New trend in treatment in patients with chronic hepatitis C

The combination of pegilált interferon plus ribavirin is significantly more effective than conventional interferon plus ribavirin, and is thus the current therapy of choice for patients with chronic hepatitis C. Forty-eight weeks of treatment with combination of pegilált interferon plus ribavirin has produced overall sustained virologic response 54-56% in patients with chronic hepatitis C. This article summarize the new therapy of chronic hepatitis C, the antiviral therapy of hepatitis C virus patients with normal aminotransferase levels, the therapy in patients with compensated cirrhosis and who were nonresponders to previous combination therapy, the effect of antiviral therapy on necroinflammation and fibrosis, and the favourable effect of haemopoetic growth factors on results of antiviral therapy. A substantial proportion of patients with chronic hepatitis C have persistently normal alanin-aminotransferase levels. Many studies have indeed provided evidence that although the majority of hepatitis C virus patients with normal alanin-aminotransferase may have active and progressive liver disease. Initiation of antiviral therapy might be decided mainly on the basis of histological findings. Extending the treatment duration from 48 to 72 weeks in patients with hepatitis C virus genotype 1 significantly reduces relapse rates and increases sustained virological rates. Induction phase with a higher dose of pegilált interferon may be of value in improving outcomes in patients with genotype 1 who were nonresponders to previous combination therapy. The combination of pegilált interferon and ribavirin was effective and well tolerated in patients with compensated cirrhosis. Interferon-based therapy may reduce hepatic inflammation in the absence of a sustained virologic response. This results suggest that interferon maintenance therapy may slow disease progression. The virologic response rates could be improved by utilizing haemopoetic growth factors, as opposed to reducing the ribavirin and interferon dose.     

Treatment of recurrent hepatitis C virus infection after liver transplantation

The main indication of liver transplantation is the final stage of liver cirrhosis developed in hepatitis C virus (HCV) infection. The recurrence of HCV infection after transplantation is a common situation. The recurrent hepatitis C is a progressive disease, in 20 percent of patients it produces liver cirrhosis without treatment beside immunosuppression within 5 years. The treatment of recurrent HCV infection is the most important factor of the survival in patients with transplantation. The authors review the factors influencing the progression of recurrent HCV infection on the basis of literary data and also on their observation. They discuss in details the effect of immunosuppressive treatment, the importance in the selection of corresponding immunosuppressive drugs. They review the main keypoints in the diagnosis of recurrent hepatitis C, underline the important role of liver biopsy carried out according to the protocol in the diagnosis, furthermore the hard consultation among pathologist, hepatologist and surgeon. They demonstrate the observations with the treatment of patients on the waiting list, the results in the early, preemptive treatment of recurrent chronic hepatitis, furthermore the treatment modalities and the results in patients with chronic hepatitis C histologically proved. The drug of choice of chronic hepatitis C after transplantation is the combined therapy with pegylated interferon and ribavirin. This therapy is able to assure virus-free stage in 20-50 percent of patients. In the virus-free patients the inflammatory activity in the liver significantly decreases, the histologic activity index improves. There are data showing the effect of treatment for inhibiting the fibrosis, but multicenter studies are necessary for the confirmation of these data. The advantage of early antiviral therapy without histologic alteration has not been confirmed by most of the trials. The anaemia and the neutropenia are frequent side effects in this patient group, that is why the applications of erythropoietin and granulocyte stimulating factor are recommended. Further trials and clinical studies are necessary for the optimal treatment of patients with recurrent hepatitis C, and to determine the dosage of pegylated interferon and ribavirin, to decrease the duration of therapy and the side effects, finally to achieve a healing phase of higher degree.     

Successful elimination of hepatitis C virus after hepatic lobectomy in a patient with hepatocellular carcinoma

Hepatocellular carcinoma develops frequently after chronic hepatitis C and B virus infections. Hepatitis B virus has a direct, while hepatitis C virus an indirect role in hepatocarcinogenesis. THE AIM OF OUR WORK: To demonstrate a very unique and interesting case where after the elimination of early detected duplex hepatocellular carcinoma with a combined therapy of PEG-interferon and ribavirin, hepatitis C virus could be eliminated. CASE PRESENTATION: A 53-year-old male patient had chronic hepatitis C infection in his anamnesis. In 1995 histological examination confirmed cirrhosis in his liver. One year later he was non-responder for conventional interferon therapy. In 2002 CT examination confirmed a process with multiple plexus in the liver. With cytologic proof of hepatocellular carcinoma, a resection of the tumor by left-lobectomy of the liver was carried out. Four years after the operation a one-year PEG-interferon-alfa-2a and ribavirin combined therapy was instituted. The patient became virologically negative. CONCLUSION: In chronic liver diseases carcinoma can develop from multiple center at the same time. PEG-interferon and ribavirin combined therapy can be effective in chronic liver disease, as well as after resection of established hepatocellular carcinoma.     

Combined interferon-alfa-2b and ribavirin therapy in patients with recurrent chronic hepatitis c after liver transplantation

Interferon with ribavirin therapy has been proposed for the treatment of hepatitis C recurring in liver transplants. AIM OF THE STUDY: Was to assess the efficacy of standard combination therapy (interferon plus ribavirin) of chronic hepatitis C in transplanted patients with recurrent severe HCV induced chronic hepatitis. METHODS: 12 patients with HCV-PCR positive reaction (genotype 1b) were treated with the therapy of interferon-alpha-2b (3 MU three times a week) and 800-1000 mg ribavirin daily. Liver biopsy had been done in every patients before and after the treatment. Study endpoints were the end of treatment and the 6 month post-therapy sustained virologic response. RESULTS: At the end of treatment 3 patients were negative for HCV-PCR and all of them had negative reaction after 6 month follow-up period. CONCLUSION: The results are in a good accordance with treatment of patients with chronic hepatitis C without liver transplantation.     

Therapeutic vaccine IC41 as late add-on to standard treatment in patients with chronic hepatitis C

We examined the effect of the hepatitis C virus (HCV) peptide vaccine IC41 on HCV-specific T-cell responses and virological relapse rates in patients with chronic HCV genotype 1 infection when added to pegylated interferon plus ribavirin standard therapy. 35 patients received 6 vaccinations with IC41 from weeks 28 to 48 of standard antiviral treatment and were followed-up for another 6 months. IC41 vaccination did not prevent HCV-RNA relapse in patients with ongoing interferon standard treatment but HCV-specific T-cell responses were inducible and were associated with lower relapse rates. An increase of HCV-specific T-cell responses occurred in 73% of patients, responses were more frequent and stronger in patients with sustained virologic response than in patients who relapsed. Optimized vaccine responses may enhance sustained virologic response rates obtained with standard treatment of chronic hepatitis C.     

Gesundheitsökonomische Aspekte chronischer Infektionskrankheiten am Beispiel der chronischen Hepatitis C

Based on the German Hepatitis C Model (GEHMO) we developed a Hepatitis C Policy Model and applied it to the heterogeneous German hepatitis C population within the German health care context. We used Markov cohort simulation to predict absolute clinical and economic outcomes for a 20-year time horizon. For the cost-effectiveness analysis, a lifelong time horizon was used. Four different strategies were compared: (1) no antiviral treatment, (2) interferon monotherapy, (3) combination therapy with interferon plus ribavirin, and (4) combination therapy with pegylated interferon plus ribavirin. Based on our model, antiviral therapy with pegylated interferon and ribavirin could prevent about 17,000 cases of cirrhosis, 580 liver transplants, and 7,600 HCV-related deaths and is expected to save about 53,000 life years at total costs of 1.3 billion Euros within the next 20 years. Pegylated interferon plus ribavirin was the most effective treatment with an incremental cost-utility ratio of 23,000 Euros per quality-adjusted life year saved.     

Liver transplantation in patients with cirrhosis secondary to hepatitis B virus and hepatitis C virus infections

Liver cirrhosis main related to hepatitis C virus constitutes the main indication of liver transplantation in Europe and the USA, representing as many as 50% of the indications in adults, while cirrhosis associated with hepatitis B virus represents around 10%. The indications for transplantation in patients with infection by both viruses are fulminant hepatitis, decompensated cirrhosis and hepatocellular carcinoma. Both injections may relapse after transplantation. The evolution of the relapse in the graft is variable and can include non-significant alterations of the liver junction tests, chronic active hepatitis and cirrhosis. Less frequently, a particularly severe form called "fibrosing cholestatic hepatitis" can develop, which rapidly evolve to graft failure. The immunoglobin against the B virus and lamivudine reduce the risk of reinfection. The principal factor associated with reinfection is active viral replication before the transplantation, thus it is considered a contraindication for liver transplantation. INF-alpha has been used in the treatment of hepatitis B virus reinfection with discouraging results. More recently, lamivudine and adefovir have been used. Post-transplantation recurrence of hepatitis C is universal and its evolution towards cirrhosis is more rapid than in immunocompetent patients, with graft dysfunction being the most frequent cause of mortality and of indication for retransplantation. Different factors have been related to the severity of the recurrence including factors related to the donor, the recipient, the virus, immunosuppression and surgery. There are no preventive treatments against recurrence of post-transplantation hepatitis C. In the treatment of the hepatitis C virus recurrence, INF-alpha and rivabirin have been used in single form or in combination with variable results, with the combined therapy being more effective. Recently, encouraging results have been described with the combination of pegylated interferon and rivabirin without a higher incidence of rejection. Finally, the results of retransplantation in patients with recurrent hepatitis B or C have not been encouraging.     

Treatment of chronic hepatitis C

Since last 5 years there have been several important advances that significantly impact therapy. The most notable advances have been the availability of sensitive, specific, and standardized tests for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SR) is the optimal surrogate endpoint of treatment. The combination of high-dose peginterferon and ribavirin is more efficacious than standard interferon and ribavirin in persons infected with HCV genotype 1 (Genotype HCV1 patients may show SR of about 40%.) Compensated HCV cirrhosis patients may also be treated with PEG-IF and ribavirin combination. Decompensated cirrhosis needs liver transplantation. Strategies to enhance response to current therapies include the development of novel interferons, nucleoside analogues, inosine 5' monophosphate dehydrogenase inhibitors, and other immunomodulators that are being evaluated as adjunctive therapy to interferon-based regimens.     

Hepatitis C virus infection--after 12 years. Advances in the management of chronic hepatitis C

Therapy of different manifestations of HCV infection is discussed--after 12 years of the discovery of HCV. In acute hepatitis C the antiviral treatment of the early phase is debated, but if 3 months after the onset the HCV viremia persists, interferon (IFN) therapy may be recommended. Asymptomatic HCV carriers with normal alanine aminotransferase (ALT) do not need antivirals. However, their serum ALT, GGT, gammaglobulin values and liver ultrasound findings should be monitored, to disclose an underlying liver disease, and biopsy is considered, if suspicion of hepatitis raises. In patients with chronic hepatitis C biopsy is mandatory, it may prove mild, moderate or severe histological activity (HAI). Moderate or severe active hepatitis C (> 2 x normal ALT, HAI > 7) should be treated. In the first period of the antiviral treatment for HCV, a standard IFN monotherapy (3 x 3 MU s.c. IFN weekly for 6-12 months) has been used, which resulted in 15-20% sustained response (SR) rate. In the second half of nineties, combination of IFN with an oral nucleoside analogue ribavirin increased the SR to 30-30%, by means of decrease in relapse rate. Recently, pegylated IFN (PEG-IFN) in combination with ribavirin can lead to 60% SR. (Genotype HCV1 patients may show SR of about 40%, HCV 2.3 ones about 80%, respectively). Compensated HCV cirrhosis patients may also be treated with this type of combination, which can possibly inhibit progression. Decompensated cirrhosis needs liver transplantation. In the prevention of HCV infection, screening of blood donors, viral inactivation of blood products, disposable needles and education of risk populations are of basic importance, HCV vaccination, however is not on the horizon yet. Thus, antiviral treatment remains of great significance. Searches for new therapeutic modalities, such as multiple antiviral combinations (e.g amantadin + ribavirin + IFN), protease- and helicase inhibitors, ribozymes and cytokines may result further advances.     

脾栓塞术后抗病毒治疗丙肝肝硬化临床观察

目的观察丙型肝炎肝硬化并脾功能亢进患者部分脾栓塞术（P SE）后小剂量干扰素联合利巴韦林抗病毒治疗的疗效,评估其安全性。方法选取部分脾栓塞术后,脾功能亢进缓解的基因2型丙型肝炎肝硬化患者,给予干扰素α-2b3MU,隔日一次,利巴韦林0.9g/d抗病毒治疗,疗程7 2周。监测肝功能、血常规、甲状腺功能、肾功能、凝血功能、HCVRNA。观察治疗期间的不良反应并及时处理,抗病毒治疗结束后继续随访2 4周。结果 1 3例丙型肝炎肝硬化患者在部分脾栓塞术后白细胞、血小板计数较术前有显著的提高（P〈0.01）;全部患者均完成抗病毒治疗并接受随访24周;3例出现溶血性贫血,减少利巴韦林剂量。其中84.6%获得持续病毒学应答（SVR）,2例复发;治疗过程中未发生死亡或严重不良反应。结论丙型肝炎肝硬化患者行部分脾栓塞术可消除脾亢性血细胞减少症,术后给予小剂量干扰素联合利巴韦林进行抗病毒治疗可获得较好的SVR,且安全性高,耐受性良好。     

Of lives and livers: emerging responses to the hepatitis C virus

Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV). HCV is an etiological agent of acute and chronic liver disease that exists throughout the world. The high genetic variability of the HCV genome is reflected by six genotypes (1 to 6). Each genotype has a characteristic geographical distribution, which is important epidemiologically. HCV is a blood-borne virus that generally circulates in low titers in the serum of infected individuals. Epidemiologic studies show that the most efficient transmission of HCV is through the transfusion of blood or blood products, the transplantation of organs from infected donors, and the sharing of contaminated needles among injection-drug users. However, fewer than half of patients with acute hepatitis C report a history of such exposure. A small number of epidemiologic studies demonstrate that perinatal, sexual, household, and occupational transmission occurs, but our understanding of the risks of transmission in these settings has been limited. The therapy for chronic hepatitis C has evolved steadily since alpha interferon was first approved for use. At present, the optimal regimen appears to be a 24- or 48-week course of a combined pegylated alpha interferon and ribavirin regimen. Currently, the combination of RNAi (LV-shIRES) with IFN-α has been proposed to prevent therapeutic resistance, and to promote enhanced antiviral activity against HCV. However, any RNAi based therapy may be years away due to off-target effects.     

Molecular virology and treatment of patients with chronic hepatitis C

Chronic hepatitis C remains the significant epidemiological and clinical problem. Its serious sequelae include cirrhosis, liver failure and hepatocellular carcinoma. The only approved treatment of chronic hepatitis C are interferon (IFN) alfa-based regimens. Pegylated IFN alfa in combination with ribavirin has been proved to be the most effective therapy with sustained virological response rate of 72%, regardless of HCV genotype. Qualifying for antiviral therapy needs careful initial assessment, regarding of contraindications and certain conditions, and then close monitoring during treatment. Despite the significant progress in hepatitis C management currently available therapies are often ineffective and unsuitable for certain patient populations. The results of molecular researches on HCV biology give rise to the new therapeutic approaches to HCV therapy.     

Pathogenesis of hepatitis C virus infection

The hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide. Chronic hepatitis C is a mayor cause of cirrhosis and hepatocellular carcinoma and HCV-related end-stage liver disease is, in many countries, the first cause of liver transplantation. HCV infection is characterized by its propensity to chronicity. Because of its high genetic variability, HCV has the capability to escape the immune response of the host. HCV is not directly cytopathic and liver lesions are mainly related to immune-mediated mechanisms that are characterized by a predominant type 1 helper cell response. Co-factor influencing the outcome of the disease including age, gender and alcohol consumption are poorly understood and other factors such as immunologic and genetic factors may play and important role. Recent studies have shown that the combination therapy with alpha interferon and ribavirin induces a sustained virological response in about 40% of patients with chronic hepatitis C. The lack of animal models and of in vitro cultures systems hampers the understanding of the pathogenesis of chronic hepatitis C and the development of new antivirals. The conjugation of polyethyleneglycol improved the pharmacodynamics and the efficacy of alpha interferon. The development of an effective vaccine remains the most difficult challenge. Because of the high protein variability of HCV, protective vaccines could be extremely difficult to produce and therapeutic vaccines seem more realistic. Considerable progress has been made in the field of HCV since its discovery 10 years ago but a major effort needs to be made in the next decade to control HCV-related disease.     

The influence of HCV infection and immunomodulating therapy (interferon-alpha and ribavirin) on the condition of minor salivary glands and oral mucosa

The aim of the study was to determine an influence of HCV infection and combination therapy with interferon - alpha and ribavirin on the condition of oral mucosa and minor salivary glands in patients with chronic hepatitis C in comparison to subjects without liver pathology on 12-month follow-up. Patients with chronic hepatitis C more commonly develop pathological changes on the oral mucosa than patients without liver pathology. Combination therapy affects the amount of pathological lesions in the oral cavity of patients suffering from chronic hepatitis C and B. The occurrence of oral lichen planus on the oral mucosa may be associated with chronic hepatitis C as well as with concomitant alpha-interferon and antiviral therapy.     

Current trends and first clinical studies of therapy for chronic hepatitis C in children using pegylated interferon alpha and ribavirin

Our aim was to evaluate the recent clinical data concerning the course of chronic hepatitis C in children and the rationale indications for therapy. There is no doubt that in adult group the pegylated interferon is better than standard interferon and results in higher response rate in combination with ribavirin. Actually complicating the issues surrounding hepatitis C in children is the lack of information on the efficacy and safety of this therapy in pediatric age group. The first preliminary data of our clinical study concerning the therapy with pegylated interferon alpha 2b and ribavirin in 10 children with chronic hepatitis C (genotype 1) suggest a good tolerance of this drug and the end of treatment virologic response in 8 children (80%).     

New therapeutic options in chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is the major etiology and the reason of chronic liver disease, liver cirrhosis, hepatic decompensation, hepatocellular cancer and liver transplantation. Less than half of patients with HCV-related chronic hepatitis achieve sustained viral clearance with current pegylated interferon and ribavirin (P+R) combination therapy. Due to the insufficient treatment success, an extended search for new, direct acting anti-HCV agents (DAAs) is ongoing, already leading to submissions of applications for marketing authorization of the protease-inhibitors boceprevir and telaprevir. Both are effective only in triple combinations with P+R. Studies demonstrate a 50% success rate advantage for triple therapies above current standards. In addition, treatment duration can be shortened, and half of the patients who failed previous therapy with P+R can be cured with triple therapies. A major concern with new DAAs is rapid development of DAA-resistant viral mutants, a reason as well as a consequence of insufficient triple therapy. Clinical studies with boceprevir and telaprevir are reviewed in this paper.     

Hungarian consensus guideline for the diagnosis and treatment of B, C, and D viral hepatitis

More than 1% of the Hungarian population is infected with hepatitis B, C, or D viruses. Since 2006 the diagnostics and therapy of these infections are carried out in treatment centers according to national guidelines - since 2010 according to financial protocols. The consensus-based guidelines for 2012 are published in this paper. The guidelines stress the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection is pegylated interferon for 48 weeks or continuous entecavir therapy. The later must be continued for at least 6 months after hepatitis B surface antigen (HBsAg) seroconversion. Tenofovir disoproxil fumarat is not yet reimbursed by the National Health Insurance Fund. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Treatment naive chronic hepatitis C patients should initially receive pegylated interferon and ribavirin dual combination therapy. In genotype 1 infection if response is insufficient at 4 or 12 weeks one of the two new direct acting antivirals (boceprevir or telaprevir) should be added. The length of treatment is usually 48 weeks; in cases of extended early viral response shorter courses are recommended. Previous treatment failure patients with genotype 1 infection should receive a protease inhibitor backed triple combination therapy, mostly for 48 weeks. However, relapsers without cirrhosis and with extended rapid viral response, shorter telaprevir based combination therapy is sufficient. Drug-drug interactions as well as emergence of viral resistance are of particular importance. For genotype 2 or 3 HCV infections 24 weeks, for genotype 4 infections 24, 48 or 72 weeks of pegylated interferon plus ribavirin therapy is recommended in general. The guidelines published here become protocols when published as official publications of the Hungarian Health Authority.     

Cost-Effectiveness of Truncated Therapy for Hepatitis C Based on Rapid Virologic Response

BackgroundShortened courses of treatment with pegylated interferon alfa and ribavirin for patients with hepatitis C virus infection who experience rapid virologic response can be effective in appropriately selected patients. The cost-effectiveness of truncated therapy is not known.ObjectiveTo assess the cost-effectiveness of response-guided therapy versus standard-duration therapy on the basis of best available evidence.MethodsWe developed a decision model for chronic hepatitis C virus infection representing two treatment strategies: 1) standard-duration therapy with pegylated interferon alfa and ribavirin for 48 weeks in patients with genotype 1 or 4 and for 24 weeks in patients with genotype 2 or 3 and 2) truncated therapy (i.e., 50% decrease in treatment duration) in patients with rapid virologic response. Patients for whom truncated therapy failed began standard-duration therapy guided by genotype. We used a Markov model to estimate lifetime costs and quality-adjusted life-years.ResultsIn the base-case analysis, mean lifetime costs were $46,623 ± $2,483 with standard-duration therapy and $42,354 ± $2,489 with truncated therapy. Mean lifetime quality-adjusted life-years were similar between the groups (17.1 ± 0.7 with standard therapy; 17.2 ± 0.7 with truncated therapy). Across model simulations, the probability of truncated therapy being economically dominant (i.e., both cost saving and more effective) was 78.6%. The results were consistent when we stratified the data by genotype. In one-way sensitivity analyses, the results were sensitive only to changes in treatment efficacy.ConclusionTruncated therapy based on rapid virologic response is likely to be cost saving for treatment-naive patients with chronic hepatitis C virus infection. Cost-effectiveness varied with small changes in relative treatment efficacy.     

Retreatment strategies for the patients with HCV infection

Despite recent advances in the treatment of chronic hepatitis C, especially introduction of combined therapy with pegylated interferons with ribavirin, significant number of patients fails to achieve sustained virologic response. Such patients may be divided into relapsers and non-responders.. Pegylated interferon-based retherapy appear to induce sustained response in 40-68% of relapsers and only in 11% of non responders. New therapeutic approaches are needed for treatment of these group of patients. Current retreatment strategies includes administration of pegylated interferon and ribavirin, maintenance therapy with pegylated interferon for prevention of liver fibrosis and daily administration of consensus interferon and ribavirin. In the work the initial results of 3 clinical investigation (HALT-C, EPIC 3 and COPILOT) are presented, in which beneficial efficacy of pegylated interferon in non responders was observed.     

Membranoproliferative glomerulonephritis in patients with cryoglobulinemia complicating hepatitis C virus: report of 11 cases

BACKGROUND: Membranoproliferative glomerulonephritis in patients with cryoglobulinemia complicating hepatitis C virus have yet been reported. Although, it remains controversial, antiviral treatment seems to be able to improve the outcome of glomerulonephritis. AIM: The objectives of the study were to analyze characteristics of this association and to report literature data and newness treatment. METHODS: It's a retrospective study including 11 patients with membranoproliferative glomerulonephritis, hepatitis C virus and mixed cryoglobulinemia. Hepatitis C virus antibodies was identified by ELISA technique. Hepatitis C virus genotype was identified in one patient. Cryoglobulins were isolated from sera of all patients at 37 degrees Celsius. RESULTS: Patients were 3 men and 8 women with a mean age of 51.9 +/- 15.5 years. Between the 11 patients, 7 had hypertension, 9 had nephrotic syndrome and 10 had chronic renal failure. Renal biopsy showed membranoproliferative glomerulonephritis lesions in all cases with fibrinoid thrombi in 8 cases. Six patients had chronic liver disease. Liver biopsy was performed in 4 patients, showing histological feature compatible with chronic active hepatitis in 2 cases. No patient had antiviral therapy. Renal failure was stable in 5 cases and progressed in 6 cases with end stage renal failure in 3 of them. One patient died, 4 months after diagnosis, because of severe pulmonary involvement in cryoglobulinemic vasculitis. In literature, treatment is dominated by antiviral therapy composed first by Interferon Alpha alone. Combination therapy associating Interferon and Ribavirin was recently used in renal involvement; it is clearly more effective than interferon alpha alone. CONCLUSION: Hepatitis C virus detection should be performed when membranoproliferative glomerulonephritis is associated with cryoglobulinemia. Antiviral treatment should be more widely used in Tunisia to evaluate his effect on renal involvement