Liver steatosis is a main histopathological feature of Hepatitis C (HCV) infection because of genotype 3. Steatosis and/or mechanisms underlying steatogenesis can contribute to hepatocarcinogenesis. ...The aim of this retrospective study was to assess the impact of infection with HCV genotype 3 on hepatocellular carcinoma (HCC) occurrence in patients with ongoing HCV cirrhosis. Three hundred and fifty‐three consecutive patients (193 men, mean age 58 ± 13 years), with histologically proven HCV cirrhosis and persistent viral replication prospectively followed and screened for HCC between 1994 and 2007. Log‐rank test and Cox model were used to compare the actuarial incidence of HCC between genotype subgroups. The patients infected with a genotype 3 (n = 25) as compared with those infected with other genotypes (n = 328) had a lower prothrombin activity 78 (interquartile range 60–85) vs 84 (71–195) %, P = 0.03 and higher rate of alcohol abuse (48%vs 29%, P = 0.046). During a median follow‐up of 5.54 years 2.9–8.6, 11/25 patients (44%) and 87/328 patients (26%) with a genotype 3 and non‐3 genotype, respectively, develop a HCC. HCC incidences were significantly different among the genotype subgroups (P = 0.001). The 5‐year occurrence rate of HCC was 34% (95% CI, 1.3–6.3) and 17% (95% CI, 5.7–9.2) in genotype 3 and non‐3 genotype groups, respectively (P = 0.002). In multivariate analysis, infection with a genotype 3 was independently associated with an increased risk of HCC occurrence hazard ratio 3.54 (95% CI, 1.84–6.81), P = 0.0002, even after adjustment for prothrombin activity and alcohol abuse 3.58 (1.80–7.13); P = 0.003. For patients with HCV cirrhosis and ongoing infection, infection with genotype 3 is independently associated with an increased risk of HCC development.
A woman with controlled HIV infection developed in late August 2016 a pruritic rash with fever and conjunctival hyperaemia after a trip to the French Caribbean islands. On day 3 after symptom onset, ...Zika virus RNA was detected in plasma, urine and vaginal samples with respective viral loads of 3.8, 6.1 and 5.3 log copies/mL. Notably, we demonstrated the presence of infectious Zika virus particles in the vaginal samples by isolation in cell culture.
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.
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