Hepatic enzyme activity is the major factor determining elimination rate of high‐clearance drugs in cirrhosis

Richard Callaghan, Paul V. Desmond, Phillip Paull, Maurice L. Mashfor – 1 July 1993 – The relative importance of alterations in hepatic enzyme activity, blood flow and drug binding to drug elimination in patients with liver disease remains controversial. In addition, liver disease appears to selectively impair drug oxidation pathways while leaving glucuronidation preserved.

Autoimmune cholangiopathy: Part of the spectrum of autoimmune chronic active hepatitis

Ziv Ben‐Ari, Amar Paul Dhillon, Sheila Sherlock – 1 July 1993 – We describe four patients with features overlapping those of primary biliary cirrhosis and autoimmune chronic active hepatitis. Three were female and one was male; only one was symptomatic. Serum biochemical study showed increases in alkaline phosphatase and α‐glutamyltranspeptidase levels. Markers of hepatitis B and C viruses were absent. In all four patients, serum mitochondrial antibodies could not be detected on immunofluorescence study and serum M2 antibodies were absent.

Normal splanchnic but impaired peripheral insulin‐stimulated glucose uptake in cirrhosis

Ehoud Shmueli, Mark Walker, George Alberti, Christopher O. Record – 1 July 1993 – The site of impaired glucose uptake in cirrhosis is uncertain. We therefore performed hyperglycemic clamps (glucose 10 mmol/L) in 10 patients with compensated alcoholic cirrhosis and impaired glucose tolerance and in six control subjects. Muscle glucose uptake was estimated in patients and controls with the forearm technique. In the cirrhotic subjects splanchnic glucose uptake was measured with hepatic vein catheterization and primed continuous infusions of indocyanine green and [6−3H]glucose.

A multivariate analysis of risk factors for hepatocellular carcinogenesis: A prospective observation of 795 patients with viral and alcoholic cirrhosis

Kenji Ikeda, Satoshi Saitoh, Isao Koida, Yasuji Arase, Akihito Tsubota, Kazuaki Chayama, Hiromitus Kumada, Masahiro Kawanishi – 1 July 1993 – To elucidate the appearance rates of hepatocellular carcinoma in cirrhosis and to assess the risk factors for hepatocellular carcinogenesis, we prospectively studied 795 consecutive patients with viral or alcoholic cirrhosis for 2 to 17 yr (median of 5.8 yr). During the observation period, hepatocellular carcinoma developed in 221 patients.

The threat of hepatitis B virus recurrence: A sword of damocles to the liver transplant recipient

Teresa Wright – 1 July 1993 – The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%.

Liver transplantation for hepatocellular carcinoma

Alan P. Venook – 1 July 1993 – Background: Liver transplantation for unresectable hepatocellular carcinoma yields disappointing results. Most cases recur within 2 years, often in the transplanted liver. Methods: A combination of neoadjuvant doxorubicin and orthotopic liver transplantation was used in 20 patients with unresectable hepatocellular carcinoma confined to the liver. Seventeen patients had tumors > 5 cm in greatest diameter, and 11 cases were stage IVA by the TNM classification.

Coupling of the antiviral drug ara‐AMP to lactosaminated albumin leads to specific uptake in rat and human hepatocytes

Robert W. Jansen, Johan K. Kruijt, THEO J. C. van Berkel, Dirk K. F. Meije – 1 July 1993 – We covalently coupled 9‐β‐D‐arabinofuranosyladenine 5′‐monophosphate (ara‐AMP) to the carrier molecule lactosaminated human serum albumin using a water‐soluble carbodiimide with a two‐step conjugation method (pH 4.5 and pH 7.5) instead of the commonly used single‐step conjugation at pH 7.5. This resulted in a predominantly monomeric conjugate (lac27‐HSA–ara‐AMP9). The conjugate was stable in buffer (pH 7.4) and blood plasma.

Effects of ethanol on prostanoid production by liver fat‐storing cells

Robert Flisiak, Enrique Baraona, Jianjun Li, Charles S. Lieber – 1 July 1993 – Fat‐storing cells participate in the development of alcoholic liver disease. To study possible effects of ethanol on prostaglandin metabolism by fat‐storing cells, we isolated them from normal rat liver. Cultured fat‐storing cells produced substantial amounts (DNA, about 2 ng/μg every 24 hr) of prostaglandin E2 and prostaglandin I2 (measured as 6‐keto prostaglandin F1α) but no significant amounts of prostaglandin F2α.

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