Hepatitis: Chuang WL

Yu ML, Chuang WL. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · J Gastroenterol Hepatol. · Pubmed #19335784 No free full text.

Abstract: The issue of best treatment for chronic hepatitis C virus (HCV) infection is in constant flux, not only in Western countries but also in Asia. Currently, pegylated-interferon plus ribavirin is the standard of care. Studies from Asia provide evidence to support the same broad treatment strategies for Asian patients as recommended in Western countries. Nevertheless, there is increasing evidence that Asians have a higher likelihood of achieving a sustained virological response (SVR) than their Caucasians counterparts when treated with the corresponding regimen. With the recommended 'standard dose and duration treatment regimens', SVR is achieved in Asia for around 70% of HCV genotype 1 (HCV-1) infected cases, approximately 90% of HCV-2/3, approximately 65% of HCV-4, and approximately 80% of HCV-6 patients. Difference of body weight in race might contribute the superior response in Asian patients. HCV genotype distribution in Asia also differs from North-America/Europe. HCV-6 and its variants, previously mistyped as HCV-1, needs accurate genotyping. Increasing data support the proposal that HCV genotype, baseline viral load and on-treatment virological response provide information for decision-making so that treatment can be individualized. Beyond the older recommendations, an abbreviated 24-week regimen could be suggested for HCV-1/4 patients with baseline viral loads < 400 000 IU/mL and a rapid virological response (RVR, HCV RNA undetectable at week 4), and an abbreviated 12-16 weeks of pegylated-interferon with weight-based doses of ribavirin could be suggested for HCV-2/3 patients with a RVR. Such tailored treatment regimens can reduce the costs of treatment and incidence of adverse events without compromising efficacy. Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis worldwide, and particularly in some countries of Asia (notably Japan) where it is now more prevalent than chronic hepatitis B virus infection. Hepatitis C virus infection can also lead to hepatocellular carcinoma (HCC). It is estimated that there are more than 170 million people chronically infected with HCV, and 3 to 4 million persons are newly infected each year. The risk for developing cirrhosis 20 years after initial HCV infection among those chronically infected varies between studies, but is estimated at around 10%-15% for men and 1-5% for women. Once cirrhosis is established, the rate of developing HCC is at 1%-4% per year. Approximately 280 000 deaths per year are related to HCV infection. Hepatitis C virus-related end-stage liver disease and HCC have become the leading cause for liver transplantation worldwide. In the Asia-Pacific area, the estimated prevalence of antibodies to HCV (anti-HCV) range from 0.3% in New Zealand to 5.6% in Thailand. In Japan, Middle East, Vietnam and Taiwan, several HCV hyper-endemic areas have been reported with an anti-HCV prevalence rate of 12% to as high as 58%. In addition to the well-known endemic status of HBV infection in most countries of the Asia-Pacific region, HCV infection presents another critical scenario of public health issue in this region, as outlined in Guidelines by the Asia-Pacific Association for Study of the Liver (APASL). Given the lack of an effective vaccine, optimal treatment of chronic HCV infection is now perceived as a 'must' in terms of public health strategies, as well as of the clinical setting for individual patients.

Yu ML, Huang CF, Dai CY, Huang JF, Chuang WL. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Oncology. · Pubmed #18087178 No free full text.

Abstract: Hepatitis C virus infection frequently causes chronic liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) and has become the main indication for liver transplantation. Interferon (IFN)-based therapy has been used in the treatment of chronic hepatitis C (CHC) for viral clearance. Several earlier studies showed long-term beneficial effects of IFN monotherapy in reducing the progression of cirrhosis, hindering HCC development, and prolonging survival among both sustained virological responders and nonresponders. However, the benefits of preventing disease progression in CHC patients without sustained virological response (SVR) no longer existed over a longer observation period. Both IFN monotherapy and IFN-ribavirin combination therapy were shown to reduce significantly the complications of liver disease, in terms of development of cirrhosis, HCC and liver-related mortality. The significance disappeared after response to antiviral treatment was taken into account. The benefits were obtained mainly from successful antiviral treatment but were not related to the antiviral regimens, suggesting that the magnitude of this preventive effect could increase through the significant improvement of SVR rate by using a more effective regimen, such as interferon-ribavirin or peginterferon-ribavirin combination therapy. Nevertheless, about one-third of patients remain resistant to the current recommended antiviral regimens. More effective treatment is needed for the population.

Chuang WL, Yu ML, Dai CY, Chang WY. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan, ROC. · Intervirology. · Pubmed #16166797 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection may lead to cirrhosis and hepatocellular carcinoma. Interferon (IFN)-alpha is effective in the treatment of chronic hepatitis C. The rate of response to IFN is enhanced by increasing the IFN dose. Extending the treatment duration can reduce the relapse rate. Addition of ribavirin to IFN increases the sustained virological response (SVR). Thus, combination therapy with IFN and ribavirin was adopted for the treatment of chronic hepatitis C in Kaohsiung Medical University Hospital in 1998. Approximately 60% of patients receiving IFN/ribavirin therapy gained SVR. IFN 6 million units three times per week combined with daily ribavirin for 6 months achieved SVR more frequently than combination therapy with 3 million units. Factors for SVR in these combination regimens were HCV genotype, viral load and early virological response. Long-term follow-up of patients treated with IFN has shown that SVR might reduce the risk of progression to cirrhosis and hepatocellular carcinoma. Pegylated (peg)-IFN has a longer half-life and better efficacy. Combination therapy with peg-IFN and ribavirin accomplished higher SVR than conventional IFN and ribavirin. A multicenter clinical trial was conducted in Taiwan to compare the efficacy of combination therapy between peg-IFN/ribavirin and conventional IFN/ribavirin for 6 months. SVR was higher in patients receiving peg-IFN and ribavirin, especially in those infected with HCV genotype 1b. Based on the results obtained, the national health insurance started to sponsor the combination therapy in October 2003, with a suggested duration for 6 months. Some small-scale studies in Taiwan have postulated higher SVR for treatment duration of 12 than of 6 months in patients with genotype 1b. Further investigation should be conducted in the near future.

Lin CC, Wu DK, Shih PM, Liu GC, Chuang WL. · Department of Medical Imaging, Kaohsiung Medical University, Kaohsiung, Taiwan. · Kaohsiung J Med Sci. · Pubmed #15481565 links to  free full text

Abstract: We report the case of a 63-year-old female who had chronic hepatitis C and who was diagnosed with hepatocellular carcinoma. Hepatic angiography showed one visible and tortuous falciform artery arising as the terminal branch of the left hepatic artery. Transcatheter arterial chemoembolization (TACE) was performed via the left hepatic artery. The patient developed supraumbilical skin rash with local tenderness on the following day. After supportive treatment by a dermatologist, the skin rash subsided gradually with sequelae of irregular skin surface and one small subcutaneous nodule. Skin biopsy of the lesion 1 year later showed fat necrosis with foreign body reaction and fibrosis. We discuss this rare complication of TACE and review the literature.

Dai CY, Chuang WL, Hsieh MY, Lee LP, Huang JF, Hou NJ, Lin ZY, Chen SC, Hsieh MY, Wang LY, Tsai JF, Chang WY, Yu ML. · College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. · Antiviral Res. · Pubmed #17400303 No free full text.

Abstract: 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.

Yu ML, Dai CY, Lee LP, Hsieh MY, Hou NJ, Huang JF, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Antivir Ther. · Pubmed #17302371 No free full text.

Abstract: 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.

Feng IC, Koay LB, Sheu MJ, Kuo HT, Sun CS, Lee C, Chuang WL, Liao SK, Wang SL, Tang LY, Cheng CJ, Tsai SL. · Hepatogastroenterology Section, Department of Internal Medicine, Chi Mei Medical Center, Yung-Kang City, Tainan, Taiwan. · J Biomed Sci. · Pubmed #17109186 No free full text.

Abstract: Acute exacerbations (AEs) of chronic hepatitis B (CH-B) are accompanied by increased T cell responses to hepatitis B core and e antigens (HBcAg/HBeAg). Why patients are immunotolerant (IT) to the virus and why AEs occur spontaneously on the immunoactive phase remain unclear. The role of HBcAg-specific CD4(+)CD25(+) regulatory T (T(reg)) cells in AE and IT phases was investigated in this study. The SYFPEITHI scoring system was employed to predict MHC class II-restricted epitope peptides on HBcAg overlapping with HBeAg that were used for T(reg)-cell cloning and for the construction of MHC class II tetramers to measure T(reg) cell frequencies (T(reg) f). The results showed that HBcAg-specific T(reg) f declined during AE accompanied by increased HBcAg peptide-specific cytotoxic T lymphocyte frequencies. Predominant Foxp3-expressing T(reg) cell clones were generated from patients on the immune tolerance phase, while the majority of Th1 clones were obtained from patients on the immunoactive phase. T(reg) cells from liver and peripheral blood of CH-B patients express CD152 and PD1 antigens that exhibit suppression on PBMCs proliferation to HBcAg. These data suggest that HBcAg peptide-specific T(reg) cells modulate the IT phase, and that their decline may account for the spontaneous AEs on the natural history of chronic hepatitis B virus infection.

Yu ML, Lin SM, Lee CM, Dai CY, Chang WY, Chen SC, Lee LP, Lin ZY, Hsieh MY, Wang LY, Chuang WL, Liaw YF. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Hepatology. · Pubmed #17058238 No free full text.

Abstract: 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.

Dai CY, Chuang WL, Chang WY, Chen SC, Lee LP, Hsieh MY, Hou NJ, Lin ZY, Hsieh MY, Wang LY, Yu ML. · Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, China. · World J Gastroenterol. · Pubmed #16015698 links to  free full text

Abstract: AIM: 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. METHODS: 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. RESULTS: 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 (P<0.001), 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). CONCLUSION: 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.

Chuang WL, Dai CY, Chen SC, Lee LP, Lin ZY, Hsieh MY, Wang LY, Yu ML, Chang WY. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Liver Int. · Pubmed #15566510 No free full text.

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=30), group B: combination therapy with ribavirin and IFN 3 MU (N=30) or group C: combination therapy with ribavirin and IFN 6 MU (N=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%, P<0.005) and group B (30%, P<0.05). 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.

Hou C, Chuang WL, Yu ML, Dai CY, Chen SC, Lin ZY, Hsieh MY, Wang LY, Tsai JF, Chang WY. · Dept of Medicine, Kaohsiung Medical, University Hospital, Taiwan. · Scand J Gastroenterol. · Pubmed #11199369 No free full text.

Abstract: BACKGROUND: The administration of interferon (IFN) could be complicated by the development of neutralizing anti-interferon antibodies (NA). This study evaluates the frequency and associated factors of NA among chronic hepatitis C patients treated with different IFNs. METHODS: Ninety-five chronic hepatitis C patients were randomized to be treated with recombinant IFN-alpha2a (n = 28), IFN-alpha2b (n = 39) or lymphoblastoid IFN-alpha1 (n = 28) given intramuscularly, 3-6 million units, thrice weekly for 24 weeks. Serum samples collected before, during and after the cessation of treatment were checked for NA. RESULTS: Three patients were withdrawn from treatment. All patients were negative for NA before treatment and 13 (14%) patients developed neutralizing antibodies. Of the 26 patients treated with IFN-alpha2a, 6 (23.1%) developed NA. whereas NA were detected in only 6 (15.4%) of 39 and 1 (3.7%) of 27 patients treated with IFN-alpha2b and IFN-alphanl, respectively. Age, gender, HCV genotype, ALT level, IFN total dose and liver histology were not associated with the development of NA. By using multivariate logistic regression it was shown that pretreatment HCV RNA level and IFN preparation were the two major factors related to the production of NA. The response of treatment was related to pretreatment viremia but not to the presence of NA. CONCLUSIONS: The frequency of development of NA among Taiwanese patients with chronic hepatitis C might be related to different IFN preparations and pretreatment HCV RNA level. The response of treatment was related to pretreatment HCV RNA level but not to the presence of NA.

Yang JF, Lin YY, Huang JF, Liu SF, Chu PY, Hsieh MY, Lin ZY, Chen SC, Wang LY, Dai CY, Chuang WL, Yu ML. · Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Kaohsiung J Med Sci. · Pubmed #19605335 links to  free full text

Abstract: With an estimated 350-400 million people worldwide chronically infected with hepatitis B virus (HBV), and the subsequent serious complications caused by liver damage including cirrhosis, liver failure, and hepatocellular carcinoma, HBV infection remains a global health issue, particularly in Taiwan, an HBV-hyperendemic area. Sensitive and accurate quantification of HBV DNA is necessary to monitor patients with chronic hepatitis B who are receiving antiviral therapy to determine treatment response and adapt therapy. We evaluated and compared the clinical performance of two HBV DNA assays based on different technologies: the RealArt HBV PCR Kit (Abbott HBV DNA PCR kit, real-time polymerase chain reaction assay, detection limit: 27 IU/mL) and the VERSANT bDNA 3.0 assay (Bayer, branched DNA signal amplification assay, detection limit: 357 IU/mL). Serum levels of HBV DNA in 173 chronic HBV carriers were determined using both the RealArt HBV PCR Kit and the VERSANT bDNA 3.0 test. Of the 173 samples analyzed for baseline viral load detection, HBV DNA was quantifiable in 147 patients (82.1%) by the RealArt HBV PCR Kit, which was significantly higher than the 92 (53.2%) samples quantified by the VERSANT bDNA 3.0 assay. A total of 86 (49.7%) samples were quantifiable by both assays, whereas 25 (14.5%) were below the detection limit of both assays. The HBV DNA quantification values measured by the RealArt HBV PCR Kit and the VERSANT bDNA 3.0 assay were positively correlated (Spearman's rank correlation coefficient r = 0.932, p < 0.001). On average, the results derived from the RealArt HBV PCR Kit were 0.67 log lower than those of the VERSANT bDNA 3.0 assay. HBV DNA concentrations were significantly higher in 63 HBV e antigen (HBeAg)-seropositive patients than in 110 HBeAg-seronegative patients (5.42 +/- 2.34 logs vs. 3.21 +/- 2.27 logs, p < 0.001). The RealArt HBV PCR Kit is more sensitive and has a wider dynamic range than the VERSANT bDNA 3.0 assay in the clinical setting of chronic hepatitis B patients. The sensitivity and wide dynamic range of the PCR assay allow optimal monitoring and timely adaptation of antiviral therapy. Nevertheless, the HBV DNA values measured by the RealArt HBV PCR Kit and the VERSANT bDNA 3.0 assay were significantly correlated.

Huang JF, Chuang WL, Yu ML, Yu SH, Huang CF, Huang CI, Yeh ML, Hsieh MH, Yang JF, Lin ZY, Chen SC, Dai CY, Chang WY. · Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, and Graduate Institute of Medicine, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan. · Kaohsiung J Med Sci. · Pubmed #19560994 links to  free full text

Abstract: Metabolic syndrome (MS) is a complicated disorder associated with a high risk of future development of micro- and macrovascular complications. The extrahepatic manifestations of hepatitis C virus (HCV) infection can include multiple metabolic abnormalities. However, the extent, severity, and characteristics of MS in HCV-infected patients have rarely been investigated in community-based settings. This study aimed to determine the difference in prevalence and distribution of the components of MS between HCV-infected patients and healthy controls. Multipurpose mass screening of adults was conducted in an HCV-endemic area of Southern Taiwan. Clinical profiles in terms of anthropometric data and MS components, as well as viral hepatitis markers, were assessed. Two hundred and thirty-seven adults (94 males; mean age, 55.5 +/- 10.8 years) were recruited. The prevalence of anti-HCV seropositivity was 39.2% (93/237). The prevalence of MS was higher in the HCV-infected individuals (24.7%, 23/93) than in the control, uninfected subjects (13.2%, 19/144, p = 0.02). In terms of MS components, HCV-infected subjects had a higher prevalence of high waist circumference (51.6% vs. 25.7%, p < 0.001) and hypertension (58.1% vs. 36.8%, p = 0.001) than controls. Multivariate logistic regression analysis demonstrated that anti-HCV positivity was significantly associated with MS (odds ratio, 6.4; 95% confidence interval, 1.82-22.84; p = 0.004). HCV infection was associated with a higher prevalence of MS. Determination of MS in patients with HCV infection could therefore be indicated.

Yeh ML, Wang LY, Huang CI, Hsieh MY, Lin ZY, Chuang WL, Chang WT, Wu CC, Chen CY. · Division of Hepato-biliary-pancreatic Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Kaohsiung J Med Sci. · Pubmed #19239994 links to  free full text

Abstract: Diagnosis of abdominal splenosis is often undiagnosed until treatment for splenic rupture or splenectomy. This report describes a patient with splenosis mimicking hepatic tumor. The patient had a history of splenic trauma with splenectomy and chronic hepatitis C. After routine abdominal ultrasound revealed a liver nodule, further imaging studies, including magnetic resonance imaging, computed tomography and angiography, were performed. After the patient eventually underwent surgery, pathology revealed splenic tissue. Despite its distinguishable clinical features, splenosis is difficult to identify by modern imaging modalities. Therefore, accurate and timely diagnosis of this disease requires constant vigilance.

Dai CY, Huang JF, Hsieh MY, Hou NJ, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL, Yu ML. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung 807, Taiwan. · J Hepatol. · Pubmed #19231011 No free full text.

Abstract: 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.

Yang JF, Hsieh MY, Hou NJ, Dai CY, Huang JF, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chuang WL, Yu ML. · Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Aliment Pharmacol Ther. · Pubmed #19210290 No free full text.

Abstract: BACKGROUND: Peginterferon-alpha-based therapy frequently leads to neutropenia. It remains unclear whether neutropenia is associated with bacterial infection in chronic hepatitis C (CHC). AIM: To evaluate the risk of bacterial infection and neutropenia in patients with CHC treated with peginterferon-alpha/ribavirin. METHODS: In all, 207 patients with CHC with (group A, n = 30) and without (group B, n = 177) baseline neutropenia were treated with peginterferon-alpha/ribavirin. RESULTS: Group A had significantly higher rates of moderate (<750 cells/microL) and severe (<500 cells/microL) neutropenia than group B (70.0% and 26.7% vs. 20.3% and 8.5% respectively, both P < 0.0001). The sustained virological response rate was similar between patients with and without neutropenia, at baseline or during treatment. Bacterial infection occurred in 4.3% of patients. Group A and patients with lower baseline neutrophil counts had substantially higher rates of bacterial infection. Patients with cirrhosis had significantly higher rates of infection during combination therapy than those without cirrhosis (15%, 3 of 20 vs. 3.2%, 6 of 187, P = 0.045). Nadir neutrophil counts were not correlated to infection episodes. CONCLUSIONS: Bacterial infection during peginterferon-based therapy for CHC was associated with comorbidity of cirrhosis, but not with neutropenia, whether at baseline or during treatment. Neutropenic CHC patients might be treated safely with close monitoring.

Huang JF, Dai CY, Yu ML, Shin SJ, Hsieh MY, Huang CF, Lee LP, Lin KD, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. · Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. · J Hepatol. · Pubmed #19155083 No free full text.

Abstract: 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.

Liu CJ, Chuang WL, Lee CM, Yu ML, Lu SN, Wu SS, Liao LY, Chen CL, Kuo HT, Chao YC, Tung SY, Yang SS, Kao JH, Liu CH, Su WW, Lin CL, Jeng YM, Chen PJ, Chen DS. · National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan. · Gastroenterology. · Pubmed #19084016 No free full text.

Abstract: BACKGROUND & AIMS: Dual chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is common in areas endemic for either virus. Combination therapy with ribavirin and pegylated interferon (peginterferon) is the standard of care for patients with HCV monoinfection. We investigated the effects of combination therapy in patients infected with both HBV and HCV (genotypes 1, 2, or 3). METHODS: The study included 321 Taiwanese patients with active HCV infection; 161 also tested positive for hepatitis B surface antigen (HBsAg) and 160 were HBsAg-negative (controls). Patients with HCV genotype 1 infection received peginterferon alfa-2a (180 mug) weekly for 48 weeks and ribavirin (1000-1200 mg) daily. Patients with HCV genotypes 2 or 3 received peginterferon alfa-2a weekly for 24 weeks and ribavirin (800 mg) daily. At 24 weeks posttreatment, patient samples were examined for a sustained virologic response (SVR) against HCV (serum HCV levels decreased to <25 IU/mL). RESULTS: In patients with HCV genotype 1 infection, the SVR was 72.2% in dually infected patients vs 77.3% in monoinfected patients after treatment. For patients with HCV genotype 2/3 infections, the SVR values were 82.8% and 84.0%, respectively, after treatment. Serum HBV DNA eventually appeared in 36.3% of 77 dual-infected patients with undetectable pretreatment levels of HBV DNA; this was not accompanied by significant hepatitis. Posttreatment HBsAg clearance was observed in 11.2% of 161 dual-infected patients. CONCLUSIONS: Combination therapy with peginterferon alfa-2a and ribavirin is equally effective in patients with HCV monoinfection and in those with dual chronic HCV/HBV infection.

Wu TC, Chuang WL, Dai CY, Huang JF, Hsieh MY, Hou NJ, Lee LP, Lin WY, Yang JF, Chiu CC, Chen SC, Hsieh MY, Chang WY, Yu ML. · Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. · Trans R Soc Trop Med Hyg. · Pubmed #18656216 No free full text.

Abstract: 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.

Huang JF, Yu ML, Dai CY, Hsieh MY, Hwang SJ, Hsiao PJ, Lee LP, Lin ZY, Chen SC, Hsieh MY, Wang LY, Shin SJ, Chang WY, Chuang WL. · Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. · Am J Gastroenterol. · Pubmed #18637090 No free full text.

Abstract: 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.

Huang JF, Dai CY, Lin YY, Yu ML, Liu SF, Lin IL, Hsieh MY, Lee LP, Lin ZY, Chen SC, Hsieh MY, Chang WY, Chuang WL. · Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. · Clin Chem Lab Med. · Pubmed #18605932 No free full text.

Abstract: 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.

Huang CF, Huang JF, Dai CY, Yu ML, Lu SN, Hsieh MY, Lee LP, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Trans R Soc Trop Med Hyg. · Pubmed #18603274 No free full text.

Abstract: 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.

Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, Lee LP, Hsieh MY, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Hepatology. · Pubmed #18508296 No free full text.

Abstract: 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.

Dai CY, Chuang WL, Ho CK, Hsieh MY, Huang JF, Lee LP, Hou NJ, Lin ZY, Chen SC, Hsieh MY, Wang LY, Tsai JF, Chang WY, Yu ML. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan. · J Hepatol. · Pubmed #18486265 No free full text.

Abstract: 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.

Lacey L, Chien RN, Chuang WL, Pwu RF. · LaceySolutions Ltd, Dublin, Ireland. · J Gastroenterol Hepatol. · Pubmed #18397486 No free full text.

Abstract: BACKGROUND AND AIMS: Chronic hepatitis B (CHB) and its sequelae are major health problems in Taiwan. The purpose of the present study was the economic evaluation of short-duration treatments of CHB and longer duration antiviral treatment for up to 5 years. METHODS: Ten-health state CHB disease progression Markov models were used for hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB patients, respectively, that included the emergence of antiviral resistance. The perspective of this economic evaluation was the Taiwan health-care system. Costs and benefits were discounted at 3% per annum. RESULTS: Short-course therapies of up to 1-year treatment had limited impact on improving patient survival. Long-term viral suppression with lamivudine and adefovir sequential rescue therapies (including add-on therapies) for up to 5 years were found to be highly cost-effective by international standards (estimated to be NT$580,000 per quality adjusted life year [QALY] for Taiwan). When Taiwan-specific model inputs were used for HBeAg-positive CHB, the cost per QALY for lamivudine plus adefovir sequential antiviral therapy increased by approximately 100% over the base-case estimate, but was still well within the estimated NT$580,000 per QALY threshold. CONCLUSIONS: In Taiwan, treatment of CHB patients with lamivudine and adefovir sequential antiviral therapies for up to 5 years results in survival benefits and is highly cost-effective.