ABSTRACT
OBJECTIVE: Dipyridamole is a vasodilator that inhibits the cellular uptake of adenosine, which physiologically reduces the resistance to hepatic arterial flow inside the liver. This study aims at assessing the acute effect of dipyridamole on functional liver plasma flow (measured as the extrarenal sorbitol clearance) and on the Doppler US Congestion Index of the portal vein (the ratio between the cross-sectional area of this vein and the mean velocity of portal flow), which correlates with the severity of portal hypertension. METHODS: We have determined the extrarenal sorbitol clearance (14 cases) and the Congestion Index (seven cases) before and at 30, 60, and 90 min after the oral administration of 25 mg dipyridamole in patients with liver cirrhosis. We also measured the effect of dipyridamole on functional liver plasma flow in six healthy subjects. RESULTS: Dipyridamole increased the extrarenal sorbitol clearance in controls (+17%, p < 0.01) and in cirrhotic patients (+15%, p < 0.01). The drug decreased the portal Congestion Index in all patients, averaging -24% (p < 0.05) 90 min after its oral administration. CONCLUSIONS: This result was due both to a mean decrease of the portal sectional area and to a mean increase in portal flow velocity. In conclusion, these data suggest that dipyridamole should decrease the vascular resistance to portal flow in cirrhosis; this effect may be mediated by an adenosine-dependent vasodilation in the intrahepatic site or along the portosystemic collaterals.
Subject(s)
Dipyridamole/pharmacology , Liver Circulation/drug effects , Liver Cirrhosis/physiopathology , Administration, Oral , Adult , Aged , Dipyridamole/administration & dosage , Female , Hemodynamics/drug effects , Humans , Male , Middle Aged , Portal Vein/diagnostic imaging , Portal Vein/drug effects , Sorbitol/pharmacokinetics , Time Factors , UltrasonographyABSTRACT
Interferon-alpha has been widely used in chronic hepatitis C, but controlled studies with intramuscular interferon-beta are lacking. We therefore performed a prospective, double-blind, randomized study comparing intramuscular IFN-alpha and -beta in patients with chronic hepatitis C. Sixty patients were randomly assigned to receive 3 MU thrice weekly intramuscularly of either recombinant IFN-alpha or leukocyte IFN-alpha or fibroblast IFN-beta for six months. Nine of 20 patients (45.0%) in the recombinant IFN, 5/19 (26.3%) in the leukocyte IFN, and none in the IFN-beta group had a complete response during therapy (recombinant IFN vs IFN-beta: P < 0.01). Only in IFN-alpha-treated patients, was infection with a single HCV genotype (type 2a or 2b) associated with significantly better long-term outcome. IFN-alpha is useful in chronic hepatitis C while intramuscular IFN-beta interferon does not exert any beneficial effect. This is probably due to an insufficient bioavailability of IFN-beta when given intramuscularly.
Subject(s)
Hepatitis C/therapy , Hepatitis, Chronic/therapy , Interferon-alpha/therapeutic use , Interferon-beta/therapeutic use , Adolescent , Adult , Aged , Double-Blind Method , Female , Genotype , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C/diagnosis , Hepatitis C/virology , Hepatitis C Antibodies/analysis , Hepatitis, Chronic/diagnosis , Hepatitis, Chronic/virology , Humans , Interferon Type I/therapeutic use , Male , Middle Aged , Prospective Studies , RNA, Viral/analysis , Recombinant ProteinsABSTRACT
Chronic hepatitis represents a frequent event after orthotopic liver transplantation (OLT). To ascertain the influence of HCV infection on the clinical and histological outcome of these patients, we have investigated the long-term outcome of 22 patients with end-stage chronic liver disease undergoing liver transplant focusing the attention on the role of different HCV genotypes in determining recurrence and severity of post-OLT liver disease. For all patients blood samples taken before OLT and 3 months, 1, 2 and 3 years after OLT were tested for antiHCV antibodies by two different enzyme-linked immuno-assays and by recombinant immuno-blot II and for the presence and type of HCV RNA by nested PCR (5' untranslated region and core gene primers). Of the 16 pre-OLT antiHCV-positive patients, 14 (87.5%) had recurrence of HCV infection while 2 cleared HCV. Pre-OLT genotype recurred in 11 of these 14 patients (2 genotype I) 8 genotype II - in 1 case associated with genotype III - and 1 genotype IV). Of the 6 pre-OLT antiHCV-negative patients, only 1 (16.6%) became persistently HCV-infected, with genotypes I and II. The recurrence of genotype II strictly related with development of severe chronic hepatitis while genotype I and IV were associated with milder forms of liver disease and were more easily cleared.
