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

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

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.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.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 aged65 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, P0.001).CHC patients carried a high prevalence of glucose abnormalities. Determination of glucose abnormalities by OGTT may be suggested.

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

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

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.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.The prevalence of positive ANA (titre1:40) 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; p0.001) and had higher mean (SD) alanine aminotransferase levels (186.9 (178.8) vs 155.50 (113.5) IU/l; p0.001) 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); p0.001) and a higher frequency of F3-4 (69/187, 36.9% vs 50/260, 19.2%; p0.001) 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.ANA is associated with a more advanced liver fibrosis and lower serum HCV RNA level in patients with CHC.

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.

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 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%), 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, χ2 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.

The G-->A transition in the tumor necrosis factor (TNF)- alpha promoter region at position -308 (TNF308.2) and -238 (TNF238.2) were determined in 141 patients with chronic hepatitis C virus (HCV) infection. Patients received combination therapy with high-dose interferon (IFN)- alpha and ribavirin for 24 weeks. A total of 100 patients (70.9%) had a sustained virologic response (SVR) after treatment. The TNF308.2 allele was independently associated with an SVR, particularly in patients with HCV genotype 1b infection and >200,000 IU of HCV RNA/mL in serum. In conclusion, the response to combination therapy with high-dose IFN- alpha and ribavirin may be associated, at least in part, with host genetic factors.

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 alpha-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.

Background: To assess the efficacy of 24- or 48-week peginterferon/ribavirin treatment of Taiwanese patients with chronic hepatitis C virus genotype-1b (HCV-1b) infection, and to identify subgroups of patients in whom the 48-week treatment has benefits. Methods: We assigned 60 patients receiving peginterferon-α-2b (80–100 mcg/week) plus ribavirin (1000–1200 mg/day), depending on body weight, for 24 or 48 weeks, with a 3:1 randomization ratio. Results: The sustained virological response (SVR) rate was significantly higher in the 48-week (80.0%, 12/15) than in the 24-week group (48.9%, 22/45, P

Background/aims We conducted a case-control study to investigate the efficacy of interferon-alpha (IFN-α) 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-α therapy, were enrolled. All patients were treated with IFN-α-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-α/ribavirin therapy. Conclusions IFN-α/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.

Chuang W-L, Dai C-Y, Chen S-C, Lee L-P, Lin Z-Y, Hsieh M-Y, Wang L-Y, Yu M-L, Chang W-Y. Randomized trial of three different regimens for 24 weeks for re-treatment of chronic hepatitis C patients who failed to respond to interferon-a monotherapy in Taiwan. Liver International 2004: 24: 595-602. r Blackwell Munksgaard 2004 Abstract: With the favorable result of interferon (IFN)-ribavirin combination therapy for 24 weeks among naive Taiwanese chronic hepatitis C (CHC) patients, the optimal regimens of re-treatment for CHC patients who failed initial IFN monotherapy is not well-established. The study evaluated the effectiveness of re-treatment for 24 weeks with 3 different regimens and predictors for sustained virological response (SVR). Methods: Total 120 Taiwanese CHC patients (81 males, 70 relapsers, mean age: 48.6 years) who failed initial IFN monotherapy were enrolled. They were assigned randomly (with a ratio of 1:1:2) to receive one of the three regimens for re-treatment for 24 weeks; group A: IFN 6 million units (MU) monotherapy (N 5 30), group B: combination therapy with ribavirin and IFN 3 MU (N 5 30) or group C: combination therapy with ribavirin and IFN 6M U (N 5 60). The intention-to-treat rate of sustained virological response (SVR) was 38.3%. The SVR rate in group C (53.3%) was significantly higher than group A (16.7%, Po0.005) and group B (30%, Po0.05). Drop-out rates were similar between the three groups. Patients achieving SVR had significant improvement histologically. Hepatitis C virus (HCV) genotype non-1b infection, lower pretreatment HCV RNA levels, combined with ribavirin and with higher IFN dose, and relapsers were independent predictors for SVR. Conclusion: We concluded that more than one-third Taiwanese CHC patients achieved SVR after 24 weeks re-treatment and combination therapy, especially with higher dose of IFN, yielded higher efficacy.

Hepatitis C virus genotype and viral loads are important predictors for sustained virologic response (SVR) to interferon-alpha therapy for chronic hepatitis C (CHC). We have conducted a prospective study on treatment of 90 patients with a tailored-dose and extended interferon-alpha regimen according to pretreatment virologic factors (low-risk, genotype non-1b/viralor =0.65 Meq./ml, 6 million units thrice weekly for 12 weeks (6 MU x 12 weeks) followed by 3 MU weeks; high-risk, genotype 1b/viral0.65 Meq./ml, 6 MU X 24 weeks followed by 3 MU X 24 weeks; medium-risk, the others, 6 MU X 12 weeks followed by 3 MU X 36 weeks), and compared to 123 patients with fixed-dose regimen (6 MU X 24 weeks). Patients with tailored-dose regimen had a significantly higher rate of SVR than those receiving fixed-dose interferon-alpha (46.7% versus 29.3%, P0.01, intention-to-treat analysis). Improved efficacy was mainly seen in the medium-risk (48.9% versus 26.6%, P=0.02) and the high-risk groups (26.1% versus 8.3%, P=0.06), but not in the low-risk group. By using multivariate logistic regression, low pretreatment viral loads and tailored-dose IFN regimens were significantly associated with higher SVR in both the high- and medium-risk groups. There were no differences in the tolerability and in the incidence of adverse effects between fixed-dose and tailored-dose groups. In conclusion, our results demonstrate the efficacy of tailored-dose interferon-alpha therapy for CHC; these could provide decision-making information for standard/pegylated interferon-alpha combining ribavirin therapy according to baseline predictors.

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

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 (r 2 =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

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

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.

We read with interest the article by Bakr et al ( GUT 2006;55:1183–7). The authors recruited 4720 residents aged 18–65 years from a rural community in Egypt, a country hyperendemic for hepatitis C virus (HCV) infection, which might be attributed to mass campaigns for intravenous antischistosomal treatment.1 They found that the HCV antibody (anti-HCV) was positive in 910 individuals (19.3%), and 38.5% of the anti-HCV-positive individuals were negative for serum HCV RNA. Interestingly, the authors concluded that women had a significantly higher HCV clearance rate (44.6% vs 33.7%, respectively; p = 0.001, adjusted OR 1.77) than men, which was similar to reports by Inoue et al 2 and Yamakawa et al 3 from Japan. We conducted a large-scale community-based study in southern Taiwan, a country hyperendemic for hepatitis B virus (HBV) …

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. …

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.Of 617 treatment-naive CHC patients prescribed a 24-week protocol of peg-IFN/RBV, 29 (4.7%) patients who terminated treatment early at20 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.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).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.

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.

Background/Aims: We aimed to evaluate the efficacy, advantage, and safety of a 24-week regimen with high-dose interferon-a (INF-a ;6 million units thrice weekly) plus ribavirin (1000-1200 mg/day) combination therapy for 46 Taiwanese chronic hepatitis C (CHC) patients with persistently normal or near-normal alanine aminotransferase (PNALT) levels. Methods: Ninety-two age- and sex-matched CHC patients with elevated ALT levels (42 times the upper limit of normal range) with a ratio of 1:2, treated with the same regimen, served as a control. Results: The sustained virologic response (SVR) rate was comparable between PNALT (67.4%) and elevated ALT (65.2%) groups (intention-to-treat analysis). The two groups had similar rates of discontinuation and incidence of adverse effects. Viral genotype 1b, baseline viral loads, body mass index, and age were significant factors negatively associated with SVR. Further decline of ALT levels throughout the follow-up period was observed in sustained responders of the PNALT group. None of the eight patients with ALT flares developed icteric hepatitis. The virologic efficacy was sustained in a 3-year extended follow-up period. Conclusion: high-dose INF-a with ribavirin combination therapy is effective, safe, and well tolerated in CHC patients with PNALT levels. The ALT assay might not be used as a single biochemical marker for determination of treatment consideration.

Summary. The aim of this study was to investigate the association between G vs A transitions in the promoter region of the tumour necrosis factor (TNF) alpha at positions −308 (TNF308.2) and −238 (TNF238.2) and clinical features of chronic hepatitis C (CHC). These two promoter TNF-alpha variants were determined in 250 biopsy-proven CHC patients by polymerase chain reaction amplification, followed by the Restriction Fragment Length Polymorphism (RFLP) method. The distribution of −308 and −238 TNF-alpha promoter genotypes were TNF308.1/TNF308.1: 187 (74.8%), TNF308.1/TNF308.2: 57 (22.8%) and TNF308.2/TNF308.2: 6 (2.4%), respectively, and TNF238.1/TNF238.1: 247 (98.8%) and TNF238.1/TNF238.2: 3 (1.2%). The frequencies of the TNF308.2 and TNF238.2 promoter alleles were 13.8% and 0.6%. Increased TNF308.2 allele copy numbers were significantly associated with increased frequency of lower pretreatment hepatitis C virus (HCV) RNA levels (

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

To elucidate the genotype-specific virus-host-drug interaction and the on-treatment viral kinetics in predicting sustained virologic response (SVR), serial serum hepatitis C virus (HCV) ribonucleic acid (RNA) levels at baseline, treatment week 2 (W2), treatment week 4 (W4), and treatment week 12 (W12) were measured in 199 chronic HCV-infected Taiwanese patients receiving interferon-alpha (INF-alpha) 6 million units (MU) three times weekly plus 1000 to 1200 mg/day of ribavirin for 24 weeks. The SVR rate was 90.5% (95/105) for HCV genotype 2 (HCV-2) patients and 47.9% (45/94) for HCV-1 patients (P0.0001). HCV-2 patients had a significantly higher rate of rapid virologic response (RVR) at W2 than HCV-1 patients. HCV RNA negativity at W4 had the highest accuracy of prediction (80%) of SVR with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81%, 79%, 78%, and 82%, respectively, for HCV-1 patients. HCV RNA negativity or 2 logs drop at W4 had the highest accuracy of prediction (92%) with sensitivity, specificity, PPV, and NPV of 100%, 20%, 92%, and 100%, respectively, for HCV-2 patients. In multivariate analysis, the significant factors associated with SVR in HCV-1 patients were HCV RNA negativity at W12 and W4. HCV RNA negativity or 2 logs drop was the only significant factor associated with SVR in HCV-2 patients. In conclusion, a RVR at W4 could predict an SVR with a high degree of accuracy to a 24-week course of high-dose IFN/ribavirin for both HCV-1 patients and HCV-2 patients. With respect to each HCV genotype, the on-treatment virologic responses are the most important factors associated with SVR.

The clinical significance of co-infection of SENV-D among patients with chronic hepatitis C (CHC) and response of both viruses to combination therapy with high-dose interferon-alfa (IFN) plus ribavirin remain uncertain and are being investigated.Total 164 (97 males and 67 females, the mean age 48.1+/-11.4 years, range: 20-73 years, 128 histologically proved) naive CHC patients were enrolled in this study. SENV-D DNA was tested by PCR method. Detection of serum HCV RNA was performed using a standardized automated qualitative RT-PCR assay (COBAS AMPLICOR HCV Test, version 2.0). HCV genotypes 1a, 1b, 2a, 2b, and 3a were determined by using genotype-specific primers. Pretreatment HCV RNA levels were determined by using the branched DNA assay (Quantiplex HCV RNA 3.0). There are 156 patients receiving combination therapy with IFN 6 MU plus ribavirin for 24 wk and the response to therapy is determined.Sixty-one (37.2%) patients were positive for SENV-D DNA and had higher mean age than those who were negative (50.7+/-10.6 years vs 46.6+/-11.6 years, P = 0.026). The rate of sustained viral response (SVR) for HCV and SENV-D were 67.3% (105/156) and 56.3% (27/48), respectively. By univariate analysis, the higher rate of SVR was significantly related to HCV genotype non-1b (P0.001), younger ages (P = 0.014), lower pretreatment levels of HCV RNA (P = 0.019) and higher histological activity index (HAI) score for intralobular regeneration and focal necrosis (P = 0.037). By multivariate analyses, HCV genotype non-1b, younger age and lower pretreatment HCV RNA levels were significantly associated with HCV SVR (odds ratio (OR)/95% confidence interval (CI): 12.098/0.02-0.19, 0.936/0.890-0.998, and 3.131/1.080-9.077, respectively). The SVR of SENV-D was higher among patients clearing SENV-D than those who had viremia at the end of therapy (P = 0.04).Coexistent SENV-D infection, apparently associated with higher ages, is found in more than one-third Taiwanese CHC patients. Both HCV and SENV-D are highly susceptible to combination therapy with high-dose IFN and ribavirin and SENV-D co-infection does not affect the HCV response. HCV genotype, pretreatment HCV RNA levels and age are predictive factors for HCV SVR.

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

Background: The clinical significance of TT virus (TTV) coinfection in chronic hepatitis C (CHC) patients and influence of TTV viremia on hepatitis C virus (HCV) response to high dose interferon-alpha therapy in Taiwan were investigated. Materials and Methods: Total 102 HCV RNA-positive CHC patients were enrolled. TTV DNA (using polymerase chain reaction primers derived from 5′ non-coding region and open reading frame 2), alanine aminotransferase (ALT), GB virus-C/hepatitis G virus (GBV-C/HGV) RNA, anti-E2 antibody, genotype and RNA levels of HCV were tested. Results: The prevalence of TTV DNA was 51.0%. The mean age of TTV viremic CHC patients was significant higher than non-viremic ones (P

To investigate the influence of immunogenetics on response to interferon (IFN)-alpha treatment, human leukocyte antigen alleles were characterized in 100 unrelated Taiwanese patients with chronic hepatitis C virus (HCV) infection. A11, B51, Cw15, and DRB1*15 were positively correlated with sustained response, whereas A24 was inversely associated with response to IFN-alpha, after adjustment for cirrhosis, pretreatment virus load, and viral genotype. Homozygote-genotype analysis showed that A24 and DQB1*05 probably had gene-dosage effect on sustained response. DRB1*15 was in strong linkage disequilibrium with DQB1*05 and DQB1*06, but only haplotype DRB1*15-DQB1*05 was associated with response to IFN-alpha. Haplotype A11-DRB1*15 was strongly associated with sustained response. This suggests a role for a complex host-immunogenetics interplay in the response to IFN-alpha, in patients with chronic HCV infection.

Revisit of Oral Glucose Tolerance Test: A Must for Diagnosis of Type 2 Diabetes in Patients With Chronic Hepatitis C

Building on Bakhtinian approaches to Wordsworth’s early poems, we extend their findings to The Prelude, using analytical tools from narratology and film criticism to trace the interplay of different views and voices. By dramatising his narrator and his problems in suturing together past and present and the viewpoints of the young “hero” and the older narrator, Wordsworth the poet is continuing his project of educating an active taste. The narrator demonstrates the processes of the imagination but in ways that reveal its artifice for others to use. The gaps and uncertainties which critics often see as suppressions are invitations for the reader to exercise a revisionary activity of his own in recognising the possibility of different stories from that which the narrator tries to tell. We analyse visual images for their dissonant suggestions and the manipulations of viewpoint that problematize any secure unity of purpose other than that of suturing the reader into the creative community that Wordsworth hails at the conclusion.

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