Treatment of HCV Carriers With Normal ALT
Treatment of HCV Carriers With Normal ALT
Background/Aims: To evaluate, in clinical practice, the efficacy and safety of combined antiviral treatment in hepatitis C virus (HCV) carriers with normal alanine aminotransferase (ALT) levels.
Methods: Eighty-eight HCV carriers with persistently normal ALT levels were enrolled. All patients received peginterferon (PEG-IFN) α-2a 180 μg once weekly plus ribavirin (RBV) 800 mg/day for 24 weeks (HCV-2 and -3) or 1000-1200 mg/day for 48 weeks (HCV-1).
Results: Rapid virological response (RVR) was seen in 66/88 patients (75%): 19/32 HCV-1 (59%), 40/46 HCV-2 (87%) and 7/10 HCV-3 patients. Younger patients, leaner subjects and patients with non-1 genotype or lower baseline HCV RNA levels were more likely to achieve an RVR. Sustained virological response (SVR) was seen in 69/88 patients (78%): 20/32 HCV-1 patients (62%), 41/46 HCV-2 patients (89%) and 8/10 (80%) HCV-3 patients. The overall SVR rate was 88% in patients with RVR (58/66) and 50% in those without RVR.
Conclusions: The combination of PEG-IFN α-2a and RBV produces, in patients with normal ALT, virological response rates that are comparable or even higher than those obtained in patients with elevated ALT levels. Thus, we suggest that in selected cases immediate therapy might be preferred to a 'wait-and-see' policy.
Historically, patients with chronic hepatitis C virus (HCV) infection and persistently normal alanine aminotransferase levels (PNALT) have been classified as 'healthy' or 'asymptomatic', not thought to progress and thus excluded from antiviral treatment. It is now accepted that most patients have some degree of histological liver damage, although usually mild. However, the association of normal alanine aminotransferase (ALT) with more severe chronic hepatitis or cirrhosis has been reported. Some studies showed that HCV carriers with normal ALT have stable disease, whereas others reported a significant progression of fibrosis. Sudden worsening of disease with ALT increase and histological deterioration has been reported after up to 15 years of follow-up and the development of hepatocellular carcinoma (HCC) in some cases has been described.
Whether patients with Chronic Hepatitis C (CHC) and normal ALT should be offered antiviral treatment in clinical practice has been disputed until recently. Interferon (IFN) treatment is associated with important side effects and is rather expensive, whereas the risk of progression of the disease in this setting is extremely low. For these reasons, the first Consensus Conferences on HCV discouraged treatment in the subjects outside clinical trials.
The introduction of the new combination therapy of peginterferon (PEG-IFN) plus ribavirin (RBV) resulted in higher response rates. To date, only one study exists evaluating efficacy and safety of therapy with PEG-IFN α-2a plus RBV in patients with PNALT. However, in this study, subjects with HCV-1 were treated with a fixed RBV dose lower than that universally recommended for this subset of patients. Simulation studies suggest that sustained virological response (SVR) in HCV-1 patients with PNALT significantly increases when the standard weight-adjusted dose of RBV is administered. Thus, the efficacy of the approved dosage of RBV (1000-1200 mg/day) has never been studied in clinical practice in patients with HCV-1 and PNALT. Aims of this study were (i) to evaluate in clinical practice the virological response rates to combined antiviral treatment in HCV patients with PNALT and (ii) to evaluate whether HCV-1 patients with PNALT treated with optimal RBV dosage (1000-1200 mg/day) might achieve a higher SVR than those obtained in previous studies with lower RBV doses.
Abstract and Introduction
Abstract
Background/Aims: To evaluate, in clinical practice, the efficacy and safety of combined antiviral treatment in hepatitis C virus (HCV) carriers with normal alanine aminotransferase (ALT) levels.
Methods: Eighty-eight HCV carriers with persistently normal ALT levels were enrolled. All patients received peginterferon (PEG-IFN) α-2a 180 μg once weekly plus ribavirin (RBV) 800 mg/day for 24 weeks (HCV-2 and -3) or 1000-1200 mg/day for 48 weeks (HCV-1).
Results: Rapid virological response (RVR) was seen in 66/88 patients (75%): 19/32 HCV-1 (59%), 40/46 HCV-2 (87%) and 7/10 HCV-3 patients. Younger patients, leaner subjects and patients with non-1 genotype or lower baseline HCV RNA levels were more likely to achieve an RVR. Sustained virological response (SVR) was seen in 69/88 patients (78%): 20/32 HCV-1 patients (62%), 41/46 HCV-2 patients (89%) and 8/10 (80%) HCV-3 patients. The overall SVR rate was 88% in patients with RVR (58/66) and 50% in those without RVR.
Conclusions: The combination of PEG-IFN α-2a and RBV produces, in patients with normal ALT, virological response rates that are comparable or even higher than those obtained in patients with elevated ALT levels. Thus, we suggest that in selected cases immediate therapy might be preferred to a 'wait-and-see' policy.
Introduction
Historically, patients with chronic hepatitis C virus (HCV) infection and persistently normal alanine aminotransferase levels (PNALT) have been classified as 'healthy' or 'asymptomatic', not thought to progress and thus excluded from antiviral treatment. It is now accepted that most patients have some degree of histological liver damage, although usually mild. However, the association of normal alanine aminotransferase (ALT) with more severe chronic hepatitis or cirrhosis has been reported. Some studies showed that HCV carriers with normal ALT have stable disease, whereas others reported a significant progression of fibrosis. Sudden worsening of disease with ALT increase and histological deterioration has been reported after up to 15 years of follow-up and the development of hepatocellular carcinoma (HCC) in some cases has been described.
Whether patients with Chronic Hepatitis C (CHC) and normal ALT should be offered antiviral treatment in clinical practice has been disputed until recently. Interferon (IFN) treatment is associated with important side effects and is rather expensive, whereas the risk of progression of the disease in this setting is extremely low. For these reasons, the first Consensus Conferences on HCV discouraged treatment in the subjects outside clinical trials.
The introduction of the new combination therapy of peginterferon (PEG-IFN) plus ribavirin (RBV) resulted in higher response rates. To date, only one study exists evaluating efficacy and safety of therapy with PEG-IFN α-2a plus RBV in patients with PNALT. However, in this study, subjects with HCV-1 were treated with a fixed RBV dose lower than that universally recommended for this subset of patients. Simulation studies suggest that sustained virological response (SVR) in HCV-1 patients with PNALT significantly increases when the standard weight-adjusted dose of RBV is administered. Thus, the efficacy of the approved dosage of RBV (1000-1200 mg/day) has never been studied in clinical practice in patients with HCV-1 and PNALT. Aims of this study were (i) to evaluate in clinical practice the virological response rates to combined antiviral treatment in HCV patients with PNALT and (ii) to evaluate whether HCV-1 patients with PNALT treated with optimal RBV dosage (1000-1200 mg/day) might achieve a higher SVR than those obtained in previous studies with lower RBV doses.
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