Treatment of chronic hepatitis C in hemodialysis patients

Hepatitis C virus (HCV) infection is especially problematic in patients with end-stage renal disease (ESRD) who are undergoing hemodialysis. Rates of HCV infection are higher among hemodialysis patients than in the general population, and several routes of transmission are thought to stem from the dialysis unit. Management of chronic hepatitis C is also more complicated in hemodialysis patients because of altered pharmacokinetics and a predisposition for drug-related toxicity, particularly ribavirin-induced anemia. Clinical trials of patients with chronic hepatitis C and healthy, functioning kidney grafts are rare because of the inherent dangers of graft rejection. As a result, most studies in patients with ESRD have focused on patients waiting for a kidney transplant. Additionally, because ribavirin is contraindicated in this patient population, many studies have examined monotherapy treatments. According to meta-analyses, conventional interferon alfa treatment yields a sustained virological response (SVR) rate of 37%, whereas studies of pegylated interferon alfa monotherapy have yielded SVR rates between 13% and 75%. Several small studies have also used the monitoring of ribavirin plasma concentrations or hemoglobin levels to facilitate the use of combination therapy. In light of the results from these clinical trials, we herein review treatment guidelines and recommend strategies to help optimize the treatment of patients with ESRD. CONCLUSION: There remains a lack of clarity surrounding the most effective treatment options for patients with chronic hepatitis C and ESRD. Treatment can be effective with many patients attaining SVR; however, unfavorable tolerability with interferon alfa-based therapy remains a concern and thus close supportive care should be aggressively pursued to help maintain adherence.     

Management of Hepatitis C in Patients with Chronic Kidney Disease

Chronic kidney disease represents a global health problem. Chronic hepatitis C virus (HCV) infection is prevalent in patients with end stage renal disease (ESRD) on hemodialysis (HD) and in renal transplant recipients with significant impact on morbidity and mortality. Furthermore, HCV can cause various forms of glomerulopathy with the predominant type being cryglobulinemia associated membranoproliferative glomerulonephritis. Liver enzymes are traditionally used as markers of liver injury; however, there is wide variation in aminotransferase levels in patients with ESRD. Therefore, diagnosis of chronic hepatitis C (CHC) in patients with ESRD is based on HCV antibody testing and further confirmation with polymerase chain reaction testing. Current standard therapy for CHC is composed of pegylated interferon and ribavirin. However, this combination is challenging in patients with ESRD due to its tolerability. We describe in this review relevant issues in epidemiology, diagnosis and management of CHC in ESRD, HD and renal transplant recipients.     

Interferon-<Emphasis Type="Italic">α</Emphasis> therapy for chronic hepatitis C in special patient populations

Interferon-α therapy for chronic hepatitis C in special patient populations raises a number of issues. Patients with hemophilia, kidney disease requiring hemodialysis, mixed cryoglobulinemia, HIV infection, and those receiving an allograft share some characteristics that complicate the treatment of hepatitis C virus infections. These patients generally have some degree of immune deficiency, higher levels of hepatitis C virus replication, and are infected with genotypes 1a or 1b. Each of these characteristics is often associated with a poor response to interferon therapy. Clinical research in this area also has been limited. Current data and clinical experience demonstrate that interferon-α therapy should be considered in patients with hemophilia who have concurrent hepatitis C viral infection. Other hepatitis C virus-infected patient populations in which interferon-α therapy may be beneficial include those undergoing hemodialysis, mixed cryoglobulinemia, or HIV infection. Further, the high incidence of relapse following treatment cessation in these patients warrants prolonged administration of interferon-α. Patients undergoing renal or hepatic allograft transplantation who develop hepatitis C virus infections are not as likely to benefit from interferon-α therapy. These patients may be at risk for allograft rejection during interferon treatment.     

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).     

Hepatitis C virus infection in patients on renal replacement therapy

Hepatitis C virus infection is a frequent clinical problem in patients on dialysis and renal transplant recipients. The local prevalence rates of hepatitis C virus infection in patients on peritoneal dialysis, hemodialysis, or after kidney transplantation are 2%, 9%, and 6%, respectively. Conventional diagnosis of hepatitis C virus infection is by anti-hepatitis C virus immunoassays. However, up to 10% of immunosuppressed patients may be negative for anti-hepatitis C virus but positive for hepatitis C virus RNA. Repeated blood transfusions and a long duration of dialysis are major risk factors for hepatitis C virus infection among patients with renal failure. Although the risk of acquiring hepatitis C virus infection through transfusions has decreased considerably with the advent of screening tests for anti-hepatitis C virus, precautionary measures should be instituted rigorously at renal units to prevent nosocomial transmission. Hepatitis C virus infection in dialysis patients often assumes a relatively mild course. In contrast, renal allograft recipients can develop potentially life-threatening exacerbations, as exemplified by fibrosing cholestatic hepatitis. Liver disease of variable severity can be observed in about two thirds of hepatitis C virus-positive renal allograft recipients. In the majority of patients, however, the adverse effect of hepatitis C virus infection on survival may not be evident in the first decade after renal transplantation. Hepatitis C virus-positive patients with renal failure should not be excluded from kidney transplantation, but should be assessed individually with regard to the severity of liver disease before transplantation. Dialysis patients with hepatitis C virus infection, especially those with a potential for kidney transplantation, should be considered for treatment with interferon, because the risk of interferon in inducing renal allograft dysfunction is too high to justify its routine use in renal allograft recipients.     

Management of Hepatitis C in Patients with End-stage Renal Disease

Hepatitis C virus infection is more prevalent in patients with chronic kidney disease on hemodialysis than in the general population. Moreover, chronic hepatitis C virus infection in hemodialysis patients and renal transplant recipients is associated with significant morbidity and even mortality, including de novo diabetes mellitus, sepsis, and glomerulonephritis posttransplantation. Strategies to treat patients on hemodialysis and in the post-renal transplant setting are limited by drug-related toxicity, particularly ribavirin-related anemia, and induction of graft rejection. However, in hemodialysis patients who are candidates for renal transplantation, treatment with interferon or pegylated-interferon results in better sustained virologic responses (SVR) than those achieved in the general population (3%–41% and 31%–37%, respectively). Moreover, SVR is maintained posttransplantation and is associated with superior graft function and prevention of de novo glomerulonephritis. Encouraging results with low doses of ribavirin have been reported in recent small studies, but monitoring of ribavirin plasma concentrations is recommended. In the kidney transplant recipient, treatment with interferon is precluded except for severe cholestatic disease.     

Kidney disease in patients with chronic hepatitis c

There is an increasing recognition of the association between chronic hepatitis C virus infection and glomerular diseases. Renal complications may be the presenting manifestation of hepatitis C virus infection. Patients may present with signs and symptoms of cryoglobulinemic systemic vasculitis, proteinuria, microscopic hematuria, acute renal failure, or nephrotic syndrome. The pathogenesis of hepatitis C virus associated with renal disease remains incompletely understood; however, deposition of circulating immune complexes in the subendothelial space and mesangium in the glomeruli seems to play a major role. The most common renal pathology associated with hepatitis C virus infection is type I membranoproliferative glomerulonephritis with or without cryoglobulinemia. In patents who do not have significant renal impairment, combination therapy with interferon alfa (IFN-α) and ribavirin seems to be the treatment of choice, although the experience with this combination is quite limited in patients with renal involvement. A prolonged course of high-dose IFN-α has been most commonly used for these patients with significant success, but relapse of hepatitis C viremia and renal disease after discontinuation of therapy have frequently occurred.     

Mutagenic effect of ribavirin on hepatitis C nonstructural 5B quasispecies in vitro and during antiviral therapy

BACKGROUND AND AIMS: Addition of ribavirin to interferon alfa treatment has substantially increased sustained virologic response rates in patients with chronic hepatitis C (CHC). Ribavirin acts as an RNA virus mutagen in vitro, thereby leading to error catastrophe. However, data in CHC are controversial. METHODS: The nonstructural (NS) 5B quasi-species heterogeneity was analyzed in Huh7 cells harboring a subgenomic hepatitis C virus (HCV) replicon system treated with ribavirin or levovirin. Accordingly, NS5B quasi-species were studied in 14 patients with CHC who received ribavirin alone or combined with pegylated interferon alfa both at baseline and during the first weeks of therapy. Analysis of NS3 quasi-species served as control. RESULTS: Cultivation of HCV replicon cells with ribavirin led to higher NS5B mutational frequencies compared with levovirin-treated or untreated cells (P < .05). Patients receiving ribavirin monotherapy showed higher overall mutational frequencies within NS3 and NS5B during therapy as compared with baseline (P < .01). Proportions of ribavirin-specific G-to-A and C-to-T transitions increased (P < .01). Paired analysis confirmed significant mean increases of mutational frequencies of approximately 5%. Ribavirin serum concentrations were positively correlated with mutational frequency changes (P < .05). In patients receiving combination therapy, a decrease of NS5B mutational frequencies ( approximately 10%) and lower proportions of G-to-A and T-to-C mutations (P < .01) were detectable. CONCLUSIONS: Ribavirin, but not its L-enantiomer levovirin, is a mutagen in HCV replicon cells. In patients with CHC, ribavirin monotherapy exhibits a moderate mutagenic effect early during therapy that is not detectable in combination with pegylated interferon alfa.     

Ribavirin in the treatment of chronic hepatitis C

Background and Aim:  Current practice guidelines recommend that individuals chronically infected with the hepatitis C virus (HCV) be treated with pegylated interferon plus ribavirin. Ribavirin, however, is associated with serious adverse events (AE), especially anemia. We review its mechanism of action, its importance in treating chronic hepatitis C (CHC) patients, the AE associated with its use, and techniques used to lessen these AE.
Methods:  Medline searches were performed using the keywords ribavirin and hepatitis, together with the keywords mechanism, anemia, liver transplant, renal function, pharmacokinetics, and dose reduction. Searches of abstracts of recent Digestive Diseases Week, American Association for the Study of Liver Diseases, and European Association for the Study of Liver Diseases meetings were also performed.
Results:  Ribavirin may be effective in treating CHC by affecting the virus or the host; for example by inducing viral mutations, blocking cellular enzymes, or affecting the host immune response. Although the pegylated interferons are the primary drugs used to treat CHC, a combination with ribavirin is more effective than pegylated interferon alone. Ribavirin-associated AE may be lessened by ribavirin dose reductions and by maintenance of the hematocrit.
Conclusions:  Treatments of ribavirin toxicities, especially anemia, can allow patients to continue full-dose combination therapy with peginterferon and ribavirin, enhancing their probability of attaining a sustained virologic response (SVR). Treatment of CHC should be tailored to individual patients, especially those with renal dysfunction, and should include agents that treat the side-effects of CHC treatment. Monitoring of plasma ribavirin concentrations during treatment may help in the future.     

Hepatitis C infection associated with renal disease and chronic renal failure

Screening of blood products and attention to stricter infection control measures in hemodialysis units have reduced the incidence of hepatitis C virus (HCV) infection among dialysis patients. HCV can be transmitted via transplanted organs. Renal transplantation may accelerate the course of liver disease, which has an impact on patient and graft survival. Interferon (IFN) alfa monotherapy has produced promising results during treatment but disappointing long-term results in patients with HCV-associated glomerulonephritis. Dialysis patients with HCV infection respond well to IFN-based therapy, and there appears to be clinical benefit in clearing HCV in renal transplantation candidates. Larger prospective trials are required to fully determine the role of IFN in these patient groups, including the potential use of IFN plus ribavirin and pegylated IFNs. IFN therapy in renal transplantation patients is not recommended because of potential graft rejection.     

Hepatitis B genotypes and the response to interferon therapy

BACKGROUND/AIMS: Possible pathogenic differences among hepatitis B virus (HBV) genotypes have been observed; however, the response to interferon therapy among HBV genotypes remains unknown. We therefore analyzed the efficacy of interferon alfa in the treatment of chronic hepatitis B patients with different HBV genotypes. METHODS: Fifty-eight genotype B or C infected chronic hepatitis B patients who had been treated with interferon alfa-2b were retrospectively studied. The response to interferon was defined as normalization of serum aminotransferase level, loss of hepatitis B e antigen and HBV DNA 48 weeks post-treatment. RESULTS: Baseline data of both groups of patients were comparable; however, genotype C patients had a higher serum aminotransferase level and a higher frequency of core promoter mutation. The response rate was 41% and 15% in genotype B and C patients, respectively (p=0.045). In those with higher serum aminotransferase levels, the response rate was 50% and 17%, respectively (p=0.025). Additionally, younger age and genotype B infection may predict a better response to interferon alfa. CONCLUSIONS: HBV genotype C, compared to genotype B, is associated with a higher frequency of core promoter mutation, and a lower response rate to interferon alfa therapy.     

Management of hepatitis C virus infection in hemodialysis patients

The prevalence of hepatitis C virus(HCV) infection in patients on maintenance hemodialysis(MHD) is relatively higher than those without MHD. Chronic HCV infection detrimentally affects the life quality and expectancy, leads to renal transplant rejection, and increases the mortality of MHD patients. With the application of erythropoietin to improve uremic anemia and avoid blood transfusion, the new HCV infections during MHD in recent years are mainly caused by the lack of stringent universal precautions. Strict implementation of universal precautions for HCV transmission has led to markedly decreased HCV infections in many hemodialysis units, but physicians still should be alert for the antiHCV negative HCV infection and occult HCV infection in MHD patients. Standard interferon alpha and pegylated interferon alpha monotherapies at a reduced dose arecurrently the main treatment strategies for MHD patients with active HCV replication, but how to increase the sustained virological response and decrease the side effects is the key problem. IFNα-free treatments with two or three direct-acting antivirals without ribavirin in MHD patients are waiting for future investigations.     

Clinical and laboratory characteristics of acute hepatitis C in patients with end-stage renal disease on hemodialysis

BACKGROUND: Patients with end-stage renal disease (ESRD) undergoing hemodialysis are a risk group for hepatitis C virus (HCV) infection. The characteristics of acute hepatitis C infection in this population are not well known. GOALS: To evaluate the clinical and laboratory characteristics of acute hepatitis C in ESRD patients treated with hemodialysis. STUDY: ESRD patients on hemodialysis with acute hepatitis C, characterized by elevated alanine aminotransferase (ALT) followed by anti-HCV seroconversion were studied. RESULTS: Thirty-six patients (58% females, 44+/-12 y), with a mean time on hemodialysis of 2 years, were included. Only 2 (6%) patients had jaundice. ALT elevation was observed in all patients. Median peak ALT was 4.7 x upper limit of normal. The median interval between ALT elevation and anti-HCV seroconversion was 1 month (0 to 8). None of the patients with detectable HCV-RNA showed spontaneous clearance of viremia within 12 weeks of follow-up. Three (8%) patients presented ALT elevation followed by anti-HCV seroconversion with undetectable HCV-RNA. CONCLUSIONS: Acute hepatitis C is frequently asymptomatic in ESRD patients on hemodialysis and should be suspected in all patients presenting elevated ALT. Determination of HCV-RNA is important for the confirmation of infection. Anti-HCV seroconversion seems to occur early and spontaneous clearance of HCV-RNA is uncommon.     

Long-term follow-up of a randomized trial of interferon therapy for chronic hepatitis B in a predominantly homosexual male population

BACKGROUND/AIMS: Extended follow-up of a previously published therapeutic trial with interferon alfa is now available to further clarify the long-term outcome of HIV-negative and HIV-positive subjects with chronic hepatitis B virus infection after interferon alfa therapy. METHODS: Forty-five subjects with compensated liver disease and chronic hepatitis B infection with evidence of active hepatitis B replication were studied. These subjects were enrolled between 1986 and 1991 and had been randomized, stratified by HIV status, to either receive interferon therapy (10 MU/m2 of lymphoblastoid interferon alfa 3 times per week for 12 weeks) or no treatment. Hepatitis B serology, serum hepatitis B viral DNA and alanine aminotransferase were measured on an annual to biannual basis. CD4-positive T lymphocyte counts and HIV RNA concentration were also obtained. RESULTS: From 9 months post-interferon alfa treatment to the end of the extended follow-up (4 to 9 years), the relative risk of seroconverting to anti-HBe positive for subjects who had received interferon alfa therapy compared to those who did not was not significant in either HIV-negative (p = 0.80) or HIV-positive (p = 0.62) subjects. CONCLUSIONS: Unlike the first 9 months following interferon alfa therapy, the rate of elimination of markers of hepatitis B virus replication, regardless of HIV status, was not increased above the natural rate beyond 9 months following interferon alfa therapy.     

Hepatitis C virus as a systemic disease: reaching beyond the liver

Chronic hepatitis C (CHC) is associated with multiple extrahepatic manifestations that may impact infected patients. The mechanisms through which these develop include those which are immunological, in which the chronic persistence of virus leads to the circulation of immune complexes (mixed cryoglobulinemia) and other autoimmune phenomena, and those which are virological and related to the extrahepatic tropism of the virus to other tissues. It is estimated that 40–74 % of patients with CHC may develop at least one extrahepatic manifestation during the course of the disease. Extrahepatic syndromes may represent the first signal of hepatitis C infection in some patients. CHC is associated with a four-fold increased risk of insulin resistance and type 2 diabetes mellitus; with cardiovascular disease in 17–37 % of patients; and with increased risk for cerebrovascular deaths, with a biological gradient of cerebrovascular mortality correlating with an increasing serum viral load. CHC is also associated with lymphoproliferative disorders, particularly non-Hodgkin B-cell lymphoma. The kidney is involved in 35–60 % of patients with CHC-associated mixed cryoglobulinemia. The prevalent type of glomerulonephritis associated with mixed cryoglobulinemia is membranoproliferative glomerulonephritis. In 30 % of cases, renal involvement begins with a nephritis syndrome and acute renal failure, while in 55 % there is only mild hematuria, microalbuminuria, proteinuria and renal insufficiency. CHC is also associated with cognitive impairment, especially in memory and concentration. Thus, extrahepatic CHC manifestations involve multiple organ systems outside the liver linked to a variety of comorbidities which may lead to significantly increased mortality from non-liver-related events.     

Distribution of HCV Genotypes in Patients with End-Stage Renal Disease According to Type of Dialysis Treatment

The objective of this study was to investigate the effects of types of dialysis treatments on hepatitis C virus infection and the epidemiologic properties of hepatitis C virus (HCV) infection at three Baskent University hospitals, in Ankara, Adana, and Izmir, Turkey, in 655, 326, and 118 patients with end-stage renal disease, respectively. One hundred thirty patients with HCV viremia among 271 patients with end-stage renal disease seropositive for HCV were included in this cross-sectional study. HCV RNA-positive patients were classified according to the renal replacement therapies (hemodialysis or continuous ambulatory peritoneal dialysis), and viral load, transaminase levels, and distribution of genotypes were compared between these subgroups. In the continuous ambulatory peritoneal dialysis group, 26 of 165 patients (16%) were serum anti-HCV positive, and 11 of 26 patients (42%) were serum HCV RNA positive. Twenty-six percent of the patients undergoing hemodialysis were anti-HCV positive, and 49% were HCV RNA positive. The prevalence of genotype 1b was 68% and 73% for patients in the continuous ambulatory peritoneal dialysis and hemodialysis groups, respectively. No significant differences were found between the genotype 1b and the non-1b groups or between different dialysis types with regard to age and sex and serum aspartate transaminase, alanine aminotransferase, and HCV RNA levels. We conclude that HCV seropositivity may differ between different types of dialysis treatments, although viral load and genotypes may be similar in persons with end-stage renal disease and those without.     

HCV in patients with end-stage renal disease

Chronic hepatitis C virus (HCV) infection remains an important cause of liver disease in patients with end-stage renal disease (ESRD) and conversely, renal failure has a significant impact on morbidity and mortality throughout the natural history of chronic HCV and its treatment. With improved awareness within dialysis units of the potential for spread and the institution of preventative measures, the prevalence of HCV infection in the hemodialysis-dependent population has continued to decline since 1995. Use of HCV (+) donor kidneys is associated with an increase in the prevalence of liver disease, but when compared with continued hemodialysis, transplantation using these kidneys is associated with improved survival. Overall, survival in patients with chronic HCV infection appears to be better after renal transplantation when compared with maintenance hemodialysis, and transplant should be considered for these patients. Data support the use of interferon and the improved efficacy of pegylated interferon formulations for treatment of chronic HCV infection in ESRD patients, although tolerability continues to be troublesome. The newest and most promising data regarding the treatment of HCV in ESRD involve the combination of reduced dose ribavirin with interferon or pegylated interferon suggesting similar enhancements in sustained virologic response (SVR) as seen in non-ESRD patients, but caution is advised, as all studies to date used ribavirin plasma concentration monitoring in patient with ESRD. Finally, with regard to postrenal transplant treatment of HCV infection, there is no evidence to support treatment with interferon-based therapy and pretransplant treatment remains the best option whenever possible.     

Treatment for hepatitis C virus in human immunodeficiency virus-infected patients: clinical benefits and cost-effectiveness

BACKGROUND: Hepatitis C virus (HCV) is an important cause of liver disease in human immunodeficiency virus (HIV)-infected patients. OBJECTIVE: To assess the cost-effectiveness of alternative management strategies for chronic HCV in co-infected patients with moderate hepatitis. METHODS: A state-transition model was used to simulate a cohort of HIV-infected patients with a mean CD4 cell count of 350 cells/ micro L and moderate chronic hepatitis C stratified by genotype. Strategies included interferon alfa (48 weeks), pegylated interferon alfa (48 weeks), interferon alfa and ribavirin (24 and 48 weeks), pegylated interferon alfa and ribavirin (48 weeks), and no treatment. Outcomes included life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. RESULTS: Treatment for moderate chronic HCV with combination therapy using an interferon-based regimen reduced the incidence of cirrhosis and provided gains in quality-adjusted life expectancy ranging from 6.2 to 13.9 months, depending on genotype. Regardless of genotype, the cost-effectiveness of interferon alfa and ribavirin for patients with moderate hepatitis was lower than $50 000 per QALY vs the next best strategy. With genotype 1, pegylated interferon alfa (vs interferon alfa) and ribavirin therapy provided an additional 1.6 quality-adjusted life-months for $40 000 per QALY. Because treatment is more effective with non-1 genotypes, pegylated interferon (vs interferon alfa) and ribavirin provided only 3 additional quality-adjusted life-months for $105 300 per QALY. For patients who were intolerant of ribavirin, monotherapy with pegylated interferon was always the most cost-effective option. CONCLUSIONS: Combination therapy for moderate hepatitis in coinfected patients will increase quality-adjusted life expectancy and have a cost-effectiveness ratio comparable to that of other well-accepted clinical interventions.     

Efficacy of longterm interferon treatment in chronic liver disease evaluated by sensitive polymerase chain reaction assay for hepatitis C virus RNA.

Effects of interferon treatment on hepatitis C virus were examined by investigating the presence of hepatitis C virus ribonucleic acid and anti-hepatitis C virus antibody in 70 patients with non-A, non-B chronic liver diseases. Twenty one patients were treated with three million units of interferon alfa 2a three times a week for 52 weeks, 24 patients were treated similarly for eight weeks, and 25 patients were given a placebo for eight weeks and served as control. Sixty six of 70 patients (94%) were positive for both hepatitis C virus RNA and second generation anti-hepatitis C virus antibody. Fourteen of 21 (67%) receiving the longterm treatment had a normalised alanine aminotransferase (ALT) activity, and in 12 of these hepatitis C virus ribonucleic acid became undetectable by the end of treatment and remained so during the three year follow up after the treatment. Anti-hepatitis C virus antibody determined by first generation assay became negative in one case at the end of the 52 week treatment, and in four cases at the end of the one year follow up. In contrast, only one of 24 (4%) who received the eight week treatment and only one of 25 (4%) who received the placebo had normalised ALT activities. Hepatitis C virus ribonucleic acid became negative in two patients undergoing short-term treatment and in none receiving the placebo. Thus, longterm interferon treatment seems effective in clearing hepatitis C virus from serum of patients with chronic liver disease.     

Hepatitis C and kidney disease:An overview and approach to management

Hepatitis C infection and chronic kidney disease are major health burden worldwide. Hepatitis C infection is associated with a wide range of extra-hepatic manifestations in various organs including the kidneys. A strong association between hepatitis C and chronickidney disease has come to light. Hemodialysis in supporting the end stage renal disease patients unfortunately carries a risk for hepatitis C infection. Despite much improvement in the care of this group of patients,the prevalence of hepatitis C infection in hemodialysis patients is still higher than the general population. Hepatitis C infection has a negative effect on the survival of hemodialysis and renal transplant patients. Treatment of hepatitis C in end stage renal disease patients using conventional or pegylated interferon with or without ribavirin remains a clinical challenge with low response rate,high dropout rate due to poor tolerability and many unmet needs. The approval of new direct acting antiviral agents for hepatitis C may dramatically change the treatment approach in hepatitis C infected patients with mild to moderate renal impairment. However it remains to be confirmed if the newer Hepatitis C therapies are safe in individuals with severe renal impairment. This review article discusses the relationship between hepatitis C and chronic kidney disease,describe the various types of renal diseases associated with hepatitis C and the newer as well as the existing treatments for hepatitis C in the context of this subpopulation of hepatitis C patients.