Treatment of hepatitis C with interferon and ribavirin

Hepatitis C is a worldwide problem that frequently results in end-stage liver disease and its complications. Treatment for hepatitis C virus (HCV) has been rather ineffective but several recent studies have clarified the role of interferon and ribavirin therapy. In line with therapeutic progress in HIV infection, hepatitis C is now entering the era of multidrug antiviral therapy. Ribavirin is an orally active synthetic guanosine analogue with theoretical antiviral and immunomodulatory actions. In this review we have evaluated the role of interferon and ribavirin in treatment-naive patients, relapsers and non-responders. In naive patients the combination results in improved end-of-treatment and sustained response rates, with an overall 41% sustained virological response rate in patients treated for 48 weeks. Therapeutic benefit also extends to the traditionally difficult to treat patients (genotype 1, high vital load and advanced fibrosis). The addition of ribavirin to interferon has also resulted in an increased toxicity profile, which has made therapy more difficult for both the patient and managing physician. However, the significant improvement in response rates for all patients makes combination therapy the most appropriate choice as the first-line therapy for suitable patients with chronic viral hepatitis C. Appropriate management with interferon and ribavirin includes assessing the patient's HCV genotype to determine the optimal duration of therapy, assessing therapeutic efficacy by measuring HCV-RNA at 24 weeks and monitoring for the additional ribavirin side-effects.     

Weight loss during pegylated interferon and ribavirin treatment of chronic hepatitis C*

SUMMARY: Treatment of hepatitis C virus (HCV) infection with interferon (IFN)-alpha, as monotherapy or in combination with ribavirin, is associated with significant side-effects including weight loss. The aim of our study was to describe the evolution of body weight during combination antiviral treatment and to examine the possible determinants of weight loss. This was a retrospective analysis of 126 patients who received combination therapy of pegylated IFN-alpha-2b and ribavirin at our unit. Body weight was recorded at each outpatient attendance during treatment and follow-up, and was expressed as a percentage of baseline value. We observed a decline of body weight during treatment. Median (range) weight values at 4, 12, 24, and 48 weeks (expressed as percentage of baseline weight) were 97.7 (91.5-110.2), 95.4 (84.4-109.4), 93.7 (80.8-106.5), and 91.1 (80.1-103.6) respectively. There was no significant association of increased weight loss with age, gender, pretreatment weight, ethnicity, pretreatment histological stage, cumulative IFN dose (adjusted for body weight), HCV genotype or treatment outcome. Median body weight returned to baseline within 6 months of stopping treatment. Patients experience significant weight loss during combination therapy. Those experiencing greater weight losses during therapy did not benefit from improved antiviral response.     

Systematic review of the treatment of established recurrent hepatitis C with pegylated interferon in combination with ribavirin

The aim of our study was to conduct a systematic review of studies evaluating antiviral therapy with pegylated interferon (PEG-IFN) alfa in combination with ribavirin for the management of recurrent hepatitis C after liver transplantation. Data sources included electronic databases and a manual search. Studies evaluating the efficacy and tolerability of PEG-IFN alfa with ribavirin in patients with recurrent hepatitis C were selected for inclusion. The information extracted from each of the selected publications included study design details, patient characteristics, treatment regimens and efficacy and tolerability end points. Nineteen studies including 611 patients were identified. PEG-IFN alfa-2b was used in 16 studies. The mean rate of SVR was 30.2% (range, 8-50%). Dose reduction and discontinuation of treatment were common in these studies (73% and 27.6%, respectively). The lack of an early virologic response (EVR) at 3months of therapy was the most frequently described predictive factor of nonresponse. Treatment discontinuation and dose reductions due to adverse events were frequent and possibly represent important obstacles to attainment of SVR. EVR at 3months of treatment should be considered an important predictor of treatment outcome.     

Serum chemokine levels are associated with the outcome of pegylated interferon and ribavirin therapy in patients with chronic hepatitis C

Aim: Serum chemokine levels and amino acid substitutions in the interferon‐sensitivity determining region (ISDR) and core region have been associated with treatment outcome of pegylated interferon and ribavirin therapy in genotype 1 hepatitis C virus (HCV)‐infected patients. The present study was conducted to clarify the association between serum chemokines and treatment outcome in patients with chronic HCV‐1 infection in a Japanese cohort. Methods: A total of six serum chemokines were quantified before, during and after pegylated interferon and ribavirin treatment in 79 genotype 1 chronic HCV patients using a multiple bead array system. Viral ISDR and core region variants were determined by direct sequencing. Results: The baseline serum levels of eotaxin, IP‐10 and RANTES were significantly higher in chronic HCV patients than in controls. High levels of eotaxin and macrophage inflammatory protein (MIP)‐1β before therapy and more than two mutations in the ISDR were associated with a sustained virological response, and patients with more than two mutations in the ISDR also had significantly higher MIP‐1β levels. Receiver–operator curve analysis showed a 77% sensitivity and 73% specificity for predicting an SVR using MIP‐1β values. Conclusion: Serum MIP‐1β levels may predict the response to HCV treatment with pegylated interferon and ribavirin and are associated with amino acid substitutions in the ISDR.     

Cutaneous sarcoidosis in a chronic hepatitis C patient receiving pegylated interferon and ribavirin therapy

A 61‐year‐old Japanese woman suffered from a small, painful, subcutaneous nodule on the sole of her foot that was 10 mm across in diameter during pegylated interferon (PEG IFN) and ribavirin (RBV) combination therapy for chronic hepatitis C. Skin biopsy revealed multiple non‐caseating granulomas composed of epithelioid histiocytes with multinucleate giant cells, which was consistent with sarcoidosis. Ophthalmologic examination revealed uveitis. Thoracic computed tomography (CT) showed multiple bilateral hilar lymphadenopathies and a diffuse micronodular interstitial pattern of the lungs. Genetic analysis indicated a probable homozygous haplotype of A*02:01‐C*15:02‐B*51:01‐DRB1*16:02‐DQB1*05:02 in human leukocyte antigen regions. The patient was observed carefully without any additional medication because no significant systemic symptoms were noted. Combination therapy was continued for 2 months afterwards. She was asymptomatic for over 3 years of follow up, and repeated hematological and biological investigations and chest CT showed improvement. In conclusion, clinicians should bear sarcoidosis in mind as a complication during PEG IFN and RBV combination therapy. They should also be aware of the usually good prognosis of PEG IFN‐induced cutaneous sarcoidosis in order not to prematurely discontinue a treatment necessary for liver disease; maintenance of PEG IFN treatment may be advised with careful follow up.     

Results of combination treatment with pegylated interferon and ribavirin in cirrhotic patients with hepatitis C infection.

BACKGROUND: The treatment of hepatitis C patients with advanced cirrhotic liver disease remains challenging and data on the outcome of treatment for this patient group is limited. RESULTS: Between September 2000 and August 2004, 61 cirrhotic patients started treatment with pegylated interferon and ribavirin (42 male, age range 29-69 years, 26 Asian). Forty-three (70%) patients were serum hepatitis C virus (HCV) RNA negative at the end of treatment and 24 (39%) achieved a sustained virological response (SVR). SVR was achieved for 35% (6/17) of patients with genotype 1, and for 39% (16/41) with genotype 3. Caucasians with genotype 3 demonstrated a higher cure rate (SVR 10/18 = 56%) than Asians (SVR 6/24 = 25%). Failure to achieve SVR was associated with lower platelet count, neutrophil count and albumin at baseline. Twenty patients suffered clinical or laboratory decompensation, five patients required hospitalization, and two patients died. Patients who experienced hepatic decompensation were older and had baseline characteristics associated with more advanced liver disease. CONCLUSION: The treatment of patients with advanced HCV is challenging, although many treated patients achieve SVR. Significant toxicity is experienced and there is treatment-related mortality. This balance of efficacy and toxicity needs to be considered before commencing treatment.     

Enhanced efficacy of pegylated interferon alpha‐2a over pegylated interferon and ribavirin in chronic hepatitis C genotype 4A randomized trial and quality of life analysis

Aim: The therapy of chronic hepatitis C genotype 4 (HCV‐4) has not been optimized yet. This randomized, prospective, parallel‐group clinical trial compared the efficacy and safety of pegylated interferon α‐2a (PEG‐IFN α‐2a) plus ribavirin and PEG‐IFN α‐2b plus ribavirin and assessed the health‐related quality of life (HRQOL) in patients with chronic HCV‐4. Methods: Eligible patients with proven chronic HCV‐4 were randomized to receive either a weekly dose of PEG‐IFN α‐2a (180 μg) or PEG‐IFN α‐2b (1.5 μg/kg) and a daily dose of ribavirin (1000–1200 mg) for 48 weeks with 24 weeks post‐treatment follow‐up. The primary end point was sustained virological response (SVR) defined by undetectable HCV RNA 24 weeks after treatment. The Short form‐36 Health Survey version 2 (SF‐36v2) and the Chronic Liver Disease questionnaires (CLDQ) were assessed before, during and after therapy. Results: The overall SVR rate of the entire cohort was 59.9%. The SVR rates were significantly higher in patients treated with PEG‐IFN α‐2a and ribavirin (Group A; n=109) compared with those treated with PEG‐IFN α‐2b and ribavirin (Group B; n=108, 70.6 vs. 54.6%, respectively; P=0.017). The relapse rates were 5.1% for PEG‐IFN α‐2a and 15.7% for PEG‐IFN α‐2b (P=0.0019). The SF‐36v2 and CLDQ were low during therapy and improved significantly after therapy successful therapy. Conclusion: Pegylated interferon α‐2a plus ribavirin was significantly more effective than PEG‐IFN α‐2b and ribavirin therapy in the treatment of chronic HCV‐4 patients. The tolerability and adverse events were comparable between the two regimens. The HRQOL improved significantly after successful PEG‐IFN α‐2a plus ribavirin therapy.     

A multicenter survey of re‐treatment with pegylated interferon plus ribavirin combination therapy for patients with chronic hepatitis C in Japan

Aim: This study aimed to clarify the factors associated the efficacy of re‐treatment with pegylated interferon (PEG IFN) plus ribavirin combination therapy for patients with chronic hepatitis C who had failed to respond to previous treatment. Methods: One hundred and forty‐three patients who had previously shown relapse (n = 79), non‐response (n = 34) or intolerance (n = 30) to PEG IFN plus ribavirin were re‐treated with PEG IFN plus ribavirin. Results: Twenty‐five patients with intolerance to previous treatment completed re‐treatment and the sustained virological response (SVR) rates were 55% and 80% for hepatitis C virus (HCV) genotype 1 and 2, respectively. On re‐treatment of the 113 patients who completed the previous treatment, the SVR rates were 48% and 63% for genotype 1 and 2, respectively. Relapse after previous treatment and a low baseline HCV RNA level on re‐treatment were associated with SVR in genotype 1 (P < 0.001). Patients with the interleukin‐28B major genotype responded significantly better and earlier to re‐treatment, but the difference in the SVR rate did not reach a significant level between the major and minor genotypes (P = 0.09). Extended treatment of 72 weeks raised the SVR rate among the patients who attained complete early virological response but not rapid virological response with re‐treatment (72 weeks, 73%, 16/22, vs 48 weeks, 38%, 5/13, P < 0.05). Conclusion: Relapse after previous treatment and a low baseline HCV RNA level have predictive values for a favorable response of PEG IFN plus ribavirin re‐treatment for HCV genotype 1 patients. Re‐treatment for 72 weeks may lead to clinical improvement for genotype 1 patients with complete early virological response and without rapid virological response on re‐treatment.     

Impact of early elevation of serum bilirubin during treatment with pegylated interferon and ribavirin in patients with chronic hepatitis C

Aim: Hemolytic anemia is a well‐known adverse effect of interferon and ribavirin combination treatment. Herein, we analyzed the impact of early elevation of serum bilirubin level as a marker for predicting severe anemia during treatment. Methods: We studied 245 chronic hepatitis C patients who received pegylated interferon and ribavirin combination treatment, and divided them using two different threshold levels: (i) elevation of total bilirubin of 0.5 mg/dL or more within 1 week of starting treatment; and (ii) drop of hemoglobin (Hb) by 3 g/dL or more within 4 weeks of starting treatment. We compared the dynamics in each group and then investigated independent factors for predicting a severe Hb drop (≥3 g/dL) at 4 weeks after beginning treatment and dose reduction of ribavirin. Results: Total bilirubin levels at 1 week were significantly higher in patients with a Hb drop of 3 g/dL or more as compared to those with a drop of less than 3 g/dL (P < 0.0001). Hb levels at 4 weeks were significantly lower in the group of 0.5 mg/dL or more increase of total bilirubin levels than in the group with a less than 0.5 mg/dL increase (P < 0.0001). Therefore, elevation of total bilirubin after 1 week of treatment was shown to be an independent factor for predicting severe Hb drop (≥3 g/dL) at 4 weeks (P < 0.0001), and dose reduction of ribavirin during treatment (P = 0.0321). Conclusion: Early elevation of serum bilirubin level was found to be a possible predictive marker of both a severe drop of Hb in the early phase of treatment and dose reduction of ribavirin.     

Comparison of low-dose pegylated interferon versus standard high-dose pegylated interferon in combination with ribavirin in patients with chronic hepatitis C with genotype 3: an Indian experience

Background and Aims: In chronic hepatitis C virus (HCV) infection with genotype 3, therapy with pegylated interferon (peg‐IFN) alfa‐2b in a dose of 1.5 μg/kg/week and ribavirin (800–1000 mg/day) is recommended for 24 weeks. Reduced doses of peg‐IFN may increase compliance and decrease cost and adverse events. This study aimed to assess the safety and efficacy of two different regimens of peg‐IFN alfa‐2b, in combination with ribavirin, in genotype 3 patients. Methods: A total of 103 liver biopsy–proven chronic HCV patients with genotype 3, having alanine aminotransferase levels >1.2 × ULN and positive HCV‐RNA were randomized into two groups: group I (n = 76; age, 43.1 ± 11.4 years; male/female, 67/9) received peg‐IFN 1.0 μg/kg/week + ribavirin 10.6 mg/kg/day, while group II (n = 27; age, 37.3 ± 11.6 years; male/female, 21/6) received peg‐IFN 1.5 μg/kg/week + ribavirin 10.6 mg/kg/day. Patients in both groups were treated for 24 weeks. End of treatment viral response (ETVR) and sustained viral response (SVR) after a 6‐month follow‐up period were assessed. Results: In both groups I and II, one patient was lost to follow‐up, while one patient in group II withdrew due to side‐effects. ETVR was seen in 72/76 (94.7%) of patients in the low dose group and 24/27 (88.9%) of patients in the high dose group (P = 0.375). SVR was seen in 60/76 (78.9%) of patients in the low dose group and 25/27 (92.6%) of patients in the high dose group (P = 0.145). Age (Pearson correlation coefficient = 0.263; P = 0.008) and fibrosis (correlation coefficient, 0.263; P = 0.008) showed a significant correlation with the SVR. Conclusion: In patients with genotype 3, peg‐IFN at 1.0 μg/kg/week with ribavirin is as effective as peg‐IFN at 1.5 μg/kg/week with ribavirin.     

Therapeutic effects of pegylated interferon plus ribavirin in chronic hepatitis C patients with occult hepatitis B virus dual infection

Background and Aim: Occult hepatitis B virus (HBV) infection is defined by the detectable serum HBV–DNA in HBV surface antigen‐negative patients. This retrospective study aims to evaluate the therapeutic effects of combined pegylated interferon (PEG–IFN) plus ribavirin (RBV) in patients with concurrent occult HBV/hepatitis C virus (HCV) dual infection. Methods: In total, 126 consecutive chronic hepatitis C (CHC) patients who received combined PEG–IFN and RBV therapy were included. Patients were divided into the occult HBV/HCV dual infection group or the HCV‐monoinfected group according to whether or not they had the detectable serum HBV–DNA. The biochemical and virological responses to combined therapy were compared between these two groups. Serum HCV‐RNA and HBV–DNA were checked before treatment, at the end of treatment as well as at 6‐ and 12‐months' follow up in the occult HBV/HCV group. Result: Six patients were seropositive for HBV–DNA and were included in the occult HBV/HCV dual infection group. There were no statistical differences in the biochemical and virological responses to combined therapy between these two groups. Undetectable serum HBV–DNA was noted at the end of the treatment and the 6‐ and 12‐months' follow up in patients with occult HBV/HCV dual infection. Conclusion: Occult HBV infection in CHC patients is rare. The biochemical and virological responses to combined PEG–IFN and RBV therapy might be similar in CHC patients with or without occult HBV infection. The serum HBV–DNA level was low in patients with occult HBV/HCV dual infection who responded to combined therapy.     

Negative HCV-RNA 2 weeks after initiation of treatment predicts sustained virological response to pegylated interferon alfa-2a and ribavirin in patients with chronic hepatitis C

Abstract

Objective. The aim of this study was to examine the early viral kinetics as predictor for sustained virological response (SVR) during hepatitis C treatment. Materials and methods. We included patients with biopsy-proven chronic hepatitis C and ALT above the upper limit of normal, who received a standard treatment of pegylated interferon alfa-2a and ribavirin. The HCV–RNA concentration (limit of detection 20 IU/mL) was determined at days 0, 1, 2, 3, 4, 7, 14, 21 and monthly thereafter. Results. Among 46 patients who completed the trial, 30 (65%) had SVR. Low baseline viral load, IL28B genotype CC and absence of cirrhosis were statistically associated with SVR. In multivariate analysis only absence of cirrhosis and HCV–RNA negativity at day 14 were independent predictors for SVR. Eight patients who became HCV–RNA negative on day 14 as well as 13 of 14 patients (93%) with HCV–RNA levels of <1000 IU/mL at day 7 obtained a SVR. Among 8 of 18 (44%) genotype 1 and 4 patients with more than a one log drop in HCV–RNA titer at day 7, 75% achieved SVR. Conclusions. We observed a correlation between low HCV–RNA titers in week 2 and SVR during pegylated interferon/ribavirin-based treatment. This may help identify a group of patients for whom SVR may be obtained without the addition of directly acting antivirals, and thereby save the patients for unnecessary side effects and the health care system for additional costs.     

Acute and chronic immune biomarker changes during interferon/ribavirin treatment in HIV/HCV co‐infected patients

Chronic viral infections lead to persistent immune activation, which is alleviated by eradicating or suppressing the infection. To understand the effects of interferon treatment on immune system activation by chronic infections, we evaluated kinetic patterns of a broad spectrum of serum biomarkers during HCV treatment in HIV/HCV co‐infected patients. HCV viral load and 50 biomarkers were analysed at baseline and 27 time points during pegylated interferon‐alpha and ribavirin (IFN/RBV) treatment of 12 HIV/HCV co‐infected patients. We evaluated biomarker changes from baseline for each time point and biomarker correlations with clinical parameters, treatment response and liver histopathology. IL‐1α, IL‐12p40, IL‐1RA, IP‐10, MIG, MIP‐1α/1β, HGF, sCD40L, TRAIL and leptin increased in the first day. IL‐12p70, IL‐17A, IL‐10, GROα, IL‐8, MCP‐3, IL‐4 and M‐CSF peaked later during week 1. IL‐1α, HGF, IP‐10, MIP‐1α, TRAIL, sCD40L, IL‐10, IL‐12p70, MCP‐3, FGFb, ENA‐78, TGF‐β, IL‐2, IFN‐γ, IL‐6, IL‐15, IL‐7 and PDGF‐BB decreased below baseline over the course of treatment. Higher BMI, baseline HCV viral load and leptin levels were associated with lack of sustained virologic response. ENA‐78 was associated with sustained viral response. Positive correlations were found between liver inflammation and baseline CD4 count, sVCAM and HGF; fibrosis stage and HGF; liver steatosis, BMI and leptin. Our findings suggest IFN/RBV treatment initially increases levels of several biomarkers, but eventually leads to a decline in many immune markers. These findings shed light on the relationship between IFN treatment and immune activation by chronic viral infections, such as HCV.     

Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1

Background and Aims: Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1. Methods: Seventy patients with either genotype 6 or genotype 1 were recruited. Both groups received 800–1200 mg of ribavirin daily plus either 180 mg of pegylated α‐interferon‐2a or 1.5 mg/kg pegylated α‐interferon‐2b weekly for 48 weeks. Their responses to treatments were compared. Results: The early virological response to combination therapy of patients with genotype 6 was significantly better than that of genotype 1 (88.6% vs 74.3%, P = 0.03). Significant difference was also identified in the end of treatment response of the two genotypes (60% vs 81.4% for genotype 1 and 6, respectively; P = 0.005). The sustained virological response (SVR) to treatment in patients with genotype 6 was also significantly superior to that of patients with genotype 1 (75.7% vs 57.1%, P = 0.02). Multiple logistic regression analysis demonstrated that age of 55 years or less, genotypes of hepatitis C virus, liver biopsy staging and baseline hepatitis C virus RNA of 200 000 IU/mL or less were independent predictors for better SVR in this cohort. Conclusion: Patients with chronic hepatitis C genotype 6 respond better to pegylated interferon and ribavirin combination treatment than patients with genotype 1.     

Combined alpha interferon and ribavirin for the treatment of hepatitis C in patients with hereditary bleeding disorders

Patients with hereditary bleeding disorders who received non-virally inactivated plasma-derived clotting factor concentrates before the mid-1980s invariably became infected with hepatitis C virus (HCV). Therapy with interferon alpha (IFN-alpha) alone has been disappointing in this group. We conducted an open-label study, using a combination of IFN-alpha2b (3 million units three times per week) and ribavirin 1-1.2 g/d in 28 patients with hereditary bleeding disorders. Twenty-one of the 28 patients had liver biopsy-confirmed chronic hepatitis (median histological activity index 5; range 1-10) and all patients were HCV RNA positive by PCR. Virological response rate to therapy at 3 months was 82% (23 out of 28). Three HIV co-infected patients showed an early virological response with loss of HCV RNA, but two subsequently relapsed after 3 and 6 months of therapy. Four patients stopped treatment early (one at 4, one at 7 and two at 9 months) because of treatment-related side effects, although three of these have maintained a virological response. Seventeen patients completed the 48-week course. Twenty of the 28 (71%) treated have had a durable virological response with a median follow-up of 16 months (range 1-24). Combination therapy represents a significant advance in the treatment of hepatitis C in patients with hereditary bleeding disorders.     

Single centre experience with pegylated interferon and ribavirin for hepatitis C: looking back before moving forward

Background: Hepatitis C treatment is successful in 40–80% of patients in drug sponsored registration trials. However, few studies have examined treatment outcomes in non‐trial, routine clinical practice settings. Aim: The aim of this study was to investigate the treatment outcomes and predictors of a sustained virological response in a routine clinical setting. Methods: Data were collected retrospectively on patients treated for hepatitis C between January 2004 and March 2010 in a tertiary hospital setting. Demographics, treatment outcomes and potential predictors of outcome (viral genotype, viral load, virological response, platelet count, alanine transaminase level, glucose, ferritin, weight, fibrosis and cirrhosis, compliance, dose reductions, adverse events, psychiatric and alcohol history) were recorded. Univariate and multiple logistic regressions were performed. Results: A total of 405 patients was treated during the study period. On an intention to treat basis, sustained virological response rates were 55%, 82% and 72% in genotypes 1, 2 and 3 respectively. Predictors of response were gender, age, genotype, weight, fibrosis, cirrhosis, platelet count and alanine transaminase on univariate analysis. Age, genotype, cirrhosis and platelet count were independently associated with sustained virological response on multiple logistic regression. Conclusion: In our cohort, treatment outcomes for genotype 1 and 2 were similar to results from clinical trials but results for genotype 3 were inferior. Clinicians should not assume that results from registration trials are transferable to their own clinical practice. This has particular relevance for the new era of triple therapy regimens containing direct antivirals.     

Prospective study of bone mineral density and metabolism in patients with chronic hepatitis C during pegylated interferon alpha and ribavirin therapy

The importance of osteoporosis as a complication of end-stage liver disease is well known. However, significant osteopenia may occur in earlier stages of chronic hepatitis C (CHC). Furthermore, antiviral therapy may influence bone metabolism. Thirty patients with CHC genotype 1 infection and without established cirrhosis were treated with peginterferon-alfa and ribavirin. Dual-energy x-ray absorptiometry was performed at baseline, after 48 weeks of therapy, and by the end of a 24-week follow-up period. Bone mineral density (BMD), T-scores, and Z-scores were assessed. Serum C-terminal propeptide of type I collagen (CICP) and osteocalcin levels were measured. Thirteen patients had osteopenia (43%) and osteoporosis was present in four patients (13%). Antiviral therapy led to significant on-treatment increases of lumbar spine and hip BMD (P < or = 0.05) as well as T-scores (P < or = 0.05) and Z-scores (P < or = 0.01) irrespective of subsequent treatment response. Further analyses showed that in patients with sustained virological response (n = 19) most parameters remained highly above baseline values by the end of the 24-week follow-up period, while patients with virological relapse (n = 11) had decreases of BMD, T-scores and Z-scores thereafter that did not differ from baseline. Serum CICP and osteocalcin levels decreased during therapy. Osteocalcin levels remained below baseline in sustained responder, but showed an increase in relapsers by the end of the 24-week follow-up (P < or = 0.05). Osteopenia is detectable in a substantial proportion of CHC patients without established cirrhosis. Antiviral therapy leads to an on-treatment increase of BMD, which may last in those patients who achieve a sustained virological response.     

Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients

Standard therapy for chronic hepatitis C (HCV) is pegylated interferon in combination with ribavirin. There is limited experience with either drug in dialysis [end stage renal disease (ESRD)]. Six haemodialysis patients, four with HCV genotype 1, one with genotype 4 and one genotype 2 were treated with pegylated interferon-alfa-2b (n = 4) and pegylated interferon-alfa-2a (n = 2) for 24-48 weeks according to genotype with a dose of 50 or 135 mug/week respectively. All patients were given reduced ribavirin doses, initially 200-400 mg/day. Ribavirin trough plasma concentrations were measured with a HPLC method previously developed for earlier treatment studies, aiming at a target concentration of 10-15 micromol/L. Interferon related side-effects were common, in one patient peg-alfa-2b was permanently reduced to 50 mug every 9-10 days with improvement in tolerance. Average ribavirin dose was 170-300 mg/day. Ribavirin-induced anaemia was treated with high doses of erythropoietin and low doses of iron. Blood-transfusions were not needed. All patients became HCV-RNA-PCR negative during treatment which was completed or nearly completed in four patients. One patient terminated therapy prematurely due to pronounced interferon related side-effects and another died of myocardial infarction probably not related to therapy. Three patients have remained HCV-RNA negative with extended follow-up, two of whom have had a successful kidney transplant. Pegylated interferons are likely to become a valuable addition for HCV therapy in ESRD and are possible to combine with ribavirin. However the pharmacokinetics and tolerability of both peg-alfa-2a and 2b need to be studied more closely in prospective studies before definite dosing recommendations can be made.