Multicenter randomized study comparing initial daily induction with high dose lymphoblastoid interferon vs. standard interferon treatment for chronic hepatitis C.

One hundred fifty-five chronic hepatitis C patients were assigned at random to receive natural lymphoblastoid interferon (IFN)alpha-n1, s.c., for 13 months in one of three treatment regimens: initial daily induction with 10 million units (MU) followed (group 1, n = 50) or not (group 2, n = 52) by 1 month of rest and then three times weekly 10 MU (2 months), 5 MU (2 months), and 3 MU (8 months); group 3 (n = 53) received tiw 5 MU (2 months) followed by 3 MU (11 months). By intention-to-treat analysis, ALT normalization at completion of treatment was greater in patients who received continuous IFNalpha-n1 therapy with initial daily induction (group 2: 24/52, 46%) compared with those given intermittent therapy with initial daily induction (group 1: 17/50, 34%) and those who received standard IFNalpha-n1 therapy (group 3, 18/53, 34%; P not significant). The sustained ALT response was 26%, 27% and 21% and the sustained virological response was 20%, 27%, and 19%, in groups 1, 2, and 3, respectively. A trend was observed towards a higher biochemical and virological end-of-treatment response in patients given induction therapy (17%) compared with standard therapy (6%, P = 0.053). Sustained biochemical and virological responses were 20%, 27%, and 17% in groups 1, 2, and 3, respectively. Platelet and leukocyte counts decreased following daily high-dose treatment and remained low until therapy cessation (P < 0.001). The data suggest that daily s.c. induction with 10 MU IFNalpha-n1 followed by intermittent or continuous maintenance therapy for 1 year does not improve the results achieved with the standard 1-year IFNalpha course in the treatment of chronic hepatitis C patients.

High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the Island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.

The molecular basis of Wilson disease (WD), an autosomal recessive disorder, is the presence of mutations in the ATP7B gene, a copper transporting ATPase. Hospital records indicated a higher prevalence of WD (1 in 2,600) in some counties in the northeastern region of the island of Gran Canaria (Canary Islands, Spain) that was around 10-fold higher than that described for European populations (1 in 30,000). The ATP7B gene was analyzed for mutations in 24 affected subjects, revealing a high prevalence of the rare Leu708Pro mutation present in 12 homozygous and 7 heterozygous individuals. In these patients, who constitute one of the largest described cohorts of WD homozygotes, we found a variable clinical presentation of the disease, although the biochemical picture was homogenous and characteristic, thereby confirming that the Leu708Pro change is indeed a mutation associated with WD. Haplotype analysis of subjects homozygous for the Leu708Pro mutation showed a conserved shared region smaller than 1 centimorgan (cM), and the region of linkage disequilibrium between the Leu708Pro mutation and neighboring microsatellite markers extended approximately 4.6 cM. When comparing the amount of linkage disequilibrium versus genetic distance from the disease mutation, it was estimated that a common ancestral Leu708Pro chromosome may have been introduced in Gran Canaria over 56 generations ago, dating it back to pre-Hispanic times. The prevalence, and the tight geographical distribution of the Leu708Pro chromosome suggests that the Canary Islands can be considered a genetic isolate for linkage disequilibrium studies.

Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal rebleeding after recent variceal hemorrhage.

Variceal hemorrhage continues to be a major cause of morbidity and mortality in cirrhotic patients. Transjugular intrahepatic portosystemic shunt (TIPS) is gaining wide acceptance as a treatment for several complications of portal hypertension. The aim of the current randomized study was to compare the transjugular shunt and endoscopic sclerotherapy (ES) for the prevention of variceal rebleeding (VB) in cirrhotic patients. Forty-six consecutive cirrhotic patients with variceal bleeding were randomly allocated to receive either transjugular shunt (22 patients) or ES (24 patients) 24 hours after control of bleeding. VB (50% vs. 9%) and early (first 6 weeks) VB (33% vs. 5%) were significantly more frequent in sclerotherapy patients; the actuarial probability of being free of VB was higher in the shunt group (P <.002). Eight patients (33%) of the sclerotherapy group and 3 patients (15%) of the shunt group died; the actuarial probability of survival was higher for the shunted patients (P <.05); 6 patients in the sclerotherapy group and none in the shunt group died from VB (P <.05). No difference was found in the proportion of patients with clinically evident hepatic encephalopathy (HE). These results show that the transjugular shunt is more effective than sclerotherapy in the prevention of both early and long-term VB. Moreover, a significant improvement in survival was found in the shunt group.

Transjugular intrahepatic portal-systemic shunt in the treatment of refractory ascites: effect on clinical, renal, humoral, and hemodynamic parameters.

Seventeen cirrhotics with refractory ascites were treated with transjugular intrahepatic portosystemic shunt (TIPS) and followed for 15.5 +/- 3.4 months. Five patients died, four within 3 months after TIPS (hepatocellular failure) and one after 22 months (cholangiocarcinoma). Six patients received transplants 1 to 10 months after the procedure. Actuarial survival at 6, 12, and 24 months was 75%, 75%, and 63%, respectively. Portosystemic venous pressure gradient decreased by 46% at 1 month and by 38% at 7 to 12 months. Eight patients presented 18 stenoses 1 to 18 months after TIPS. Twelve stenoses required balloon dilatation. Tense ascites was present before TIPS in 100% of the patients, whereas it was mild or absent in 56% at 1 month, in 66% at 3 to 6 months, in 57% at 7 to 12 months, and in 100% at 24 months after TIPS. Requirements for diuretics and paracentesis decreased after TIPS (P < .001, both). One month after TIPS, urinary and fractional sodium excretion increased (P < .001, both), plasma renin activity, plasma aldosterone (P < .005, both), and plasma norepinephrine (P < .05) decreased and cardiac output (P < .01) increased, systemic vascular resistances (P < .005) decreased, and arterial pressure did not change. Acute hepatic encephalopathy was frequent early after TIPS but was responsive to treatment and caused no long-term disability. In conclusion, TIPS is useful in the treatment of refractory ascites through lowering portal pressure and improving renal sodium excretion. This effect could be attributable to an increase in effective blood volume causing deactivation of vasopressor systems.

Color Doppler-US guidance in transjugular placement of intrahepatic portosystemic shunts.

Percutaneous placement of portosystemic shunts requires access to the portal system from a transjugular approach. Color Doppler sonography was used to direct the transjugular puncture in intrahepatic portosystemic shunt procedures in four patients. In each case, the technique allowed quick, safe transjugular puncture of the portal vein and close real-time monitoring of the procedure.

[The treatment of primary biliary cirrhosis with ursodeoxycholic acid. The short- and median-term results and their relation to the study of the disease]. / Tratamiento de la cirrosis biliar primaria con ácido ursodesoxicólico. Resultados a corto y medio plazo y relación con el estudio de la enfermedad.

We present the results of the treatment with ursodeoxycholic acid (UDCA, 7-9 mg/kg body weight daily) of 17 patients with primary biliary cirrhosis (8 in stages I-II; 9 in stages III-IV). At two months the mean values of alkaline phosphatase, gammaglutamiltranspeptidase, alanine and aspartate aminotransferase were reduced (p less than 0.001, p less than 0.001, p less than 0.01 and p less than 0.01 respectively). This improvement persisted without increase during the first year. At two months the total bilirubin value was reduced (p less than 0.01) associated with a reduction in the conjugated fraction (p less than 0.05). Cholesterol and gammaglobulin mean values also decreased at two months (p less than 0.05). We found no changes in IgM levels and antimitochondrial antibody titers. The improvement was similar in both groups (early I-II and advanced III-IV stages) and the treatment showed no undesirable effects either in early or advanced stages. Almost all the patients with pruritus (6 out of 7) improved with the treatment and the use of cholestyramine was reduced in all.