SummaryHDV infection still remains a serious public health problem in Amazonia. There are few data regarding the biomolecular aspects of HBV/HDV co‐infection in this region. We studied 92 patients HBsAg+/anti‐HDV IgG+ followed at the Hepatitis Referral Centers of Porto Velho (RO), Rio Branco and Cruzeiro do Sul (AC), Brazil, from March 2006 to March 2007 for whom the HDV and/or the HBV genotype could be determined. The HDV genotype could be determined in 90 patients, while the HBV genotypes could be positively determined in 74. HBV subgenotype F2 is the most prevalent (40.2%), followed by the subgenotypes A1 (15.2%) and D3 (8.7%), while 16.4% were other subgenotypes or genotypes, 4.3% were discordant and 15.2% were unamplifiable. Surprisingly, HDV genotype 3 (HDV‐3) was found in all of the HBV/HDV‐infected patients that could be genotyped for HDV, confirming that HDV‐3 can associate with non‐F HBV genotypes. However, a HDV‐3 mutant was found in 29.3% of patients and was more frequently associated with non‐F HBV genotypes (P < 0.001) than were nonmutant strains, suggesting that the mutation may facilitate association of HDV‐3 with non‐F HBV genotypes.

Summary. Hepatitis delta virus (HDV) coinfection or superinfection in hepatitis B virus (HBV)‐infected patients results in a more aggressive liver disease, with more often fulminant forms and more rapid progression to cirrhosis and hepatocellular carcinoma. The mechanism(s) for this pejorative evolution remains unclear. To explore a specific HDV pathogenesis, we used a model of transient transfection of plasmids expressing the small (sHDAg or p24) or the large (LHDAg or p27) delta antigen in hepatocyte cell lines. We found that the production of reactive oxygen species was significantly higher in cells expressing p27. Consequently, p27 activated the signal transducer and activator of transcription‐3 (STAT‐3) and the nuclear factor kappa B (NF‐κB) via the oxidative stress pathway. Moreover in the presence of antioxidants (PDTC, NAC) or calcium inhibitors (TMB‐8, BAPTA‐AM, Ruthenium Red), p27‐induced activation of STAT‐3 and NF‐κB was dramatically reduced. Similarly, using a mutated form of p27, where the cysteine 211‐isoprenylation residue was replaced by a serine, a significant reduction of STAT‐3 and NF‐κB activation was seen, suggesting the involvement of isoprenylation in this process. Additionally, we show that p27 is able to induce oxidative stress through activation of NADPH oxidase‐4. These results provide insight into the mechanisms by which p27 can alter intracellular events relevant to HDV‐related liver pathogenesis.

Genome diversity is a hallmark of hepatitis B virus (HBV), which allowed its classification into 10 genotypes (A-J) and numerous subgenotypes. Among them, Genotype D is currently segregated into eight subgenotypes (D1-D8). Here, we report the identification and characterization of a novel subgenotype within genotype D of HBV from chronic hepatitis B e antigen (HBeAg)-negative patients of Eastern India. Phylogenetic tree analysis based on complete genome sequences revealed that six of 39 HBV/D isolates formed a distinct cluster supported by high bootstrap value and had nucleotide divergence >4% relative to the known D subgenotypes (D1-D8), justifying their assignment into a new subgenotype (D9). By comparing the amino acid sequences of the four ORFs of HBV/D9 with D1-D8, 36 specific residues, including a unique one (E(112) in the core region), were identified that could be considered as a signature of D9. Further analysis by Simplot, BootScan and jpHMM demonstrated that D9 resulted from a discrete recombination with genotype C over the precore-core region. This type of recombination has not been described previously as all C/D recombinants reported so far possessed genotype C backbones with mosaic fragments derived from HBV/D. Interestingly, compared to other subgenotypes of HBV/D, D9 isolates had a higher frequency of mutations (A1762T and G1764A) in the basal core promoter region that had been implicated in the development of hepatocellular carcinoma. Further investigations are needed to determine the overall prevalence and clinical significance of these newly characterized D9 strains and to assess the impact of inter-genotypic recombination on viral properties.

During the next few decades, vaccination against hepatitis B virus (HBV) will dramatically change the epidemiological profile of this worldwide infection especially when Heath Policies encourage including HBV vaccination program for the newborns. However, it is still estimated that more than 2000millions living people have met HBV. Symptomatic hepatitis with jaundice is less frequent than asymptomatic infection; however, as much as 350millions of individuals remain chronically infected by HBV. In these cases, the need for efficient antiviral therapy remains clear when a viral replication is observed to control the risk of progression and the need for liver transplantation, which represents the only end-stage treatment. Indeed, patients having chronic hepatitis B (CHB) can now be successfully treated using nucleos(t)ide analogs (NA) or pegylated interferon (PEG-IFN). Therefore, beside vaccination, prevention of the progression of the disease to cirrhosis and liver decompensation, leading to end-stage liver disease and/or to hepatocellular carcinoma, by inhibiting viral replication seems to represent the best approach to improve survival. At last but not least, co-morbidities and other viral infections, leading also to chronic liver cirrhosis or liver inflammation such as the specific satellite delta virus (HDV), human immunodeficency virus (HIV) and/or hepatitis C (HCV) virus, are able to accelerate the progression and have to be taken in account. Interestingly, in treated infection, the dogma of the irreversibility of the liver fibrosis, when the cirrhosis is constituted, is tumbling down. In this review, we will focus on the clinical, virological and therapeutic aspects of hepatitis B infection in order to expose the proposals to follow-up and treat HBV-infected patients and the prevention of drug-resistant HBV mutants that frequently arise, leading to treatment failure and progression to liver disease.

NEW COMPOUNDS, RESISTANCE) S253prothrombin time activity (PTA), the extent of hepatic encephalopathy (HE), and blood urine nitro (BUN), serum potassium (SK), and total white blood cell (WBC) are the main factors.The efficient to predict the probability of dying of main factors were assorted as follows: PTA > HE > BUN > TB > SK > WBC.The best COX model was expressed as h(30) = 0.0418E (0.7184HE + 0.0029TB + 0.1038BUN + 1.2453K + 0.0599WBC -0.0901PTA) (excluding serum potassium, the value of all factors in the equation were measuring value; SK is 1 when serum potassium is normal or higher than normal, SK is 0 when serum potassium is lower than normal).The predict value of PI is 3.17 and can be used as multivariate severity index.When a patient with PI higher than 3.17, his possibility of dying in one month is 99.05%.When analysis PI with survival time and live state by partial correlate analysis, the partial correlation coefficient were 0.88.When our patients were divided by PI into three groups, the survive rate of our patients is 93.33%, 66.67%, and 32.26% as the PI is less than 1.8, 1.8-3.65,and higher than 3.65. Conclusions:The multivariate severity index here with these main factors are useful to divide the different extent liver damage, predict the prognosis and to choice the best management measure in chronic liver failure patients.

Background We previously reported high prevalence of hepatitis C virus genotype 5a (HCV 5) (14%) in Central France.Aim To identify the risk factors associated with HCV5 infection and to characterize local HCV5 lineages.Method A case-control study and phylogenetic analysis were conducted.Results In all, 131 HCV5 and 343 HCV non 5 infected patients were enrolled. No HCV5 patient was born in sub-Saharan Africa and only two were injection drug user. HCV5 contamination was associated with living in a rural area called Vic le Comte (VLC) in non-transfused patients (OR = 17.7), with transfusion in patients living outside VLC (OR = 3.8) and with receiving injections in patients from VLC (OR = 3.1). More than 80% of the patients from outside VLC were contaminated by transfusion and those from VLC mainly by an iatrogenic factor - injections performed before 1972 by the local physician. Phylogenetic analysis of HCV5 isolates evidenced no distinct genetic cluster, but close relationships between the isolates of spouse pairs and between blood donors and recipients.Conclusions Our results suggest that HCV5 spread in our district by iatrogenic route before 1972 and then via transfusion to the whole district. Collaborative studies are underway to study viral sequences from different parts of Africa and Europe to estimate the origin of our HCV 5a strains.

Conclusion:We describe a new familial syndrome of noncirrhotic portal hypertension related to a congenital abnormal portal anatomy.This syndrome is charactenzed by noncirrhotic portal hypertension, absence of intrahepatic portal venules or fibrosis on liver biopsy, and abnormal extrahepatic portal venous anatomy on imaging Severe pulmonary hypertension may also be associated with this syndrome 16881