Risk factors and long-term course of thyroid dysfunction during antiviral treatments in 221 patients with chronic hepatitis C.

AIM: To identify the predictive factors of dysthyroidism during treatment for chronic viral hepatitis C and to evaluate the long-term outcome of these patients. METHODS: Patients treated for chronic viral hepatitis C between 1990 and 2001 were analyzed retrospectively. Patients with dysthyroidism before treatment and patients positive for hepatitis B surface antigen or human immunodeficiency virus antibodies were excluded. Dysthyroidism was defined by an abnormal serum TSH level on two separate occasions. RESULTS: 221 consecutive patients were included. Among them, a hundred were treated twice by interferon alpha, 21 had 3 treatments and 3 had 4 treatments. Fifteen of these patients (7%) had dysthyroidism during antiviral therapy. There was no significant difference in the frequency of dysthyroidism during the first and the second treatment [respectively 4,1% (N = 9) and 6% (N = 6)]. Female gender and the presence of antimicrosome or antithyroperoxydase (anti-TPO) antibodies before antiviral treatment were predictive factors of dysthyroidism. Treatment by interferon and ribavirin did not increase the risk of dysthyroidism compared to monotherapy with interferon. Pegylated interferon (N = 49) was not a risk factor compared to standard interferon. Thirteen patients had hypothyroidism (2 of them as a result of biphasic thyroiditis) and 2 had hyperthyroidism. The antiviral treatment was continued in 11 patients. Seven out of 13 patients with hypothyroidism required an indefinite treatment (follow-up: 15 to 90 months). CONCLUSIONS: In our series, 7% of patients with chronic viral hepatitis C had a dysthyroidism during antiviral therapy. Predictive factors were female gender and positive antimicrosome or anti-TPO antibodies before treatment. Absence of dysthyroidism during a first antiviral treatment did not preclude from the risk of dysthyroidism during a second treatment.

Efficacy of celecoxib versus ibuprofen in the treatment of acute pain: a multicenter, double-blind, randomized controlled trial in acute ankle sprain.

Ankle sprain is a common acute soft-tissue injury that often results in pain, inflammation, and ecchymosis. In this multicenter, double-blind, randomized parallel-group study, 445 adult patients received celecoxib 400 mg/day, ibuprofen 2,400 mg/day, or placebo for 10 days. Patients had experienced grade 1 or 2 ankle sprains within 48 hours and had moderate to severe ankle pain. Patient's Global Assessment of Ankle Injury responses, given on days 4 and 8, showed that the celecoxib group improved significantly more than the placebo group did, with 67% of the celecoxib group versus 55% of the placebo group improving at day 4 (P < .05). Patient's Assessment of Ankle Pain Visual Analog Scale on Weight Bearing responses, also given on days 4 and 8, showed that celecoxib was as efficacious in the treatment of ankle sprain as the maximum therapeutic dosage of ibuprofen and that, compared with placebo, it reduced pain significantly more (P < .05). The celecoxib group recovered and returned to function earlier (after 5 days) than did either the placebo group (8 days) or the ibuprofen group (6 days); the celecoxib-placebo difference was significant. Celecoxib, a cyclo-oxygenase-2-specific inhibitor with platelet-function-sparing properties, may be useful as a multimodal adjuvant in the treatment of ankle sprain.

Thiamine deficiency in hepatitis C virus and alcohol-related liver diseases.

Thiamine deficiency is a common feature in chronic alcoholic patients, and its pathophysiology remains poorly understood. Until now, thiamine deficiency has been considered to be mainly the result of alcoholism irrespective of the underlying liver disease. The aims of the study were to compare the prevalence of thiamine deficiency in alcohol- and hepatitis C virus-(HCV-) related cirrhosis and in patients with chronic hepatitis C without cirrhosis. Forty patients with alcoholic cirrhosis (group A), 48 patients with HCV-related cirrhosis (group B), and 59 patients with chronic hepatitis C without cirrhosis (group C) were included prospectively. Thiamine status was evaluated by concomitant determination of erythrocyte transketolase activity, thiamine diphosphate (TDP) effect, and direct measurement of erythrocyte thiamine and its phosphate esters by HPLC. Thiamine was mainly present in erythrocytes in its diphosphorylated form. Prevalence of thiamine deficiency and levels of TDP in thiamine-deficient patients were similar in patients of group A (alcoholic cirrhosis) and of group B (viral C cirrhosis). None of the patients with chronic hepatitis (group C) was deficient. Thiamine deficiency was not correlated with the severity of the liver disease or disease activity. No impairment of thiamine phosphorylation was found in the three groups. conclusion, alcoholic or HCV-related cirrhotics have the same range of thiamine deficiency, while no patient without cirrhosis has thiamine deficiency, and impaired phosphorylation does not account for the deficiency observed in cirrhotics. We suggest that thiamine should be given to patients with cirrhosis irrespective of its cause.

Daily or three times per week interferon alpha-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C not responding to previous interferon alone.

BACKGROUND/AIMS: We compared the efficacy and safety of the combined therapy of daily interferon alpha-2b and ribavirin with those of interferon alpha-2b three times per week alone or in combination with ribavirin in non-responder patients with hepatitis C virus (HCV) infection. METHODS: A total of 376 patients were randomly assigned to receive interferon alpha-2b (6 MU three times per week for 24 weeks followed by 3 MU three times per week for 24 weeks) alone (group A) or in combination with ribavirin for 48 weeks (group B), or daily interferon alpha-2b (3 MU per day for 24 weeks followed by 3 MU three times per week for 24 weeks) and ribavirin (group C). RESULTS: After 24 weeks of therapy, HCV RNA was undetectable in 11.7, 24.0, and 37.8% for groups A, B, and C, respectively. Sustained virological response was more frequent in patients who received combination therapy with three times weekly interferon (20.9%) or daily interferon (26.0%) than in patients who received interferon alone (5.8%) (P<0.001). The predictive HCV parameters for sustained response were a low viral load on day 7 and a negative HCV RNA on week 12. CONCLUSIONS: In conclusion, in non-responder patients with chronic hepatitis C, virological response with daily interferon and ribavirin, compared to interferon monotherapy, was significantly improved during treatment, although sustained virological response was similar for both combination therapies with ribavirin and three times a week or daily interferon.

Daily or three times a week interferon alfa-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C.

BACKGROUND/AIMS: Data on hepatitis C virus (HCV) viral dynamics and on the effect of interferon in blocking virion production have suggested a rationale for daily administration of interferon in patients with chronic hepatitis C infection. We compared the efficacy and safety of daily interferon alfa-2b in combination with ribavirin with those of interferon alfa-2b three times a week alone or in combination with ribavirin. METHODS: We randomly assigned 321 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin for 48 weeks or daily interferon alfa-2b (3 million units per day for 12 weeks then 3 million units three times per week for 24 weeks) and ribavirin (36 week treatment). RESULTS: The rate of sustained virologic response (defined as an undetectable serum HCV-RNA level 72 weeks after initiation of treatment) was higher in patients who received combination therapy with three times weekly interferon (51.7%) or daily interferon (46.1%) than in patients who received interferon alone (25%) (P=0.0001 and P=0.002, respectively). Independent predictive factors for sustained virologic response were combination therapy, weight, genotype and viral load. In conclusion, in patients with chronic hepatitis C, combination therapy with induction treatment (daily interferon for 12 weeks) and shorter duration of treatment was not different from combination therapy for 48 weeks without induction treatment. CONCLUSIONS: Induction treatment with interferon for 12 weeks and combination therapy for a total duration of 36 weeks could therefore be cost effective.

Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.

BACKGROUND & AIMS: Type 1 hepatorenal syndrome (HRS) is a severe complication of cirrhosis associated with a short median survival time (<2 weeks). Although the administration of terlipressin improves renal function, its effect on survival is unknown. This study investigated predictive factors of survival in patients with type 1 HRS treated with terlipressin. METHODS: Ninety-nine patients with type 1 HRS treated with terlipressin in 24 centers were retrospectively studied. Terlipressin-induced improved renal function was defined as a decrease in serum creatinine value to <130 micromol/L or a decrease of at least 20% at the end of treatment. RESULTS: At inclusion, the Child-Pugh score was 11.8 +/- 1.6 (mean +/- SD). Terlipressin (3.2 +/- 1.3 mg/day) was administered for 11 +/- 12 days. Renal function improved in 58% of patients (serum creatinine decreased by 46% +/- 17% from 272 +/- 114 micromol/L). Median survival time was 21 days. Survival rate was 40% at 1 month. Multivariate analysis showed that improved renal function and Child-Pugh score < or =11 at inclusion were independent predictive factors of survival (P < 0.0001 and 0.02, respectively). Thirteen patients underwent liver transplantation (92 +/- 95 days after HRS onset), 10 of whom had received terlipressin and had had improved renal function. CONCLUSIONS: This retrospective uncontrolled study shows that in patients with type 1 HRS, terlipressin-induced improved renal function is associated with an increase in survival. Thus, a randomized trial investigating the effect of terlipressin on survival in patients with type 1 HRS should be performed.