Adiponectin changes in HCV-Genotype 4: relation to liver histology and response to treatment.

Recently, attention has been focussed on adiponectin and its changes in different types of chronic liver disease. Its relation to hepatic fibrosis and insulin resistance in post-hepatitis liver disease is not clear. The aim of this study was to clarify the adiponectin changes in genotype 4 hepatitis C virus (HCV)-infected patient in relation to liver histology and insulin resistance, and its usefulness as a predictor of hepatic fibrosis and response to treatment. Total adiponectin and its high molecular weight (HMW) form as well as insulin levels were studied in 92 chronic HCV, genotype 4 and 66 healthy control volunteers. Neither total adiponectin (r = 0.101, P = 0.220) nor HMW adiponectin (r = 0.081, P = 0.328) correlated with viral load. Total and not HMW adiponectin was significantly correlated with hepatic fibrosis and inflammation (r = 0.267, P = 0.002, r = 0.278, P < 0.001, respectively).In addition, total adiponectin (r = 0.224, P = 0.002) and HMW adiponectin (r = 0.266, P < 0.0006) significantly correlated with insulin resistance. As fibrosis did not correlate with insulin resistance (r = 0.081, P = 0.204), the correlation between total adiponectin and fibrosis was not mediated by insulin resistance. Multivariable regression analysis, (including pretreatment cases and controls) revealed that total adiponectin was significantly associated with gender, being lower among male subjects (X(2) = 13.04, P = 0.0001). The multivariable regression model supported the lack of association between insulin resistance and total adiponectin levels (X(2) = 1.88, P = 0.171), while non cirrhotics had significantly lower total adiponectin levels than cirrhotics (X(2) = 10.90, P = 0.004) and lower level of inflammation significantly lower total adiponectin levels than more severe inflammation (X(2) = 8.95, P = 0.003). Total or HMW adiponectin did not yield receiver operating characteristic (ROC) curves with area under the curve (AUC) >75%, thus the cutoff points have poor sensitivity/specificity as predictors of fibrosis. However, as a predictor of end-of-treatment response, the ROC curve of adiponectin index gave yield an AUC = 81.4%. We can conclude that total adiponectin level, in HCV genotype 4 patients, increases with progression of hepatic fibrosis regardless of insulin resistance. Its high molecular form does not have such correlation. The adiponectin changes are not related to viral load, insulin resistance or other demographic data suggesting that this change is histologically related. In spite of this, no adiponectin cutoff level had reasonable sensitivity/specificity for predicting hepatic fibrosis stage, while this may be used as a predictor for antiviral response possibly reflecting improvement in hepatic inflammation post treatment.

Hepatitis B and C viral infections in chronic liver disease: a population based study in Qatar.

We investigated the incidence of hepatitis B (HBV) and C (HCV) virus infection among patients with liver disease in Qatar from 2000 to 2005. The grading and staging of HBV and HCV cases were obtained from pathology reports at the principal reference laboratory for Qatar. Of the 915 liver patients studied, 29.4% had HCV and 2.5% had HBV. The incidence of HBV and HCV infection was greater in non-Qataris than Qatari nationals and in males than females, especially for HCV. Most cases were uncomplicated (89.0%) and had no inflammation (76.4%). The incidence of HCV has been increasing in liver patients in recent years up to a rate of 481 per 1000 patients with liver disease in 2005.

Hepatitis B and C viral infections in chronic liver disease: a populationbased study in Qatar

We investigated the incidence of hepatitis B [HBV] and C [HCV] virus infection among patients with liver disease in Qatar from 2000 to 2005. The grading and staging of HBV and HCV cases were obtained from pathology reports at the principal reference laboratory for Qatar. Of the 915 liver patients studied, 29.4% had HCV and 2.5% had HBV. The incidence of HBV and HCV infection was greater in non-Qataris than Qatari nationals and in males than females, especially for HCV. Most cases were uncomplicated [89.0%] and had no inflammation [76.4%]. The incidence of HCV has been increasing in liver patients in recent years up to a rate of 481 per 1000 patients with liver disease in 2005

Viral kinetic of HCV genotype-4 during pegylated interferon alpha 2a: ribavirin therapy.

Kinetics of hepatitis C virus (HCV) during pegylated interferon (PEG-IFN) and early monitoring of viral decline were recently described to predict treatment outcomes and in turn reduce the course of treatment, adverse effects and cost. However, there is limited (if any) information on the viral dynamics of HCV-4. Our aim is to follow the HCV-RNA kinetics during PEG-IFN alpha 2a and ribavirin therapy and the best time for predicting sustained viral response (SVR) in genotype-4 patients. Serum HCV-RNA levels before initial dosing (baseline level) and at 24 h, week 1, week 4, week 12, week 24, week 48 and week 72 were assessed in 84 HCV genotype-4 patients treated weekly by PEG-IFN alpha 2a and daily ribavirin. At the end of treatment, out of the 84 treated patients, 19 (22.6%) were non-responders while 65 (77%) showed end-of-treatment response (ETR). However, 8 patients relapsed (9.5%), thus the SVR was observed in 57 patients (67.9%). Younger patients were more likely to attain SVR, where the odds of SVR increased by a factor of 0.94 for each year increase in age (95% CI: 0.90-0.99, P = 0.019). Although a significant negative correlation between stage of fibrosis and rate of viral decline at weeks 1 and 4 (P < 0.005 and 0.001, respectively) was seen, neither fibrosis stage (χ(2) = 3.4882, P > 0.1) nor grade of inflammation (χ(2) = 0.0057, P > 0.1) significantly predicted response to treatment. Non-responders had no or only a limited decline at week 1 and week 4, whereas sustained virological responders had a significant decline at both week 1 and week 4. Area under the (receiver operating characteristic) curve (AUC) revealed that week 12 is better than any other time point in predicting the SVR (AUC = 0.97; 95% CI: 0.94-1.01), (sensitivity 98.3%; 95% CI: 90.7-99.9), (specificity 88.5%; 95% CI: 71.0-96.0), positive predictive value of 94.9% and negative predictive value of 95.8%. A drop of more than 1.17 log viral load at week 1 and viral clearance or decline >3 log were considered as the earliest predictors of SVR. In genotype-4 patients, while failure to achieve an EVR at week 12 predicts non-response, an RVR at week 1 and week 4 98% guaranteed SVR. These findings further re-enforce the value of week 12 in the course of IFN treatment. Genotype-4 patients who show significant viral clearance (>1.17 log viral load) by the first week of treatment and viral clearance >3 log by week 4 are expected to show SVR and should therefore be assigned to a shorter drug regimen lasting for 24 weeks. Those unfortunate cases who do not achieve viral clearance by week 1 or week 4 should not be deprived from the treatment but rather given more time till week 12 before being classified as non-responders.

Treatment of hepatitis C virus genotype 4 with peginterferon alfa-2a: impact of bilharziasis and fibrosis stage.

AIM: To evaluate pegylated interferon alpha2a (PegIFN-alpha2a) in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate. METHODS: A total of 73 naive patients (61 with history of bilharziasis) with compensated chronic HCV genotype 4 were enrolled into: group A (38 patients) who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B (35 patients) received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed. RESULTS: Significant improvement in both end of treatment response (ETR) (P < 0.002) and sustained response (SR) (P < 0.05) was noted with pegylated interferon, where ETR was achieved in 29 (76.3%) and 14 patients (40%) in both groups respectively, and 25 patients in group A (65.8%) and 9 (25.7%) in group B could retain negative viraemia by the end of follow up period. Sustained virological response (SVR) showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR (P < 0.001), but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis (grade 3 and 4) with PegIFN-alpha2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect; both drugs were comparable. CONCLUSION: PegIFN-alpha2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.