A short course of pegylated interferon-alpha in acute HCV hepatitis

Acute hepatitis C virus (HCV) infection evolves to chronicity in 50-84% cases. Treatment with interferon-alpha (IFN-alpha) was repeatedly found to provide sustained cure rates higher than that in chronic HCV infection, but the optimal treatment strategy has not yet been defined. In a multicentre open-label study, we investigated the therapeutic performance of a short course of pegylated (peg) IFN-alpha in patients with acute HCV hepatitis. Peg IFN-alpha2b, 1.0-1.5 micro g/kg weekly, was administered for 12 weeks. Forty-six patients were enrolled; 26 of them were intravenous drug users. Eleven patients had jaundice. Treatment was started within 1-90 days from the peak alanine aminotransferase. Treatment was well tolerated with a single dropout (2%). Thirty-three of 46 patients (72%) had a sustained virological response (SVR) after a 6 months post-treatment follow-up, 8 (17%) relapsed after treatment and 4 were nonresponders (9%). A lower peak viraemia, receiving at least 1.2 micro g/kg of peg IFN-alpha, and a negative HCV-RNA at week 4 and week 12 were predictors of SVR. Thus, in patients with early (week 4) viral response, a short course of peg IFN-alpha at a weekly dose >1.2 micro g/kg, may be a valuable option for the treatment of acute HCV hepatitis.     

Treatment of acute hepatitis C infection in HIV-infected patients: a retrospective analysis of eleven cases

Studies on hepatitis C virus (HCV) monoinfected patients suggest high sustained treatment response rates of up to 98% when interferon monotherapy is administered during the acute phase of HCV-infection. To clarify whether early treatment of acute hepatitis C is similarly efficient in human immunodeficiency virus (HIV) positive patients, we conducted a retrospective survey of HIV-positive patients with acute HCV infection. Eleven HIV-positive patients who had been treated with interferon or interferon/ribavirin were identified at eight HIV-specialty outpatient clinics. The patients had been treated over a median 25 weeks with standard interferon (two patients), pegylated interferon (four patients) and pegylated interferon in combination with ribavirin (five patients). A post-treatment response (negative serum HCV-RNA at the end of treatment) was seen in 10 of 11 patients and HCV-RNA remained undetectable 24 weeks after the end of treatment in all the 10 responders. Alanine aminotransferase (ALT) normalized in eight patients while two virological responders and one nonresponder showed persistent mild ALT elevations. In conclusion, early treatment of acute hepatitis C seems to achieve high sustained virological treatment response rates also in patients with HIV-infection.     

Sustained virological response in chronic hepatitis C patients after a 6- and a 36-month interferon-alpha2b treatment schedule: a multicenter, randomized, controlled study

BACKGROUND: In patients with chronic hepatitis C (HCV) Interferon-alpha (IFN) treatment for 12-18 months is more effective than 6 months in inducing a sustained virological response. METHODS: In a multicenter, randomized, controlled trial, 88 patients with chronic HCV were enrolled (47 treated with IFN-alpha2b and 41 constituted an untreated control group). Treatment consisted of 5 million units (MU) IFN thrice a week (tiw) for 8 weeks and subsequently 2.5 MU IFN tiw for 16 weeks ('standard treatment'). After week 24 ('long-term treatment'), in virological non-responders treatment was continued using 5 MU IFN tiw for up to week 156, whereas in virological responders IFN was discontinued. In case of a virological relapse, treatment with 5 MU IFN tiw was restarted and continued up to week 156. RESULTS: Sustained virological response rate was 6/47 (13%) after standard treatment and increased to 19/47 (40%) after long-term treatment (McNemar paired test; P = 0.002). Of the 18 patients with a breakthrough or relapse during or after standard treatment, 14 (78%) became sustained virological responders upon long-term treatment. Of the 4 patients who did not have a sustained virological response after long-term treatment, 3 did not receive complete treatment due to side effects and/or non-compliance. In patients who failed to respond to standard treatment, no virological response was observed during long-term treatment. In the control group, no spontaneous clearance of HCV was observed. CONCLUSIONS: Long-term IFN (re)treatment enhanced the virological sustained response rate significantly and was particularly effective in patients with a breakthrough or relapse following standard treatment.     

Retreatment with interferon-alpha and ribavirin in primary interferon-alpha non-responders with chronic hepatitis C

BACKGROUND/AIMS: Combination therapy with interferon-alpha (IFN-alpha) plus ribavirin is more efficacious than IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-alpha relapse. Only limited data are available in IFN-alpha non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-alpha-resistant chronic hepatitis C. METHODS: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-alpha-2a (3 x 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-alpha dose of 3 x 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. RESULTS: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-alpha dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). CONCLUSIONS: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-alpha non-responders. Higher IFN-alpha induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1.     

Efficacy of early treatment of acute hepatitis C infection with pegylated interferon and ribavirin in HIV-infected patients

BACKGROUND: Treatment of acute hepatitis C (HCV) in HIV-infected patients has been poorly addressed. OBJECTIVE: To evaluate the efficacy and tolerability of a 24 week course of pegylated interferon alfa 2a (PegIFNalpha2a) and ribavirin for the treatment of acute HCV infection in HIV-infected patients. METHODS: This was a prospective pilot study of 25 consecutive HIV-infected men with acute HCV infection defined by documented HCV seroconversion to anti-HCV positive antibody and positive qualitative HCV RNA measurement. Patients with detectable HCV RNA (> 50 IU/ml) 12 weeks after diagnosis were offered treatment with PegIFNalpha2a (180 microg/week) and ribavirin (800 mg/day) for 24 weeks. Sustained virological response was defined by a negative qualitative HCV RNA measurement 24 weeks after the end of treatment. RESULTS: At baseline, 23 patients were taking HAART, 23 patients had HIV RNA < 200 copies/ml and a median CD4 count of 345 cells/microl. Only one patient, with genotype 3 HCV, had a spontaneous clearance of HCV RNA. Of the remaining 24 patients, four refused anti-HCV therapy, ribavirin was contraindicated in one and 19 initiated anti-HCV therapy. Median time between acute HCV diagnosis and initiation of study treatment was 14 weeks. Of the 14 patients who have achieved the post-treatment follow-up at 24 weeks, 10 had a sustained virological response (71%). Study treatment was well tolerated, with no change in CD4 cell count. CONCLUSION: Early treatment of acute HCV infection with PegIFNalpha2a and ribavirin for 24 weeks yields a high sustained virological response rate in HIV-infected patients.     

Thyroid dysfunction during treatment of chronic hepatitis C with interferon alpha: no association with either interferon dosage or efficacy of therapy

OBJECTIVES: Treatment of chronic hepatitis C with interferon-alpha (IFN-alpha) may induce thyroid disorders. We evaluated whether this risk is related to the dosage of IFN-alpha or the virological treatment response. Other possible risk factors as well as the evolution of the thyroid abnormalities were also studied. METHODS: In this prospective trial (n=254), thyroid-stimulating hormone (TSH), free thyroxin (fT4) and thyroid peroxidase autoantibodies were measured before, during and after treatment for hepatitis C virus (HCV). The patients were randomized to either induction therapy [IFN-alpha 6 million units (MIU) daily for 4 weeks and 3 MIU 3/7 days for 22 weeks] or conventional therapy [IFN-alpha 3 MIU 3/7 days for 26 weeks]. In addition, all patients received ribavirin (1000 or 1200 mg) daily. Sustained virological response was defined as loss of detectable HCV RNA at 6 months follow-up. Thyroid dysfunction was defined as TSH level below or above the normal range (0.2-4.5 MIU L-1). RESULTS: Biochemical thyroid dysfunction developed in 30 (11.8%) of 254 patients. Hypothyroidism (TSH > 4.5 MIU L-1) was seen in 20 and hyperthyroidism (TSH < 0.2 MIU L-1) in 10 patients. Nine of the 30 patients developed symptomatic thyroid disease and HCV treatment was discontinued because of thyroid dysfunction in three of these patients. Thyroid dysfunction occurred in 15 (11.7%) of 128 patients who received high-dose IFN-alpha induction therapy as compared with 15 (11.9%) of 126 patients who received conventional IFN-alpha therapy (P=0.96). Amongst 231 patients who completed all 6 months of HCV treatment, a sustained virological response was obtained in 19 (66%) of 29 with thyroid dysfunction and 109 (54%) of 202 without (P=0.24). By multivariate analysis female gender and Asian origin were independent predictors of developing biochemical thyroid dysfunction (P < 0.01). CONCLUSION: Thyroid dysfunction occurred in 11.8% of patients treated for chronic hepatitis C with IFN-alpha and ribavirin. Neither the IFN-alpha dosage nor the virological response to treatment were related to the incidence of thyroid dysfunction.     

Pegylated interferon alpha therapy in acute hepatitis C: relation to hepatitis C virus-specific T cell response kinetics

Pegylated interferon alpha (PEG IFN-alpha) improves sustained virological response rates in chronic hepatitis C, but neither its role in acute hepatitis C nor the biologic basis for its action has been defined. This prospective study assessed the efficacy of PEG IFN-alpha treatment in acute hepatitis C in relation to the kinetics of hepatitis C virus (HCV)-specific CD4(+) T cell responses during therapy and follow-up. Forty subjects with proven acute hepatitis C who received either PEG IFN-alpha plus ribavirin (n = 20) or PEG IFN-alpha monotherapy (n = 20) for 24 weeks in addition to 14 untreated subjects with acute hepatitis C were prospectively followed. Serum HCV RNA, HCV-specific CD4(+) T cell responses, and cytokine production were measured before and during therapy and at follow-up and correlated to the outcome. The sustained virological response rate was 85% with PEG IFN-alpha/ribavirin combination and 80% with PEG IFN-alpha monotherapy. Five untreated subjects had spontaneous recovery. The frequency, magnitude, and breadth of HCV-specific CD4(+) T helper 1 responses were significantly higher in treated subjects compared with untreated subjects with self-limited disease or subjects with chronic evolution. The CD4(+) T cell responses were maintained in subjects with sustained virological responses and self-limited disease but fluctuated in those who developed chronic infection. In conclusion, PEG IFN-alpha therapy in acute hepatitis induces high rates of sustained virological response and prevents choronicity, probably through efficient early stimulation of multispecific HCV-specific CD4(+) T helper 1 responses.     

Effect of interferon-alpha induction therapy on genotype 2b/3a and low viral load hepatitis C virus infection. A randomized multicentre study

BACKGROUND: Interferon monotherapy for chronic hepatitis C virus (HCV) infection leads to sustained viral eradication in a minority of patients. However, in selected groups of patients, sustained virological response is observed in as many as 50% of patients. High initial interferon dose (induction therapy) has been reported to increase the initial response rate. We have studied the effect of interferon induction therapy in patients infected with HCV genotype 2b/3a, low viral load and no cirrhosis. METHODS: A total of 71 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis, with genotype 2b or 3a, viral load < or = 3 million copies per ml and no cirrhosis were randomized to receive either standard interferon therapy (3 MIU interferon-alpha-2a thrice weekly) for 26 weeks or 6 MIU interferon-alpha-2a daily for 4 weeks (induction group) followed by the standard dose (3 MIU thrice weekly) for 22 weeks. Those with persistent HCV RNA at 4 weeks stopped treatment. Patients were monitored for HCV RNA during and following treatment, and data were interpreted according to intention-to-treat analysis. RESULTS: Viral clearance occurred more rapidly (after 4 weeks) in the induction group (33/36 = 92%) compared to the standard interferon group (21/35 = 60%) (P = 0.01). Among the initial responders, 23/33 (induction group) compared to 16/21 (standard group) were persistently HCV RNA-negative at the end of treatment. At 52 weeks (6 months' follow-up), 22/36 (61%) (induction group) compared to 10/35 (29%) (standard group) were HCV RNA-negative. Among initial responders, 22/33 (induction group) and 10/21 (standard group) achieved a sustained virological response. Among end-of-treatment responders, 22/24 (induction group) and 10/16 (standard group) were HCV RNA-negative at 6 months' follow-up (P = 0.013). CONCLUSIONS: In patients infected with HCV genotype 2b/3a, low viral load and without cirrhosis, IFN induction therapy increases the initial viral clearance and reduces the risk of relapse in end-of-treatment responders. A sustained virological response was achieved in 61% of the patients receiving IFN induction therapy.     

Treatment of early diagnosed HCV infection in hemodialyzed patients with interferon-alpha. Treatment of hepatitis C

BACKGROUND: Acute and early diagnosed hepatitis C virus (HCV) infections are rare diagnoses. Patients on regular dialysis treatment (RDT) are at risk of acquiring HCV infection. AIMS OF THE STUDY: (1) To determine the efficacy and safety of two-phase induction treatment of acute and early diagnosed HCV infections in patients on RDT, and (2) to establish the importance of serum HCV RNA testing at defined time points of treatment for the prediction of the therapeutic effect. THERAPEUTIC PROTOCOL: Antiviral treatment consisted of two different phases: phase A therapy was interferon (IFN)-alpha 2b 10 million units (MU) s.c. administered daily for 21 days followed by phase B with IFN-alpha 2b 3 MU s.c. administered 3 times weekly for 12 weeks. RESULTS: (1) Efficacy of the treatment: A sustained virological response (SVR) was achieved in a total of 13/18 patients (72%). Safety: We did not observe any serious side effects of the treatment. The most pronounced side effect was the myelosuppression caused by IFN-alpha. (2) SVR prediction: Patients with negative serum HCV RNA at day 6 achieve SVR more frequently than those with positive HCV RNA at day 6 (p = 0.074). CONCLUSIONS: Treatment of acute and early diagnosed HCV infections in hemodialyzed patients is much more effective than treatment of chronic infection. Even relatively high doses of IFN at the beginning of therapy (10 MU daily) are tolerated well by the patients.     

Effectiveness of a multi-disciplinary standardized management model in the treatment of chronic hepatitis C in drug addicts engaged in detoxification programmes

AIM: To evaluate the effect of a multi-disciplinary standardized management model on the efficacy of pegylated (Peg)-interferon alpha-2b plus ribavirin treatment of chronic hepatitis C in drug addicts undergoing substitutive or antagonist therapy. DESIGN: Observational prospective multi-centre study. SETTING: Six clinical infectious disease centres in collaboration with 11 drug dependency units (DDU) in five Italian regions. PARTICIPANTS: Intravenous drug users affected by chronic hepatitis C engaged in detoxification programmes. METHODS: Application of a multi-disciplinary standardized management model for HCV treatment involving DDU operators, psychologists or psychiatrists and infectious disease specialists. MEASUREMENTS: Very early, early, end-of-treatment and sustained virological response to Peg-interferon alpha-2b plus ribavirin. FINDINGS: Fifty-three subjects were studied [43.4% with hepatitis C virus (HCV) genotypes 1 or 4]. Intent-to-treat analysis showed an end-of-treatment virological response in 58.5% of patients (39.1% genotypes 1 or 4; 73.4% genotype 3) and a sustained virological response in 54.7% (34.8% genotypes 1 or 4; 70.0% genotype 3). There were 19 (35.8%) dropouts and three (5.7%) non-responders: one genotype 1 and two genotype 4. Two (3.8%) patients relapsed: genotypes 1 and 3. On-treatment analysis showed negative HCV-RNA in 40 (93.1%) of 43 subjects who completed the first 12 treatment weeks and in 35 who completed the first 24 treatment weeks. All subjects with an end-of-treatment response, except one with genotype 3 infection, had a sustained response. CONCLUSIONS: Our data show that antiviral treatment in the context of a multi-disciplinary standardized management model helps many HCV-positive drug addicts achieve a good virological response.     

Efficacy and tolerance of interferon-alpha in the treatment of chronic hepatitis C in end-stage renal disease patients on hemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) show a high prevalence of hepatitis C, with a negative impact on the survival on hemodialysis and after renal transplantation. We evaluated the efficacy and tolerance of interferon-alpha (IFN-alpha) in HCV-infected ESRD patients on dialysis. METHODS: Forty-six HCV-RNA-positive ESRD patients were studied. IFN-alpha regimen consisted of 3 million units three times a week for 12 months, and the patients were followed up for 6 months. End-of-treatment, and sustained biochemical and virological responses were evaluated and tolerance was assessed monthly. RESULTS: A sustained virological response (SVR) was observed in 10/46 patients (22%) and in 10/29 who completed the treatment (34%). Alanine aminotransferase was elevated in 63% of the patients at the beginning of the study and returned to normal levels within the first month in all patients with SVR. Treatment was discontinued because of side effects in 11/46 patients (24%) and six patients (13%) were lost to follow-up. CONCLUSIONS: IFN-alpha monotherapy for hepatitis C in dialysis patients shows a high frequency of adverse effects. However, the SVR is high (34%) in patients who complete treatment, emphasizing the importance of careful selection and close follow-up in order to minimize and control possible side effects.     

Twelve-week treatment of acute hepatitis C virus with pegylated interferon- alpha -2b in injection drug users.

Injection drug use is the leading risk factor for infection with hepatitis C virus, and interferon (IFN) treatment in this context is associated with a poor rate of adherence. In this article, we review our experience with injection drug users with acute hepatitis C who are treated with pegylated IFN- alpha -2b for 12 weeks. Acute hepatitis C was diagnosed according to standardized criteria, and patients were treated with a median dosage of IFN- alpha -2b of 1.33 microg/kg per week. A sustained virological response was achieved in 17 (74%) of 23 patients. A sustained virological response was achieved in 14 (87%) of 16 patients treated with a dosage of >or=1.33 microg/kg per week and in 3 (43%) of 7 patients treated with a lower dosage. Sustained virological response was significantly associated only with a pegylated IFN- alpha -2b dosage >or=1.33 microg/kg per week (P=.022). A 12-week regimen of pegylated IFN to treat injection drug users with hepatitis C has a compliance that is much higher than that reported with a 24-week regimen. Adverse effects are minimal if patients are carefully selected.     

Twelve weeks of follow-up is sufficient for the determination of sustained virologic response in patients treated with interferon alpha for chronic hepatitis C

BACKGROUND/AIMS: The current standard for the determination of sustained virologic response in patients treated for hepatitis C is undetectable hepatitis C virus (HCV) RNA 24 weeks following the completion of therapy. Sensitive molecular tests may permit earlier determination of sustained virologic response following the completion of therapy in end-of-treatment responders. METHODS: We examined this possibility in 1441 patients, who received 48 weeks of treatment with either standard or pegylated interferon alpha-2a. HCV RNA was determined by polymerase chain reaction assay (Amplicor HCV Monitor vs. 2.0) at baseline and monitored at 4-week intervals throughout the treatment and 24-week post-treatment follow-up periods. RESULTS: End-of-treatment and sustained response were achieved in 624 and 342 patients, respectively. For all treatments, relapse was most frequent at weeks 52 and 56 and became rare following week 60. Only six patients out of 348 patients (2%) became HCV RNA positive between weeks 60 and 72. Analysis of baseline characteristics failed to identify a specific set of parameters associated with early relapse. CONCLUSIONS: This finding suggests that determination of HCV RNA levels at 12 weeks of follow-up may be sufficient for making decisions related to the management of most patients treated with standard or pegylated interferon alpha.     

Treatment of chronic hepatitis C in patients with drug dependence: time to change the rules?

AIMS: Approximately 170 million people world-wide are chronically infected with the hepatitis C virus (HCV). While the seroprevalence in the general population ranges between 0.2 and 2%, 50-90% of injection drug users are chronically HCV-infected. However, most patients who are drug abusers are still excluded from treatment of chronic HCV infection with interferon (IFN)-alpha. Due to the recent treatment advances resulting in sustained response rates between 50 and 80%, it becomes increasingly important to reflect the still existing contraindications and restrictions for IFN-alpha treatment, especially for patients with intravenous drug use (IDU) with or without psychiatric comorbidity. METHODS: We reviewed clinical trials that focus on the treatment of chronic hepatitis C in patients with drug addiction published between 1987 and 2003. FINDINGS: Only seven clinical trials investigating HCV treatment among drug users were found: four open prospective uncontrolled trials and three controlled trials. Thus far, no trials using pegylated IFN-alpha have been conducted. Data about sustained response and adherence in HCV-infected methadone substituted patients were either comparable to control groups or to representative clinically controlled trials using the same treatment regimen (IFN-alpha monotherapy or combined with ribavirin). Patients with former or present drug abuse seem more likely to discontinue treatment early. HCV-infected IDUs tended to be older with higher inflammatory activity and stage of fibrosis when interferon treatment was started. Psychiatric comorbidity did not negatively influence adherence or treatment outcome. CONCLUSIONS: There is no clinical evidence suggesting that HCV treatment with IFN-alpha should be limited to IDUs or methadone substituted patients. However, more prospective controlled trials on HCV treatment for patients with IDU are needed to establish and apply new rules and guidelines.     

Treatment of acute hepatitis C virus infection in HIV-infected MSM: the effect of treatment duration

We evaluated hepatitis C virus (HCV) treatment and the effect of treatment duration (24 versus 48 weeks) on treatment outcome among 50 HIV-infected men who have sex with men with acute HCV infection in Amsterdam. Overall sustained virological response (SVR) rate was 76%. Treatment duration was not significantly associated with SVR (adjusted odds ratio = 2.32; 95% confidence interval 0.39-13.97), suggesting that 24-week treatment may be sufficient for acute HCV infection in HIV-coinfected patients.     

Expert opinion on the treatment of patients with chronic hepatitis C

Summary.  The current preferred treatment for patients with hepatitis C virus (HCV) is combination therapy consisting of pegylated interferon alfa and ribavirin (RBV) for 24–48 weeks. Although this approach appears to be highly effective for patients with HCV genotypes 2 or 3, who have a sustained virological response (SVR) of approximately 80%, the treatment algorithm is less effective for patients with HCV genotype 1, as these patients have SVR rates of just 40–50%. In order to improve treatment outcomes, this article explores potential approaches for the optimization of treatment for patients with HCV genotype 1: considering shorter treatment periods for patients with a rapid virological response (RVR), increasing treatment periods for slow responders, and increasing RBV dose are all suggestions. Results from clinical trials suggest that approximately 20% of the HCV genotype 1-infected population are slow responders, and around 15% of all HCV genotype-1 infected patients could benefit from a shorter treatment duration without compromising the SVR rate. Interest has also focused on whether treatment duration could be individualized in some patients with genotype 2 and 3 infection. Here all the findings from recent studies are translated into practical advice, to help practitioners make evidence-based treatment decisions in everyday clinical practice. Although there are areas where currently available data do not provide conclusive evidence to suggest amending treatment approaches, there is clearly potential for individualized treatment in all aspects of hepatitis treatment in the future.     

Treatment with interferon-alpha2a alone or interferon-alpha2a plus ribavirin in patients with chronic hepatitis C previously treated with interferon-alpha2a. CONSTRUCT Group

BACKGROUND: Preliminary results from combination therapy with interferon-alpha and ribavirin (IFN/Rib) in patients with chronic hepatitis C have been promising, with up to 50% sustained hepatitis C virus (HCV) RNA response. The aim of this study was to investigate whether a sustained HCV RNA response could be obtained with combination therapy in patients who were non-responders or relapsers after IFN treatment. METHODS: In a multicenter study we randomized 53 HCV RNA-positive patients into 2 treatment groups. They all had biopsy-confirmed chronic hepatitis C, and all were recruited from a previous IFN study: 26 were previous non-responders and 27 responders with relapse. Group A received interferon-alpha2a, 4.5 MIU thrice weekly for 6 months, and group B received ribavirin, 1000-1200 mg/day, in combination with the same dose of interferon-alpha2a for 6 months. Median Knodell index was 5.0 in both groups. Genotype 1 was found in 24 (45%), type 2 in 3 (6%), and type 3 in 26 (49%). RESULTS: Sustained clearance of HCV viremia 6 months after interferon-alpha2a treatment stop was obtained in 12 of 53 patients (23%): 6 of 27 in the IFN group (22%) and 6 of 26 (23%) in the IFN/Rib group (NS). Nine of 27 (33%) former responders with relapse, compared with 3 of 26 (12%) non-responders, obtained a sustained HCV RNA response (P = 0.054). In previous relapse patients sustained loss of viremia was more frequent in genotype 3 (50%) than in genotype 1 (11%) patients (P = 0.022). CONCLUSIONS: In a group of previous IFN-alpha2a-treated chronic HCV patients we obtained a similar sustained clearance of viremia when retreated either with IFN-alpha2a alone or with a combination of IFN-alpha2a and ribavirin for 6 months. Previous relapse patients with HCV genotype 3 obtained sustained loss of viremia significantly more often (50%) than type-patients (11%). Previous IFN responders with relapse responded better than previous non-responders.     

Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study

Early treatment of acute hepatitis C with interferon alpha-2b for 24 weeks prevents chronic infection in almost all patients. Because pegylated interferons have replaced conventional interferon in the therapy of chronic hepatitis C, the aim of this study was to analyze the efficacy of an early treatment of acute hepatitis C with peginterferon alpha-2b. Between February 2001 and February 2004, 89 individuals with acute HCV infection were recruited at 53 different centers in Germany. Patients received 1.5 microg/kg peginterferon alpha-2b for 24 weeks; treatment was initiated after a median of 76 days after infection (range 14-150). End-of-treatment response and sustained virological response were defined as undetectable HCV RNA at the end of therapy and after 24 weeks of follow-up, respectively. In the total study population, virological response was 82% at the end of treatment and 71% at the end of follow-up. Of 89 individuals, 65 (73%) were adherent to therapy, receiving 80% of the interferon dosage within 80% of the scheduled treatment duration. End-of-treatment and sustained virological response rates in this subpopulation were 94% and 89%, respectively. A maximum alanine aminotransferase level of more than 500 U/L prior to therapy was the only factor associated with successful treatment. In conclusion, in acute HCV infection, early treatment with peginterferon alpha-2b leads to high virological response rates in individuals who are adherent to treatment. The high number of dropouts underlines the importance of thorough patient selection and close monitoring during therapy. Thus, future studies should identify factors predicting spontaneous viral clearance to avoid unnecessary therapy.     

Leukocyte Interferon Alpha Early Retreatment for Child A HCV Genotype 1b-Infected Cirrhotics Intolerant to Pegylated Interferons

Abstract Background and Aim:   The pegylated interferon (PEG-IFN)/ribavirin combination has been shown to be effective for hepatitis C virus (HCV)-related compensated cirrhosis, but it frequently causes adverse events, leading to premature termination. In this open study we evaluated the safety and efficacy of early retreatment with leukocyte IFN-alpha in Child A HCV genotype 1b-infected cirrhotics intolerant to PEG-IFNs. Patients and Methods:   61 patients were treated with PEG-IFN (either alpha-2b 1.2–1.5 lg/kg weekly or alpha-2a 180 lg/weekly) plus ribavirin (1,000 mg/day) for 48 weeks. During the first 6 months, patients who discontinued treatment because of side effects were retreated with leukocyte IFN-alpha (6 MU/three times weekly) plus ribavirin (1,000 mg/day) for 48 weeks after a 1-month wash-out. The primary end points were safety and efficacy in terms of sustained virological response (SVR). Results:   At intention-to-treat analysis of the 61 patients receiving PEG-IFNs plus ribavirin revealed that 18 (29.5%) obtained a SVR. 16 patients (26.2%) prematurely discontinued treatment and were retreated with leukocyte IFN-alpha plus ribavirin. The switch was well tolerated, and all but one patient completed the treatment period. As a result of the switch, 4 of these 16 (25%) patients also obtained a SVR. Thus, the overall SVR rate of this study was 22/61 (36.1%). Conclusions:   These results suggest that an early retreatment with leukocyte IFN-alpha may be a safe and valid therapeutic option among difficult-to-treat HCV cirrhotic patients who cannot tolerate PEG-IFNs.     

Which patients with genotype 1 chronic hepatitis C can benefit from prolonged treatment with the 'accordion' regimen?

The on-treatment virological response to pegylated interferon plus ribavirin therapy is a useful tool in the management of patients with chronic hepatitis C. The time at which hepatitis C virus RNA becomes undetectable by a sensitive PCR assay has a huge impact on the probability of achieving a sustained virological response, particularly in genotype 1 patients, and may be useful in selecting patients for prolonged therapy. Indiscriminate extension of treatment in patients with hepatitis C virus genotype 1 is not beneficial. However, there is a subgroup of patients - the so-called 'slow responders' - who benefit from extending treatment from 48 to 72 weeks and can be readily identified after 4-12 weeks of combination therapy. Thus, it is important to distinguish slow responders from null responders. In the TeraVIC-4 study virological relapse rates were significantly lower, and sustained virological response rates were significantly higher, in those treated for 72 weeks with peginterferon alfa-2a (40 kDa) plus ribavirin (45% vs. 32% with 48 weeks, P=0.014). Patients are best served by quantitative determination of the hepatitis C virus RNA level at weeks 4, 12 and 24. The results of these determinations can then be used to tailor the length of therapy.