Chronic hepatitis C infection is associated with insulin resistance and lipid profiles.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan. METHODS: We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested. RESULTS: When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P < 0.001, P = 0.023, P = 0.017, and P = 0.011, respectively), and significantly lower TG level (P = 0.023), total cholesterol, and HDL-C and LDL-C levels (all P < 0.001) than 480 controls. In multivariate logistic regression analyses, a low total cholesterol, a low TGs, and a high HOMA-IR are independent factors significantly associated with chronic HCV infection. In the 160 CHC patients (41 patients with high HOMA-IR [> 2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. CONCLUSIONS: Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics.

Feasibility and efficacy of helical tomotherapy in cirrhotic patients with unresectable hepatocellular carcinoma.

BACKGROUND: This study is to evaluate the toxicity and outcomes of helical tomotherapy (HT) in patients treated for unresectable hepatocellular carcinoma (HCC). METHODS: From March 2008 to September 2010, 38 patients with unresectable HCC were treated with HT. The median patient age was 67 years (range, 45-85). The median follow-up period was 17.2 months (range, 7-46). All patients had liver cirrhosis. Median radiation dose was 54 Gy (range, 46-71.8) delivered in 1.8 to 2.4-Gy fractions. The planning target volumes were 241.2 ± 153.1 cm(3) (range, 45.8-722.4). Treatment responses were assessed in 3-6 months after HT. RESULTS: There was a complete response in 2 patients (5.2 %), partial response in 18 patients (47.4 %), stable disease in 13 patients (34.2 %), and progressive disease in 5 patients (13.2 %). The median overall survival was 12.6 months, and 1- and 2-year overall survival rates were 56.2 and 31.7 %, respectively. Eastern Cooperative Oncology Group (ECOG score, p = 0.008), Child-Pugh classification (p = 0.012), albumin (p = 0.046), and hemoglobin (p = 0.028) were significant parameters that predicted primary tumor response to radiotherapy in multivariate analysis. ECOG score (p = 0.012), Child-Pugh class (p = 0.026), and response to radiotherapy (p = 0.016) were independent prognostic factors for overall survival in multivariate analysis. Responders had better overall survival than non-responders (23.6 vs. 5.8 months, p < 0.001). The 1- and 2-year overall survival rates for responders were 68.3 and 57 %, respectively, while for non-responders, they were 0 %. The 1- and 2-year local control rates were 88.2 and 82.3 %, respectively. Five patients (13.2 %) had grade 3 or greater liver toxicity, and one patient (2.6 %) had a grade 3 gastric ulcer. No treatment-related liver failure or death was documented in this study. CONCLUSIONS: Radiotherapy using HT seems to be a safe and effective treatment option for unresectable HCC patients. This study indicates that HT is a feasible treatment even in patients without good performance status and hepatic function reservation.

Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication.

BACKGROUND & AIMS: Hepatitis C virus (HCV)-infected patients with cirrhosis remain at risk of hepatocellular carcinoma (HCC) even after achieving sustained virological response (SVR). The aim of the study was to explore the incidence and risk for HCC among non-cirrhotic patients with an SVR. METHODS: A total of 642 patients with an SVR after peginterferon/ribavirin therapy were enrolled with a median follow-up period of 53.0 months (range: 6-133 months). RESULTS: Thirty-three of the 642 (5.1%) patients developed HCC over 2324.8 person-years of follow-up. Cox regression analysis revealed that the strongest predictive factor of HCC occurrence was liver cirrhosis (HR 4.98, 95% CI 2.32-10.71, p<0.001), followed by age (HR 1.06, 95% CI 1.02-1.11, p=0.005) and γGT levels (HR 1.008, 95% CI 1.004-1.013, p<0.001). The incidence of HCC did not differ between patients with high and low baseline γGT levels among patients with cirrhosis (p=0.53), but the incidence of HCC was significantly higher in non-cirrhotic patients with high γGT levels compared with those with low γGT levels (p=0.001). Cox regression analysis revealed that the strongest factors associated with HCC development in non-cirrhotic sustained responders were baseline γGT levels (HR 6.44, 95% CI 2.20-18.89, p=0.001) and age (HR 3.68, 95% CI 1.33-10.17, p=0.012). The incidence of HCC was not different between older non-cirrhotic patients with high γGT levels and cirrhotic patients (p=0.34). CONCLUSIONS: HCC remains a threat in non-cirrhotic patients with an SVR. Serum γGT levels helped to identify potential patients at high risk.

Urinary transforming growth factor α and serum α-fetoprotein as tumor markers of hepatocellular carcinoma.

This case-control study aimed to evaluate the diagnostic application of urinary transforming growth factor (TGF) α and serum α-fetoprotein (AFP) in hepatocellular carcinoma (HCC). TGFα and AFP were determined in 90 pairs of age- and gender-matched patients with cirrhotic HCC and patients with cirrhosis alone and 60 healthy controls. The results indicated that TGFα and AFP levels in patients with HCC were higher than in those with cirrhosis alone or healthy controls (each P = 0.0001). Multivariate analysis indicated that TGFα (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.05-1.16) and AFP (OR 1.03, 95% CI 1.01-1.06) were closely associated, in a dose-related fashion, with the development of HCC. The optimal cutoff values, determined with the receiver operating characteristic (ROC) curves, were 29 µg/g creatinine for TGFα and 100 ng/ml for AFP, respectively. The areas under ROC curve (AUC) were 0.74 for TGFα and 0.78 for AFP, respectively. Both biomarkers showed the same sensitivity (52.2%), high specificity, high positive predictive value, and moderate positive likelihood ratio. Determination of both markers in parallel significantly increased the AUC (0.91) and diagnostic accuracy (92.2%), with a high sensitivity (86.7 %), specificity (97.8%), positive predictive value (PPV; 97.5%), and moderate positive likelihood ratio (PLR; 39.4). Among 31 cirrhotic HCC with AFP ≤ 20 ng/ml, the calculated AUC for TGFα was 0.79, with a sensitivity of 64.5%, specificity of 96.7%, PPV of 87.0%, and PLR of 19.5. In conclusion, urinary TGFα and serum AFP are complementary tumor markers for detection of HCC with low AFP production.

Treatment efficacy of pegylated interferon plus ribavirin therapy in chronic hepatitis C patients with mixed genotype 1/2 infection.

BACKGROUND AND AIM: The treatment efficacy of patients with mixed hepatitis C virus (HCV) genotype 1/genotype 2 (HCV-1/2) remains unknown. We aimed to elucidate the sustained virological response (SVR) rate in patients with HCV-1/2 infection. METHODS: One hundred and ten HCV-1/2 patients treated with response-guided peginterferon/ribavirin therapy (24 weeks for patients with a rapid virological response [RVR] and low viral loads; 48 weeks for patients without a RVR or high viral loads) were allocated. Two hundred HCV-1 patients were selected as a historical control. Interleukin-28B (IL-28B) rs8099917 genotype was tested for the association with an SVR. RESULTS: The rates of RVR, sustained virologic response (SVR), and relapse rate were 71.8%, 87.3%, and 11.1%, respectively. The SVR rate was significantly higher in patients with an abbreviated regimen as compared with those with 48-week regimen (95.5% vs 75.0%, P = 0.002), and both were similar to the HCV-1 historical control. Stepwise logistic regression analysis revealed that lower baseline viral loads were the single factor predictive of an RVR (odds ratio/95% confidence intervals [OR/CI] of 41.62/9.72-178.19, P < 0.001). The achievement of an RVR was the single best factor predictive of an SVR (OR/CI: 7.5/1.33-42.27, P = 0.02). Nevertheless, an abbreviated regimen became the single factor associated with an SVR if treatment regimen was taken into consideration (OR/CI: 11.0/1.25-96.79, P = 0.03). The SVR rate did not differ between patients with rs8099917 TT and TG/GG genotype (91.7% vs 87.5%, P = 0.63). CONCLUSIONS: The treatment efficacy of patients with HCV-1/2 was satisfactory. The role of IL-28B genetic variants in the population with response-guided therapy was limited.

Clinical utility of host genetic IL-28B variants in hepatitis C virus genotype 1 Asian patients retreated with pegylated interferon plus ribavirin.

BACKGROUND AND AIM: Host interleukin-28B (IL-28B) genetic variants determine a sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) treatment-naïve patients. Its impact on treatment-experienced Asian patients with peginterferon/ribavirin in is to be elucidated. METHODS: IL-28B rs8099917 genotype was determined in 70 HCV-1 treatment-experienced patients retreated with 48-week peginterferon/ribavirin. RESULTS: The SVR rate was 60.0% and was significantly higher in previous relapsers than in nonresponders (72.7% and 13.3%, P < 0.001). Multivariate analysis revealed that the most important factor predictive of an SVR was previous relapse (Odds ratio [OR]/95% confidence interval [CI]: 14.76/2.72-80.06, P = 0.002), followed by the carriage of rs8099917 TT genotype (OR/95% C.I.: 7.67/1.27-46.49, P = 0.03). Comparing to patients with TG/GG genotype, those with TT genotype had significantly higher rates of rapid virological response (29.3% vs 0%, P = 0.03), end-of-treatment virological response (86.2% vs 50.0%, P = 0.01), SVR (69.0% vs 16.7%, P = 0.002), and lower relapse rate (22.0 % vs 66.7%, P = 0.04). The SVR rate was similarly low between previous nonresponders with different rs8099917 genotypes (12.5% vs 14.3%, P = 1). On the contrary, previous relapsers with rs8099917 TT genotype had a significantly higher SVR rate than those who carried rs8099917 TG/GG genotype (78.0 % vs 20.0%, P = 0.02). Stepwise logistic regression analysis revealed that the only factor predictive of an SVR in previous relapsers was the carriage of rs809997 TT genotype (OR/95% CI:18.50/1.82-188.39, P = 0.014). CONCLUSIONS: Host IL-28B genetic variants played a role in Asian relapsers but not nonresponders retreated with peginterferon/ribavirin. Direct antiviral agents might be possibly avoidable in Asian relapsers with favorable IL-28B genotype.

Interleukin-28B genetic variants in identification of hepatitis C virus genotype 1 patients responding to 24 weeks peginterferon/ribavirin.

BACKGROUND & AIMS: A substantial proportion of hepatitis C virus genotype 1 (HCV-1) patients achieved a sustained virological response (SVR, HCV RNA seronegative throughout 24 weeks of post-treatment follow-up) after 24 weeks peginterferon/ribavirin therapy. We explored the role of interleukin-28B genotype in identifying patients who responded to the regimen. METHODS: Interleukin-28B rs8099917 genotype was determined in 226 HCV-1 patients with 24 weeks peginterferon/ribavirin. RESULTS: Compared to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly higher rapid virological response (RVR, HCV RNA seronegative at treatment week 4, 54.0% vs. 17.9%, p<0.001) and SVR (64.7% vs. 25.6%, p<0.001) rates, and lower relapse rate (28.0% vs. 54.5%, p=0.01). Logistic regression analysis revealed that the strongest factor predictive of a RVR was the carriage of rs8099917 TT genotype (odds ratio/ 95% confidence intervals [OR/CI]: 6.24/2.34-16.63), followed by lower viral loads (OR/CI: 5.29/2.81-9.93) and age (OR/CI:0.94/0.91-9.97). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 22.23/9.22-53.58), followed by the carriage of rs8099917 TT genotype (OR/CI: 3.38/1.18-9.65), lower viral loads (OR/CI: 2.23/1.00-4.93) and ribavirin exposure dose (OR/CI: 1.17/1.06-1.30). The determinant power of rs8099917 genotype on SVR was mainly restricted to non-RVR patients, particularly those with higher baseline viral loads. Combination of the two pretreatment predictors, interleukin-28B genotype and baseline viral loads, could predict treatment efficacy with a positive predictive value of 80% and a negative predictive value of 91%. CONCLUSIONS: Interleukin-28B genotype could help identifying patients who are or are not candidates for an abbreviated regimen before treatment.

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

UNLABELLED: Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r2 = 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P = 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) = 4.27, 95% confidence interval (CI) = 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR = 0.28, 95% CI = 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR = 3.10, 95% CI = 1.34-7.21, P = 0.008), and the pretreatment level of aspartate aminotransferase (OR = 0.996, 95% CI = 0.99-1.00, P = 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI = 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. CONCLUSION: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients.

The efficacy and safety of pegylated interferon plus ribavirin combination therapy in chronic hepatitis c patients with hepatocellular carcinoma post curative therapies - a multicenter prospective trial.

BACKGROUND & AIMS: Evidence on the efficacy of antiviral treatment in chronic hepatitis C (CHC) patients with hepatocellular carcinoma (HCC) after curative treatment is scarce. We aimed to evaluate the efficacy and safety of pegylated interferon-alpha plus ribavirin (pegIFN/RBV) combination therapy in these patients, compared to cirrhotic patients. METHODS: This prospective, multicenter, case-control study recruited 82 consecutive CHC patients with HCC after curative management and 87 sex/age-matched cirrhotic patients. All patients received pegIFN-alpha-2a and weight-based RBV according to current treatment recommendations. The primary outcome measurement was sustained virological response (SVR, seronegative of hepatitis C virus RNA throughout the 6-month post-treatment follow-up period). RESULTS: The SVR rate was significantly lower in the HCC group compared to the cirrhosis group (48.8% vs 64.4%, p=0.04). However, the significantly lower rate of SVR in the HCC group was observed among genotype-1 patients (33.3% vs 60.7%, p=0.005) but not among genotype-2/3 patients (70.6% vs 71.0%, p=0.88). In patients who achieved 80/80/80 adherence, there was no significant difference of SVR rate between groups (50.7% vs 64.2%, p=0.12) Multivariate logistic regression analysis demonstrated that rapid virological response (viral clearance during the first 4 weeks of treatment, odds ratio=22.1, p<0.001) and adherence (odds ratio=3.1, p=0.05) were predictive factors associated with SVR, whilst previous occurrence of HCC was not associated with SVR (Odds ratio=0.4, p=0.09). The incidence of severe adverse events did not differ between the two groups. CONCLUSIONS: The study proved the feasibility of pegIFN/RBV therapy with current treatment guidelines in CHC patients after successful eradication of HCC, with careful monitoring.

Efficacy and safety of pegylated interferon combined with ribavirin for the treatment of older patients with chronic hepatitis C.

BACKGROUND: The present study evaluated the efficacy and safety of pegylated interferon (PegIFN)/ribavirin treatment in elderly patients with hepatitis C virus (HCV) infection. METHODS: Seventy elderly patients with hepatitis C virus (HCV) infection (group A; age, > or = 65 years) and 140 sex- and HCV genotype-matched controls (group B; age, 50-64 years) were allocated to receive a PegIFN-alpha-2a/ribavirin standard-of-care regimen. RESULTS: Group A had a significantly higher rate of treatment discontinuation (21.4% vs 6.4%; P = .001) and grade 3 or 4 adverse events (34.3% vs 20%; P = .002) than group B. In intention-to-treat analysis, the sustained virologic response (SVR) rate was substantially lower in group A than in group B (67.1% vs 78.6%; P = .07). The inferiority of the SVR rate in group A was observed among patients with HCV genotype 1 (HCV-1) (51.9% vs 75.9%; P = .03) but not among patients with HCV genotype 2 or 3 (HCV-2/3) (76.7% vs 80.2%; P = .65). Among patients in group A who had a rapid virologic response, those infected with HCV-1 and those infected with HCV-2/3 had similar SVR rates (80% and 87.9%, respectively). For patients receiving treatment for >80% of its expected duration, SVR rates were similar between the 2 groups (80.4% vs 82.6%, respectively), regardless of viral genotype. CONCLUSIONS: Older patients with HCV infection, especially those in the subgroup infected with HCV-1, had a greater frequency of adverse events and poorer adherence to the standard-of-care regimen, which may be the major reason for treatment inferiority. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00629824 .

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

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection has been shown to be associated with a low platelet count. This study aimed to elucidate the association between virologic status and platelet count in individuals with HCV infection. METHODS: A large-scale survey, enrolling 11,239 residents, was conducted in the Kaohsiung area of Taiwan. Serum HCV RNA and non-invasive markers of fibrosis (FibroTest) were tested for antibody to HCV (anti-HCV)-positive subjects. The platelet counts of age- and sex-matched, biopsy-proven, hospital-based patients and community-based patients with minimal fibrosis were compared. RESULTS: Anti-HCV was positive in 703 (6.2%) subjects and was significantly associated with older age, female sex, abnormal alanine aminotransferase (ALT) value and low platelet count (<150,000/microl). The independent factors significantly associated with low platelet count were abnormal ALT value (odds ratio [OR]: 3.70, 95% confidence intervals [CI]: 2.18-6.28) and positive HCV RNA (OR: 2.00, 95% CI: 1.01-3.97). After adjustment for the fibrosis, HCV RNA remained significantly associated with platelet counts. CONCLUSIONS: Our results evaluating the association between platelet count and HCV viremia and taking the influences of fibrosis into consideration implicate that platelets may be affected directly by HCV.

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

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

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

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection carries a significant risk for development of insulin resistance (IR) and/or diabetes mellitus. Recently, retinol-binding protein 4 (RBP4) has been reported as a protein contributing to IR. This study aimed to assess the correlation between RBP4 and disease severity of chronic HCV infection (CHC). METHODS: Serum RBP4 was measured in 105 treatment-nai ve CHC patients and its correlation with the homeostasis model assessment of insulin resistance index (HOMA-IR), liver histology, virology and metabolic factors was investigated. Patients were stratified into different stages of glucose tolerance by oral glucose tolerance test. RESULTS: There was a significant decreasing linear trend of RBP4 dependent on both histological grading (from 35.8+/-16.5 microg/mL of minimal to 19.2+/-12.5 microg/mL of severe, P=0.002) and staging (from 34.2+/-10.0 microg/mL of F0 to 22.2+/-11.9 microg/mL of F3-4, P=0.02) progression, whilst a significant increment of HOMA-IR was found. Multivariate regression analysis showed BMI (1.1, 95% CI 0.44 ~ 1.77, P=0.001), HDL-C (-0.40, 95% CI -0.73 ~ -0.06, P=0.02), and LDL-C (0.31, 95% CI 0.02 ~ 0.61, P=0.04) were the significant variables for prediction of RBP4. CONCLUSIONS: Disease severity may limit the role of RBP4 as a predictor of IR in CHC.

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

BACKGROUND/AIMS: Insulin resistance (IR) might be associated with hepatitis C virus (HCV) infection. This study aimed to elucidate impact of IR and beta-cell function on the response to peginterferon-alpha (PEG-IFN)/ribavirin combination therapy in chronic hepatitis C (CHC) patients. METHODS: Three hundred and thirty patients without overt diabetes were treated with combination therapy with (PEG-IFN)/ribavirin for 24 weeks. The IR and beta-cell function were evaluated by homeostasis model assessment of IR (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-beta) before treatment. RESULTS: HCV genotype, pretreatment HCV RNA level and pretreatment HOMA-IR, but not HOMA-beta, were independent factors associated with sustained virologic response (SVR). In 150 patients with genotype 1b infection, pretreatment HCV RNA level, HOMA-IR and age were independent predictors for SVR. The significantly lower SVR rate in high HOMA-IR patients was observed in 76 patients with high HCV RNA levels (>or=400,000IU/mL) who were defined as 'difficult-to-treat' patients. The mean HOMA-IR of 'difficult-to-treat' patients was significantly lower in 42 sustained responders than in 34 non-responders. CONCLUSIONS: IR was associated with SVR to (PEG-IFN)/ribavirin therapy for CHC, especially among 'difficult-to-treat' patients. These findings suggested clinical application of pretreatment HOMA-IR could enable treatment outcome to be predicted and treatment regimens to be determined.

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

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

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

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

Heat shock protein A1B 1267 polymorphism is highly associated with risk and prognosis of hepatocellular carcinoma: a case-control study.

We conducted a case-control study to elucidate the role of heat shock protein A1B (HSPA1B) 1267 single nucleotide polymorphism (SNP) on the risk and prognosis of hepatocellular carcinoma (HCC). Subjects enrolled included 150 pairs of sex- and age-matched HCC patients and unrelated controls. Genomic DNA was typed for HSPA1B1267 SNP using polymerase chain reaction with restriction fragment length polymorphism. The frequencies of the HSPA1B P2/P2 genotype and the HSPA1B P2 allele in HCC patients were higher than in unrelated controls (each p = 0.0001). Multivariate analysis identified the following independent risk factors for HCC: HSPA1B P1/P2 genotype (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.07-5.11), HSPA1B P2/P2 genotype (OR, 12.06; 95% CI, 4.43-32.79), hepatitis B surface antigen (HBsAg) (OR, 25.95; 95% CI, 11.88-56.68), and antibodies to hepatitis C virus (anti-HCV) (OR, 70.43; 95% CI, 21.89-226.64). There was an additive interaction between HSPA1B P2 allele carriers and the presence of either HBsAg (synergy index = 2.48) or anti-HCV (synergy index = 1.52). However, as HSPA1B1267 SNP is a silent mutation, it is a surrogate genetic marker for increasing risk of HCC. Our findings indicate that patients with chronic hepatitis B/hepatitis C virus infection who harbor this SNP represent a high-risk group for HCC. They should receive more intensive surveillance for early detection of HCC. Moreover, patients with the HSPA1B P2 allele had significantly longer survival (p = 0.002).The limitations of this study include the unknown functional significance of the HSPA1B1267 polymorphism, the relatively small sample size, the fact that this was not a prospective study of cases and controls, and the questionable generalizability of the findings given the specific ethnic composition of the population studied.

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

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

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

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

Abdominal splenosis mimicking hepatic tumor: a case report.

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.