Revised cutoff values of ALT and HBV DNA level can better differentiate HBeAg (-) chronic inactive HBV patients from active carriers.

BACKGROUND AND AIMS: ELISA is still used as primary test for diagnosis HBV disease. However, ELISA-positive patients were marked as HBV inactive after confirmation with PCR and vice versa. Our aim was to assess the performance of new cut-off value of ALT, HBV DNA load and significance of AST as screening tool for HBeAg (-) chronic active or inactive patients in Pakistani population. MATERIALS AND METHODS: In a cross-sectional, cohort study, 567 HBeAg (-) patients followed for one year were selected. Patients with persistent elevated ALT than normal and HBV DNA ≥ 100,000 copies/mL were taken as active chronic. Diagnostic values for ALT, AST and HBV DNA load in HBV HBeAg (-) chronic active and inactive patients compared using receiver operation characteristic (ROC) curves. RESULTS: Of 567 HBeAg (-) patients, 228 were classified as chronic inactive and 339 as active. HBV infection was dominant in male. Serum ALT, AST and HBV DNA levels showed significant and high AUROC to differentiate chronic HBeAg (-) inactive patients from active. AUROC for Serum ALT, AST and HBV DNA were observed 0.997, 0.969 and 1.000, respectively. For revised cut off value for ALT (30 IU/L for male and 19 IU/L for female) and HBV DNA load ≥100,000 copies/mL, a PPV of 97%, NPV of 94%, a sensitivity of 98%, and a specificity of 92% was observed to discriminate active carriers from inactive carriers. We also observed 93.5% specificity, 83.1% sensitivity, 82% PPV and 89.5% NPV for AST ≤20 IU/L to differentiate inactive carriers from active ones in our study group. CONCLUSIONS: Revised cut off value of ALT and NIH derived HBV DNA value can better discriminate between HBeAg (-) chronic active and inactive patients.

HCV genotype-specific correlation with serum markers: higher predictability for genotype 4a.

BACKGROUND: Several factors have been proposed to assess the clinical outcome of HCV infection. The correlation of HCV genotypes to possible serum markers in clinical prediction is still controversial. The main objective of this study was to determine the existence of any correlation between HCV genotypes to viral load and different clinical serum markers. METHODS: We performed a prospective cross-sectional and observational study. About 3160 serum HCV RNA positive patients were chosen from 4020 randomly selected anti-HCV positive patients. Statistical analysis was performed using the SPSS 16 software package. ROC (receiver operating characteristics) curves were used to compare diagnostic values of serum markers to predict genotypes. RESULTS: The most prevalent genotype was 3a (73.9%) followed by 1a (10.7%), 4a (6.4%) and 3b (6.1%) in Pakistani population. No correlation was found between viral load and serum markers for genotype 3a in a large no. of sample (n = 2336). While significant correlation was observed between viral load and AST in genotype 3b, ALP with viral load and ALT for genotype 1a. Patients with genotype 4a showed a significant inverse correlation with viral load and Hb level and AST with ALP. For genotype 4a, AUC (area under the curve) of ALT, ALP, AST, bilirubin, Hb level and viral load was 0.790, 0.763, 0.454, 0.664, 0.458 and 0.872 respectively. CONCLUSIONS: In conclusion, there was a significant variable response of HCV genotypes with serum markers. Severity of disease is independent of serum marker level in genotype 3a, while the liver damage in genotype 4a may associate with viral cytopathic effect as well as the immune-mediated process. An index using six serum markers may correctly predict genotype 4a in patients with ≥ 75% accuracy.

Association of laboratory parameters with viral factors in patients with hepatitis C.

BACKGROUND AND AIMS: HCV infection may lead to hepatic fibrosis. In this study, we tried to determine whether there is any correlation of HCV genotypes and viral load to the clinical parameters such as ALT, AST, ALP, bilirubin, Hb level, patient's age and gender; and then correlated this association with disease progression in liver biopsy samples. METHODS: In cross-sectional and observational study, 6048 serum HCV RNA positive patients were chosen. The study consists of 53 months from March 2006 to September 2010. Patients were divided into three cohorts to validate our data. Statistical analysis and correlation of lab parameters with viral factors was determined by using SPSS version 16. RESULTS: The most prevalent genotype was 3 (70.9%) followed by 1 (13.3%) and 4 (7.4%), collectively. During Univariate analysis, in all cohorts; serum bilirubin, ALP, ALT and AAR showed significant correlation with genotypes, however multivariate analysis showed that all genotypes except 4a have no association with host biochemical markers. Disease progression was also independent of all genotypes. Serum ALP, ALT, bilirubin and viremea levels were significantly elevated in patients with genotype 4a. Viral load showed negative association with serum bilirubin (r = -0.112, P = 0.000) and ALP levels (r = -0.098, P = 0.000). We observed positive correlation of ALP and bilirubin levels, while negative associations of viral load with HCV liver disease progression. CONCLUSION: Disease progression seems independent of the genotypes. Relationship between ALP and bilirubin with viral load may be an attractive marker to guess disease progression in patients with hepatitis C.

A comparison of four fibrosis indexes in chronic HCV: development of new fibrosis-cirrhosis index (FCI).

BACKGROUND: Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers. METHODS: We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)]. RESULTS: Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%. CONCLUSIONS: The fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.