Discordance between biochemical markers of liver activity and fibrosis (Actitest-Fibrotest) and liver biopsy in patients with chronic hepatitis C.

INTRODUCTION: The purpose of this clinical trial was to determine in routine practice and in comparison with liver biopsy the limitations of two blood tests, Actitest and Fibrotest, for the evaluation of hepatic activity and fibrosis in patients with chronic hepatitis C. METHODS: Routine blood tests, Actitest and Fibrotest, and liver biopsy were performed in 96 patients with chronic hepatitis C attending routine outpatient clinics. Receiver operating characteristics (ROC) curves were used to assess the diagnostic value of the biochemical tests in comparison with the METAVIR classification. RESULTS: The study population was predominantly male (63.5%) with a mean age of 48 years; 83.3% of the patients had genotype 1 hepatitis C virus infection. Treatment status was naive (62.5%), nonresponders (17.7%), relapsers (7.3%), or unknown (12.5%). The comparison of F0-F2 versus F3-F4 estimated the negative predictive value at 92% and the positive predictive value at 52% for a cut-off of 0.455. Discrepancies in activity score were more frequently due to a higher score of the biochemical test compared to biopsy (18 cases out of 19). Discrepancies for fibrosis were observed in 18 patients with a higher score for biochemical test in eight and a higher score for liver biopsy in 10 cases. A significant increase of gamma-glutamyl-transferase (GGT) (p=0.0001) and alanine aminotransferase (ALT) (p<0.0001) was observed in case of biochemical test overestimation of activity, and a significant increase of alpha2-macroglobulin (p=0.006) and GGT (p=0.018) in case of biochemical test overestimation of fibrosis. CONCLUSION: This prospective study confirms the good diagnostic value of biochemical tests for necrotico-inflammatory activity and fibrosis as compared with the histological analysis of liver biopsy. Clinicians must interpret Actitest and Fibrotest results with caution in patients with a significant elevation of ALT, and/or GGT and/or alpha2-macroglobulin which could overestimate hepatic injury.

Epidemiology of chronic hepatitis B infection in France: risk factors for significant fibrosis--results of a nationwide survey.

BACKGROUND: Epidemiological data concerning hepatitis B are scarce in France. AIM: To describe epidemiological, clinical, virological and histological features of HBsAg-positive patients followed at non-academic hospitals in France. METHODS: Clinical, biological, virological and histological data of all HBsAg-positive consecutive patients observed from April 1, 2001 to May 31, 2002 in participating centres were recorded prospectively. Multivariate analyses of factors associated with significant fibrosis and cirrhosis were performed. RESULTS: Nearly 1166 HBsAg-positive patients were seen in the 58 centres: 671 males and 495 females from metropolitan France (32%) and from outside metropolitan France (68%); mean age 41 +/- 15 years. Twenty-nine percent of patients were probable HBsAg inactive carriers, while 50% had chronic hepatitis; 43% of these were HBeAg-positive and 57% HBeAg-negative. Liver biopsy had been performed in 558 (51%) patients; 205 (17.6%) patients had cirrhosis. By multivariate analysis, factors associated with significant fibrosis were: age >40 years (P < 0.05), HBeAg-negative status (P < 0.02) and histological activity (P < 0.0001). Factors associated with cirrhosis: age (P < 0.0001), platelet count <150 000/mm(3) (P < 0.0001) and viral co-infection (P < 0.03). CONCLUSION: HBV infection represents a significant workload for hepatogastroenterologists at non-academic hospitals in France.

[Hepavir, the first observational study of one cohort of patients treated with alpha-2a interferon, monotherapy. Evaluation of asthenia and its social consequences]. / Hépavir, première étude observationnelle d'une cohorte de malades traités par interféron alpha-2a en monothérapie. Evaluation de l'asthénie et de ses répercussions sociales.

OBJECTIVES: The aim of this observational study in patients with chronic hepatitis C and treated with interferon alpha-2a was to assess 1) monitoring in everyday practice, 2) the acceptability of treatment and 3) the intensity of fatigue. METHODS: Three hundred and fifty four patients were enrolled by physicians in both teaching and general hospitals, or private practice. Before treatment, clinical, epidemiological, and virological data were collected as well as a self-evaluation of fatigue using a visual analogic scale. Clinical follow-up was assessed every 3 months during treatment and 6 months after the end of treatment and included an evaluation of fatigue and the number of workdays missed due to sickness. RESULTS: Two hundred and nineteen men and 135 women, mean age 45 +/- 13, were included. The epidemiological, histological and virological features of this group were similar to those patients usually treated for chronic hepatitis C. Before treatment, the mean measurement of fatigue was 41 on a scale from 0 (perfect form) to 100 (exhausted). Fatigue was unrelated to age, source of infection, biological activity, or histological score. It worsened in patients who stopped interferon after 3 or 6 months, but was stable in patients who continued treatment for 12 months. Fatigue decreased after the end of treatment and was unrelated to treatment response. The need to stop work was strongly related to the intensity of fatigue and the number of workdays missed due to sickness represented nearly two months out of three in 25% of active patients during the first quarter and in 15% of patients thereafter. 61% of patients self-injected interferon (mainly previous drug users) whereas 30% of patients used nurse care throughout treatment. CONCLUSION: This study not only provides a realistic evaluation of fatigue in patients with chronic hepatitis C, before, during and after treatment, but also highlights its social and economic consequences. It shows the need for further cost-effectiveness studies on new therapeutic strategies using combined treatments.

[Treatment of Wilson's disease with zinc. 5 cases]. / Traitement de la maladie de Wilson par le zinc. Cinq cas.

Zinc treatment of Wilson's disease was introduced by Schouwink en 1961 and is still uncommon in France. We evaluated the effectiveness and safety of zinc in 5 patients with Wilson's disease aged from 19 to 40 years. There were three neurological, one hepatic and one asymptomatic cases. Zinc was administered in doses of 120 to 272 mg/day, alone in 3 cases and combined with D-penicillamine in 2 cases. After 1 to 7 years of zinc therapy, our experience is consistent with data from recent literature and provides further evidence of zinc effectiveness. Zinc may be prescribed as first treatment in most patients, including asymptomatic cases. The only exception concerns patients with severe symptoms in whom it is recommended to combine zinc with D-penicillamine during the early phase of treatment for more rapid effectiveness. Because of its safety, zinc is particularly indicated in cases of intolerance to D-penicillamine and trien.

[Liver damage induced by the ingestion of a product of phytotherapy containing wild germander. Four cases]. / Atteinte hépatique associée à la prise d'un produit de phytothérapie contenant de la Germandrée petit-chêne. Quatre cas.

We report 4 cases of patients who developed hepatic injury during administration of herbal medicines for loosing weight with Wild Germander. Three developed jaundice and one had fatigue. Aminotransaminase activities were increased in all patients. Outcome was favorable after drug withdrawal in all patients. Liver biopsy showed centrolobular necrosis and portal lymphoplasmocytic infiltration. Another drug than Wild Germander might have been implicated in hepatic injury in two patients. The similarity of these cases suggests, however, that Wild Germander, like other herbal medicines, may be responsible for hepatic injury.

Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis.

Ninety patients with histologically documented chronic non-A, non-B hepatitis were randomly allocated to receive SC injections of placebo or of 1 or 3 MU of recombinant interferon alfa-2b three times weekly for 24 weeks. Complete normalization of alanine aminotransferase levels occurred posttreatment in 43.3% of patients receiving 3 MU, in 20% of those receiving 1 MU, and in 6.7% of untreated patients (P less than 0.0005 vs. those treated with 3 MU). Alanine aminotransferase normalization was sustained for 6 months after therapy in 13.3% of the patients treated with 3 MU and in 3.3% of those given 1 MU or placebo. The decline of alanine aminotransferase levels following interferon therapy showed independent, positive correlations with female sex (P less than 0.03) and younger age (P less than 0.05). The Knodell's fibrosis score was strongly positively correlated with age (P less than 0.0001). It is concluded that 3 MU of interferon is a more effective dose than 1 MU for controlling disease activity in non-A, non-B chronic hepatitis patients. Women and younger and noncirrhotic patients are more likely to respond.

Therapeutic potential of acyclovir and of the interferons in HBV-related chronic active hepatitis due to HBV with or without HDV superinfection.

Acyclovir only demonstrated activity in CAH patients with low HBV replication (DNA-p less than or equal to 80 cpm). In those, oral acyclovir 4 g/day for 4 months was able to permanently inhibit DNA-p in 5/5 cases without significant side-effects.

Therapeutic activity of vidarabine in symptomatic chronic active hepatitis related to HBV.

The potential inhibitory effects of nucleoside analogues such as ARA-A and acyclovir on HBV-DNA-polymerase were first demonstrated in vitro and then confirmed in vivo in open dose finding studies. The therapeutic efficacy of both ARA-A and ARA-AMP which appeared the most potent drugs was then confirmed by various studies in symptomatic HBeAg-positive patients. These studies demonstrated a similar benefit of therapy with 38 and 40% of treated patients given ARA-A and ARA-AMP, respectively, who permanently cleared HBV replication after a single course, and 67-80% who did so after two courses. Significant improvement in transaminases and histologic activity was also documented (P less than 0.001). Myalgias were observed in 10 and 30% of the patients, respectively. Patients who failed to respond to nucleosides, and those coinfected with HDV, were treated with interferons. Out of 8 cases of HDV/CAH given 5 MU thrice weekly of fibroblast beta-interferon (UPSA) for 3 months, DNA-p activity fell transiently in all 6 initially elevated cases. A parallel decrease in anti-HD titers (P less than or equal to 0.05), inflammation (P less than or equal to 0.001) and necrosis (P less than or equal to 0.05) were observed. alpha-Recombinant interferon was given i.m. for 4 months (2-7 MU/m2 X 2/7 days) to 10 CAH with high DNA-p values. HBV replication was permanently inhibited in 4 cases and dramatically reduced in 3 additional patients. Three failed to respond. Careful monitoring of DNA-p values appeared to be the single most important factor in assessing activity.