A case of deep venous thrombosis associated with pegylated interferon α2b plus ribavirin treatment of chronic hepatitis C

We present a case of deep venous thrombosis (DVT) during pegylated interferon (peg-IFN)-α2b plus ribavirin treatment of chronic hepatitis C (CHC). A 67-year-old man, who had been under treatment for hypertension and diabetes mellitus, was admitted to our hospital for peg-IFN-α2b plus ribavirin treatment for CHC. His serum hepatitis C virus (HCV) RNA level became undetectable 1 week after the initiation of peg-IFN-α2b plus ribavirin treatment. He suffered from severe pain, flare, and edema in both of his lower legs 6 weeks after the initiation of peg-IFN-α2b plus ribavirin treatment. He was diagnosed as having DVT because of the presence of a thrombus in the right soleus vein by ultrasonography. Peg-IFN-α2b plus ribavirin treatment was discontinued because a causal relationship between DVT and peg-IFN-α2b plus ribavirin treatment was suspected. DVT was not observed and the symptoms in both of his legs were improved after the administration of warfarin potassium. Subsequently, DVT has not recurred, and he has remained HCV-RNA negative.     

Long-term lamivudine treatment for chronic hepatitis B in Japanese patients： A project of Kyushu University Liver Disease Study

AIM:To determine the efficacy of long-term lamivudinetreatment of a large number of Japanese patients withchronic hepatitis B.METHODS:In this retrospective,multi-center trial,318 Japanese patients with chronic hepatitis B received100 mg of lamivudine daily for up to 36(median 21)mo.Virological response was a decline to a serumHBV DNA level less than 3.7 log copies/mL.Virological breakthrough was defined as the reappearance of aserum HBV DNA level to more than 10-fold the minimumduring treatment.RESULTS:Lamivudine produced virological responsein 86.8% of the 318 patients at 6 mo,in 80.2% of252 patients at 12 mo,in 69.2% of 133 patients at 24mo,and in 53.6% of 28 patients at 36 mo.Forwardstepwise logistic regression analysis showed an HBV DNAlevel less than 6.8 log copies/mL(P<0.0001),HBeAgnegativity(P<0.0001),a platelet count of 100×10~9/L ormore(P=0.0162)at baseline,and a decline of the HBVDNA level of more than 3.2 log copies/mL as comparedwith the baseline level at 3 mo after the start oftreatment(P=0.0003)to be significantly associated withvirological response.Among patients with a virologicalresponse,virological breakthrough was seen in 5.3%of 19 patients who responded virologically at 1 mo,in20.7% of 203 patients at 3 mo,in 27.5% of 51 patientsat 6 mo,in 33.3% of 12 patients at 9 mo,and in 100%of 3 patients at≥15 mo.A virological breakthrough wasfound significantly more often in patients with delayedvirological response.CONCLUSION:Lamivudine treatment could suppressserum HBV DNA in most of the tested Japanese patients.Long-term efficacy might be seen in patients withoutHBeAg at baseline,in the absence of cirrhosis,and inpatients with a decline in HBV DNA level soon after thestart of treatment.     

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2： A project of the Kyushu University Liver Disease Study Group

AIM: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2, a multi-center study was retrospectively analyzed. METHODS: In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS: The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9% vs 92.9%), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8% vs 92.0%). CONCLUSION: The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16 weeks.     

Immunogenicity of recombinant hepatitis B vaccine in treatment-naive and treatment-experienced chronic hepatitis C patients： The effect of pegylated interferon plus ribavirin treatment

AIM: To retrospectively evaluate the vaccination-induced anti-HBs seroconversion rates in treatment-naive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment. METHODS: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20 microg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups: Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05). RESULTS: Fifty-eight of 70 group A patients (82.85%), 20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CHC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 (20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%, P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up. CONCLUSION: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.     

Amantadine in treatment of chronic hepatitis C virus infection?

Summary. Treatment of chronic hepatitis C (CHC) continues to be an important and growing challenge. As the response rate to FDA-approved treatment improved over the past decade, we are facing increasing number of difficult-to-treat patients such as those who have failed prior anti-viral therapy. The role of amantadine in the treatment of CHC remains unclear. Studies thus far have produced conflicting results, and type II error could not be excluded. This review summarized results published in the literature from 1997 to 2003, and reviewed the existing questions and controversies regarding the use of amantadine. Current literature suggests that amantadine is ineffective as monotherapy. Amantadine increased the sustained virologic response of certain treatment naïve patients when used in combination with interferon, and may be effective as an adjunct to interferon-based combination therapy in some patients who have failed or relapsed on prior therapy. Factors such as small sample size, patient characteristics, and differences in treatment protocols including amantadine preparation and duration of therapy might explain the conflicting observations of various studies. Further investigations are needed to define optimal dosing and formulation of amantadine, and its appropriate role in management of CHC infection.     

Immunogenicity of recombinant hepatitis B vaccine in treatment-nave and treatment-experienced chronic hepatitis C patients: The effect of pegylated interferon plus ribavirin treatment

AIM: To retrospectively evaluate the vaccination-induced anti-HBs seroconversion rates in treatment-naive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment. METHODS: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20μg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups: Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05). RESULTS: Fifty-eight of 70 group A patients (82.85%), 20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CMC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 (20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%, P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up. CONCLUSION: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.     

Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon α 2a therapy for chronic hepatitis C virus infection

The combination of pegylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP) associated with Peg-IFN-α 2a (Pegasys) after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection. She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course, neurological findings, an electromyogram (EMG), nerve conductions studies (NCS), muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin (IVIG) including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits.     

Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon α 2a therapy for chronic hepatitis C virus infection

The combination of pegylated interferon （Peg-IFN） and ribavirin is the standard of care for chronic hepatitis C virus （HCV） infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg- IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy （AIDP） associated with Peg-IFN-α 2a （Pegasys） after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection. She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course, neurological findings, an electromyogram （EMG）, nerve conductions studies （NCS）, muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin （IVIG） including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits.     

Pegylated interferon α-2b plus ribavirin for Japanese chronic hepatitis C patients with normal alanine aminotransferase

Aim: To investigate the efficacy and safety of a pegylated interferon (PEG‐IFN) α‐2b plus ribavirin (RBV) combination treatment for patients with chronic hepatitis C virus (HCV) infection who have persistently normal alanine aminotransferase (NALT). Methods: This multicenter study included 989 patients with HCV genotype 1 (114 with NALT and 875 with elevated ALT) who received weight‐based doses of PEG‐IFN α‐2b plus RBV for 48 weeks. We compared the sustained viral response (SVR) rates of patients with NALT and elevated ALT who received at least 80% or more of the target dosage of PEG‐IFN α‐2b and 60% or more of the target RBV (minimum acceptable dosage). Results: No significant difference was found in the overall SVR rate between the NALT (42.1%) and elevated ALT groups (37.3%). No significant difference in the SVR rates was found between NALT (63.3%) and elevated ALT group (61.6%) patients who received minimum acceptable dosage. Multivariate analysis showed that age (<65 years old) and total cholesterol (≧220 mg/dL) were significantly independent positive factors associated with an SVR in the NALT group. Twenty‐four weeks after treatment, an ALT increase above the normal range was observed for 34.0% (18 of 53) of the non‐responsive group of NALT patients. Conclusions: The efficacy and safety of PEG‐IFN α‐2b plus RBV combination therapy for patients with chronic HCV infection are similar for patients with NALT and those with elevated ALT levels. These results indicate that patients with NALT should be considered for treatment with PEG‐IFN α‐2b plus RBV.     

Treatment of chronic hepatitis C with high-dose interferon α-2b

A comparative study of three different high-dose regimens of interferon--2b (IFN) was conducted in patients with chronic hepatitis C to determine which was better at obtaining a sustained remission. A total of 126 patients were assigned randomly to one of three groups: group A was given 10 million international units (MIU) of IFN six times a week for eight weeks; group B was given 10 MIU IFN six times a week for four weeks followed by three times a week for an additional eight weeks; group C was given 10 MIU IFN six times a week for two weeks followed by three times a week for 12 weeks. The total dose administered to each group was 480 MIU/patient. Only the dosing schedule varied among the three groups. Among 98 efficacy-evaluable patients, a sustained alanine aminotransferase (ALT) response, defined as persistent normalization of the ALT for greater than six months after the termination of treatment, was achieved in 21.2% (7/33) of group A, 42.3% (11/26) of group B, and 54.5% (18/33) of group C patients. Similarly, a sustained loss of measurable serum hepatitis C virus RNA was observed in 28.6% (8/28) of group A, 40.9% (9/22) of group B, and 48.3% (14/29) of group C patients. Based upon these data, it can be concluded that 10 MIU of IFN administered six days a week for two weeks followed by three times a week for an additional 12 weeks produces the highest rate of both biochemical and virological responses to IFN therapy in patients with chronic HCV.     

Pegylated interferon ��-2b plus ribavirin for older patients with chronic hepatitis C

AIM:To analyze the efficacy and safety of a combination therapy of pegylated interferon(PEG-IFN) α-2b plus ribavirin(RBV) in older Japanese patients(65 years or older) infected with hepatitis C virus(HCV).METHODS:This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk.RESULTS:At 24 wk after the end of combination therapy,the overall sustained virologica...     

Triple combination treatment for chronic hepatitis C with protease inhibitors, pegylated interferon and ribavirin: 'lead-in or no lead-in'?

Direct acting antiviral agents for the management of chronic hepatitis C infection have recently been licensed. These new protease inhibitors are combined with pegylated interferon and ribavirin and markedly increase the proportion of patients who respond to antiviral therapy. The protease inhibitors may be used with a 'lead-in' phase of pegylated interferon and ribavirin and the value of this approach has been much debated with those supporting 'lead in' citing the advantages of assessing the early response to therapy before commencing the direct acting antiviral agent. Those opposed to the 'lead-in' phase cite the complexity of the regime and the lack of robust evidence showing an improvement in clinical outcome in those treated in this fashion.     

Serum PAI-1 is a novel predictor for response to pegylated interferon-α-2b plus ribavirin therapy in chronic hepatitis C virus infection

Obesity and insulin resistance have been reported as negative predictors for sustained virological response (SVR) in hepatitis C virus (HCV) genotype 1 infected patients treated with pegylated interferon-α plus ribavirin. They are also known to affect serum levels of several cytokines including adipocytokines. But the association between these cytokines and treatment outcome has not been fully elucidated. We examined pretreatment serum levels of 14 cytokines among 190 patients who were treated with pegylated interferon-α-2b plus ribavirin for chronic HCV-1b infection with high viral load (≥ 5 log IU/mL) and analyzed their contribution to treatment response. Plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor, and 11 clinical factors showed significant association with SVR in univariate logistic regression analysis. Four significant factors in multivariate analysis; serum PAI-1 (odds ratio [OR] = 15.42), body mass index (OR = 4.56), rs8099917 (OR = 4.95) and fibrosis stage (OR = 5.18) were identified as independent predictors. We constructed a simple and minimally invasive prediction score for SVR based on the presence of these factors except for fibrosis stage. The accuracy of this score was 73%, and was confirmed using an independent validation cohort consisting of 31 patients (68%). The strongest correlation was between PAI-1 level and platelet count (r = 0.38, P = 1.8 × 10(-7)), and PAI-1 level was inversely correlated with fibrosis stage. Serum PAI-1 is a novel predictor for the response to combination therapy against chronic HCV-1b infection and may be associated with liver fibrosis.     

Predictive value of different hepatitis C serological assays in the treatment of chronic hepatitis C with interferon α

In order to predict the complete response rate of natural interferon-α (nIFN-α) treatment in patients with chronic active hepatitis C, we examined the predictive value (PV) of different hepatitis C serological assays. We performed first generation (ver.1) and second generation (ver.2) hepatitis C virus (HCV) branched DNA-probe assays (bDNA-probe), HCV core protein assay (core protein), HCV Amplicor Monitor assay (amplicor monitor), and HCV competitive polymerase chain reaction (competitive PCR) assay, using serum samples collected immediately before initiation of treatment. For each marker, we studied, in patients stratified by serological group (Gr), which predictive value (PV) of the HCV titers showed association with the therapeutic effect. In 59 Gr 1 patients, complete response to nIFN-α treatment was predicted from the following PVs for each marker: 0.5 Meq/ml or less (odds ratio 11.7; P = 0.0010) with ver.1, 1.0 Meq/ml or less (odds ratio 5.3; P = 0.0119) with ver.2 of the bDNA-probe, 50 pg/ml or less (odds ratio 10.3; P = 0.0062) with core protein, 200 × 10³ copy/ml or less (odds ratio 7.8; P = 0.0031) with amplicor monitor, and 10⁴ copy/ml or less (odds ratio 6.2; p = 0.8395) with competitive PCR. In 27 Gr 2 patients, the PV for each marker indicating complete response was as follows: There was no relationship between PV and therapeutic effect with ver.1 of the bDNA-probe, while the PVs for the other markers were 0.2 Meq/ml or less (odds ratio 2.2; P = 0.3788) with ver.2, 20 pg/ml or less (odds ratio 5.6; P = 0.0597) with core protein, 400 × 10³ copy/ml or less (odds ratio 4.0; P = 0.2965) with amplicor monitor, and 10^5.5 copy/ml or less (odds ratio 29.2; P = 0.0096) with competitive PCR. Our findings showed that complete response to the treatment may be predicted using the appropriate PV for each marker. (Received Apr. 13, 1998; accepted Aug. 28, 1998)     

Favorable factors for re-treatment with pegylated interferon α2a plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus

Aim: Effect of re‐treatment for pegylated interferon (PEG‐IFN) plus ribavirin was not fully evaluated. We examined the effects of re‐treatment with PEG‐IFN plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus who failed to achieve a sustained virological response (SVR) with combination therapy. Methods: We examined 38 patients who were re‐treated with PEG‐IFN α2a plus ribavirin for more than 60 weeks, among whom 14 were non‐responders and 24 were relapsers after previous treatment with PEG‐IFN α2b plus ribavirin. IL28B genotyping was done in 21 patients. Results: The overall SVR rate was 34%. Analysis of baseline characteristics showed that the relapsers had a significantly higher SVR rate than the non‐responders (50.0%, 12/24 vs. 7.1%, 1/14, respectively, P = 0.012) The SVR rates of re‐treated patients who had turned hepatitis C virus (HCV) RNA‐negative at weeks 8, 12, 24, and 48 of the previous therapy were 67% (4/6), 67% (4/6), 29% (2/7), and 25% (1/4), respectively. Re‐treatment achieved an SVR in five of 12 patients with IL28B major alleles and three of nine patients with IL28B minor alleles. During the re‐treatment, patients with complete viral suppression at week‐12 achieved a significantly higher SVR rate (P = 0.001). Conclusions: Re‐treatment with PEG‐IFN α2a plus ribavirin therapy is effective in patients who relapse after a course of PEG‐IFN α2b plus ribavirin therapy. Re‐treatment is a particularly useful option for patients who achieve early viral clearance during previous therapy.     

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM:TT virus (TTV) is a newly described DNA virus relatedto postransfusion hepatitis that produces persistent viremiain the absence of clinical manifestations.PEG-IFN plusribavirin have been useful in the treatment of chronic hepatitisC infection.This study investigated the responses of TT virus(TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirintherapy.METHODS:Fifteen patients infected with HCV were treatedwith PEG-IFN(0.5 μg/body weight/week) and ribavirin(1000 mg-1 200 mg/daily) for 48 weeks,Blood samples weredrawn at the beginning and the end of the therapy.SerumTTV DNA and HCV RNA were quantified by real time PCR.RESULTS:At the beginning of treatment,TTV infection wasdetected in 10/15 (66.6%) of HCV-infected patients.Lossof serum TTV DNA at the end of therapy occurred in 6/10(60%) patients.Out of these 6 patients,4 (67%) becamepositive for TTV DNA after 6 months of therapy.RegardingHCV viremia,11/15 (73%) patients were negative for serumHCV RNA after 48 weeks of therapy,7/11 (64%) of thesecases also became negative for TTV DNA following thecombined treatment.In the 3/4 (75%) patients who werepositive for HCV RNA at the end of therapy,TTV DNA wasdetected as well.Sustained HCV response at 6 months aftertreatment was 53% (8/15).CONCLUSION:No TTV sustained response can be achievedin any patient after PEG-IFN plus ribavirin administration.     

Combined interferon α2b and cyclosporin A in the treatment of chronic hepatitis C: controlled trial

Background. Only 15% to 20% of patients with chronic hepatitis C have a sustained virological response to interferon monotherapy. The aim of the present study was to compare the efficacy and safety of interferon, in combination with oral cyclosporin A, with interferon monotherapy in the treatment of chronic hepatitis C. Methods. We assigned 120 patients with chronic hepatitis C to receive the standard Japanese dose of interferon α2b alone for 24 weeks or that dose of interferon α2b in combination with cyclosporin A, at doses of 200 mg daily for the first 4 weeks and 100 mg daily for the following 20 weeks. All patients were assessed for drug safety, tolerance, and efficacy at the end of weeks 4, 12, 24, and 48. Efficacy was assessed by the disappearance of serum hepatitis C virus (HCV)-RNA by polymerase chain reaction and normalization of serum aminotransferase. The primary endpoint was a sustained virological response; i.e., sustained undetectable serum HCV RNA at 48 weeks. Results. The sustained virological response rate was significantly higher in the combination therapy group (42/76) than in the monotherapy group (14/44; P = 0.01). The sustained biochemical response rate was also higher in the combination therapy group (46/76) than in the monotherapy group (17/44; P = 0.017). In patients with genotype 1 and high viral loads, the sustained virological response rate was markedly higher in the combination therapy group (16/38) than in the monotherapy group (1/21; P = 0.006). Side-effect profiles were similar in the two groups. Conclusions. In patients with chronic hepatitis C; combined interferon and cyclosporin A treatment was more effective than interferon monotherapy. The benefit was mostly achieved in patients with a high viral load and HCV genotype 1. Received: March 12, 2002 / Accepted: November 22, 2002 RID="*" ID="*" Reprint requests to: K. Inoue     

Evolution of Sjögren syndrome associated with hepatitis C virus when chronic hepatitis C is treated by interferon or the association of interferon and ribavirin

Hepatitis C virus is one of the most likely candidates as a potential pathogenic agent causing Sjogren's syndrome (SS) in a subset of patients. Nobody has until now described the evolution of SS associated with HCV when chronic hepatitis C is treated with antiviral therapy, interferon being an auto-immunity inductor. This is the purpose of our study. METHODS: Prospective study of 12 patients with a HCV-associated SS defined as certain according to the first european criteria and treated with interferon or interferon/ribavirin for their chronic hepatitis C. RESULTS: More than fifty percent of these patients developed a severe immunological complication especially when they were treated with interferon alone. Ribavirin may have had a protective role on interferon-mediated immunological complications. These complications went on after cessation of therapy. Sicca syndrome was improved only in the patients treated with the association (in 50% of the cases), but these patients also had a sustained virological response. It is difficult to tell if this improvement was due to the hepatitis C virus eradication or ribavirin treatment. CONCLUSION: Hepatitis C virus is implicated in the development of SS in a specific subset of patients for which we can propose the term SS "secondary to HCV" and this disease is not utterly benign especially after the introduction of interferon therapy. Ribavirin when associated with interferon gives a significative sustained virological response and could lower the incidence of immunological interferon-mediated complications with a favorable outcome of sicca syndrome.