Pilot Study of Ofloxacin and Interferon-Alpha Combination Therapy for Chronic Hepatitis C without Sustained Response to Initial Interferon Therapy

Abstract

A controlled trial comparing combination therapy with ofloxacin (OFLX) and interferon (IFN) versus IFN monotherapy was conducted in patients with chronic hepatitis C who failed IFN therapy. Twenty patients were assigned randomly to two groups. Equal doses of recombinant IFN alpha-2b were administered to each group for 24 weeks. For the IFN plus OFLX group, OFLX was administered for 12 weeks at a daily dose of 600 mg. Levels of hepatitis C virus RNA declined significantly from the first month after the start of IFN treatment compared with those before administration in both groups. Serum alanine aminotransferase levels were significantly lower in the IFN plus OFLX group at two and six months after the start of treatment than levels in the IFN group. The fraction of subjects whose levels of serum ALT normalized was also higher in the IFN plus OFLX group. Larger clinical trials should be undertaken.

Fluoroquinolones Inhibit HCV by Targeting its Helicase

“…Previous studies assessing the efficacy of ofloxacin and ciprofloxacin in patients with chronic hepatitis C have produced conflicting results. Two pilot studies initially suggested a potential benefit of combining ofloxacin with IFN-a [28,29]; however, later trials recruiting a larger number of patients failed to reproduce these results convincingly [30,31]. Fluoroquinolones that have tested as highly potent in our experiment have not been tested on patients yet.…”

What should we advise about adjunctive therapies, including herbal medicines, for hepatitis C?

“…Ofloxacin, an antibiotic, given in a dose of 600 mg/day was evaluated in two pilot studies as an adjuvant to IFN therapy. 59,60 Both the studies demonstrated the efficacy of the combination therapy in decreasing the ALT levels as well as HCV RNA levels. However, in another study, the combination did not show any advantage in overcoming IFN non‐responsiveness.…”

Use of Fluoroquinolones in Patients with Chronic Hepatitis C Virus-Induced Liver Failure

“…The only sustained HCV responses occurred in two patients who received combination therapy. In a similar study reported by Komatsu et al, 20 noncirrhotic interferon nonresponders were randomized to either 22 weeks of ofloxacin (600 mg/day) plus interferon (3 ϫ 10 6 to 6 ϫ 10 6 U/wk) or interferon alone (7). Once again, the only two sustained viral responders were in the combination group.…”

“…In two additional studies, fluoroquinolones were used in combination with interferon (7,13). In a study by Tsutsumi et al, 20 noncirrhotic interferon nonresponders were randomized to either 12 weeks of combination therapy with ofloxacin (600 mg/day) superimposed on a 6-month course of high-dose interferon or high-dose interferon alone (13).…”

“…They have also been reported to possess antiviral properties against both DNA and RNA viruses, including HCV (6,10,11). However, their value in HCV has largely been limited to patients with relatively mild, precirrhotic chronic hepatitis (7,12,13). If equally effective in patients with more advanced disease, these agents would represent an attractive therapeutic option for HCV-infected patients awaiting liver transplantation who require PSE and spontaneous bacterial peritonitis prophylaxis.…”