Influence of pretreatment lesions on histologic response to interferon therapy in chronic hepatitis C.

We have assessed the predictive value of the grade of pretreatment liver lesions on histologic response to interferon therapy in patients with chronic hepatitis C. In 93 patients with chronic hepatitis C virus (HCV) infection who showed an initial response to interferon therapy, HCV RNA load and serum aminotransferase levels together with grade of liver histologic lesions were assessed at baseline and 6 months after treatment cessation. Regression of portal and periportal necroinflammation was observed only in sustained responders (normalization of aminotransferase levels and HCV RNA clearance). Neither short-term response nor the absence of virus was associated with significant histologic changes in the liver biopsies. Logistic regression analysis showed that pretreatment histologic lesion was an independent predictive factor of biologic response in the histologic regression of lesions 6 months after cessation of interferon treatment. In conclusion, a dense inflammatory necrotic activity is a positive predictor of histologic response in interferon-treated patients with HCV.

Maximal biliary transport of sulfobromophthalein in patients with a T-tube placed in the common bile duct.

In 19 adult patients with choledocholithiasis who were operated on, excretion of free and conjugated sulfobromophthalein (BSP) in the bile collected through a T-tube inserted in the common bile duct was determined. The transport maximum (Tm) for BSP was calculated by the constant-infusion technique after an intravenous infusion of the dye at a rate of 0.3 and 0.09 mg/kg/min for the first and second hour, respectively. Free and conjugated BSP were measured in blood samples obtained at 30, 40, and 50 min of each hourly-infusion period, and in bile collected during the first 30 min (sample A) and between 30-50 min (sample B) after starting the first BSP infusion, and during the first 30 min (sample C) and between 30-50 min (sample D) after starting the second infusion. No correlations between Tm of BSP and glutathione transferase activity and between Tm and bilirubin and alkaline phosphatase in serum were found. Although there was an overall correlation between Tm of BSP and biliary excretion of BSP after 30 min of starting the BSP infusion (samples B, C and D) (r = 0.4716; P = 0.41), Tm values were always lower than recoveries of free BSP in bile. It seems that Tm of BSP (measured with the Wheeler's method) overestimates the actual values of biliary excretion of free BSP, and that the percentage of conjugated BSP in serum is related to the degree of impairment of biliary transport of BSP.

Plasma sulfobromophthalein disappearance in Gilbert's syndrome.

BACKGROUND/AIMS: We studied the metabolism of sulfobromophthalein and its relationship with serum bilirubin levels in 40 patients with Gilbert's syndrome (type I 30; type II 6; type III 4). MATERIAL AND METHODS: Plasma sulfobromophthalein disappearance studies were carried out and 72 hours later, serum bilirubin concentrations (total and unconjugated fraction) were determined at baseline and after 24 and 48 hours of dietary restriction to 400 calories/day. RESULTS: The fractional transfer rate of sulfobromophthalein from plasma to liver was significantly higher in types I (14.7 +/- 3.4 ml/min) and II (14.9 +/- 2.7 ml/min) than in type III (8.7 +/- 1.5 ml/min). The fraction of the plasma sulfobromophthalein pool irreversibly cleared per min was significantly higher in type I (12.2 +/- 2.6 ml/min) than in types II (9.5 +/- 1.5 ml/min) and III (9.3 +/- 3.8). In all patients, serum bilirubin concentrations were significantly higher after fasting as compared with baseline. There was a significant correlation between the increments of serum unconjugated bilirubin levels after the fasting test and the transfer rate of sulfobromophthalein from plasma to liver (F = 9.8411, r = -0.4535, p = 0.003). CONCLUSION: These findings indicate the presence of an active uptake system shared by bilirubin and sulfobromophthalein.

Immune response to hepatitis B vaccine in parenteral drug abusers.

Responsiveness was assessed to a programme of vaccination of hepatitis B vaccine in a cohort of 197 intravenous drug addicts (mean age, 23.7 years) and their antibody response was compared with that of 271 healthy controls (mean age, 24.2 years). All participants were seronegative for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). The vaccination schedule consisted of three intramuscular injections (deltoid area) at months 0, 1 and 2. Although 70% of parenteral drug abusers received the three doses of vaccination, only 43.6% were evaluable for immune response. Fifty-eight per cent of heroin addicts and 80% of controls had evidence of anti-HBs seroconversion at 1 month after vaccination (chi 2 = 15.52, p less than 0.001). Geometric mean antibody titres were also significantly higher in controls (69.1 IU l-1; confidence interval 95%, 56.83 and 84.04) than in parenteral drug abusers (18.2 IU l-1; confidence interval 95%, 12.85 and 25.73) (F = 20.951, p less than 0.0001). The anti-HBs response was not influenced by coexistent anti-HBc, HCV antibody or HIV antibody seropositivity.