Interferon-associated hepatic steatosis is related to discrepancies in biochemical and virological responses of chronic hepatitis C to IFN-based therapy.

BACKGROUND AND AIMS: A discrepancy in virological and biochemical responses may occur throughout interferon-based therapy for hepatitis C virus (HCV). We aimed to explore the risk, associated factors, potential mechanisms, and impact on the treatment outcome of the discrepancy. SUBJECTS AND METHODS: Consecutive 496, chronic HCV-infected patients receiving interferon/ribavirin or peginterferon/ribavirin for 24 weeks with a 24-week follow-up period were enrolled. Of 433 patients with pretreatment liver biopsy, 46 received serial liver biopsies at the end of treatment and end of follow-up to explore the corresponding change in liver histopathology. A virological/biochemical discrepancy was defined as persistently elevated alanine aminotransferase levels throughout the treatment period, despite the seronegativity for HCV RNA at least at the end of treatment. The sustained virological response (SVR) was defined as seronegativity for HCV RNA 6 months after the end of treatment. RESULTS: Virological/biochemical discrepancy was observed in 28.7 % (137/478) patients. The SVR rate was comparable between patients with (75.2 %, 103/137) and without discrepancy (81.2 %, 277/341, p = 0.14). For patients with discrepancy and SVR, 78 (75.7 %) had a subsequent normalization of alanine aminotransferase. Hepatic steatosis, advanced fibrosis, obesity, older age, peginterferon preparation, and low viral load were independently predictive of a virological/biochemical discrepancy. Serial liver histology showed that significant transient aggravation of hepatic steatosis during interferon-based therapy was observed among patients with a virological/biochemical discrepancy (difference 0.64 ± 0.93, p = 0.022), but not among those without it (difference 0.09 ± 0.69, p = 0.447). CONCLUSIONS: A virological/biochemical discrepancy no longer exists after treatment cessation in most patients, and had little impact on the HCV treatment outcome. Treatment-related hepatic steatosis might play an important role in the pathogenesis of the discrepancy.

Antinuclear antibody titer and treatment response to peginterferon plus ribavirin for chronic hepatitis C patients.

Positive serum antinuclear antibody (ANA) is not infrequent in chronic hepatitis C virus (HCV)-infected patients. This prospective study evaluated the impact of ANA on the response to and safety of peginterferon/ribavirin combination therapy for chronic hepatitis C patients in clinical practice. We enrolled 243 consecutive patients who were treated with a 24-week regimen of peginterferon-α plus ribavirin, with a 24-week follow-up period. ANA titer was determined before antiviral treatment. The primary end-point was sustained virological response (SVR), defined as HCV RNA <50 IU/mL throughout the follow-up period. Overall, 187 (77.0%) patients experienced a SVR. In the 105-patient HCV genotype non-1 group, patients with ANA titer ≥1:80 had a significantly lower SVR rate than those with ANA titer <1:80 (67.7% vs. 95.8%, respectively, p = 0.013). In contrast, in the 138-patient HCV genotype 1 group, the SVR rate did not differ between patients with and without ANA titer ≥1:80. Multivariate regressive analyses showed that ANA ≥1:80, age and HCV RNA levels were independent factors associated with SVR in HCV genotype non-1 patients; whereas HCV RNA levels and hepatic fibrosis were prognostic predictors of SVR in HCV genotype 1 patients. The frequencies of adverse events were similar between patients with and without ANA seropositivity. Peginterferon/ribavirin combination therapy is effective and safe in ANA-positive chronic hepatitis C patients. A high ANA titer was a negative prognostic factor for treatment response in HCV genotype non-1 patients.

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

UNLABELLED: 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 (r2 = 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.

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.

Early identification of achieving a sustained virological response in chronic hepatitis C patients without a rapid virological response.

BACKGROUND AND AIM: A number of hepatitis C virus (HCV) patients without a rapid virological response (RVR) achieved a sustained virological response (SVR) with peginterferon-alpha-2a/ribavirin. The aim of this study was to identify factors associated with SVR in non-RVR patients. METHODS: Baseline and on-treatment factors were used to explore the prognostic factors for SVR in 113 HCV genotype-1 (HCV-1) and 20 HCV-2 non-RVR patients in two randomized trials. RESULTS: The SVR rate in HCV-1 patients with a complete early virological response (cEVR) and partial early virological response was 91.9% versus 45% (P < 0.001) and 21.4% versus 10% (P = 0.62), respectively, after 48 and 24 weeks of treatment. The SVR rate in HCV-2 patients with a cEVR was 90.9% versus 57.1% (P = 0.25), respectively, after 24 and 16 weeks of treatment. Multivariate analysis showed that cEVR and standard regimen were independently associated with SVR. Viral kinetic study revealed that HCV viral loads < 10,000 IU/mL at week 4 were the best predictor of cEVR for both HCV-1 and HCV-2 non-RVR patients with the accuracy of 81% and 95%, respectively, and also of SVR with the accuracy of 78% and 92%, respectively, in patients receiving standard of care. The most important independent predictors for cEVR were HCV viral loads < 10(4) IU/mL at week 4, followed by increased ribavirin dose within 12 weeks of treatment. CONCLUSIONS: Achieving a cEVR with standard of care is the most important predictor of SVR in non-RVR patients. Week 4 viral loads < 10,000 IU/mL could accurately predict cEVR early and following SVR in non-SVR patients.

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 .

Comparison of adverse effects related to pegylated interferon-based therapy for patients with chronic hepatitis B and chronic hepatitis C in Taiwan.

PURPOSE: Pegylated interferon (Peg-IFN)-based therapy is effective in treating chronic hepatitis B (CHB) and C (CHC) but frequently induces adverse events (AEs). This study was conducted to compare the incidence of Peg-IFN-based therapy-associated AEs in Taiwanese patients with CHB and CHC. METHODS: Fifty-six patients with CHB and 103 age-, sex- and treatment duration-matched patients with CHC were enrolled. Patients with CHB were treated with Peg-IFN-α-2a 180 µg/week for 24 weeks (HBeAg(+), n = 31) or 48 weeks (HBeAg(-), n = 25); patients with CHC were treated with Peg-IFN-α-2a 180 µg/week plus ribavirin 1,000-1,200 mg/day for 24 weeks (genotype 2/3, n = 57) or 48 weeks (genotype 1, n = 46). RESULTS: Significantly higher incidences of Peg-IFN-related AEs, especially neuropsychiatric symptoms, and ribavirin-associated skin manifestations were observed in patients with CHC compared with those with CHB, with either the 24- or 48-week regimen. Frequencies of laboratory abnormalities, except for anemia, were comparable in both groups. Neither group showed overt hepatic decompensation. Frequency of dose reduction was similar between the groups. Substantially higher rates of early termination and severe AEs were observed in patients with CHC. CONCLUSIONS: Patients with CHB treated with Peg-IFN had fewer AEs than patients with CHC treated with Peg-IFN/ribavirin. All patients were treated safely.

Human leukocyte antigen alleles and the response to pegylated interferon/ribavirin therapy in chronic hepatitis C patients.

Human leukocyte antigens (HLAs) may play a role in the clinical evolution of hepatitis C virus (HCV) infection. The present study was aimed at elucidating the association between the HLA loci and responses to combination therapy with pegylated interferon-alpha 2a (PEG-IFN) and ribavirin in Taiwanese. We enrolled a total of 208 treatment-naïve Taiwanese chronic hepatitis C (CHC) patients treated with combination therapy. Patients with sustained virological response (SVR) had a significantly higher frequency of genotype non-1b infection, lower pretreatment HCV RNA levels and a higher frequency of mild hepatic fibrosis (fibrosis score: F: 0-2). The HLA A24 and B40 alleles were significantly associated with SVR after adjusted for the other three confounding factors including HCV genotype, hepatic fibrosis and pretreatment serum HCV RNA levels. Haplotypes (B40-DRB1*3, B46- DRB1*9, Cw1- DQB1*3, and Cw1- DRB1*9) were significantly associated with SVR to combination therapy. For 167 patients with genotype 1b infection and viral load < or =5.6 logIU/ml or genotype non-1b infection, the B46 was significantly associated with sustained response with OR (odds ratio) [95% CI (confidence interval) of 0.047 (0.168-0.988)]. Haplotypes B40-DRB1*3, B46- DRB1*9, Cw1- DQB1*3, Cw1- DRB1*9 and DQB1*3- DRB1*9 were found to be associated with SVR to PEG-IFN/ribavirin therapy with OR (95% CI) of 0.179 (0.032-0.989), 0.313 (0.107-0.918), 0.350 (0.145-0.845), 0.282 (0.105-0.759) and 0.412 (0.174-0.978), respectively. We concluded that the virological and the host immunogenetic factors may possibly predict the response to combination therapy in CHC patients.

Hepatitis C virus viremia and low platelet count: a study in a hepatitis B & C endemic area in Taiwan.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

HBV infection in indigenous children, 20 years after immunization in Taiwan: a community-based study.

OBJECTIVES: Hepatitis B virus infection is hyperendemic in Taiwan. In the past, the infection rate has been higher in indigenous villages. The prevalence of chronic HBV infection among indigenous children after immunization remains unknown. METHODS: A total of 843 indigenous children were checked for the hepatitis B seromarker. Another 606 metropolitan children were enrolled for comparison in 2005. RESULTS: The seroprevalences (%) of HBsAg, (hepatitis B surface antigen) anti-HBs, (antibody to hepatitis B surface antigen) and anti-HBc (antibody to hepatitis B core antigen) among indigenous and metropolitan children were 3.2 vs. 0.17 (p<0.001), 47.4 vs. 51.2 (p=0.164), and 10.7 vs. 1.7 (p<0.001), respectively. Among the indigenous children, who were divided into three age groups, the prevalences of HBsAg and anti-HBc increased with age, while anti-HBs decreased significantly (p=0.025, 0.002, and <0.001, respectively). Children with positive HBsAg had a significantly higher mean (SD) age (10.2 (2.2) vs. 9.2 (2.1) years, p=0.024) and a higher ALT value (16.4 (8.0) vs. 10.6 (8.3) IU/L, p=0.001). In a multivariable analysis, indigenous residency, older age group and abnormal ALT value were independent factors associated with positive HBsAg. CONCLUSIONS: The seroprevalence of hepatitis B infection has obviously declined among indigenous children 20 years after mass immunization programs launched in Taiwan. However, it is still higher than that of metropolitan children. Higher rates of chronic HBV infection in the mothers might be one important explanation for this finding.

Insulin resistance predicts response to peginterferon-alpha/ribavirin combination therapy in chronic hepatitis C patients.

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 (>or=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.

Serum retinol-binding protein 4 is inversely correlated with disease severity of chronic hepatitis C.

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-nai 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+/-16.5 microg/mL of minimal to 19.2+/-12.5 microg/mL of severe, P=0.002) and staging (from 34.2+/-10.0 microg/mL of F0 to 22.2+/-11.9 microg/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.

Association between transforming growth factor-beta 1 polymorphism and virologic characteristics of chronic hepatitis C.

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.

Changing prevalence of hepatitis C virus infection among teenagers in an endemic area in Taiwan.

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.

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.

Hepatitis C virus infection among children in aboriginal areas in Taiwan.

The prevalence of hepatitis C virus (HCV) infection among adults in aboriginal areas has been shown to be higher than in urban areas in Taiwan. Whether the prevalence of HCV infection is also higher among children in aboriginal areas remains unclear. In total, 1176 schoolchildren in four aboriginal areas were invited to participate in the study. All children were tested for serum antibodies to HCV (anti-HCV) and liver enzymes. The age range of children was 6-13 years. Another 606 sex- and age-matched schoolchildren from an urban area served as controls. There was no statistically significant difference in prevalence of anti-HCV between aboriginal and Han Chinese students in aboriginal areas. The prevalence of anti-HCV was 0.3% (4/1176) in aboriginal areas, which was similar to the prevalence of 0% (0/606) in the urban area. The four anti-HCV seropositive aboriginal children were all negative for HCV RNA. Our data suggest that the high prevalence of anti-HCV among aboriginal adults might be due to subsequent exposure to risk factors after school age.

Performance characteristics of a real-time RT-PCR assay for quantification of hepatitis C virus RNA in patients with genotype 1 and 2 infections.

BACKGROUND: Polymerase chain reaction (PCR) methods play an essential role in providing data relating to diagnosis, monitoring and treatment of hepatitis C virus (HCV) infection. The real-time reverse transcription PCR (RT-PCR) assay is an established and promising tool in terms of quantifying HCV RNA for clinical application. This study aimed to evaluate the performance characteristics of a real-time RT-PCR-based test in a clinical setting. METHODS: Validation and reproducibility tests were performed using a standard panel. Sera from 197 chronic HCV patients were analyzed by the real-time RT-PCR assay and the results were compared with the Versant bDNA3.0 assay (bDNA3.0). RESULTS: The real-time RT-PCR assay showed an acceptable linear response (r2=0.989-0.995) in the serial dilutions regarding genotypes 1b, 2a, 2b and 1b+2a. HCV viral loads were quantifiable in all 197 patients (100%) by the real-time RT-PCR assay and in 194 (98.5%) by the bDNA3.0. HCV RNA quantification values measured by the real-time RT-PCR and bDNA3.0 assays were positively correlated (Pearson's correlation coefficient r=0.734, p<0.001). The real-time RT-PCR assay values were on average 0.13 logs higher than the bDNA3.0 results. The correlation coefficients with genotypes 1b, 2a, 2b and mixed were 0.737, 0.711, 0.791 and 0.766, respectively (p<0.01). CONCLUSIONS: The real-time RT-PCR assay showed comparable performance with bDNA3.0 regarding quantification of HCV viral loads with genotype 1 and 2 HCV infections.

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.

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

UNLABELLED: 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. 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.

Hepatic steatosis and fibrosis in chronic hepatitis C in Taiwan.

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.