Seven patients with cardiovascular disease had clinical episodes and marked transaminase elevations that suggested viral hepatitis, but all had morphologic evidence (from liver biopsy or autopsy specimens) that documented centrilobular necrosis (ischemic hepatitis) with no evidence of viral or drug injury. Several also had moderate or marked passive congestion of the liver so the liver biopsies of 15 additional patients were retrospectively reviewed. In this latter group congestion alone was associated with normal or minimal elevation in transaminases while all patients with notable (greater than 5 times normal) transaminase elevations had centrilobular necrosis. Congestion alone, no matter how severe or prolonged, seems to do little if any damage to the liver. Centrilobular necrosis, or ischemic hepatitis, correlates with significant hypertransaminasemia, appears to result from failure of hepatic perfusion (with or without preceding hypotension), and presents with clinical and laboratory manifestations that suggest viral hepatitis.
Septic shock decreases preload, increases splanchnic blood pooling and edema formation, and induces hepatic dysfunction. We hypothesized that the hemodynamic effects of endotoxemic shock on the portal venous (PV) and hepatic arterial (HA) vascular beds contribute to this picture. Multipoint pressure-flow relationships were generated to evaluate the slope (resistance or conductance) and effective back pressure (Pback) in each bed in an intact porcine model of endotoxemia. Slope and Pback were determined during endotoxemia over 300 min (n = 8) and compared with sham-treated control studies (n = 5). At time (t) = 60 min, HA slope significantly decreased (P < 0.05) without a change in Pback. The HA buffer response (HABR), defined as a decrease in HA resistance produced by reduction in PV flow (Qpv), was abolished at t = 90 min. The PV Pback significantly increased without a change in PV slope. At t = 300 min, HA slope returned to baseline, and the HABR was present while PV slope and Pback increased (P < 0.05). Fractional flow (flow relative to cardiac output) was constant except for a transient increase in HA fractional flow at t = 60 min. Histological studies showed focal necrosis and hemorrhage without evidence of vasoconstriction or thrombosis. In conclusion, endotoxic shock leads to time-dependent impairment of Qpv with increased PV resistance, causing an increase in splanchnic blood pooling and subsequent decrease in venous return. The HA bed is dilated early with an absent HABR. Later an HABR is present but defined by increased HA resistance for a given Qpv.(ABSTRACT TRUNCATED AT 250 WORDS)
Thirty-one patients with sclerosing cholangitis underwent reconstruction of their hepatic duct bifurcation and long-term stenting between 1980 and 1987. Indications for surgery were persistent jaundice in 29 and recurrent cholangitis in two. The mean serum bilirubin level before surgery was 10.4 mg/dl. Liver biopsy revealed that 26 patients had varying degrees of hepatic fibrosis, and five patients had progressed to secondary biliary cirrhosis. In 29 patients the major obstructive duct disease was at or near the hepatic duct bifurcation, and in two patients it was in the distal common duct. The operative procedure consisted of: (1) excision of the hepatic duct bifurcation and extrahepatic biliary tree, (2) dilatation of the intrahepatic ducts, (3) insertion of Silastic transhepatic biliary stents, and (4) bilateral hepaticojejunostomies. Two of the five patients (40%) with cirrhosis died after surgery. In contrast, only one of 26 patients (3.9%) with hepatic fibrosis died after operation. The 1-, 3-, and 5-year actuarial survival rates for patients with cirrhosis were 20%, 20%, and 20%, respectively. The only long-term survivor underwent a liver transplant. The 1-, 3-, and 5-year actuarial survival rates for patients with hepatic fibrosis were 92%, 87%, and 71%, respectively. In addition, the mean serum bilirubin levels of patients with hepatic fibrosis at 1, 2, 3, 4, and 5 years were 3.4 mg/dl, 2.9 mg/dl, 4.0 mg/dl, 5.4 mg/dl, and 4.3 mg/dl, respectively. Two of the long-term survivors subsequently underwent a liver transplant. Patients with sclerosing cholangitis, persistent jaundice, and biliary cirrhosis should be referred for consideration of liver transplantation. However, in the absence of biliary cirrhosis, if the major obstructive disease is at the hepatic duct bifurcation, primary biliary reconstruction and long-term stenting should be considered.
The role of nitric oxide (NO) in the liver vasculature during baseline and endotoxic shock states was evaluated in 17 anesthetized pigs. Mean systemic arterial pressure, pulmonary arterial pressure, and portal venous pressure and flow, hepatic arterial pressure and flow, and cardiac output were measured. Pressure-flow (P-Q) relationships defined resistances as a back pressure and a slope. Inhibition of nitric oxide synthase (NOS) with NG-nitro-L-arginine methyl ester (L-NAME) at baseline increased mean arterial pressure, pulmonary arterial pressure, hepatic arterial pressure, and the slopes of their P-Q relationships (P < 0.05) but had no effect on portal venous pressure or its P-Q relationship. After endotoxin (10 micrograms/kg iv), NO induced arterial dilation and attenuated increases in portal venous and pulmonary arterial resistances (P < 0.05) that were reversed by L-NAME. NOS inhibition was stereospecifically reversed by L-arginine. Local control of liver blood flow at baseline via the hepatic arterial buffer response and hepatic arterial autoregulation were increased in gain after L-NAME. Endotoxic shock ablated the hepatic arterial buffer response and autoregulation independent of either NO or an alpha-adrenergic-receptor agonist (P < 0.05). Under baseline conditions, NO modulates pulmonary, systemic, and hepatic arterial but not portal venous resistances. NO production during endotoxic shock induces arterial hypotension and hepatic arterial vasodilation and attenuates increases in both portal and pulmonary resistances. NOS inhibition in endotoxic shock could increase morbidity due to a loss of local control of liver blood flow and marked increases in resistance to venous return across both the liver and lungs.
A double-blind prospective controlled trial of d-penicillamine in 40 patients with acute alcoholic liver disease revealed no improvement in survival or liver function tests in the experimental group. Nevertheless, greater reduction in fibrosis and hepatocellular injury was suggested in penicillamine-treated biopsied patients; this observation remains tentative and preliminary, however, because of the potential for sampling error.
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