Interferon retreatment of nonresponders with HCV-RNA-Positive chronic hepatitis C

Interferon has been shown to be an effective treatment for some patients with chronic hepatitis C. In this study, the value of retreatment of nonresponders to interferon was investigated. Thirty-eight patients with hepatitis C virus (HCV)-RNA-positive chronic hepatitis C virus (HCV)-RNA-positive chronic hepatitis C who had been treated with betainterferon but still showed an alanine aminotransferase (ALT) level>50 KU upon completion of therapy were retreated with alpha-interferon. Eight patients (21.1%) had normalization of ALT levels after interferon retreatment were studied. Of 16 patients with transient HCV-RNA negativity 1 month after the initial interferon therapy, 7 (43.8%) had a complete response, with normalization of ALT levels and undetectable HCV-RNA, more than 6 months after interferon retreatment. On the other hand, of the 22 patients with HCV-RNA activity 1 month after the initial interferon therapy, only 1 (4.5%) had a complete response. Multivariate analysis, using a multiple logistic model, indicated that a complete response to readministration of interferon was most strongly correlated to transient negative conversion for HCV-RNA after the initial course of treatment.     

Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon. The Consensus Interferon Study Group.

Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment with consensus interferon (CIFN). Some nonresponders to initial IFN treatment have a transient response defined as undetectable HCV RNA or normalization of ALT during treatment, but subsequently have a "breakthrough" while still on treatment. The aim of this study was to determine if nonresponders who had breakthroughs responded differently to CIFN retreatment than nonresponders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 mcg CIFN or 3 MU IFN-alpha2b 3 times per week). HCV-RNA breakthroughs were observed in 86 of 467 (18%) of all treated patients, and ALT breakthroughs were observed in 90 of 467 (19%) of all treated patients. There was no association between breakthroughs and the presence of either binding or neutralizing anti-IFN antibodies. When the patients who were nonresponders to initial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27% of those with viral breakthroughs had a sustained viral response compared with 8% in prior nonresponders without breakthroughs (P =.102). Sustained ALT responses were observed in 39% with breakthroughs compared with 10% in those without breakthroughs (P =.014). The data suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. However, most breakthrough patients would be missed unless repeated HCV-RNA testing were conducted during therapy.     

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.     

Permanent response to alpha-interferon therapy in chronic hepatitis C is preceded by rapid clearance of HCV-RNA from serum

Background/Aims: Prediction of response to interferon therapy is important in the management of chronic hepatitis C. Pre-therapy data are valuable but they may be inaccurate in some cases. Our aim was to investigate whether the biochemical and virological events that occur early during interferon therapy in chronic hepatitis C may predict the final result of the treatment.Methods: ALT and serum HCV-RNA were serially measured in 53 HCV-RNA-positive patients who received a standard 6-month course of interferon therapy. Eleven patients with a sustained response, 23 who responded but subsequently relapsed and 19 who did not respond were studied. HCV-RNA was measured with a commercial kit (Amplicor HCV).Results: After 4 weeks of treatment, HCV-RNA became negative in 73% of sustained responders, in 26% of transient responders (p=0.02) and in none of the non-responders. Corresponding figures after 8 weeks of therapy were 82% in sustained responders, 61% in transient responders and 9% in non-responders. The difference between sustained and transient responders at this times was not significant. After 4 weeks of therapy, 82% of sustained responders, 52% of transient responders and none of the non-responders presented normalization of alanine transferase. The difference between sustained and transient responders was not significant. Corresponding figures for normalization of alanine transferase at 8 weeks were 82%, 96% and 0% respectively. At the end of treatment, all sustained responders, 70% of transient responders and none of the non-responders had cleared HCV-RNA from serum.Conclusions: A rapid normalization of alanine transferase induced by interferon therapy is associated with response, but does not differentiate between transient and permanent response. In contrast, clearance of HCV-RNA after 4 weeks of treatment, but not after 8 weeks, is significatively associated with sustained response. Testing for HCV-RNA early during interferon administration may be valuable for further decisions concerning therapy in patients with chronic hepatitis C.     

Interferon retreatment in chronic hepatitis C: which patients to choose, and what schedule to use.

OBJECTIVE; To evaluate the results of a large cohort of non-responder or relapsing responder patients with chronic hepatitis C retreated with various schedules of interferon (IFN). METHODS: Our study included 276 patients (158 non-responders and 118 relapsing responders) who underwent IFN retreatments. Among the non-responder group, 158 patients underwent further courses of IFN. In particular, 108 patients underwent one course of IFN retreatment, 40 patients underwent two courses, eight patients underwent three courses, and two patients underwent four courses. Regarding the relapsing responder group, the 118 patients were retreated with the same dosage for varying periods. In particular, 50 patients were treated for 6 months, 43 patients for 12 months, and 25 for 24 months. Patients in the subgroups of IFN retreatment were homogeneous as far as age and gender distribution, as well as virological and histological characteristics, are concerned. Qualitative and quantitative HCV-RNA was evaluated at baseline, at the end of treatment and at the last check-up of follow-up. HCV genotype was determined on baseline serum samples. Alanine transaminase (ALT) levels were tested monthly. RESULTS: Long-term biochemical (normal ALT levels) and virological (HCV-RNA negative) response was obtained in 2.6% of non-responder retreated patients, and in 33.9% of relapsing responder retreated patients. Evaluation of response on the basis of the duration of treatment showed that 48%, 19% and 16% of relapsing responder patients retreated for 24, 12 and 6 months, respectively, obtained long-term biochemical and virological response. CONCLUSION: Non-responder patient retreatment is inefficient especially in cirrhotic and/or genotype 1 b patients. IFN retreatment is warranted in relapsing responder patients. In particular, 24-month therapy induces significant long-term biochemical and virological response.     

Retreatment with interferon for chronic hepatitis C after transient response

Approximately half of all patients with chronic hepatitis C show an initial biochemical response to interferon, but only 15% to 20% of patients achieve a sustained response. We studied the efficacy of retreatment with interferon for patients with chronic hepatitis C who showed transient biochemical responses to initial treatment. Thirty patients who relapsed were retreated 1 to 52 months (median 14) after the end of initial treatment, according to the previously used regimens. The responses were correlated with the pre-retreatment patient data. The liver histologic grades, compared with those found before the initial treatment, were better in eight (27%) patients but worse in six (20%), whereas the fibrosis stage was improved in five (17%) but worsened in eight (27%). All patients displayed end-of-retreatment biochemical responses. Of the 30 patients, 10 (33%) achieved sustained aminotransferase normalization and serum hepatitis C virus (HCV) RNA clearance, but the remaining 20 patients showed relapse within 1 year after cessation of retreatment. Univariate analysis associated the sustained response with low pre-retreatment viral loads (0.8 +/- 0.7 MEq/mL vs. 9.1 +/- 6.5 MEq/mL; p = 0.006), short treatment intervals (13 +/- 13 months vs. 22 +/- 14 months; p = 0.031), and low histologic grades (1.3 +/- 0.7 vs. 1.9 +/- 0.7; p = 0.039). However, multivariate analysis indicated that only the pre-retreatment viral load was predictive of the sustained response (p = 0.049). These findings suggest that transient responders to interferon are likely to respond to retreatment but the achievement of a sustained response depends on the HCV viral load before retreatment.     

Short and long-term effects of interferon on serum markers of hepatitis C virus replication

Abstract Hepatitis C virus RNA (HCV-RNA) and serological markers of HCV infection were measured in 30 patients with chronic hepatitis C who had been treated with interferon (IFN). Patients were classified into four groups according to serum alanine aminotransferase (ALT) levels after treatment. These were: as complete responders (CR); partial responders (PR); transient responders (TR); and non-responders (NR). In all 11 patients in the CR group, HCV-RNA disappeared from serum for at least 24 months and anti-c100-3 decreased progressively during this time. In the PR group, four of five patients were positive for HCV-RNA in spite of the improvement of ALT levels and decline of anti-c100-3. In the TR and NR groups, HCV-RNA disappeared transiently or remained persistently positive. The results indicate that IFN-mediated improvement of ALT and decrease of anti-HCV (anti-c100-3) were not always related to the disappearance of HCV-RNA from serum. On the other hand, sustained disappearance of HCV-RNA from serum was demonstrated in the patients who did not have post-treatment ALT relapse. This indicates that IFN can eradicate HCV from serum in some patients and provide a clinical remission of chronic hepatitis C.     

Combined treatment of relapse of chronic hepatitis C with high-dose alpha2b interferon plus ribavirin for 6 or 12 months

BACKGROUND/AIMS: Retreatment of relapses of chronic hepatitis C with a standard regimen of interferon plus ribavirin for 6 months obtains a sustained response in a minority of patients with high viraemia and genotype 1b. We aimed to assess whether increasing the interferon dose and prolonging the time of combined treatment may enhance the effectiveness, and also to evaluate the tolerability, and to identify the determinants of sustained response. METHODS: Fifty subjects with chronic hepatitis C who had relapsed after one or more courses of a-interferon monotherapy were randomised to receive alpha2b interferon (6 MU tiw) plus ribavirin (1000-1200 mg daily) for 6 or 12 months. ALT normalisation and serum HCV-RNA clearance at the end of treatment and 6 months after stopping therapy were used as markers for sustained response. RESULTS: End-of-treatment response was achieved in 48 patients (96%) and 27 (54%) had a complete sustained response. Patients treated for 12 months had a higher rate of sustained response (18/25, 72%; 95% C.I. 0.54-0.89) than those treated for 6 months (9/25, 36%; 95% C.I. 0.17-0.55, p=0.01). Twelve months of therapy was significantly more effective for patients with genotype 1b and baseline serum HCV-RNA greater than 450 000 copies/ml (p=0.005). Seven subjects (14%) discontinued treatment because of side effects. Logistic regression analysis showed 12 months of therapy, young age and low pre-treatment serum HCV-RNA to be independent predictors of sustained response. CONCLUSIONS: Relapsers with genotype 1b and high levels of HCV-RNA will benefit from a 12-month course of 6 MU tiw interferon plus ribavirin, while subjects with genotype 1b and low levels of serum HCV-RNA or with genotype other than 1b may be treated for 6 months.     

Is delayed normalization of alanine aminotransferase a poor prognostic predictor in chronic hepatitis C patients treated with a combined interferon and ribavirin therapy?

BACKGROUND AND AIMS: Decreased alanine aminotransferase (ALT) level is the accepted basic indicator of an interferon (IFN) therapeutic effect in chronic hepatitis C. This study assessed whether delayed normalization of ALT predicts a poor response to a combined therapy of IFN and ribavirin in patients with chronic hepatitis C virus (HCV) infection. METHODS: Patients were treated with IFN-alpha 2b three times weekly and oral ribavirin for 24 weeks. The ALT values were assessed monthly and patterns of changes in ALT activity were analyzed. Serum HCV-RNA was checked at weeks 0, 12, 24, and 48. RESULTS: A total of 103 patients completed therapy and 69 (67%) of them achieved a sustained viral response (SVR). There was no significant difference in the SVR between patients with or without early normalization (week 12) of ALT level (69 vs 56%). Of the sustained responders, nine patients (13%) with delayed ALT normalization had a SVR. Nine of the 12 patients (75%) with abnormal ALT and negative HCV-RNA at week 12 had a SVR compared with none of four patients who had positive HCV-RNA at week 12 (P = 0.0192). CONCLUSIONS: Lack of normalization of the ALT level at week 12 does not preclude successful virological outcome in hepatitis C patients receiving a combined therapy of IFN and ribavirin. Hepatitis C virus RNA at week 12 may be a useful predictor of treatment outcome in patients without early biochemical response.     

Evaluation of long-term biochemical responses to combination therapy of interferon plus ribavirin in those infected with hepatitis C virus genotype 1b and high baseline viral load

Aim: The aim of this study was to determine the long-term effects in non-responders (NRs) to 48-week interferon (IFN) and ribavirin combination treatment in patients infected with hepatitis C virus (HCV) genotype 1b and high baseline viral loads. Methods: We measured serum alanine aminotransferase (ALT) and HCV-RNA levels in 52 consecutive patients infected with HCV genotype 1b and high viral loads who received combination therapy for 48 weeks. Results: Sustained virologic response (SVR) was noted in 30 patients (57.7%). Virologic response (VR), that is serum HCV-RNA negativity by the end of treatment and positivity during follow-up, was noted in nine patients (17.3%). Thirteen (25.0%) patients were NRs. Significantly lower serum albumin (P = 0.007) and ribavirin doses according to body weight (P = 0.021) and higher gamma glutamyl transpeptidase (GGT,P = 0.038) were noted at baseline in the NR group than in the SVR and VR groups. ALT normalization rates at six months after the completion of treatment were 55.6% (5/9) in VR and 61.5% (8/13) in NRs. Sustained ALT normalization at two years after the completion of treatment was noted in 55.6% (5/9) and 58.3% (7/12), respectively. Conclusion: Our study indicates a high rate of ALT normalization in patients infected with HCV genotype 1b and high baseline viral loads who received combination therapy and that such a rate could be maintained after the completion of therapy, even in NRs. Our results suggest that combination therapy should be continued in NRs who show ALT normalization in order to prevent potential hepatocarcinogenesis.     

Viral and Host Factors in Determining Response of Relapsers with Chronic Hepatitis C to Retreatment with Interferon

In chronic hepatitis C the rate of relapse afteran end-of-treatment response to interferon may exceed50%. The usefulness of retreatment of relapsers withinterferon in obtaining a complete sustained response and the role of clinical, virological andimmunological features in determining long-term efficacyof retreatment are unclear. We aimed to assess theefficacy of interferon retreatment in obtaining acomplete sustained response, to evaluate whetherincreasing the dose may enhance responsiveness, and toidentify possible predictors of sustained response. Weenrolled 42 patients with biopsy-proven chronichepatitis C without cirrhosis who had previouslyresponded to a six-month course ofInterferon-_2b (total dose: group A, 22patients, 234 MU; group B, 20 patients, 468 MU) and thenrelapsed. All, except one, were HCV-RNA negative at the end of first cycle ofinterferon; most (31/42, 74%) were infected by HCV 1b.Subjects were randomly allocated to receive anothercycle of interferon either at the original dose (group A₁: 234 MU, 11 patients; groupB 468 MU, 10 patient) or twice the original dose (groupA₂: 468 MU, 11 patients; group B : 936 MU, 10patients). At the end of the second cycle of interferon,24 subjects (57%) had normal ALT and were HCV-RNAnegative, and 16 (39%) had normal ALT, but were HCV-RNApositive. A complete sustained response was obtained ineight patients (19%), at a similar rate in all treatment groups. Complete sustainedresponders were different from the other patients interms of age (35.9 ± 10.4 vs 44.1 ± 8.8,P = 0.027), rate of infection with non-1b HCV (6/8 vs5/34, P = 0.0005), serum HCV-RNA (74,016 vs 321,428median copies/ml, P = 0.037) and serum levels of90K/MAC-2 BP (5.76 ± 3.01 vs 10.25 ± 5.16units/ml, P = 0.02), an N-glycoprotein implicated incellular defense functions. Multivariate logistic analysisvalidated age and HCV genotype as independent predictorsof CSR. Among noncirrhotic relapsers who received atotal interferon dose 234 MU in the first cycle,retreatment usually induced end-of-treatment response. Acomplete sustained response was obtained in only one ofevery five subjects. Increasing the dose of interferonabove that of the first cycle did not enhance the rate of sustained response. In conclusionwe might assert that young subjects infected by non-1bHCV and with low levels of HCV-RNA and of 90K/MAC-2 BPare the best candidates for retreatment.     

State of the iron metabolism in patients with chronic hepatitis C type C does not influence antiviral treatment with interferon and ribavirin

BACKGROUND/AIMS: Comparison of the iron status in patients who responded and did not respond to combination treatment with interferon alpha and ribavirin in chronic hepatitis C. METHODOLOGY: The study group comprised of 61 patients with chronic hepatitis C (genotype 1) treated with alpha 2b interferon and ribavirin. The iron metabolism was evaluated based on serum iron level, total iron binding capacity, transferrin saturation, serum ferritin concentration and hepatic iron concentration. In the evaluation of antiviral treatment efficacy biochemical and virological responses were taken into account. RESULTS: End of treatment response was observed in 38 patients (62%). Significant differences in iron parameters were not observed between responders and non-responders. Also, sustained viral response, 6 months after treatment completion, was reached in 32 patients (52.5%). Iron metabolism parameters did not differ significantly in the group of sustained responders versus non- responders. Finally, ALT normalization was observed in 42 patients (68.9%). Again, no significant differences in iron status were observed between patients with and without biochemical response excluding significantly higher serum ferritin concentration in non-responders. CONCLUSIONS: Results of this study show that iron status does not significantly influence the efficacy of treatment with interferon and ribavirin in patients with chronic hepatitis C.     

Long-term histological prognosis and serum fibrosis markers in chronic hepatitis C patients treated with interferon

BACKGROUND: Interferon (IFN) therapy is effective in 20-40% of patients with chronic hepatitis C, but the relationship between histological changes and the response to interferon is still unclear. We investigated the long-term histological prognosis and the changes of serum fibrosis markers after interferon therapy relation to the response. METHODS AND RESULTS: One hundred and eighteen patients with chronic hepatitis C who received interferon therapy were divided into four groups based on the detection of viremia and the serum alanine aminotransferase (ALT) level after treatment. A histological examination was performed by using the histological activity index and the criteria of the METAVIR score. Serum fibrosis markers were used to measure the levels of hyaluronic acid and type IV collagen 7s. Responders, whose serum ALT levels became normal after treatment, demonstrated histological improvement. Histological improvement was more rapid in sustained virological responders with hepatitis C virus (HCV) RNA seronegativity than in biochemical responders with HCV-RNA seropositivity. Only sustained virological responders exhibited histological cure. In partial responders, whose serum ALT levels decreased to less than twice the upper of normal, and non-responders whose serum ALT levels were not reduced, liver fibrosis was unchanged or showed progression. Serum fibrosis markers increased with progression of the histological stage and varied depending on the response to interferon. CONCLUSION: Normalization of serum ALT levels after interferon therapy led to a histological improvement, and that with viral clearance achieved histological cure. Serum fibrosis markers were useful indicators for long-term according to the response of IFN therapy.     

Treatment of chronic hepatitis C in patients who failed interferon monotherapy: effects of higher doses of interferon and ribavirin combination therapy. The Virginia Cooperative Hepatitis Treatment Group

OBJECTIVE: The present study was designed to evaluate the effectiveness of interferon-ribavirin combination therapy for treatment of chronic hepatitis C virus (HCV) in patients who failed previous treatment with interferon monotherapy. METHODS: A total of 140 patients with well-documented chronic HCV who failed to achieve a virological (if HCV-RNA was assessed) or biochemical response (if HCV-RNA was not assessed) to interferon monotherapy, 3 mU three times weekly (TIW) for 3-18 months, were randomly assigned to one of three treatment groups. Group A patients were treated with 5 mU interferon TIW for 6 months. Ribavirin (1000-1200 mg daily) was added in those patients HCV-RNA positive at month 3. Group B patients were treated with 3 mU interferon TIW plus ribavirin (1000-1200 mg daily) for 6 months. The dose of interferon was increased to 5 mU TIW in those patients HCV-RNA positive at month 3. Group C patients were treated with 5 mU interferon TIW plus ribavirin (1000-1200 mg daily) for 6 months. Serum ALT and HCV-RNA were monitored during and after treatment for a total of 15 months. RESULTS: Seventeen percent of patients in group A became HCV-RNA negative by treatment month 3. Adding ribavirin resulted in one additional patient becoming HCV-RNA negative. However, none of the patients in this group achieved sustained virological response. Twenty-six percent of patients in group B became HCV-RNA negative by treatment month 3. Increasing the dose of interferon from 3 to 5 mU TIW increased virological response to 30%. However, sustained virological response was observed in only 14%. Thirty percent of patients in group C became HCV-RNA negative, but sustained virological response was observed in only 12%. Sustained virological response was found to be significantly greater in patients with a nontype I HCV genotype (p < 0.002) and in patients who had a decline in HCV-RNA titer to a value < 100,000 copies/ml during their previous course of interferon monotherapy (p < 0.0001). None of the 12 sustained responders were African Americans (p < 0.013). CONCLUSIONS: Retreatment of nonresponders with interferon-ribavirin combination therapy results in limited benefit; only 13% of patients achieved sustained virological response. Response was extremely poor in African Americans and those with HCV genotype 1.     

Iron depletion is not effective in inducing a virologic response in patients with chronic hepatitis C who failed to respond to interferon therapy

OBJECTIVE: Some studies have suggested that increased iron stores may impact negatively on the response to interferon in patients with chronic hepatitis C infection. We performed this prospective trial to determine the effects of iron depletion on ALT and HCV-RNA levels in patients with chronic hepatitis C infection and to assess whether the response to interferon in patients who had previously failed to respond to interferon was enhanced by iron depletion. METHODS: Patients with chronic hepatitis C resistant to interferon therapy and no evidence of iron overload underwent weekly phlebotomies until the serum ferritin level was below lower limits of normal for the subject's age and sex. Patients were then started on interferon-alpha2b, 3 million units subcutaneously three times per week for a period of 24 weeks. Iron studies, ALT, and HCV-RNA levels were monitored at baseline, after phlebotomy and at 12 and 24 weeks of interferon therapy. RESULTS: Thirty-three patients were enrolled, 28 completed the study. A mean of 7.2 units of blood were removed to achieve iron depletion. ALT levels decreased significantly with phlebotomy (142 IU/L before phlebotomy vs 82 IU/L after phlebotomy; p < 0.001), but log HCV-RNA levels remained unchanged (6.49 before phlebotomy vs 6.51 after phlebotomy). Interferon therapy did not improve ALT levels further. HCV-RNA levels were minimally reduced during interferon therapy (log HCV-RNA 6.49 before interferon vs 6.00 after 24 weeks of interferon therapy). Two patients achieved a virologic end of treatment response, both relapsed within 3 months after discontinuation of interferon. No patient achieved a sustained virologic response. CONCLUSIONS: In patients who previously failed treatment with interferon, iron depletion induced by phlebotomy improves ALT levels but is ineffective in achieving viral eradication in patients retreated with interferon 3 million units three times per week.     

Effect and side-effects of alpha interferon treatment in haemophilia patients with chronic hepatitis C

To evaluate the effect and side-effects of alpha interferon 2B (IFN) treatment in haemophilia patients with chronic hepatitis C (positive HCV antibody test, positive HCV-RNA test and ALT levels >2.5 × upper limit of normal) eight HIV and HBs-ag negative haemophilia patients were treated with IFN for 26 weeks in a dosage of 5 mega units (MU) daily for 2 weeks, 2.5 MU daily for 4 weeks and 1.5 MU 3 times a week for 20 weeks. Patients who were transient or non-responders after 26 weeks of IFN therapy were treated for 2.5 years with 5 MU IFN three times a week. At the end of 3 years follow-up, four patients were considered complete responders (HCV-RNA negative) with complete and sustained ALT normalization and disappearance from HCV-RNA from blood, two patients only showed a transient response and two patients were non-responders.
All patients experienced the common side-effects of IFN treatment. Two patients complained about feelings of depression and impotence. For both this was the reason to stop IFN treatment. In one patient, IFN treatment was stopped 90 weeks after start of therapy because of persistent fatigue. In another patient the dosage was adjusted because of a decrease in platelet count.
No effect of IFN on bleeding frequency and chronic arthopathy was seen.
We conclude that the clinical effects and side-effects of IFN therapy in patients with haemophilia and chronic hepatitis C are comparable with those of non-haemophilia patients with chronic hepatitis C. Haemophilia patients can be treated for chronic hepatitis C infection in the same way as patients without haemophilia.     

Effect of in vitro interferon-beta administration on hepatitis C virus in peripheral blood mononuclear cells as a predictive marker of clinical response to interferon treatment for chronic hepatitis C

AIM:To test whether in vitro incubation of peripheral blood mononuclear cells (PBMC) with interferon (IFN) could efficiently decrease hepatitis C virus-RNA (HCV-RNA) amount and to analyze whether this effect was associated with clinical response to IFN.METHODS:Twenty-seven patients with histologically proven chronic hepatitis C were given intravenous administration of 6 million units (MU) IFN-β daily for 6 weeks followed by three times weekly for 20 weeks. PBMC collected before IFN therapy were incubated with IFN-β and HCV-RNA in PMBC was semi-quantitatively determined.RESULTS: Twenty-five patients completed IFN therapy.Eight patients (32%) had sustained loss of serum HCV-RNA with normal serum ALT levels after IFN therapy (complete responders).HCV-RNA in PBMC was detected in all patients,whereas it was not detected in PBMC from healthy subjects.In vitro administration of IFN-β decreased the amount of HCV-RNA in PMBC in 18 patients (72%). Eight of these patients obtained complete response. On the other hand,none of the patients whose HCV-RNA in PBMC did not decrease by IFN-β was complete responders. Multiple logistic regression analysis revealed that the decrease of HCV-RNA amount in PBMC by IFN-β was the only independent predictor for complete response (P&lt;0.05).CONCLUSION:The effect of in vitro IFN-β on HCV in PBMC reflects clinical response and would be taken into account as a predictive marker of IFN therapy for chronic hepatitis C.     

Efficacy of ursodeoxycholic acid in association with alpha-interferon for chronic hepatitis C in alpha-interferon non-responder patients

BACKGROUND: The aim of the present study was to evaluate the effect of combined treatment with alpha-interferon (alpha-IFN) and ursodeoxycholic acid (UDCA) on liver function tests and serum HCV-RNA in patients with chronic hepatitis C who had not responded to alpha-IFN alone. METHOD: One hundred and three patients (60 men, 43 women, mean age 49 +/- 1.3 years) who had not responded (both HCV-RNA positive and increased serum ALT levels) to 4 consecutive months of treatment with alpha-IFN (3 MU three times weekly) were randomly assigned to receive UDCA (IFN-UDCA, 53 patients, 600 mg/day) in addition to the same alpha-IFN dose, or to continue alpha-IFN alone (IFN-controls, 50 patients). After stopping alpha-IFN, patients who had received UDCA continued to receive UDCA for an additional 6-month period. The two groups were comparable for sex, basal ALT, basal yGT, genotype distribution and liver histology, while mean age was lower in controls (53 +/- 1.8 vs 46 +/- 1.8 years; P< 0.01). RESULTS: Twenty (38%) out of 53 IFN-UDCA patients had normal ALT, compared with only six (12%) out of 50 IFN-control patients (P < 0.01). HCV-RNA became undetectable in four IFN-UDCA patients. Three months after withdrawal of alpha IFN, 15 IFN-UDCA responders, but none of the IFN-controls, had normal ALT values (P< 0.01); 6 months after withdrawal, nine IFN-UDCA responders still had normal ALT (P= NS) and HCV-RNA was still undetectable in four of them. Portal and periportal inflammation showed a statistically significant improvement (Fisher's exact test P< 0.01) in IFN-UDCA patients as compared with IFN-controls, while no effect was observed on portal fibrosis. CONCLUSIONS: These data demonstrate that UDCA improves the response rate to alpha-IFN. Furthermore, in 8% of IFN-UDCA patients the response rate was sustained and associated with HCV-RNA clearance.