Shinn-Cherng Chen

Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: A randomized trial

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 μg/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. Conclusion: 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. (HEPATOLOGY 2008;47:1884–1893.)

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients.

Genome‐wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin‐28B gene to the hepatitis C virus genotype 1 (HCV‐1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV‐2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV‐2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r 2 = 0.94‐0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow‐up). The rs10853728 genotype did not predict RVR or SVR in HCV‐2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P = 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) = 4.27, 95% confidence interval (CI) = 2.31‐7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR = 0.28, 95% CI = 0.15‐0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR = 3.10, 95% CI = 1.34‐7.21, P = 0.008), and the pretreatment level of aspartate aminotransferase (OR = 0.996, 95% CI = 0.99‐1.00, P = 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI = 8.89‐42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. Conclusion: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV‐2 patients. (Hepatology 2011)

The role of hepatitis B and C viruses in hepatocellular carcinoma in a hepatitis B endemic area. A case‐control study

To investigate the role of hepatitis B (HBV) and C viruses (HCV) in hepatocellular carcinoma (HCC) in an HBV endemic area and elucidate the interaction of these two viruses, a case‐control study of 128 patients with HCC and 384 age‐matched and sex‐matched control subjects was done. The positive rates of hepatitis B surface antigen (HBsAg, 77.3%, 99 of 128) and anti‐HCV (19.5%, 25 of 128) in patients with HCC were significantly higher than in control subjects (P < 0.001). Both HBsAg and anti‐HCV were important risk factors for HCC (relative risks, 13.96 and 27.12, respectively), and the risk for HCC was elevated significantly to 40.05 (95% confidence interval, 12.57 to 127.6) when HBsAg and anti‐HCV were considered simultaneously. These results suggested that HBV and HCV were associated highly with HCC in an HBV endemic area and that these two viruses might contribute independent but synergistic effects to the pathogenesis of HCC.

Associations between hepatitis C viremia and low serum triglyceride and cholesterol levels: A community-based study

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.

Efficacy and Safety of Pegylated Interferon Combined with Ribavirin for the Treatment of Older Patients with Chronic Hepatitis C

BACKGROUND The present study evaluated the efficacy and safety of pegylated interferon (PegIFN)/ribavirin treatment in elderly patients with hepatitis C virus (HCV) infection. METHODS Seventy elderly patients with hepatitis C virus (HCV) infection (group A; age, > or = 65 years) and 140 sex- and HCV genotype-matched controls (group B; age, 50-64 years) were allocated to receive a PegIFN-alpha-2a/ribavirin standard-of-care regimen. RESULTS Group A had a significantly higher rate of treatment discontinuation (21.4% vs 6.4%; P = .001) and grade 3 or 4 adverse events (34.3% vs 20%; P = .002) than group B. In intention-to-treat analysis, the sustained virologic response (SVR) rate was substantially lower in group A than in group B (67.1% vs 78.6%; P = .07). The inferiority of the SVR rate in group A was observed among patients with HCV genotype 1 (HCV-1) (51.9% vs 75.9%; P = .03) but not among patients with HCV genotype 2 or 3 (HCV-2/3) (76.7% vs 80.2%; P = .65). Among patients in group A who had a rapid virologic response, those infected with HCV-1 and those infected with HCV-2/3 had similar SVR rates (80% and 87.9%, respectively). For patients receiving treatment for >80% of its expected duration, SVR rates were similar between the 2 groups (80.4% vs 82.6%, respectively), regardless of viral genotype. CONCLUSIONS Older patients with HCV infection, especially those in the subgroup infected with HCV-1, had a greater frequency of adverse events and poorer adherence to the standard-of-care regimen, which may be the major reason for treatment inferiority. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT00629824 .

A simple noninvasive index for predicting long-term outcome of chronic hepatitis C after interferon-based therapy†

Changes in hepatic fibrosis after interferon‐based therapy may be important in determining the long‐term outcome of chronic hepatitis C (CHC). The use of liver biopsy for posttreatment assessment is not a viable option as a routine follow‐up procedure. This study evaluated the predictive value of a simple noninvasive index, the aspartate aminotransferase (AST)‐to‐platelet ratio index assessed 6 months after end of treatment (APRI‐M6). We evaluated APRI‐M6, platelet‐M6, AST‐M6, and α‐fetoprotein‐M6 of 776 CHC patients with interferon‐based therapy as well as the parameters at baseline of 562 untreated patients who were evaluated to predict the risk of hepatocellular carcinoma (HCC) and mortality, during a mean follow‐up period of 4.75 (1.0–12.2) and 5.15 (1.0–16) years, respectively. Based on analysis of receiver operating characteristics (ROC) and using optimized cutoff point, the APRI‐M6 and platelet‐M6 had superior prediction models for long‐term outcome with area under the curve of 0.870–0.875 and 0.824–0.847, respectively, and accuracy of 78%–81% and 76%–78%, respectively, for interferon‐based‐treated patients. The predictive values of all 4 parameters were poor in untreated patients. In subgroup analysis, the APRI‐M6 provided a more consistent prediction ratio than platelet‐M6 for sustained responders and cirrhosis‐free subgroups; both parameters had similar prediction power for nonresponders and were unsatisfactory in patients with cirrhosis. According to Cox proportional hazards analysis, cirrhosis and APRI‐M6 were the 2 most important factors for predicting HCC. In conclusion, APRI‐M6 can accurately predict the long‐term outcome of patients subjected to interferon‐based treatment. Nevertheless, the data needs further validation, particularly since the predictive accuracy for patients with cirrhosis is low. (HEPATOLOGY 2006;44:1086–1097.)

Risk factors for gallstones among Chinese in Taiwan. A community sonographic survey.

A health survey of adults aged 30 years or more was carried out in southwest Taiwan to determine the prevalence of gallstones and to study risk factors associated with gallstones. Blood samples were collected and abdominal sonographic examination and anthropometric measurements were performed on a total of 923 people. The 40 gallstone cases detected resulted in a prevalence of 4.3%. The risk factors explored included age, sex, hepatitis, obesity, hyperlipidemia, and diabetes mellitus (DM). Age and DM were the only significant factors associated with gallstones in our study. With a reference group of 30–39-year-olds as a comparison, multiple logistic regression analysis showed a trend effect with odds ratios of 1.73, 3.74, and 6.32 for age groups of 40–49, 50–59, and 60 or above, respectively. The odds ratio for DM was as high as 2.59. However, sex, body weight index, chronic hepatitis B, and hyperlipidemia were not significantly associated with gallstones.

Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication

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<0.001), followed by age (HR 1.06, 95% CI 1.02-1.11, p=0.005) and γGT levels (HR 1.008, 95% CI 1.004-1.013, p<0.001). The incidence of HCC did not differ between patients with high and low baseline γGT levels among patients with cirrhosis (p=0.53), but the incidence of HCC was significantly higher in non-cirrhotic patients with high γGT levels compared with those with low γGT levels (p=0.001). Cox regression analysis revealed that the strongest factors associated with HCC development in non-cirrhotic sustained responders were baseline γGT levels (HR 6.44, 95% CI 2.20-18.89, p=0.001) and age (HR 3.68, 95% CI 1.33-10.17, p=0.012). The incidence of HCC was not different between older non-cirrhotic patients with high γGT levels and cirrhotic patients (p=0.34). CONCLUSIONS HCC remains a threat in non-cirrhotic patients with an SVR. Serum γGT levels helped to identify potential patients at high risk.

Viral Hepatitis Infections in Southern Taiwan: A Multicenter Community-based Study

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major causes of liver disease in Taiwan and have a great impact on the health of this country. This study investigated the seroprevalence of HBV and HCV in southern Taiwan. Screening programs were performed from September 1999 to August 2005 for community‐based surveillance of liver disease. A total of 28,797 adults from southern Taiwan, including Kaohsiung City (n = 14,036), Kaohsiung County (n = 7,713), and Pingtung County (n = 7,048) were participated. The mean age was 50.3 ± 14.6 years (range, 20‐97 years), with 41.0% were men. Hepatitis B surface antigen (HBsAg), antibody to HCV (anti‐HCV), and liver function tests were performed. Among the 28,797 adults, the prevalence of HBsAg(+) was 15.1% and that for anti‐HCV(+) was 8.6%. The seroprevalence of HBsAg in Kaohsiung County was 18.2%, which was higher than in Kaohsiung City (14.7%, p < 0.001) or Pingtung County (12.5%, p < 0.001). The seroprevalence of anti‐HCV in Kaohsiung County was 17.2%, which was higher than in the other regions (Kaohsiung City = 5.8%, p < 0.001; Pingtung County = 4.6%, p < 0.001). The prevalence of dual HBsAg and anti‐HCV was 1.1% (323 patients). Tzukuan Township in Kaohsiung County was endemic for HBsAg (19.1%, 1,026/5,375 patients), anti‐HCV (22.4%, 1,203/5,375 patients), and dual HBsAg/anti‐HCV (3.6%, 191/5,375 patients). Subjects with anti‐HCV(+) were older and had higher alanine transaminase levels than their HBsAg(+) counterparts (p < 0.001 and p < 0.001, respectively). The current study shows the epidemiological characteristics of HBV and HCV infections among adults in southern Taiwan. Viral hepatitis infections remain widely endemic in this region.

The PNPLA3 I148M polymorphism is associated with insulin resistance and nonalcoholic fatty liver disease in a normoglycaemic population

Background and Aims: The adiponutrin/patatin‐like phospholipase‐3 (PNPLA3) I148M polymorphism has recently been found to contribute to differences in hepatic lipid content. Nonalcoholic fatty liver disease (NAFLD) has recently been considered a hepatic component of insulin resistance and a risk factor in the emergence of type 2 diabetes. However, whether there is an association between PNPLA3 I148M and insulin resistance and NAFLD in a normoglycaemic population is still unknown.