Combination PEG-IFN a-2b/ribavirin therapy following treatment of hepatitis C virus-associated hepatocellular carcinoma is capable of improving hepatic functional reserve and survival.

BACKGROUND/AIMS: Hepatitis C virus (HCV) associated HCC shows a high rate of recurrence even after curative treatment. Outcomes of pegylated interferon PEGIFN a-2b/ribavirin (RBV) therapy for HCV-associated HCC have yet to be elucidated. We investigated therapeutic response and hepatic functional reserve improvement in patients receiving PEG-IFN a-2b/RBV after curative HCC treatment. METHODOLOGY: We investigated survival rate, metachronous recurrence and hepatic functional reserve in 54 patients with initial HCV-associated Stage I/II HCC; 29 patients were administered a preparation of PEG-IFN a-2b/RBV after HCC treatment (Secondary IFN group) and 25 were not (Non-secondary IFN group). RESULTS: A significant difference was observed in cumulative survival rates among HCV-associated HCC patients with rates of 100% after 1 year and 90.2% after 3 years in the secondary IFN group compared to 96.0% and 61.2%, respectively, in the non-secondary IFN group. Univariate analysis identified secondary IFN treatment, alanine aminotransferase and albumin levels as factors contributing to survival. Serum albumin level decreased temporarily but subsequently increased and improved hepatic functional reserve was observed in PEG-IFN a-2b/RBV therapy. CONCLUSIONS: PEG-IFN a-2b/RBV therapy after HCC treatment can improve hepatic functional reserve and may therefore represent a therapeutic option in the event of recurrence. PEG-IFN a-2b/ RBV therapy following HCC treatment shows promise for improving the prognosis of HCC.

Surfactant protein-D is more useful than Krebs von den Lungen 6 as a marker for the early diagnosis of interstitial pneumonitis during pegylated interferon treatment for chronic hepatitis C.

BACKGROUND/AIMS: To examine the usefulness of serum Krebs von den Lungen 6 (KL-6) and surfactant protein-D (SP-D) as markers of interstitial pneumonitis. Many antiviral therapies have become available for chronic hepatitis C, including pegylated interferon (PEGIFN) plus ribavirin. Since interstitial pneumonitis is a serious adverse drug reaction during interferon therapy, interferon treatment requires caution in respiratory disease patients. Hence, the predictors of interstitial pneumonitis have not been elucidated. METHODOLOGY: Fifty-two chronic hepatitis C patients who received PEG-IFN plus ribavirin were studied; 14 patients received PEGIFN-α 2a, and 38 received PEG-IFN-α 2b. Serum KL-6 and SP-D levels were measured during treatment. Time changes in serum KL-6 and SP-D levels, as well as the presence of interstitial pneumonitis, were investigated. RESULTS: No cases of pneumonitis in which both markers were below the standard values were seen. Interstitial pneumonitis developed in 1 of the 5 patients in whom both markers were above standard values. Patients whose KL-6 levels alone exceeded the standard value had bacterial pneumonia and emphysema, not interstitial pneumonitis. Though no correlation between SP-D and KL-6 levels was observed, KL-6 levels tended to increase after interstitial pneumonitis was detected on imaging, but SP-D levels increased before imaging detection. CONCLUSIONS: It is important to monitor changes in levels of serum markers and other factors to avoid interstitial pneumonitis during PEG-IFN therapy. SP-D in particular may be important for early detection of interstitial pneumonitis.

Failure to achieve 2-log10 viral decrease in first four weeks of peg-IFNalpha-2b plus ribavirin therapy for chronic hepatitis C with genotype 1b and high viral titer is useful in predicting non-response: evaluation of response-guided therapy.

BACKGROUND/AIMS: To clarify clinical parameters predicting sustained viral response (SVR) during 48 weeks pegylated-interferon (peg-IFN)alpha-2b plus ribavirin therapy for Japanese patients with chronic hepatitis C [CH(C)] genotype 1b and high viral titers. METHODOLOGY: One hundred and fifty-one (151) patients receiving peg-IFNalpha-2b plus ribavirin therapy for 48 weeks were enrolled. SVR and clinical parameters were evaluated. The relationship between virological parameters (substitutions in the core and NS5A) and the degree of early viral decrease was also studied. RESULTS: Seventy (46.4%) patients achieved SVR (per protocol analysis). Negative predictive value (NPV) of <2-log10 decrease after 4 weeks of therapy for SVR was 78.0%; similar to that for failing to achieve early viral response (EVR) at 12 weeks (82.2%). CONCLUSIONS: Failure to achieve 2- log10 decrease in the first 4 weeks may be an important predictor of non-SVR during 48 weeks of peg-IFNalpha-2b plus ribavirin therapy; thus, therapeutic plans should be reassessed at that point.

Complete early virological response was highly achieved by double filtration plasmapheresis plus IFN-beta induction therapy for HCV-1b patients with relapse or no response after previous IFN therapy.

The efficacy of double filtration plasmapheresis (DFPP) plus interferon (IFN)-ß induction therapy was preliminarily investigated in re-treated patients with chronic genotype 1b hepatitis C and high viral load (patients with relapse or non-response to previous IFN therapies). In eight patients with chronic hepatitis C, DFPP was performed five times over 2 weeks during IFN-ß therapy, and 3 MU of IFN-ß was administered twice a day for 2 weeks. Combination therapies with ribavirin and pegylated IFN-α2b (PEG-IFN-α2b) or pegylated IFN-α2a (PEG-IFN-α2a) were subsequently used. After 4 weeks, hepatitis C virus (HCV)-RNA tended to be more greatly decreased with DFPP combination therapy than with previous IFN therapy (4.5 ± 2.0 log(10) IU/mL vs. 2.9 ± 1.2 log(10) IU/mL). Rates of both rapid virological response and complete early virological response were significantly higher with DFPP and IFN-ß induction therapy than with previous IFN therapy. DFPP plus IFN-ß induction therapy produced a great reduction of viral load during the early stage of treatment and achieved a high early virological response, suggesting that this combination therapy may be useful as a new treatment modality for chronic hepatitis C patients in difficult-to-treat states. This combination may contribute to sustained virological response (SVR). The effects of DFPP on SVR and its significance remain to be clarified.