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.

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 .

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.

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.

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.

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.

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.

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.

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.

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.

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.

Adefovir dipivoxil treatment of lamivudine-resistant chronic hepatitis B.

Adefovir dipivoxil (ADV)-resistant mutations have been identified in treating hepatitis B virus (HBV) infection. This study aimed to analyze the response, the incidence of ADV resistance and the virologic characteristics of ADV therapy. A total of 29 CHB patients with confirmed lamivudine (LAM)-resistant HBV were treated with ADV for more than 52 weeks. Serum HBV DNA, HBV genotypes and sequences of HBV polymerase reverse-transcriptase domain were determined. Rates for the biochemical response, HBeAg loss, HBeAg seroconversion and virologic response (< 200 copies/mL of HBV DNA) were 82.8, 23.5, 11.8, and 48.3%, respectively, at week 52 of treatment. Lower pre-treatment mean HBV DNA level was the only significant factor associated with negative HBV DNA after ADV therapy. Six (20.7%) patients had clearance of LAM-resistant YMDD variants with replacement by the wild type HBV at week 52. The rtN236T, rtA181V/T and rtI233V were not identified before ADV therapy and the genotypic mutation of rtN236T was detected in one (3.4%) patient. In conclusion, the 52-week ADV treatment for patients with LAM-resistant HBV variants significantly achieved normalization of ALT levels, reduced serum HBV DNA levels and induced HBeAg loss and seroconversion. The emergence of ADV-resistant mutations seemed rare at weeks 52.

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.

Qualitative application of COBAS AMPLICOR HCV test version 2.0 assays in patients with chronic hepatitis C virus infection and comparison of clinical performance with version 1.0.

The objective of this research was to investigate the clinical performance of COBAS AMPLICOR hepatitis C virus (HCV) test version 2.0 Assays (CA V2.0). Eight serial samples with standard HCV ribonucleic acid (RNA) concentration and 10 times serial dilution of the 500 IU/mL samples were tested in triplicate by CA V2.0 (the limit of detection was 50 IU/mL). HCV RNA was investigated with CA V2.0 in 220 specimens from 100 chronic hepatitis C (CHC) patients, 60 chronic hepatitis B patients, and 60 healthy blood donors. The sensitivity was 99% and the specificity was 98.3%. Sera of 84 naïve CHC patients receiving standard interferon plus ribavirin for 24 weeks were tested by CA V2.0 and CA V1.0 at weeks 2, 4 and 8. The positive detection rates of CA V2.0 were significantly higher than CA V1.0 at week 2 (60.7% vs. 51.2%; p < 0.01) and week 8 (27.4% vs. 21.4%; p < 0.05). At weeks 2, 4 and 8, the positive predictive values were 90.91%, 83.02% and 78.69% with CA V2.0, and 90.24%, 82.14% and 72.73% with CA V1.0. The negative predictive values were 58.82%, 77.42% and 86.96% with CA V2.0, and 67.44%, 82.14% and 83.33% with CA V1.0. However, there was no significant difference between CA V2.0 and CA V1.0 for predicting sustained virologic response.

Outcome of chronic hepatitis C patients who required early termination of pegylated interferon-alpha plus ribavirin combination therapy.

BACKGROUND: Pegylated interferon/ribavirin (peg-IFN/RBV) combination therapy is effective for chronic hepatitis C (CHC) but frequently causes adverse events, leading to early termination. Little is known about the outcome of CHC patients who required early termination. METHODS: Of 617 treatment-naive CHC patients prescribed a 24-week protocol of peg-IFN/RBV, 29 (4.7%) patients who terminated treatment early at <20 weeks were recruited to evaluate the rate of and the factors associated with sustained virological response (SVR), defined as seronegativity of hepatitis C virus (HCV) RNA throughout the 24-week off-treatment follow-up period. RESULTS: The reasons for early termination were flu-like symptoms/signs (n=9, 31.0%), irritability (n=1, 3.4%), severe urticaria (n=1, 3.4%), insomnia (n=2, 6.9%), pulmonary tuberculosis (n=1, 3.4%/o), suicide idea (n=2, 6.9%), poor response (n=2, 6.9%), depression (n=2, 6.9%), unwilling to continue (n=1, 3.4%), mortality (n=1, 3.4%), gastrointestinal upset (n=1, 3.4%), pancytopenia complicated with cellulitis (n=1, 3.4%), anaemia (n=3, 10.3%), overseas work (n=1, 3.4%) and an unknown cause (n=1, 3.4%). Five (17.2%) patients achieved an SVR, comprising none of 16 HCV genotype-1 and five of the 13 (38.5%) genotype-2 patients (P=0.001). All sustained responders were HCV RNA seronegative at week 4 of treatment. The SVR rate among HCV-2 patients was 0% (0/1), 0% (0/2), 25% (1/4), 33% (1/3) and 100% (3/3) in those who received peg-IFN/RBV for 1-3, 4-7, 8-11, 12-15 and 16-19 weeks, respectively (P=0.019, chi2 with linear trend). CONCLUSIONS: Based on this limited study, we observed that an SVR might be achieved in patients who required early termination of a 24-week regimen of peg-IFN/RBV, especially for HCV-2 patients with HCV RNA seronegativity at week 4.

Early mortality in Taiwanese lamivudine-treated patients with chronic hepatitis B-related decompensation: evaluation of the model for end-stage liver disease and index scoring systems as prognostic predictors.

BACKGROUND: Both Model for End-stage Liver Disease (MELD) and Index scores have been used to predict mortality in patients with end-stage liver disease and cirrhosis in Western countries. OBJECTIVES: This study aimed to determine mortality rates, identify prognostic indicators, and determine the usefulness of these 2 scoring systems in predicting short-term (6-month) survival in Taiwanese patients with chronic hepatitis B (CHB)-related decompensation who were treated with lamivudine. METHODS: This study was conducted at the Kaohsiung Medical University Hospital and the Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan. Eligible patients were aged 18 to 85 years with CHB with related decompensation (with either serum total bilirubin level, >or=3 mg/dL or prolonged prothrombin time, >or=3 seconds) and were treatment naive. All patients were treated with lamivudine 100 mg PO (tablet) once daily; surviving patients were treated for at least 6 months. The clinical data, including hepatitis B surface antigen, hepatitis B e antigen, and hepatitis B virus (HBV) DNA, were measured before treatment. Pre-treatment MELD and Index scores were calculated for all patients. RESULTS: Ninety-six patients were enrolled (79 men, 17 women; mean [SD] age, 44.5 [15.2] years). Thirteen (13.5%) patients died within 6 months. Higher international normalized ratio (INR) for prothrombin time, lower albumin level, and higher HBV DNA level (>or=10(5) copies/mL) were factors significantly associated with death. The areas under the receiver operating characteristic curve for predicting survival by the MELD and Index scores were 0.822 and 0.788, respectively. Albumin level, which was not included in the scoring systems, also was found to be a significant predictor. CONCLUSIONS: : We found that with a 13.5% mortality rate, albumin, INR, and HBV DNA levels were good prognostic indicators in Taiwanese patients with CHB-related decompensation treated with lamivudine therapy. The MELD and Index scoring systems were good predictors of 6-month survival in the patients in this study.

Prevalence and clinical significance of HGV/GBV-C infection in patients with chronic hepatitis B or C.

Hepatitis G virus/GB virus-C (HGV/GBV-C) is a newly identified Flavivirus. Its clinical significance in chronic hepatitis B and C remains controversial. Infection with HGV/GBV-C was surveyed in 500 blood donors, 130 patients with chronic hepatitis B and 173 with hepatitis C, with chronic liver disease, cirrhosis, and/or hepatocellular carcinoma (HCC). HGV/GBV-C RNA was detected by reverse transcription-polymerase chain reaction. An antibody to HGV/GBV-C's second envelope protein (anti-E2 Ab) was detected using an enzyme immunoassay. The prevalence of HGV/GBV-C RNA was 3.4% and the exposure rate 10.2% in blood donors. The prevalence of HGV/GBV-C RNA in patients with chronic hepatitis B and hepatitis C was 7.7 and 17.3%, respectively (P = 0.002). The prevalence of the HGV/GBV-C infection in hepatitis B carriers increased with the severity of chronic liver disease and risk of HCC. The age and duration of hepatitis B virus infection were the more important contributing factors. Clinical and virological characteristics were comparable between those with and without coinfection of HGV/GBV-C and hepatitis C. The seroconversion rate was high. Coinfection of HGV/GBV-C with hepatitis B or C does not affect disease severity, but accelerates the progression of chronic liver disease and the development of HCC.

Viral interaction and responses in chronic hepatitis C and B coinfected patients with interferon-alpha plus ribavirin combination therapy.

BACKGROUND/AIMS: We conducted a case-control study to investigate the efficacy of interferon-alpha (IFN-alpha) and ribavirin combination therapy for patients with chronic hepatitis C and B virus (HCV/HBV) coinfection and to elucidate the interaction of these two viruses. METHODS: Forty-two chronic HCV/HBV-coinfected patients (29 IFN-naive, 13 IFN-relapsed) and 84 HCV-monoinfected controls, matched for age, sex and previous history of IFN-alpha therapy, were enrolled. All patients were treated with IFN-alpha-2b 6 MU three-times weekly plus ribavirin 1000-1200 mg daily for 24 weeks. Serum HCV RNA and HBV DNA were determined every 24 weeks for 72 weeks. RESULTS: The rate of HCV sustained virological response (SVR) was comparable among IFN-naive and IFN-relapsed HCV/HBV-coinfected patients and IFN-naive and IFN-relapsed HCV-monoinfected patients (69.0%, 69.2%, 67.2% and 57.7%, respectively; intention-to-treat analysis). HCV genotype 1b, high pretreatment HCV RNA levels and liver fibrosis were significantly associated with a lower HCV SVR. Of 16 baseline HBV viraemic patients, five (31.3%) achieved HBV SVR, which correlated negatively to HCV genotype non-1b and HCV SVR. Only one (6.3%) had simultaneous seroclearance of HCV and HBV. Antibodies to HBV surface antigen seroconversion developed in five (11.9%) patients during long-term follow-up. HCV responders had significantly higher rates of HBV DNA resurgence than HCV non-responders during and after treatment. Reciprocal viral interference was noted between HCV and HBV after IFN-alpha/ribavirin therapy. CONCLUSIONS: IFN-alpha/ribavirin combination therapy is effective for HCV/HBV-coinfected patients in eradicating HCV infection and might promote HBV seroclearance, and there is a mutual viral response and reciprocal viral interaction between HBV and HCV.

Polymorphisms in the interferon-gamma gene at position +874 in patients with chronic hepatitis C treated with high-dose interferon-alpha and ribavirin.

To investigate the influence of the T-to-A polymorphic sequence at position +874 in the interferon (IFN)-gamma gene (+874 IFN-gamma) on the response to combination therapy with high-dose interferon and ribavirin, the single nucleotide polymorphisms were determined by using a polymerase chain reaction sequence-specific primers approach in 150 histologically proved chronic hepatitis C (CHC) patients. The distribution of genotypes for +874 IFN-gamma were T/T: 6 (4.0%), T/A: 31 (20.7%) and A/A: 113 (75.3%) and 24.7% (37/150) of patients were inherited T allele. After undergoing combination therapy with high-dose IFN-alpha and ribavirin, 70.7% (106/150) of patients achieved sustained viral response (SVR). Based on multivariate regression analyses, the independent factors predicting HCV SVR after combination therapy were HCV genotype non-1b (P<0.001) and low pretreatment HCV RNA levels (P=0.041) (odds ratios/95% C.I.: 10.150/4.023-25.609 and 0.581/0.345-0.979, respectively). No association between genotypes, A or T alleles of +874 IFN-gamma and response to combination therapy with high-dose IFN-alpha and ribavirin. In conclusion, we found that with high SVR rates after combination therapy with high-dose IFN-alpha and ribavirin, HCV genotypes and pretreatment serum HCV RNA levels, but not inheritance of the IFN-gamma polymorphism at the position +847, were predictors for SVR.

High versus standard doses interferon-alpha in the treatment of naïve chronic hepatitis C patients in Taiwan: a 10-year cohort study.

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 naive 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.