o Fabrizi

Hepatitis B virus infection and the dialysis patient.

Prevention of nosocomial transmission of hepatitis B virus (HBV) has been a signal achievement in the management of chronic kidney disease. The rate of serum hepatitis B surface antigen (HBsAg) seropositivity in patients on maintenance hemodialysis in the developed world is currently low (0–10%) but outbreaks of acute HBV infection continue to occur in this setting. The prevalence of HBV infection within dialysis units in developing countries appears higher (2–20%) based on relatively few reports. Although data are limited, HBV infection in dialysis population diminishes survival; HBV viral load in HBsAg‐positive dialysis patients is reportedly low and stable over time. Updated recommendations for the management of HBsAg chronic carriers on maintenance dialysis have been issued. No rigorously controlled treatment trials for treatment of hepatitis B with either interferon or lamivudine therapy in dialysis patients are currently available.

Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality?

Summary.u2002 Recent evidence has been accumulated showing that anti‐HCV‐positive serologic status is significantly associated with lower survival in dialysis populations, but the mechanisms underlying this negative relationship are still unclear. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus (HCV) infection on all‐cause and disease‐specific mortality of patients on regular dialysis. The relative risk of all‐cause, cardiovascular and liver disease‐related 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 effect pooled estimates for mortality with HCV across the published studies. We identified fourteen observational studies involving 145u2003608 unique patients on long‐term dialysis. Pooling of study results demonstrated that anti‐HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (all‐cause mortality) was 1.35 with a 95% confidence interval (CI) of 1.25–1.47. Stratified analysis showed that the adjusted RR for liver disease‐related death was 3.82 (95% CI, 1.92; 7.61); heterogeneity statistics, Riu2003=u20030.58 (P‐value by Q‐testu2003=u20030.087). The adjusted RR for cardiovascular mortality was 1.26 (95% CI, 1.10; 1.45); no heterogeneity was found (NS). This meta‐analysis of observational studies indicates that anti‐HCV‐positive patients on dialysis have an increased risk of either liver or cardiovascular disease‐related mortality compared with anti‐HCV‐negative patients. Further studies are in progress to understand better the link between HCV and cardiovascular risk among patients on maintenance dialysis.

Hepatitis C virus and kidney disease

Hepatitis C virus (HCV) infection remains frequent in patients on renal replacement therapy and has an adverse impact on survival in infected patients on chronic hemodialysis as well as renal transplant (RT) recipients. Nosocomial spread of HCV within dialysis units continues to occur. HCV is also implicated in the pathogenesis of renal dysfunction often mediated by cryoglobulins leading to chronic kidney disease as well as impairing renal allograft function. The role of antiviral therapy for hepatitis C in patients with renal failure remains unclear. Monotherapy with conventional interferon (IFN) for chronic hepatitis C is probably more effective in dialysis than in non-uraemic patients but tolerance is lower. Limited data only are available about monotherapy with pegylated interferon and combination therapy (pegylated IFN plus ribavirin) for chronic HCV in the dialysis population. Clinical experience with antiviral therapy for acute HCV in dialysis population is encouraging. Interferon remains contraindicated post-RT because of concerns about precipitating graft dysfunction. Sustained viral responses obtained by antiviral therapy in renal transplant candidates are durable after renal transplantation and may reduce HCV-related complications after RT (post-transplant diabetes mellitus, HCV-related glomerulonephritis, and chronic allograft nephropathy).

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.

Meta‐analysis of observational studies: hepatitis C and survival after renal transplant

Recent evidence has shown that anti‐HCV‐positive serologic status is significantly linked to lower patient and graft survival after renal transplant, but conflicting results have been given on this point. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on all‐cause mortality and graft loss after RT. The relative risk of all‐cause mortality and graft loss 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‐effect pooled estimates for mortality and graft loss with HCV across the published studies. We identified eighteen observational studies involving 133 530 unique renal transplant recipients. The summary estimate for adjusted relative risk (aRR) of all‐cause mortality was 1.85 with a 95% confidence interval (CI) of 1.49; 2.31 (P < 0.0001); heterogeneity statistics, Ri = 0.87 (P‐value by Q‐test = 0.001). The overall estimate for adjusted RR of all‐cause graft loss was 1.76 (95% CI, 1.46; 2.11) (P < 0.0001), heterogeneity statistics, Ri = 0.65 (P‐value by Q‐test = 0.001). Stratified analysis did not change meaningfully these results. Meta‐regression showed that living donor rate had a favourable influence on patient (P = 0.031) and graft survival (P = 0.01), whilst diabetes mellitus having a detrimental role on patient survival (P = 0.001). This meta‐analysis of observational studies supports the notion that HCV‐positive patients after RT have an increased risk of mortality and graft loss. Further studies are in progress to understand better the mechanisms underlying the relationship between HCV and mortality or graft dysfunction after renal transplant.

Combined antiviral therapy of hepatitis C virus in dialysis patients: meta‐analysis of clinical trials

Summary.u2002 The efficacy and safety of combined interferon (IFN) plus ribavirin in patients on long‐term dialysis and chronic hepatitis C remains unclear, although a number of small clinical trials have addressed this issue. We evaluated the efficacy and safety of combination antiviral therapy (conventional or pegylated interferon plus ribavirin) in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta‐analysis of clinical trials. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was drop‐out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 10 clinical studies (151 unique patients), one (10%) of which was a controlled clinical trial. Most (97.4%) patients were on long‐term haemodialysis. The summary estimate for SVR and drop‐out rate was 56% [95% Confidence Intervals (95% CI) 28–84] and 25% (95% CI, 10–40), respectively. The most frequent side effects requiring interruption of treatment were anaemia (26%) and heart failure (9%). These results occurred irrespective of type of interferon (conventional or peg‐IFN, peg‐IFNalfa‐2a or alfa‐2b), trial design (controlled or cohort study), or clinical characteristics of patients (naïve, nonresponders or relapsers). The studies were heterogeneous with regard to SVR and drop‐out rate. Combination antiviral therapy (interferon plus ribavirin) gives encouraging results in terms of efficacy and safety among dialysis patients even if the limited number of patients enrolled in our meta‐analysis hampers definitive conclusions.

Pegylated interferon monotherapy of chronic hepatitis C in dialysis patients: Meta-analysis of clinical trials

The efficacy and safety of pegylated interferon monotherapy in patients with chronic renal failure and chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue. A systematic review of the literature with a meta‐analysis of clinical trials was performed in order to assess efficacy and safety of initial pegylated interferon monotherapy in chronic renal failure patients with chronic hepatitis C. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop‐out rate (as a measure of tolerability). The random effects model of Der Simonian and Laird was used, with heterogeneity and sensitivity analyses. Sixteen clinical trials (254 unique patients) were identified, five (31%) being controlled studies; the majority (15/16u2009=u200994%) regarded patients on long‐term dialysis. The summary estimate for sustained virological response and drop‐out rate was 33% [95% Confidence Intervals (95%CI) 24–43] and 23% (95%CI, 14–33), respectively. The most frequent side‐effects requiring interruption of treatment were haematological (18%) and gastrointestinal (14%). In the group of controlled clinical trials, the summary estimate for sustained viral response and drop‐out rate was 38% (95% CI, 18–59), and 15% (95% CI, 3–26), respectively. The studies were heterogeneous with regard to sustained virological response and drop‐out rate. Pegylated IFN does not provide an added benefit in terms of virological response in comparison with standard IFN monotherapy. Tolerance to pegylated‐IFN monotherapy was unsatisfactory. Prospective trials are in progress to assess the optimal antiviral therapy for chronic hepatitis C in dialysis patients. J. Med. Virol.

Terlipressin for hepatorenal syndrome: a meta-analysis of randomized trials

Background Hepatorenal syndrome (HRS) is a severe complication of end-stage renal disease whose management still constitutes a big challenge. Various approaches have been used for hepatorenal syndrome treatment, including vasoconstrictor therapy. Terlipressin, a vasopressin analogue, has frequently been used. Aim To evaluate the efficacy and safety of terlipressin in patients with HRS by performing a systematic review with a meta-analysis of controlled, clinical trials. Methods Only prospective, placebo-controlled, randomized clinical trials (RCTs) were included. We used the random effects model of DerSimonian and Laird, with heterogeneity and subgroups analyses. The primary end-point of interest was the HRS reversal after terlipressin (or placebo) therapy in study patients vs. control patients (as a measure of efficacy). The secondary outcome was the rate of ischemic side-effects in study patients vs. placebo patients (as a measure of tolerability). The additional end-point was the impact of terlipressin on survival in the HRS population. Results We identified five studies involving 243 unique patients with HRS. Pooling of study results showed a significant increase in HRS reversal among study (terlipressin) versus control (placebo) patients; the pooled odd ratio (OR) of HRS reversal was 8.09; 95% CI, 3.521; 18.59; p=0.0001. The p-value was 0.5 for our test of study heterogeneity. In a subgroup analysis excluding case-control trials these results did not change. The rate of severe ischemic events was higher in study than control patients, pooled OR=2.907; 95% CI, 1.094; 7.723 (p=0.032). The test for heterogeneity was not significant. Terlipressin use had no significant impact upon survival (pooled OR for survival rate, 2.064; 95% CI, 0.939; 4.538; p=0.07). No significant heterogeneity (NS) was found. Conclusions Our meta-analysis shows that terlipressin has higher efficacy than placebo in reversing renal function in the HRS population. There was no apparent impact of terlipressin therapy on survival in HRS patients but further large-size trials are needed. Terlipressin use in the HRS population requires careful selection of patients and close clinical surveillance. These results support the use of terlipressin for reversal of renal function in the HRS population.

Antiviral therapy (pegylated interferon and ribavirin) of hepatitis C in dialysis patients: meta‐analysis of clinical studies

Information on the antiviral treatment (pegylated interferon plus ribavirin) of chronic infection by hepatitis C virus (HCV) in patients on long‐term dialysis is extremely limited. We evaluated the efficacy and safety of combination antiviral therapy (pegylated interferon plus ribavirin) in patients on long‐term dialysis with chronic hepatitis C by performing a systematic review of the literature with a meta‐analysis of clinical studies. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random‐effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eleven clinical studies (287 unique patients), two of them being controlled clinical trials. The summary estimate for SVR and dropout rate was 0.60 (95% Confidence Intervals, 0.47; 0.71) and 0.18 (95% CI, 0.08; 0.35), respectively; studies being heterogeneous with regard to both the outcomes. Stratified analysis reported a higher SVR rate in controlled trials, 0.86 (95% CI, 0.27; 0.99). The most common sources of dropout were anaemia (11/46 = 23%) and infections (6/46 = 13%). Meta‐regression analysis showed a detrimental impact of HCV genotype 1 (P = 0.036) and dropout (P = 0.0001) rate upon the frequency of SVR. Antiviral therapy based on pegylated interferon plus ribavirin for HCV gives encouraging results in terms of efficacy and safety among patients on long‐term dialysis; such approach should be considered the current standard of care for HCV‐infected individuals on regular dialysis.