336 CHC patients (male/female: 204/132, mean age: 46.1 ± 11.7 years) were enrolled in the study; 32 patients (9.8%) were positive for hepatitis B surface antigen (HBsAg). The histological characteristics of livers were described according to the Knodell and Scheuer scoring system. Results: The proportion of non-intralobular necrosis (score 0) was significantly lower and the mean intralobular necrosis score was higher among CHC patients with HBV coinfec- tion than those without coinfection (43.8% vs 64.5%; 0.84 ± 1.05 vs 0.53 ± 0.89). The epidemiological and virological parameters, and other histological scores (periportal necrosis, portal inflammation, total necroinflammation and fibrosis) were not significantly different between these two groups. Conclusion: Chronic hepatitis C patients with HBV coinfection tend to have more severe intralobular necrosis than those with isolated HCV infection.

Cytokines activation is a common feature in chronic hepatitis C (CHC) infection. Visfatin, as a recently-recognized adipocytokine, may correlate with metabolic abnormalities. We aimed to elucidate the characteristics of visfatin in CHC patients.This retrospective study included 102 treatment-naïve CHC patients and 97 sex-/age-matched healthy adults. Serum visfatin levels were examined by an enzyme linked immunosorbent assay test. The correlation between visfatin and hepatitis C virus (HCV) infection in terms of virological, metabolic, and histopathological profiles was analyzed. The impact of visfatin on the treatment response to pegylated interferon plus ribavirin (PEGIFN/RBV) therapy was also assessed.The visfatin level was correlated significantly with fibrosis scores (r = 0.23, P = 0.02) in CHC patients. A significant higher visfatin level was observed in CHC patients with histological activity index scores of mild and more (P = 0.01) and advanced fibrosis (P = 0.04). The mean visfatin level (0.81 ± 0.28 log ng/mL) of 26 CHC patients with metabolic syndrome was significantly lower than their counterparts (0.95 ± 0.30 log ng/mL) (P = 0.03). There was no significant correlation between visfatin and HCV genotypes, viral load, and treatment response to PEGIFN/RBV therapy. Multiple logistic regression analyses demonstrated that metabolic syndrome was the leading negative variable (odds ratio = 0.09, 95% confidence interval = 0.02-0.46, P = 0.004) associated with high visfatin level, followed by advanced fibrosis (odds ratio = 2.88, 95% confidence interval = 1.06-6.78, P = 0.03).Serum visfatin was correlated with disease severity and metabolic syndrome in CHC patients.

This study aimed to elucidate the rate and predictors of early (6 months) therapeutic responses to lamivudine, the rate of early mortality and the use of the model for end-stage liver disease (MELD) and Index in predicting the survival in patients with a clinical diagnosis of non-cirrhotic chronic hepatitis B with decompensation. Ninety-eight patients with lamivudine therapy were enrolled and MELD and Index scores were calculated. Surviving patients were treated with lamivudine for more than 6 months. Four (4.1%) of the 98 patients died after initiation of lamivudine therapy. After a 6-month lamivudine therapy, 80 (85.1%) patients and 71 (75.5%) patients had normal alanine aminotransferase (ALT) values and negative hepatitis B virus (HBV) DNA (200 copies/mL), respectively, and hepatitis B e antigen (HBeAg)-negative patients had a significantly higher rate of negative HBV DNA than HBeAg-positive patients (P=0.002). The rates of HBeAg seroconversion and negative HBV DNA were 28.8 and 63.5%, respectively, and patients with HBeAg seroconversion had a significantly higher rate of negative HBV DNA (P=0.004). By multivariate analyses, older age, HBV nongenotype B infection, negative HBeAg and higher ALT levels were factors associated with negative HBV DNA, and a higher ALT level was associated with HBeAg seroconversion at month 6 after lamivudine therapy. MELD score and Index score were significantly associated with death and areas under the receiver operating characteristic curve for predicting survival were 0.936 and 0.907 respectively. We concluded that after 6-month lamivudine therapy, the patients who survived achieved favourable biochemical, virological responses and rate of HBeAg seroconversion. Both MELD and Index scoring systems are good models to predict the 6-month survival.

To assess the efficacy of 24- or 48-week peginterferon/ribavirin treatment of Taiwanese patients with chronic hepatitis C virus genotype-1b (HCV-1b) infection, and to identify subgroups of patients in whom the 48-week treatment has benefits.We assigned 60 patients receiving peginterferon-alpha-2b (80-100 mcg/week) plus ribavirin (1000-1200 mg/day), depending on body weight, for 24 or 48 weeks, with a 3:1 randomization ratio.The sustained virological response (SVR) rate was significantly higher in the 48-week (80.0%, 12/15) than in the 24-week group (48.9%, 22/45, P0.05). The 60 patients were classified into two subgroups according to the presence of unfavorable baseline predictors: viral loadsor = 400,000 IU/ml or a hepatic fibrosis score of 3-4. In 19 patients without an unfavorable predictor, the SVR rate was comparable in the 24-week (78.6%) and 48-week (75.0%) groups; in patients with either unfavorable predictors, the SVR rate was significantly higher in the 48-week (81.1%, 9/11) than in the 24-week group (36.7%, 11/30, P = 0.015). The discontinuation rate was significantly higher in the 48-week (20.0%, 3/15) than in the 24-week group (2.2%, 1/45, P0.05).A 48-week course of peginterferon-alpha-2b/ribavirin was more effective than a 24-week course in Taiwanese HCV-1b patients, mainly in those with high viral loads and/or advanced hepatic fibrosis.

Background Interferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naïve Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues. Methods We performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80) or 6-MU (n = 134) thrice weekly for 24 weeks, in Taiwan between 1992 and 2001. Results There was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%). The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR) were significantly higher in 6-MU regimen (37.1%) than in 3-MU regimen (23.7%, p < 0.05) in per protocol analysis. Based on multivariate analysis, baseline viral load was strongly associated with SVR, followed by hepatitis C virus genotype, interferon-alpha regimen, and liver fibrosis. A histological improvement in necroinflammatory activity, but not in fibrosis was observed in the follow-up biopsy performed 0.5–5.5 years (mean: 1.9 years, n = 51) after end-of-treatment. Among patients without SVR, there was more activity improvement in 6-MU group. The durability of SVR was 100% (18/18) and 97.8% (45/46) for 3-MU and 6-MU group, respectively, in a mean follow-up period of 6.81 years (5.25–9.18 years). For 163 baseline non-cirrhotic patients, 9 of 84 (10.7%) non-responders and 3 of 79 (3.8%) sustained responders progressed to cirrhosis during a mean follow-up period of 5.52 and 5.74 years, respectively (p = 0.067, Kaplan-Meier survival analysis, log-rank test). For all 200 patients, hepatocellular carcinoma was detected in 12 of 113 (10.6%) non-responders and one of 87 (1.1%) sustained responders during a mean follow-up period of 5.67 and 5.73 years, respectively (p < 0.01, Kaplan-Meier survival analysis, log-rank test). Conclusion We confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis.