Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma

AIM： To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METHODS： The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA （HBV DNA） level and hepatitis B e antigen （HBeAg） were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS： During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio： 95.74 （12.13-891.31）, P 〈 0.0001], male sex [odds ratio： 7.61 （2.20-47.95）; P = 0.006], and higher Iogzo HBV DNA [odds ratio： 4.69 （1.16-20.43）; P 〈 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio： 26.51 （2.36-381.47）; P = 0.007], presence of precore mutants [odds ratio： 4.23 （1.53-19.58）, P = 0.02] and presence of basal core promoter mutants [odds ratio： 2.93 （1.24-7.57）; P = 0.02] were independent predictors for progression to hepatocellular carcinoma. CONCLUSION： Our results show that high levels of baseline serum HBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.

APRI as a predictor of early viral response in chronic hepatitis C patients

AIM:To evaluate the aspartate aminotransferase(AST) to platelet ratio index(APRI) as a predictive factor of early viral response in chronic hepatitis C naive patients.METHODS:We performed an ambispective case-control study.We enrolled chronic hepatitis C naive patients who were evaluated to start therapy with PEGylated interferon α-2b(1.5 μg/kg per week) and ribavirin(>75 kg:1200mg and <75kg:1000mg).Patients were allocated into two groups,group 1:Hepatitis C patients with early viral response(EVR),group 2:Patients without EVR.Odds ratio(OR) and 95% confi dence interval(CI) were calculated to assess the relationship between each risk factor and the EVR in both groups.RESULTS:During the study,80 patients were analyzed,45 retrospectively and 35 prospectively.The mean ± SD age of our subjects was 42.9 ± 12 years;weight 70 kg(±11.19),AST 64.6 IU/mL(±48.74),alanine aminotransferase(ALT) 76.3 IU/mL(±63.08) and platelets 209000 mill/mm3(±84 429).Fifty-five(68.8%) were genotype 1 and 25(31.3%) were genotype 2 or 3;the mean hepatitis C virus RNA viral load was 2 269 061 IU/mL(±7220266).In the univariate analysis,APRI was not associated with EVR [OR 0.61(95% CI 0.229-1.655,P=0.33)],and the absence of EVR was only associated with genotype 1 [OR 0.28(95% CI 0.08-0.94,P=0.034)].After adjustment in a logistic regression model,genotype 1 remains signifi cant.CONCLUSION:APRI was not a predictor of EVR in chronic hepatitis C;Genotype 1 was the only predictive factor associated with the absence of EVR in our patients.

Impact of IL28B gene polymorphisms rs8099917 and rs12980275 on response to pegylated interferon-α/ribavirin therapy in chronic hepatitis C genotype 4 patients

Host genetic factors may predict the outcome and treatment response in hepatitis C virus（HCV）infection.One of these factors is the single nucleotide polymorphisms of the interleukin 28B（IL28B）gene.We sought to evaluate the outcome of pegylated interferon and ribavirin therapy in association with IL-28B rs8099917 and rsl2980275 in patients infected with HCV genotype 4.A total of 180 patients with chronic hepatitis C were selected from Egyptians who have received combined therapy with pegylated interferon and ribavirin for 6 months and their response was evaluated after follow-up at 0,6,12,24 and 48 weeks from the beginning of the therapy.Blood samples were collected from responders and non-responders.Genomic DNA was extracted from whole blood and genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism（PCR-RFLP）.Our results showed that TT genotype of rs8099917 was associated with higher sustained viral response（SVR）rates and G allele represented a risk factor for failure of response（OR=3.7,CI=1.8：7.64）while rs12980275 was not significantly associated with SVR in genotype 4 Egyptian patients.The determination of 1L-28B SNPs may be useful in enhancing correct prediction of SVR achievement in treating this group of genotype 4 patients.