Mahasen Mabrouk

Peginterferon alpha‐2a is associated with higher sustained virological response than peginterferon alfa‐2b in chronic hepatitis C: Systematic review of randomized trials

A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (peginterferon alpha‐2a or peginterferon alfa‐2b) is most effective. We performed a systematic review of head‐to‐head randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently extracted data from each eligible trial report. We statistically combined data using a random effects meta‐analysis according to the intention‐to‐treat principle. We identified 12 randomized clinical trials, including 5,008 patients, that compared peginterferon alpha‐2a plus ribavirin versus peginterferon alfa‐2b plus ribavirin. Overall, peginterferon alpha‐2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus peginterferon alfa‐2b (47% versus 41%; risk ratio 1.11, 95% confidence interval 1.04–1.19; P = 0.004 [eight trials]). Subgroup analyses of risk of bias, viral genotype, and treatment history yielded similar results. The meta‐analysis of adverse events leading to treatment discontinuation included 11 trials and revealed no significant differences between the two peginterferons. Conclusion: Current evidence suggests that peginterferon alpha‐2a is associated with higher SVR than peginterferon alfa‐2b. However, the paucity of evidence on adverse events curbs the decision to definitively recommend one peginterferon over the other, because any potential benefit must outweigh the risk of harm. (HEPATOLOGY 2010.)

Application of data mining techniques to explore predictors of HCC in Egyptian patients with HCV related chronic liver disease

BACKGROUND Hepatocellular carcinoma (HCC) is the second most common malignancy in Egypt. Data mining is a method of predictive analysis which can explore tremendous volumes of information to discover hidden patterns and relationships. Our aim here was to develop a non-invasive algorithm for prediction of HCC. Such an algorithm should be economical, reliable, easy to apply and acceptable by domain experts. METHODS This cross-sectional study enrolled 315 patients with hepatitis C virus (HCV) related chronic liver disease (CLD); 135 HCC, 116 cirrhotic patients without HCC and 64 patients with chronic hepatitis C. Using data mining analysis, we constructed a decision tree learning algorithm to predict HCC. RESULTS The decision tree algorithm was able to predict HCC with recall (sensitivity) of 83.5% and precession (specificity) of 83.3% using only routine data. The correctly classified instances were 259 (82.2%), and the incorrectly classified instances were 56 (17.8%). Out of 29 attributes, serum alpha fetoprotein (AFP), with an optimal cutoff value of ≥50.3 ng/ml was selected as the best predictor of HCC. To a lesser extent, male sex, presence of cirrhosis, AST>64U/L, and ascites were variables associated with HCC. CONCLUSION Data mining analysis allows discovery of hidden patterns and enables the development of models to predict HCC, utilizing routine data as an alternative to CT and liver biopsy. This study has highlighted a new cutoff for AFP (≥50.3 ng/ml). Presence of a score of >2 risk variables (out of 5) can successfully predict HCC with a sensitivity of 96% and specificity of 82%.

Low Serum Alpha-fetoprotein Level an Important Predictor for Therapeutic Outcome in Egyptian Patients with Chronic Hepatitis C: A Data-Mining Analysis

Background Data mining can build predictive models for the response to antiviral therapy in chronic HCV patients. Objective To develop a prediction model for therapeutic outcome in chronic HCV genotype-4 patients using different decision-trees learning algorithms. Study Design Data of 3719 chronic HCV patients who had received PEG-IFN/RBV therapy at Cairo-Fatemia Hospital, Egypt was retrieved. Factors predictive of SVR were explored using data mining analysis. Weka implementations C4.5, classification and Reduced Error Pruning tree were constructed using 22 attributes from initial patients’ data. Results End of treatment response and estimated SVR were 61.6%, 52.5% respectively. Low median AFP; 2.9 ng/ml was significantly associated with SVR; compared to relapse group 5.06 ng/ml; p value<0.01. AFP was identified as the most decisive variable of initial split by both decision-tree models. Various cutoff levels were related to different probability of SVR. Baseline AFP ≤2.48 ng/ml was associated with 72%SVR while levels ≥ 7.8 ng/ml demonstrated 32%. Other attributes such as age, BMI, ALT, hepatic fibrosis and activity were less decisive in prediction of response. This was further confirmed by univariate logistic regression analysis; p value<0.01. Conclusion Low AFP Levels were significantly related to SVR in an HCV population presumably genotype-4 as demonstrated by data mining.

Data mining of routine laboratory tests can predict liver disease progression in Egyptian diabetic patients with hepatitis C virus (g4) infection: a cohort study of 71 806 patients

Objectives Hepatitis C virus (HCV) and diabetes mellitus (DM) are prevalent diseases worldwide, associated with significant morbidity, mortality, and mutual association. The aims of this study were as follows: (i) find the prevalence of DM among 71 806 Egyptian patients with chronic HCV infection and its effect on liver disease progression and (ii) using data mining of routine tests to predict hepatic fibrosis in diabetic patients with HCV infection. Patients and methods A retrospective multicentered study included laboratory and histopathological data of 71 806 patients with HCV infection collected by Egyptian National Committee for control of viral hepatitis. Using data mining analysis, we constructed decision tree algorithm to assess predictors of fibrosis progression in diabetic patients with HCV. Results Overall, 12 018 (16.8%) patients were diagnosed as having diabetes [6428: fasting blood glucose ≥126 mg/dl (9%) and 5590: fasting blood glucose ≥110–126 mg/dl (7.8%)]. DM was significantly associated with advanced age, high BMI and &agr;-fetoprotein (AFP), and low platelets and serum albumin (P⩽0.001). Advanced liver fibrosis (F3–F4) was significantly correlated with DM (P⩽0.001) irrespective of age. Of 16 attributes, decision tree model for fibrosis showed AFP was most decisive with cutoff of 5.25 ng/ml as starting point of fibrosis. AFP level greater than cutoff in patients was the first important splitting attribute; age and platelet count were second important splitting attributes. Conclusion (i) Chronic HCV is significantly associated with DM (16.8%). (ii) Advanced age, high BMI and AFP, low platelets count and albumin show significant association with DM in HCV. (iii) AFP cutoff of 5.25 is a starting point of fibrosis development and integrated into mathematical model to predict development of liver fibrosis in diabetics with HCV (G4) infection.

942 The Effect of Peginterferon ALPHA-2A vs. Peginterferon alpha-2B in Treatment of NaïVE Chronic HCV Genotype-4 Patients: A Cohort Egyptian Study

3a affect the response to pegylated-interferon-alpha 2b and ribavirin combination therapy. METHODS: Six hundred sixty-five patients with chronic hepatitis C were enrolled. There were 375 men and 290 women (mean age, 57.7 ± 13.5 years). HCV genotypes 1a (N = 18), 1b (N = 428), 2a (N = 137), 2b (N = 71), and 3a (N = 11) were detected. The NS5A region (IFN sensitivity-determining region (ISDR)) in each genotype was examined by direct sequencing. The proto-type for each genotype were defined and the counting the number of mutations to the sequence of proto-type in the ISDR and the strains which have more than two mutations were defined as mutant-type. Detection of the SNP of IL28B (rs8099917) was done by a real-time PCR system with specific probes. Patients received pegylated-IFNalpha 2b once each week plus oral ribavirin daily for 24 -72weeks. RESULTS: Of the 665 patients, 365 (54.9%) showed sustained virologic response (SVR). SVR rates according genotype 1a, 1b, 2a, 2b, and 3a were 44.4, 43.6, 72.9, 70.4, and 80.1%, respectively. Factors related to SVR in genotype 1a were IL28B TT allele (p=0.0359) and ISDR mutanttype (p=0.0229). The IL28B and mutation in the ISDR were the factors related to SVR on multivariate analysis in patients with genotype1b. The best SVR was achieved in patients with mutant-type ISDR and IL28B T allele (70.5%), and the worst was achieved in patients with wild-type ISDR and IL28B G allele (11.1%) in genotype 1a and 1b. Of the 137 patients, 100 (72.9%) achieved SVR in patients with genotype 2a. SVR was achieved in 65.5% of patients with wild-type ISDR and 86% of patients with mutant-type (p = 0.0097). Achievement of SVR occurred in patients with T allele (66.7%) and those with G allele (74.8%). There were no significant differences in SVR according to IL28B in genotype 2a. Similar results were found in genotype 2b. Both ISDR and IL28B in patients with genotype 3a were not associated with SVR. CONCLUSIONS: Both ISDR and IL28B were significantly associated with SVR in genotype 1a and 1b. Only ISDR was useful for predicting the IFN response in genotype 2a and 2b. The impact of ISDR and IL28B on SVR was different in each genotype and these concepts should consider in choosing optimal therapy.

Real-Life Comparison of Pegylated-Interferon 2a Versus 2b Combination Therapy of Chronic Hepatitis C Virus Reply

A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (peginterferon alpha-2a or peginterferon alfa-2b) is most effective. We performed a systematic review of head-to-head randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently extracted data from each eligible trial report. We statistically combined data using a random effects meta-analysis according to the intention-to-treat principle. We identified 12 randomized clinical trials, including 5, 008 patients, that compared peginterferon alpha-2a plus ribavirin versus peginterferon alfa-26 plus ribavirin. Overall, peginterferon alpha-2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus peginterferon alfa-26 (47% versus 41% ; risk ratio 1.11, 95% confidence interval 1.04-1.19 ; P = 0.004 [eight trials]). Subgroup analyses of risk of bias, viral genotype, and treatment history yielded similar results. The meta-analysis of adverse events leading to treatment discontinuation included 11 trials and revealed no significant differences between the two peginterferons. Conclusion: Current evidence suggests that peginterferon alpha-2a is associated with higher SVR than peginterferon alfa-2b. However, the paucity of evidence on adverse events curbs the decision to definitively recommend one peginterferon over the other, because any potential benefit must outweigh the risk of harm. (HEPATOLOGY 2010 ; 51:1176-1184.)

Hepatitis C intervention research – Where are we now and where should we be heading?

In this paper we outline some of the major pending research questions that lie ahead in hepatitis C intervention research. We argue why these should be answered with randomised clinical trials and we stress how Egypt and other Arab countries can play an important role in this context. We delineate a number of design issues relevant to recent and future hepatitis C randomised clinical trials and provide insights on how and why randomised clinical trial designed in a pragmatic and evidence-based framework will efficiently answer pending research questions.