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BackgroundThe contribution of chronic hepatitis B virus (HBV) infection in the pathogenesis of hepatocellular carcinoma (HCC) through progressive stages of liver fibrosis is exacerbated by the acquisition of naturally occurring mutations in its genome. This study has investigated the prevalence of single and combo mutations in the genome of HBV-genotype D from treatment naïve Indian patients of progressive liver disease stages and assessed their impact on the disease progression to HCC.MethodsThe mutation profile was determined from the sequence analysis of the full-length HBV genome and compared with the reference HBV sequences. SPSS 16.0 and R software were used to delineate their statistical significance in predicting HCC occurrence.ResultsAge was identified as associated risk factor for HCC development in chronic hepatitis B (CHB) patients (p≤0.01). Beyond the classical mutations in basal core promoter (BCP) (A1762T/G1764A) and precore (G1862T), persistence of progressively accumulated mutations in enhancer-I, surface, HBx and core were showed significant association to liver disease progression. BCP_T1753C, core_T147C, surface_L213I had contributed significantly in the disease progression to HCC (p<0.05) in HBeAg positive patients whereas precore_T1858C, core_I116L, core_P130Q and preS1_S98T in HBeAg negative patients. Furthermore, the effect of individual mutation was magnified by the combination with A1762T/G1764A in HCC pathogenesis. Multivariate risk analysis had confirmed that core_P130Q [OR 20.71, 95% CI (1.64–261.77), p = 0.019] in B cell epitope and core_T147C [OR 14.58, 95% CI (1.17–181.76), p = 0.037] in CTL epitope were two independent predictors of HCC in HBeAg positive and negative patients respectively.ConclusionsThus distinct pattern of mutations distributed across the entire HBV genome may be useful in predicting HCC in high-risk CHB patients and pattern of mutational combinations may exert greater impact on HCC risk prediction more accurately than point mutations and hence these predictors may support the existing surveillance strategies in proper management of the patients.

A novel reactor system, the rotating disk bioreactor (RDBR), was used to mimic the niche environmental conditions of three salt-tolerant estuarine actinobacteria isolated from the Sundarbans region off the Bay of Bengal, designated MS310 (99% similar in its 16S rRNA gene sequence to Streptomyces parvallus), MS3/20 and MS1/7. The RDBR, operated at a rotational speed of one revolution per day, 50% submergence of discs, aeration rate of 1.0 vvm, and with a sucrose-containing medium, faithfully mimicked the intertidal estuarine habitat of these marine isolates, and supported biofilm formation and production of antimicrobial metabolites-in particular, actinomycin D by MS310. Onset of antibiotic production by MS310 occurs at 20 h in the RDBR compared to 55 h in a conventional stirred-tank bioreactor (STBR). Furthermore, peak antimicrobial activity is attained much earlier in the RDBR with MS310 (at 45 h) than that reported with a terrestrial strain of S. parvallus grown in a STBR (at 144 h). Peak antimicrobial activity of metabolites produced by MS1/7 and MS3/20 were also attained earlier in the RDBR (at 25 and 12 h, respectively) than in a STBR (at 80 and 28 h, respectively). Antibiotic synthesis in the three isolates, in general, appears to be associated with their growth. Overall, the RDBR may be considered the preferred alternative to the STBR for production of antimicrobials by biofilm-forming estuarine bacteria for its much higher surface/volume ratio, lower costs, and easy operability.

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