Li-Po Lee

A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C

Background: The recommended treatment for patients infected with hepatitis C virus genotype 2 (HCV2) is pegylated interferon (peginterferon) and ribavirin for 24 weeks. Aim: To assess whether a shorter 16-week treatment is as effective as a standard 24-week treatment. Methods: Patients with HCV2 infection were randomised in a 1:2 ratio to either 16 weeks (n = 50) or 24 weeks (n = 100) of treatment with peginterferon α-2a (180 μg/week) and weight-based ribavirin 1000–1200 mg/day, with a 24-week follow-up period. A rapid virological response (RVR) was defined as seronegative for HCV RNA at 4 weeks of treatment, and the primary end point, sustained virological response (SVR), as seronegative for HCV RNA at the 24-week follow-up. Results: The rate of RVR and SVR was 86% (43/50, 95% confidence interval (CI) 76% to 96%) and 94% (47/50, CI 87% to 100%), respectively, in the 16-week group, which was comparable to 87% (87/100, CI 80% to 94%) and 95% (95/100, CI 91% to 99%) in the 24-week group. Patients with RVR had a significantly higher SVR rate than patients without RVR in both 16-week (100% vs 57%, p = 0.015) and 24-week groups (98% vs 77%, p = 0.002). Multivariate analysis showed that RVR and age were independent factors associated with SVR. Both treatment arms were equally well tolerated. The incidence of alopecia was significantly higher in the 24-week group (49%) than in the 16-week group (20%, p = 0.001). Conclusion: 16 weeks and 24 weeks of peginterferon treatment with weight-based ribavirin at a dose of 1000–1200 mg/day provided equal efficacy in patients with HCV2 who achieved RVR at 4 weeks.

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.)

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.

Hepatitis C Viremia Increases the Association With Type 2 Diabetes Mellitus in a Hepatitis B and C Endemic Area: An Epidemiological Link With Virological Implication

OBJECTIVES:There is growing evidence with regard to the association between hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM). However, the mutual link and related virological implication have not been fully clarified. The impact of hepatitis B virus (HBV) infection on the epidemiological link remains unclear. This study aimed to elucidate the link between T2DM and viral hepatitis infections, especially HCV infection. It also aimed to analyze the associated virological characteristics and implication.METHODS:Cross-sectional analysis of a computer-sampling survey among 10,975 participants (aged 40–65 yr) was performed in an area endemic for HBV and HCV infections in Taiwan. Outcome measures included prevalence of T2DM among different groups of viral hepatitis infection, and comparison of related biochemical and virological profiles.RESULTS:Of 10,975 participants studied, 9,932 eligible participants were analyzed. The prevalence of T2DM, seropositivity for HBV surface antigen (HBsAg) and HCV antibodies (anti-HCV), and HCV viremia was 12.5%, 13.1%, 6.5%, and 4.8%, respectively. Prevalence of HCV viremia showed significant difference between T2DM and non-T2DM subjects (6.9% vs 4.5%, P < 0.001), whereas anti-HCV seropositivity showed borderline significance (7.8% vs 6.3%, P = 0.047). There was no HCV genotype-specific difference between HCV genotype 1 and 2 in the association with T2DM. On the other side, the prevalence of HBsAg (+) did not differ between T2DM and non-T2DM subjects (12.5% vs 13.9%, P = 0.19). The prevalence of T2DM among HCV viremic subjects (18.0%, 86/478) was significantly higher than HBsAg (+) subjects (11.4%, 155/1,363, P = 0.001) and those negative for both viral hepatitis markers (12.5%, 997/8,004, P = 0.001). Multivariate logistic regression analyses showed that HCV viremia was the leading significant factor associated with T2DM, followed by male gender, hypertension, body mass index, and age.CONCLUSIONS:HBV infection did not increase the association with T2DM. A significant mutual link between T2DM and HCV viremia existed in this HBV/HCV endemic area. There was no HCV genotype-specific difference between HCV genotype 1 and 2 in the association with T2DM.

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.)

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 incidence and risks of liver biopsy in non-cirrhotic patients: An evaluation of 3806 biopsies

Liver biopsy plays a crucial role in the diagnosis and management of liver diseases. For the past decade, this invasive procedure has become a safe one with the prevailing application of an ultrasound-guided method, the use of thinner gauge needles and improved operational techniques. Over the past years, the debatable issue of liver biopsy has mainly focused on the safety and suitability of a shorter observation time with respect to cost savings.1–3 Referring to this issue, Beddy et al even shortened their observation time to 1 hour and indicated that only one haemorrhagic complication occurred within one hour amongst 500 liver biopsy occasions. …

Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C

Aims: Positive serum antinuclear antibody (ANA) is present in a number of patients with chronic hepatitis C virus (HCV) infection. This study aimed to evaluate the prevalence of ANA in patients with chronic hepatitis C (CHC) and to elucidate its clinical implications in virological and histological characteristics of CHC infection. Methods: A total of 614 CHC patients were enrolled in this prospective, hospital-based study. The serum levels of aspartate aminotransferase, alanine aminotransferase and ANA, and HCV genotype, HCV RNA level, and histological activity index scores for liver histopathology, were determined. Results: The prevalence of positive ANA (titre >1:40) was 35.0%. Women had a significantly higher prevalence than men (41.2 vs 31.0%; p = 0.012). Patients positive for ANA were significantly older (mean (SD), 53.7 (10.5) vs 49.7 (11.3) years; p<0.001) and had higher mean (SD) alanine aminotransferase levels (186.9 (178.8) vs 155.50 (113.5) IU/l; p<0.001) and lower mean (SD) HCV RNA levels (5.2 (0.9) vs 5.4 (1.0) log IU/ml; p = 0.048) than those without ANA. Among 447 patients undergoing liver biopsy, those positive for ANA had a significantly higher mean (SD) fibrosis score (2.0 (1.3) vs 1.5 (1.1); p<0.001) and a higher frequency of F3–4 (69/187, 36.9% vs 50/260, 19.2%; p<0.001) than those negative for ANA. Multivariate logistic regression analyses showed that advanced fibrosis, lower HCV RNA levels and age were significant factors related to positive ANA. Conclusion: ANA is associated with a more advanced liver fibrosis and lower serum HCV RNA level in patients with CHC.

Reappraisal of the characteristics of glucose abnormalities in patients with chronic hepatitis C infection.

OBJECTIVES: There is growing evidence suggesting the mutual link between type 2 diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection. However, the impact of HCV infection on the suite of glucose abnormalities has rarely been investigated. The study aimed to determine the difference regarding the prevalence and the characteristics of glucose abnormalities between chronic hepatitis C (CHC) patients and community-based controls. It also aimed to investigate the related clinical, virological, and histological features of glucose abnormalities in HCV infection.METHODS: Six hundred eighty-three CHC patients and 515 sex-/age-matched controls were included. Oral glucose tolerance test (OGTT) was performed in 522 CHC patients and 447 controls without known T2DM. Clinical data were assessed upon the different stages of glucose abnormalities based on OGTT results.RESULTS: The prevalence of normoglycemia, IGT, and T2DM in 683 CHC patients was 27.7%, 34.6%, and 37.8%, respectively. There was a significant linear trend from normoglycemia to T2DM in terms of age, family history of T2DM, and advanced liver fibrosis in CHC patients. For those CHC patients without fibrosis, the prevalence of glucose abnormalities reached 67.9% high. All CHC patients carried a significantly higher prevalence than controls regarding those aged <65 yr. For those without known DM, there was a 3.5-fold increase in the prevalence of glucose abnormalities in CHC (65.8%) patients in comparison with controls (35.3%) (OR 3.51, 95% CI 2.70–4.56, P < 0.001).CONCLUSIONS: CHC patients carried a high prevalence of glucose abnormalities. Determination of glucose abnormalities by OGTT may be suggested.

The role of thyroid autoantibodies in the development of thyroid dysfunction in Taiwanese chronic hepatitis C patients with interferon‐alpha and ribavirin combination therapy

Summary.  To investigate the role of thyroid autoantibodies in the development of thyroid dysfunction among chronic hepatitis C (CHC) patients receiving interferon‐alpha (IFN‐α) plus ribavirin (RBV) combination therapy, 95 Taiwanese naïve patients with baseline euthyroidism were enrolled. They were treated with IFN‐α2b, 6 million units thrice weekly, plus RBV 1000–1200 mg daily for 24 weeks. Thyroid function, anti‐thyroglobulin and antiperoxidase autoantibodies were tested at enrolment (M0), at the end‐of‐treatment (M6) and 6 months after end‐of‐treatment (M12). The percentages of thyroid autoantibodies were 8.4%, 11.6% and 9.5%, at M0, M6 and M12 respectively. Fourteen (14.7%) patients developed thyroid dysfunction at M6 or M12. Thyroid dysfunction occurred during treatment in five (62.5%) of the eight patients with baseline thyroid autoantibodies, which was significantly higher than nine (10.3%) of 87 patients without baseline thyroid autoantibodies (P = 0.0001). Among 14 patients who developed thyroid dysfunction, four (80.0%) of five patients with baseline thyroid autoantibodies recovered at M12, in contrast to two (25%) of eight without baseline thyroid autoantibodies recovered at M12 (P < 0.05). In conclusion, thyroid autoantibodies, either occurred before or during IFN‐α plus RBV combination therapy, carry a high prediction of subsequent thyroid dysfunction. There also exists difference in the clinical manifestations of thyroid dysfunction in CHC patients treated with combination therapy.