["Hepatitis" A virus g: myth or reality? VHG/GBH-C: diagnosis, epidemiology, transfusion risk, and pathogenicity]. / "Hépatite" A virus g: mythe ou réalité? VHG/GBV-C: diagnostic, épidémiologie, risque transfusionnel et pathogénicité.

The recently discovered G virus (also called either GBV-C or HGV) is transmitted by blood transfusion as well as by sexual intercourse. The global prevalence of GBV-C is high, not only in those groups classically known to be exposed to parenteral risks (i.v. drug users, polytransfused patients), but also in the blood donors population. The diagnosis of active infection lies on the search of GBV-C RNA by Polymerase Chain Reaction whereas that of resolved (past) infection lies on the presence of specific antibodies. Till now, it has not been possible to correlate convincingly the presence of GBV-C RNA with any acute or chronic hepatopathy. On the contrary, a lot of arguments tend to suggest that the GBV-C is not pathogenic for the liver, although some modes of transmission are common with those of other (known and probably not known) hepatotropic viruses. According to the actual knowledge of the consequences of GBV-C infection, it appears as non relevant to instaure a systematic screening of this new virus in blood donors.

Efficacy of interferon dose and prediction of response in chronic hepatitis C: Benelux study in 336 patients.

BACKGROUND/AIMS: In an attempt to improve the limited efficacy of treatment of chronic hepatitis C with interferon-alpha 3 MU tiw, we studied the effects of double-dose therapy followed by downward titration, and analyzed the pre- and pertreatment factors associated with response or non-response. METHODS: Three hundred and fifty-four consecutive patients in 19 centers were randomized to interferon-alpha 3 MU tiw for 6 months or 6 MU tiw for 8 weeks followed by down-titration (3,1 MU tiw) till alanine aminotransferase remained normal and plasma HCV RNA was repeatedly undetectable. The primary outcome measure was sustained alanine aminotransferase and HCV RNA response 6 months after treatment. RESULTS: Three hundred and thirty-six patients received treatment. The sustained response rate for patients receiving 3 MU tiw for 6 months was 14% (9-21%,) and for patients receiving double dose tiw for 8 weeks and thereafter titrated therapy 15% (10-21%) (p=0.8). Pretreatment factors associated with a sustained alanine aminotransferase plus HCV RNA response were the absence of cirrhosis, presence of genotype 2 or 3, a low viral load and, in addition, a low alanine aminotransferase/aspartate aminotransferase ratio; a model was developed to allow estimation of the chance of response for the individual patient. The most powerful predictor of sustained response, however, was plasma HCV RNA at week 4; a positive test virtually precluded a sustained response (1.7%, 0.4-5.0%). If week 4 HCV RNA was not detectable, the chance of a sustained response was 21% (12-34%) for genotype 1 versus 40% (28-54%) for the others (p=0.02). Six MU tiw led to a significantly higher week 4 HCV RNA response (47% not detectable) than 3 MU (37%) (p=0.02). During down-titration this difference in viral on-treatment response was lost. CONCLUSIONS: In the treatment of hepatitis C, an early HCV RNA response is a prerequisite for long-term efficacy. Doubling the initial interferon dose increases this early response, but subsequent downward titration negates this effect, especially in genotype 1.

Insulin secretion, clearance, and action on glucose metabolism in cirrhotic patients.

To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test (0.3 g glucose/kg BW) in nine compensated cirrhotic patients and nine healthy volunteers well matched for age, sex, and body weight. The insulin secretion rate was derived by the deconvolution of plasma C-peptide levels, insulin sensitivity was calculated using Bergman's minimal model method, and insulin clearance was estimated by dividing the 0-180 min area under the curve of insulin secretion rate by that of peripheral plasma insulin levels. The cirrhotic patients were characterized during the frequently sampled i.v. glucose tolerance test by a 60% greater insulin secretion rate (P < 0.05), a markedly reduced insulin sensitivity index (SI; 2.82 +/- 0.75 vs. 5.86 +/- 0.68 x 10(-4) min/mU.L; P < 0.01) and a 40% reduced insulin clearance (725 +/- 169 vs. 1165 +/- 99 mL/min.m-2; P < 0.05). The reduction of insulin clearance was significantly correlated with the amplitude of the portosystemic shunt, measured using an isotopic method (r = 0.75; P < 0.02). In conclusion, cirrhosis is characterized by an important peripheral hyperinsulinism, resulting from both a higher insulin secretion rate and a reduced insulin hepatic clearance; the severe insulin resistance explains the glucose metabolism alterations.

[Medical treatment of primary biliary cirrhosis]. / Le traitement médical de la cirrhose bilialre primitive.

The medical treatment of primary biliary cirrhosis can be divided into two parts: the treatment of the complications (cholestasis and portal hypertension) and the treatment of the underlying disease. As regards the treatment of the disease itself, there is to date no drug which has been shown to ameliorate the pathological process and to prolong survival: cyclosporine and ursodeoxycholic acid, recently used have shown promising responses in liver biochemistry but long-term controlled studies are required to assess their effectiveness on the disease process and on survival.

[Effect of a serotonin S2 receptor antagonist on portal hypertension due to cirrhosis. Preliminary results of a heart and liver hemodynamic study]. / Effects d'un antagoniste des récepteurs S2 de la sérotonine sur l' hypertension portale de la cirrhose. Résultats préliminaires d'une étude hémodynamique cardiaque et hépatique.

In 10 cirrhotic patients, with two balloon catheters introduced in the right internal jugular vein, the following parameters were measured before and after injection of ketanserine (0.1 mg/kg): cardiac output using the thermo-dilution method, free supra-hepatic pressure, wedged supra-hepatic pressure at rest and during cough, right atrial pressure, pulmonary capillary and arterial pressures. After 30 minutes, the following modifications were recorded: the cardiac output goes from 8.0 +/- 2.4 l/min to 8.7 +/- 2.5 l/min (p less than 0.05); the mean arterial pressure goes from 107.0 +/- 18.8 mmHg to 94.7 +/- 25.9 mmHg (p less than 0.02); the wedged supra-hepatic pressure, during coughing goes from 85.2 +/- 36.1 mmHg to 64.6 +/- 23.1 mmHg (p less than 0.005). As in non-cirrhotic patients, ketanserine causes a drop in the mean arterial pressure and a transient elevation of the cardiac output. Ketanserine is able to lower portal pressure of cirrhotic patients at rest as well as during coughing. These results seem to indicate that the activation of serotonin S2 receptors may play a role in determining the portal hypertension in cirrhotic patients.

Serum beta 2-microglobulin levels in chronic post-transfusion non A non B liver disease.

Serum beta 2-microglobulin (beta 2 mu), a reliable marker of T-cell activation, was measured in 25 patients with chronic post-transfusion non A non B (NANB) liver disease and in 21 patients with HBsAg positive chronic liver disease. beta 2 mu levels were elevated in NANB patients when compared with controls but not in comparison with the HBsAg carriers. In NANB patients, beta 2 mu concentrations were significantly correlated with serum IgG (P less than 0.001) and with circulating immune complex activity, assessed by the 125IClq binding test (P less than 0.01). These findings suggest that, in addition to T-cells, the B-cells contributed also to the beta 2 mu production. Patients with "active disease" (chronic active hepatitis and active cirrhosis) had significantly higher beta 2 mu levels (P less than 0.001) than did those with "inactive disease" (chronic persistent hepatitis and inactive cirrhosis). This relation of serum beta 2 mu concentrations and histological activity was also observed in the HBsAg carriers and suggests that the course of post-transfusion NANB chronic hepatitis could be determined by host's immune response rather than by a direct effect of the virus.

[Effects of sotalol on blocked suprahepatic pressure in cirrhotic patients]. / Effets du sotalol sur la pression sus-hépatique bloquée de malades cirrhotiques.

With the use of two balloon catheters inserted in the right jugular vein, the following parameters were measured before and after injection of sotalol (1.5 mg/kg): cardiac output with the thermodilution method, hepatic output with the indocyanin green perfusion method, free sub-hepatic pressure, blocked sub-hepatic pressure recorded at rest and during coughing. After 30 minutes, the following modifications were recorded: the cardiac output goes from 6.8 +/- 2.1 to 5.9 +/- 1.9 L/min (NS), the hepatic output goes from 1.9 +/- 1.1 to 1.5 +/- 0.6 L/min (NS), the hepatic pressure gradient goes from 18.2 +/- 6.1 to 11.5 +/- 5.4 mmHg (p less than or equal to 0.0005); the blocked sus-hepatic pressure at rest goes from 25.0 +/- 7.8 to 19.8 +/- 8.0 mmHg (p less than or equal to 0.025); the blocked sus-hepatic pressure during coughing goes from 92 +/- 32 to 82 +/- 39 mmHg (NS). This study demonstrates: a) that the drop in the hepatic pressure gradient induced by a dose of sotalol is more important than that observed by Westaby et al. with propranolol: 37% vs 31% (NS); b) that sotalol cannot lower the blocked sub-hepatic pressure during coughing. This result suggests that the potential protective effect of sotalol toward esophageal varices rupture disappears during coughing.

Hepatotoxicity of mebendazole. Relationship with serum concentrations of the drug.

We report the case of a 47-year-old female patient, suffering from multiple hydatid cysts of the liver, in whom hepatitis developed after mebendazole treatment. Clinical manifestations of hypersensitivity were absent. A correlation was found between serum mebendazole concentrations and the degree of cytolysis; this is compatible with a direct hepatotoxic effect of mebendazole.

Cimetidine increases serum mebendazole concentrations. Implications for treatment of hepatic hydatid cysts.

In eight patients (five with peptic ulcer disease and three with hydatid cysts), the [14C]-aminopyrine breath test (ABT) and maximum serum concentration of mebendazole following a dose of 1.5 g of mebendazole three times daily were determined before and after treatment with cimetidine (400 mg three times daily for 30 days). Serum mebendazole concentrations were measured in blood samples taken 2 h after each drug intake. Cimetidine lowered the 14CO2 specific activity (SA) at 1 h (P less than 0.01) and increased the maximum serum concentration of mebendazole (P less than 0.01). A significant correlation was found between SA at 1 h and the highest concentration of mebendazole before (r = -0.71, P less than 0.05) and after (r = -0.82, P less than 0.05) cimetidine ingestion. Combined administration of cimetidine and mebendazole resulted in the complete resolution of previously unresponsive hydatid cysts.

[The role of plasma alpha 1-glycoprotein acid in the binding of aminopyrine]. / Rôle de l' alpha 1-glycoprotéine acide plasmatique dans la fixation de l'aminopyrine.

Under certain pathological conditions the binding of various substances by serum proteins is altered. The plasma concentrations of alpha 1-acid glycoprotein, also known as orosomucoid are reported to be elevated in stressful situation and in certain disease states like acute myocardial infarction. The binding of aminopyrine to serum proteins and alpha 1-acid glycoprotein was determined using equilibrium dialysis. It appears that alpha 1-acid glycoprotein has specific binding sites for aminopyrine. Aminopyrine was also bound to other serum proteins. On addition the results indicate that an increase of alpha 1-acid glycoprotein to concentrations such as those seen in some pathological states does not really alter the percent of aminopyrine bind to serum proteins.