Vivek Dixit

Hepatitis C virus antibody status and survival after renal transplantation: Meta-analysis of observational studies

The natural history of hepatitis C virus (HCV) among patients after renal transplantation (RT) remains incompletely defined. We conducted a systematic review of the published medical literature on the impact of hepatitis C antibody status on survival of patients who received RT. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk (RR) for mortality and graft loss with HCV seropositivity across the published studies.

Post-transplant diabetes mellitus and HCV seropositive status after renal transplantation: Meta-analysis of clinical studies

Hepatitis C virus (HCV) infection has a detrimental role on patient and graft survival after renal transplantation (RT). Some studies have also implicated HCV in the development of post‐transplant diabetes mellitus (PTDM). We conducted a systematic review of the published medical literature of the relationship between anti‐HCV seropositive status and DM after RT. The risk of DM occurrence in anti‐HCV‐positive and ‐negative patients after RT was regarded as the most reliable outcome end‐point. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the Odds Ratio (OD) of new onset DM in HCV‐positive and ‐negative patients after kidney transplantation. Ten studies involving 2502 unique RT recipients were identified. The incidence of PTDM after RT ranged between 7.9% and 50%. The summary estimate for adjusted OR was 3.97 with a 95% confidence interval (CI) of 1.83–8.61 (p‐value for homogeneity <0.0473). Thus, pooling of study results demonstrated the presence of a significant link between anti‐HCV seropositive status and DM after RT. This relationship provides one potential explanation for the adverse effects of HCV on patient and graft survival after RT.

The impact of hepatitis C virus infection on survival in dialysis patients: meta‐analysis of observational studies

Summary.  The impact of hepatitis C virus (HCV) infection on mortality of patients receiving regular dialysis remains unclear. The assessment of the natural history of HCV in dialysis population is difficult because of the low progression of HCV‐related liver disease over time and the reduced life expectancy in patients with end‐stage renal disease. The aim of the study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on the survival of patients undergoing maintenance dialysis. The relative risk of mortality was regarded as the most reliable outcome end‐point. Study‐specific relative risks were weighted by the inverse of their variance to obtain fixed‐ and random‐effects pooled estimates for mortality with HCV across the published studies. We identified seven studies involving 11 589 unique patients on maintenance dialysis; two (29%) were case–control studies. Pooling of study results demonstrated that presence of anti‐HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (aRR) (all‐cause mortality) was 1.34 with a 95% confidence interval (CI) of 1.13–1.59. Heterogeneity statistics, Ri = 0.48 (P‐value by Q‐test = 0.13). In a sensitivity analysis including only (n = 5) cohort studies, the pooled aRR was 1.38 (95% CI, 1.20–1.59); heterogeneity statistics Ri = 0.46. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among anti‐HCV‐positive than ‐negative dialysis patients. Our meta‐analysis indicates that anti‐HCV‐positive patients on dialysis have an increased risk of mortality compared with HCV‐negative patients. The excess risk of death in HCV‐positive patients may be at least partially attributed to chronic liver disease with its attendant complications.

Meta‐analysis: interferon for the treatment of chronic hepatitis C in dialysis patients

Background : The efficacy of interferon monotherapy in dialysis patients with chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue.

Meta-analysis: Effect of hepatitis C virus infection on mortality in dialysis.

Background : The natural history of hepatitis C virus infection among patients on long‐term dialysis treatment remains incompletely understood. Efforts to elucidate the natural history of hepatitis C virus in this population are difficult because of the slowly progressive nature of hepatitis C virus with often an unrecognized onset in patients whose life‐expectancy is substantially diminished by end‐stage renal disease.

HBsAg Seropositive Status and Survival After Renal Transplantation: Meta‐Analysis of Observational Studies

The natural history of hepatitis B virus (HBV) infection after renal transplantation (RT) remains unclear. We conducted a systematic review of the published medical literature on the impact of HBV surface antigen (HBsAg) seropositivity on survival of RT recipients. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for mortality and graft loss in HBsAg positive RT recipients across the published studies. We identified six observational studies (6050 unique patients); all of them being cohort, retrospective studies. Pooling of study results demonstrated that HBsAg in serum was an independent and significant risk factor for death after RT; the summary estimate for relative risk was 2.49 with a 95% confidence interval (95% CI) of 1.64–3.78. A test for homogeneity of the relative risk across the studies gave a p‐value of <0.0001. HBsAg seropositivity was an independent and significant risk factor for graft failure after RT; the summary estimate was 1.44 with a 95% CI of 1.02–2.04 (homogeneity test, p <0.0001). This meta‐analysis shows that HBsAg positive RT recipients have an increased risk for mortality and graft failure compared to seronegative patients.

Histopathological Features Of Hepatitis C In Renal Transplant Candidates1

BACKGROUND Although hepatitis C virus (HCV) infection is common in renal transplant candidates, its clinical significance remains unclear in this population. Little detailed information is available about the histological severity of HCV infection in these patients. We evaluated the liver biopsy features of chronic HCV in a large population of renal transplant candidates and investigated associations between histopathological changes and host- and virus-related factors. METHODS Thirty-seven patients seropositive for anti-HCV with chronic renal failure (CRF) referred to UCLA Medical Center for kidney or kidney/liver transplantation during the period 1992-1997 were included. HCV genotype and viral load were measured. A multivariate analysis by logistic regression model was performed: age, gender, race, HCV load and genotype, CRF level, aspartate and alanine aminotransferase activity, duration of HCV infection, underlying nephropathy, and alcohol abuse were independent variables; liver histology score was assumed a dependent variable. RESULTS Liver disease was present in all HCV-infected patients. Logistic regression analysis revealed that histological damage was (P = 0.0017) independently associated with the CRF level; the severity of liver disease, as shown by univariate analysis, being significantly higher in CRF patients not requiring dialysis than among dialysis population. All patients on dialysis showed mild or moderate necroinflammatory activity; the majority (22/28 = 79%) of these individuals had fibrosis, three (3/28 = 11%) dialysis patients had established cirrhosis. Thirty-one (84%) of 37 patients were tested by polymerase chain reaction, 25 (81%) patients had detectable HCV RNA in serum, the mean HCV load among viremic patients was 10.9x10(5) copies/ ml. The most frequent HCV genotypes were la (8/24 = 33%) and 1b (7/24 = 29%), followed by genotype 2b (3/24 = 12%). CONCLUSIONS Pathological changes on liver biopsy were observed in all HCV-infected patients awaiting renal transplantation. The severity of histologic damage observed on liver biopsy was less in dialysis than predialysis CRF patients. All dialysis patients had mild or moderate necroinflammatory activity; fibrosis was frequent with 11% of them having cirrhosis. The HCV viral load was rather low; no relationship between liver histology changes and virological features of HCV or aminotransferase activity was apparent. Further studies with repeat liver biopsies after kidney transplantation to observe the evolution of HCV-related liver disease after immunosuppressive therapy are indicated. We suggest including liver biopsy in the evaluation of the HCV-infected renal transplant candidate.

Meta‐analysis: terlipressin therapy for the hepatorenal syndrome

The hepatorenal syndrome is a severe and well‐known complication of end‐stage liver disease, but its management is controversial. Recent reports have shown the efficacy of terlipressin therapy, a vasopressin analogue, in hepatorenal syndrome patients.

Meta-analysis: anti-viral therapy of hepatitis C virus-related liver disease in renal transplant patients

The efficacy and safety of interferon‐based therapy in renal transplant recipients with hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue.

Cryopreserved microencapsulated hepatocytes--transplantation studies in Gunn rats.

Hepatocyte transplantation has been shown to provide significant metabolic support in several animal models of liver diseases. However, for it to be a viable alternative for supplementation of liver function in disease, large quantities of isolated hepatocytes would be necessary. At the present time there are no inexpensive routine methods for cryopreservation of hepatocytes. Existing procedures are cumbersome and require expensive programmable freezers. Hepatocyte cultures are sensitive and easily damaged in handling. By utilizing techniques of microencapsulation and cryopreservation we have attempted to overcome these problems. We have developed a simple, convenient, and inexpensive technique for the long-term storage of hepatocytes. Biological activity of the nonfrozen isolated encapsulated hepatocytes (IEH) and cryopreserved IEH (cIEH) was assessed both in tissue culture and by transplantation in Gunn rats. Significant urea and protein syntheses were detectable during the 10-day culture period even in the 30-day cIEH. Additionally, transplanted IEH and cIEH significantly reduced hyperbilirubinemia in Gunn rats for up to 30 days posttransplantation. Control (empty) microcapsules did not lower serum bilirubin levels. Thus we conclude: (1) cryopreservation of IEH is a convenient and cost-effective method for preserving and storing hepatocytes; (2) cryopreserved IEH function as well as nonfrozen IEH both in vitro and in vivo; (3) microencapsulation may protect hepatocytes from the adverse effects of cryopreservation.