Efficacy of pegylated interferon plus ribavirin combination therapy for hepatitis C patients with normal ALT levels: A matched case-control study

Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Journal of Gastroenterology (Impact Factor: 4.52). 08/2011; 46(11):1335-43. DOI: 10.1007/s00535-011-0455-1
Source: PubMed


The antiviral effect of pegylated interferon (Peg-IFN) plus ribavirin combination therapy in chronic hepatitis C (CHC) patients with normal alanine aminotransferase (ALT) levels (N-ALT) has been reported to be equivalent to that for patients with elevated ALT levels (E-ALT). However, the actual antiviral effect in N-ALT patients remains obscure because efficacy can be overestimated in patients with an advantageous background.
In this study, 386 patients were extracted, for a matched case-control study, from 1320 CHC patients treated with Peg-IFN alpha-2b plus ribavirin combination therapy; 193 N-ALT patients [116 with hepatitis C virus genotype 1 (HCV-1), 77 with HCV genotype 2 (HCV-2)] were matched with 193 E-ALT patients by a propensity score method using the variables of age, sex, IFN treatment history, body mass index, and platelet counts.
On multivariate analysis for sustained virological response (SVR) in N-ALT patients, younger age, low HCV RNA level at baseline, and HCV-2 were significant factors. The matched case-control study showed that the SVR rates of N-ALT patients were equivalent to those of E-ALT patients; at 49 and 40% in the HCV-1 group (P = 0.146), and 78 and 81% in the HCV-2 group (P = 0.691). However, in N-ALT patients with non-SVR, approximately 40% showed ALT elevation at 24 weeks post-treatment.
Our findings indicate that the antiviral effect of Peg-IFN plus ribavirin therapy in N-ALT patients is comparable to that for E-ALT patients irrespective of their advantageous background; however, the application of this therapy for N-ALT patients, especially for those with HCV-1, should be considered carefully.

6 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis C virus (HCV) infection causes chronic hepatitis, which frequently leads to hepatic fibrosis and hepatocellular carcinoma (HCC). Alanine aminotransferase (ALT) is a biomarker of hepatocyte injury and is associated with the progression of hepatic fibrosis. Advanced hepatic fibrosis also predisposes HCV carriers to a risk of HCC. In contrast, some cases with persistent HCV infection have normal ALT levels that persist for a long time, and these HCV carriers have no or mild hepatitis and hepatic fibrosis. These HCV carriers are defined as persistent normal ALT (PNALT) cases and their risk of HCC is low compared to HCV carriers with abnormal ALT. However, there are various definitions of normal ALT and PNALT, and advanced hepatic fibrosis may be missed without a liver biopsy. In addition, there is also a risk of ALT elevation in HCV carriers with PNALT, which increases the risk of progression to hepatic fibrosis and HCC. Most HCV carriers with PNALT have asymptomatic or nonspecific symptoms. HCV carriers with PNALT are also considered to be responsive to interferon-based treatment. Thus, assessment of hepatic fibrosis is important in HCV carriers, and the eradication of HCV infection is more likely in HCV carriers with evidence of hepatic fibrosis, regardless of their ALT levels.
    Hepatitis Monthly 02/2012; 12(2):77-84. DOI:10.5812/hepatmon.829 · 1.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: In this study, our objective is to evaluate histological changes in livers of hepatitis C virus (HCV)-infected patients with normal alanine aminotransferase (ALT) levels. Methods: 72 patients over 16 years old, with chronic hepatitis C (CHC) and normal ALT levels were evaluated in this multicenter retrospective study. Persistently normal ALT level was defined as 2 or 3 normal ALT levels at intervals of at least 1 month during 6 months. Demographic data, year of diagnosis, at least 2 ALT values within 6 months, hepatitis markers, results of HCV RNA and the liver biopsy were all evaluated. Serological markers have been tested with different kits. HCV RNA has been studied by RT-PCR with dynamic range and sensitivity of different kits. All biopsies were evaluated again by the same pathologist. Results: The mean age was 44±13 years and 61.1% were female. HCV RNA levels were between 1.53x102-1.13x108 IU/ml. The mean ALT levels were 30.3±9.6 IU/lt. The mean grade of necroinflammation was 4.67±1.96 and mean staging of fibrosis was 1.03±1.13. The ratios of minimal, mild and moderate activity in the liver biopsies were 48.6%, 45.3% and, 2.8%, respectively. Rate of portal-periportal fibrosis, bridging fibrosis and incomplete cirrhosis were 51.4%, 6.9%, and 1.4%, respectively. Conclusions: ALT level is a poor indicator of liver disease activity in patients with CHC. Patients with indication for treatment should be evaluated for liver biopsy.
    Klimik Dergisi 09/2012; 25(1):19-23. DOI:10.5152/kd.2012.06
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: This study was conducted to evaluate Japanese treatment guidelines for patients with chronic hepatitis C virus (HCV) infection and normal alanine aminotransferase (N-ALT) levels from the viewpoint of the incidence of hepatocellular carcinoma (HCC). Methods: Four groups of patients with chronic HCV infection treated with pegylated interferon (Peg-IFN) plus ribavirin, and classified according to the N-ALT guidelines, were examined for HCC incidence: group A (n = 353), ALT ≤30 IU/L and platelet (PLT) ≥15 × 10(4)/mm(3); group B (n = 123), ALT ≤30 IU/L and PLT <15 × 10(4)/mm(3); group C (n = 233), 30 < ALT ≤ 40 IU/L and PLT ≥15 × 10(4)/mm(3); and group D (n = 100), 30 < ALT ≤ 40 IU/L and PLT <15 × 10(4)/mm(3). The mean observation period was 36.2 ± 16.5 months Results: In groups A and C, the HCC incidence was low even in patients with non-response (NR) (cumulative rates at 3 years, 0.0 and 2.9 %, respectively). In groups B and D, 14.5 and 5.3 % of NR patients had developed HCC at 3 years, but none of the patients with sustained virologic response (SVR) or relapse had developed HCC. In group B, no patients with mild fibrosis developed HCC irrespective of the antiviral effect of the treatment. Among patients with PLT <15 × 10(4)/mm(3) (group B plus group D), the HCC incidence was significantly lower in patients with SVR and relapse than in NR patients (p < 0.001, p = 0.021, respectively). Conclusion: These results suggest that N-ALT patients with PLT <15 × 10(4)/mm(3) could be candidates for early antiviral therapy.
    Journal of Gastroenterology 09/2012; 48(4). DOI:10.1007/s00535-012-0657-1 · 4.52 Impact Factor
Show more

Similar Publications