Hepatitis Status and Mortality in Hemodialysis Population

The role of hepatitis B (HBV) and C (HCV) virus infection in mortality among MHD patients is poorly understood. Recent studies have shown that HCV positivity is associated with significantly higher cardiovascular mortality, especially in dialysis patients younger than 65 years. However, little information is available in European renal registries about mortality among HBV and HCV positive MHD patients. We prospectively followed all patients (prevalents and incidents) attending the dialysis center in the Sicilian region since January 1, 1999, up to December 31, 2000. Those who died for any cause after the starting point were identified and included in the cases population. In all, 698 eligible cases were found. For each case, three controls extracted from the Registry were matched by age at death (within five years) and sex. We calculated the sample size of 698 cases and three controls for each case, assuming the power of the study to be 80%, with an estimated prevalence of exposure among controls of 3.0%. The χ² and the t-test were used to evaluate possible differences among cases and controls for the different variables under investigation. The ORs of the association between hepatitis infection and mortality, adjusted for each of the possible confounding factors, was calculated using the Mantel-Haenszel test. The prevalence of Hepatitis C (HCV) was much higher among case compared with controls, both in males (23.4%?vs. 17.7?%) and females (25.0%?vs. 22.4%). In the multivariate model, the association between HCV and mortality maintained a significant association only among women aged?<65 years with an OR of 1.77 (95%?CI: 1.12–2.79). We also observed a correlation between increased risk of mortality in hemodialysis and HCV-positive patients with a longer time on dialysis. Our results suggest that HCV positivity among MHD patients is associated with significantly higher mortality in female aged?<65 years. For this reason we should be more aggressive in identifying, preventing, and treating HCV infection among patients with end stage renal disease.     

Hepatitis C virus and liver transplantation: where do we stand?

The hepatitis C virus (HCV) infects more than 180 million people globally, with increasing incidence, especially in developing countries. HCV infection frequently progresses to liver cirrhosis leading to liver transplantation or death, and HCV recurrence still constitutes a major challenge for the transplant team. Antiviral therapy is the only available instrument to slow down this process, although its actual impact on liver histology, in responders and nonresponders, is still controversial. We are now facing a “new era” of direct antiviral agents that is already changing the approach to HCV burden both in the pre‐ and in the post‐liver transplantation settings. Available data on sofosbuvir/ledipasvir and sofosbuvir/simeprevir in patients with decompensated cirrhosis sustain a SVR12 of 89% 1 , but one‐third of patients do not clinically improved. The sofosbuvir/ribavirin treatment in stable cirrhotic patients with HCC before liver transplantation is associated with 2% recurrence rate if liver transplantation is performed at least one month after undetectable HCV‐RNA is achieved. The treatment of recurrence with the new antiviral drugs is associated with a SVR that ranges between 60 and 90%. In this review, we have focused on the evolution of antiviral therapy for HCV recurrence from the “old” interferon‐based therapy to the “new” interferon‐free regimens, highlighting useful information to aid the transplant hepatologist in the clinical practice.     

Monitoring HCV RNA viral load by locked nucleic acid molecular beacons real time PCR

Locked nucleic acids (LNA) based real time PCR was used in particular situations where there are difficulties in primer design due to sequence complexity. In this study a new real time RT-PCR assay was developed using LNA modified primers and LNA molecular beacon probes to monitor hepatitis C virus (HCV) viral load in plasma and serum samples. The technique did not suffer from an heterogeneity of the HCV genome and, in addition, an internal RNA control was amplified in the same reaction tube with different short primers and beacon probe. Due to the short consensus LNA primers length, the PCR efficiency was close to 100% with no formation of hairpin loop structures. In summary a new LNA molecular beacon based real time RT-PCR assay was used successfully to measure quantitatively the total level of HCV RNA in both experimental and clinical specimens. The high sensitivity (50 IU/ml), the wide range of genotype detection, increased specificity and robustness obtained with this test are particularly useful for screening large number of specimens and measuring viral loads to monitor the progress of the disease.     

The effect of hepatitis C virus infection on insulin resistance in chronic haemodialysis patients

PURPOSE: To investigate the contribution of HCV infection to insulin resistance in chronic haemodialysis patients. MATERIALS AND METHODS: The study was performed with 55 patients who were on regular haemodialysis therapy three times per week. Of the 55 patients, 34 (20 females and 14 males with an average age of 40.9 years) were anti-HCV (+) and were defined as the HCV (+) group. The remaining 21 patients (8 females and 11 males with an average age of 50 years) were negative for HCV and other viral markers and were defined as the HCV (-) group. BMI of all patients were below 27. Insulin resistance (IR) was calculated according to the HOMA formula and patients were called HOMA-IR (+) if their HOMA scores were higher than 2.5. All of the HOMA-IR (+) patients in both groups were called the HOMA-IR (+) subgroup. None of the patients had a history of drug use or any diseases that were related to insulin resistance except uremia. In both groups and the healthy control group, insulin and glucose levels were studied at three different venous serum samples taken at 5- minute intervals after 12 hours of fasting. Other individual variables were studied at venous serum samples taken after 12 hours of fasting. RESULTS: HOMA scores were (3)2.5 in 22 of 34 HCV (+) patients (64.7%) and 7 of 21HCV (-) patients (33.33%) (p=0.024). Insulin levels of HCV (+) group (13.32 +/- 9.44mIU/mL) were significantly higher than HCV (-) (9.07 +/- 7.39mIU/mL) and the control groups (6.40 +/- 4.94mIU/ mL) (p=0.039 and p=0.021 respectively). HCV (+) patients were younger (40.94 +/- 17.06 and 52.62 +/- 20.64 years, respectively) and had longer dialysis duration (7.18 +/- 3.61 and 2.91 +/- 2.69 years, respectively). Significant positive correlations of HOMA score with insulin (r=0.934, p=0.000) and fasting glucose levels (r=0.379, p=0.043) were found in the HOMA- IR (+) subgroup. Also, a significant positive correlation was found between ALT and insulin levels in the HOMA IR (+) subgroup. C-peptide levels of both HCV (+) and (-) groups were significantly higher than the control group (p < 0.001). There were not any significant correlations between HOMA score and some of the other individual variables including levels of triglyceride, ferritin, ALT, iPTH and Mg in any of the groups. CONCLUSION: In chronic haemodialysis patients; HCV infection is related to a high prevalence of insulin resistance, higher insulin and glucose levels.     

Interaction of antivirals with a heptameric bundle model of the p7 protein of hepatitis C virus

A series of ligands are known experimentally to affect the infectivity cycle of the hepatitis C virus. The target protein for the ligands is proposed to be p7, a 63 amino acid polytopic channel‐forming protein, with possibly two transmembrane domains. Protein p7 is found to assemble into functional oligomers of various sizes, depending on the genotype (GT). Nine ligands are docked to various sites of a computationally derived heptameric bundle of p7 of GT1a. The energy of interaction, here binding energy, is calculated using three different docking programs (Autodock , MOE , LeadIT ). Three protein regions are defined to which the ligands are placed, the loop region and the site with the termini as well as the mid‐region which is supposed to track poses inside the putative pore. A common feature is that the loop sites and poses either within the pore or at the intermonomer space of the bundle are preferred for all ligands with proposed binding energies smaller than −10 kJ/mol. BIT225, benzamine, amantadine, and NN‐DNJ show good overall scoring.