Weight-based dosing: which impact on efficacy and safety of therapy?

Pegylated interferons (PEG-IFNs) in combination with ribavirin represent the most recent advance in the treatment of patients with chronic hepatitis C (CHC): two large clinical trials have shown a superior efficacy in clearing HCV in almost 60% of treated naïve patients. Responses to antiviral treatment of CHC vary according to both viral and host factors. Managing patients with CHC infection requires individualised treatment strategies to optimise outcomes. Several landmark publications on PEG-IFNs have reported that weight is a significant predictive factor for SVR in the treatment of CHC with fixed-dose drug administration. With fixed-dose treatment, there is a direct correlation between increasing body weight and decreasing rate of SVR. As patient's weight increases, fixed-dose therapy provides proportionately lower amounts of drug. Therefore, under this dosing scheme, heavier patients do not have an equal chance at achieving SVR as do lighter patients. Unfortunately though, lighter patients may also suffer, as fixed dosing can provide these patients with an excessive amount of drug, increasing their risk for adverse events. Individualised weight-adjusted dosing of both PEG-IFN and ribavirin might represents the best treatment strategy to assure that all patients have the same opportunity to achieve SVR.

Pegylated interferon α plus ribavirin for the treatment of chronic hepatitis C: a multicentre independent study supported by the Italian Drug Agency.

BACKGROUND: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in "real world" chronic hepatitis C patients in Italy. METHODS: Independent observational multicentre study including consecutive patients receiving Peg-interferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. RESULTS: 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase: 325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) during the prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%). During multivariate analysis genotypes 2/3 were significantly associated with higher sustained virological response rates; cirrhosis and γ-glutamil-transpeptidase >2 times the normal limit were associated with poorer response. CONCLUSIONS: The response to Peg-interferon/ribavirin therapy in "real world" clinical practice is distinctly lower than in registration trials. The difference in response rates was more pronounced among easy-to-treat than among difficult-to-treat hepatitis C virus genotypes.

Current practice of hepatitis C treatment in Southern Italy.

BACKGROUND: Only a small proportion of subjects referring to hospitals for hepatitis C virus (HCV) positivity receives antiviral therapy. AIM: To evaluate the rate of antiviral treatment and the causes for no treatment in HCV-RNA positive subjects seen in hospital settings. PATIENTS AND METHODS: A prospective study enrolling over a 6-month period (February-July 2009) all consecutive anti-HCV positive subjects initially referred (naïve patients) to 12 liver units in Southern Italy for HCV treatment. RESULTS: Out of 608 subjects evaluated, 74 (12.2%) had no detectable HCV-RNA in the serum and thus were excluded. Of the remaining 534 HCV-RNA positive subjects, 357 (66.9%) were not treated for the following reasons: 49.9% were older than 65 years of age (75% of them >70 years), 14.3% had normal liver enzymes, 13.2% had compensated/decompensated cirrhosis, 10.4% refused treatment, 9.8% had ongoing substance or alcohol abuse. Multivariate analysis showed that females (O.R. 2.27; C.I. 95% 1.05-4.90) and subjects with low educational level (O.R. 4.38; C.I. 95% 1.27-15.11) were more likely to decline therapy. CONCLUSIONS: The majority of patients with HCV infection does not receive antiviral treatment. The effectiveness of the current standard therapy for HCV infection is low despite its good efficacy.

Pegylated interferon therapy in chronic hepatitis C: lights and shadows of an innovative treatment.

Pegylated interferon (PEG-IFN) in combination with ribavirin is the standard of treatment for chronic hepatitis C. Several viral and host factors influence the outcome of treatment, such as hepatitis C virus (HCV) genotype, baseline viral load, viral kinetics, race, body weight, advanced liver disease, HIV co-infection, and adherence to therapy. Monitoring the response of HCV to treatment during the early time points (4 weeks or 12 weeks) after initiation of therapy has emerged as a critical tool to predict sustained virologic response (SVR), defined as undetectable serum HCV RNA 24 weeks after the end of therapy. To counterbalance the influence of host and viral factors, treatment duration can be individualised to achieve an optimal treatment outcome, potentially reduce costs, and minimize side effects.

Peg-interferon alone or combined with ribavirin in HCV cirrhosis with portal hypertension: a randomized controlled trial.

BACKGROUND/AIMS: Risks and benefits of antiviral therapy in HCV cirrhosis with portal hypertension are poorly known. METHODS: We performed a randomized controlled trial in 102 HCV patients with compensated cirrhosis and portal hypertension: 51 received 1 microg/kg/week of Pegylated-interferon alpha-2b and 51 Pegylated-interferon plus 800 mg/day of ribavirin up to 52 weeks. RESULTS: By intention-to-treat analysis, five patients on monotherapy and eleven on combination therapy achieved a sustained virological response (9.8% vs. 21.6%, p=0.06). The response was more frequent for genotypes 2 or 3 than genotype 1 (66.6% vs. 11.3%, p=0.001). Genotype 1, who had low viral load at start of therapy, were HCV-RNA negative at 4 weeks, and were adherent to the scheduled therapy had a higher probability of sustained virological response. Patients with sustained virological response had less disease events compared to nonresponders (6.2% vs. 38.3%, p=0.03 by log rank test) during follow-up. CONCLUSIONS: In HCV cirrhosis with portal hypertension Peg-interferon plus ribavirin is a feasible treatment. Although the rate of viral eradication is modest, tailoring by genotype and early viral response allows to keep patients on treatment who are more likely to have viral eradication. Patients with viral eradication have fewer disease complications during follow-up.