Lifetime prolongation in voluntary alcohol-consuming rats (SHR) treated with clofibrate.

Clofibrate affects lipid and alcohol as well as drug and eicosanoid metabolism. Spontaneous hypertensive rats (SHR) further increase their high voluntary alcohol consumption during clofibrate feeding. The interaction of alcohol and clofibrate was studied in two long-term trials. Seventy-nine male SHR (aged 27 weeks) were offered increasing concentrations of ethanol, up to 30% (tap water ad lib), and 3 months later 0.5% clofibrate-food. Four groups were established: N, normal controls; NA, standard diet+alcohol; C, clofibrate feeding; and CA, clofibrate feeding + alcohol. Food intake, alcohol consumption, body weight, and laboratory values were recorded continuously. Life duration (weeks) after the start of the trial was 63.3 +/- 3.3 in N, 73 +/- 2.6 in NA, 77.7 +/- 4.3 in C, and 90.3 +/- 2.8 in CA. There were no alcohol-related liver findings in NA and CA. Most of the animals died of cardiac and renal failure. An increase of tumors in clofibrate-treated rats was not observed. Voluntary alcohol consumption or clofibrate feeding significantly lengthens lifetime, which is prolonged by 42% if ethanol is combined with clofibrate. This is obviously not mediated by the lipid lowering effect or an influence on body weight and blood pressure of either clofibrate or alcohol.

Enhancement of voluntary alcohol consumption in rats by clofibrate feeding.

Clofibrate is known to be an inducer of alcohol- and acetaldehyde dehydrogenase. Therefore, male rats were offered increasing amounts of alcohol over a period of three months. Eventually they could choose between a 30% alcohol solution and tap water which was available ad lib. Animals were sacrificed after further 1 1/2 months of clofibrate feeding. Before clofibrate feeding voluntary intake of alcohol was 3.47 g/kg per day and increased up to 7.77 g/kg per day, i.e., by 123% within the clofibrate feeding period while the alcohol intake of controls increased from 3.84 to 4.88 g/kg per day, i.e., by only 27%. Food consumption increased in the clofibrate control group, whereas in the alcohol drinking clofibrate group the total caloric intake increase was due mainly to the enhancement of alcohol consumption. Relative liver weight was increased by clofibrate in the non-drinking as well as in the drinking group by 59%. Measurements of triglycerides and cholesterol exhibited changes typical for clofibrate in ethanol drinking and non-drinking animals. Probably the clofibrate-alcohol interaction results in accelerated ethanol metabolism and increased metabolic tolerance by induction of the ethanol detoxifying system in the liver.

[Total liver failure in the scintigram of alcoholic liver cirrhosis]. / Totalausfall der Leber im Szintigramm bei alkoholischer Leberzirrhose.

Case reports are given of 3 female patients suffering from advanced, hypertrophic alcoholic cirrhosis of the liver with portal hypertension. The livers of these patients were not demonstrable by scintigraphy. The patients died a few months afterwards from liver failure. This syndrome - failure of the liver to show up in scintigraphy - may have diagnostic and prognostic implications; it may be caused by deficient blood circulation and by reduced phagocytic capacity of the kupfer cell system.

Deficiency of antibody formation to HBsAg in the pathogenesis of chronic hepatitis and cirrhosis?

UNLABELLED: Sera of 832 healthy persons and patients suffering from chronic inflammatory liver disease were investigated by radioimmunoassay for HBsAg and anti-HBs. Diagnosis in patients was secured by biopsy. The persons were divided into: 1. Healthy persons: n = 478 blood donors, hospital especially exposed to HBV, patients with healed hepatitis; 2. PATIENTS: n = 354 acute hepatitis, chronic persistent and aggressive hepatitis, post-hepatitic, cryptogenic and alcoholic cirrhosis. The results demonstrate considerable accumulation of HBsAg in chronic liver disease (72% in CAH, 66% in posthepatic liver cirrhosis) whereas anti-HBs was more frequently observed in healthy persons (38% in hospital staff, 49% in healed hepatitis). Furthermore, HBsAg and anti-HBs were frequently observed simultaneously in chronic hepatitis and cirrhosis (23% in CAH). A strong shift in the relation of antigen to antibody to the disadvantage of antibody in the examined collectives of chronic hepatitis and cirrhosis is evident. Chronic inflammatory HBsAg positive liver disease should therefore be regarded as chronic virus infection. We suppose an absolute or relative deficiency of antibody to HBsAg is probably an important factor for the development of chronicity of hepatitis B.

[Pseudocholinesterase in patients with and without liver diseases (author's transl)]. / Pseudocholinesterase bei hepatischen und nichthepatischen Erkrankungen.

The activity of plasma pseudocholinesterase (PChE) was determined on admission and prior to discharge from the hospital in 200 patients admitted consecutively to a medical ward specialized in liver and infectious diseases. In 24% of patients without liver diseases and without malignant growths the pseudocholinesterase-activity was below normal on admission but increased during the observation period toward normal values. There was a negative correlation between pseudocholinesterase-activity and the intensity of the inflammatory activity as measured by granulocyte count, ESR, body temperature and IgA. This correlation could be established for patients without demonstrable liver pathology as well as for liver diseases. Elevated pseudocholinesterase-levels were observed only in three cases of toxic liver injury (2 heavy drinkers, 1 case of polytoxicomania). In all patients with malignant diseases subnormal values of pseudocholinesterase were observed. Only one patient had normal pseudocholinesterase-activity on admission, but the pseudocholinesterase decreased within a few weeks to subnormal values as the underlying malignant melanoma progressed. The decrease of pseudocholinesterase-activity in malignant diseases was independent of the presence of liver metastases.

[Quantitative serum immunoglobulin determination: differential diagnostic significance for liver disease (author's transl)s]. / Differntialdiagnostische Bedeutung der quantitativen Serumimmunglobulinbestimmung bei Lebererkrankungen

The serum immunoglobulin (Ig) G, A, and M levels were investigated with respect to their differential diagnostic significance, pathogenesis and estimation of prognosis of different forms of liver disease. The sera of 204 patients with acute hepatitis, fatty liver I and II, and cirrhosis, and of 110 healthy adutls were quantitatively determined for immunoglobulins. 1. IgG- and IgA-concentrations higher than 2000 mg% and 330 mg%, respectively, indicate chronic aggressive hepatitis or cirrhosis, and exclude all other groups. 2. A clear correlation between HBsAG (Australia Antigen) and immunoglobulin content could not be demonstrated in any group; 3. A significantly elevated level of IgA was observed in alcoholic cirrhosis when compared to non-alcoholic cirrhosis. No such differences were found inhe other groups. 4. Acute and chronic persistent hepatitis show a similar increase of immunoglobulins. Thus persistent high levels of Ig following acute hepatitis indicate the development into a chronic hepatitis. 5. A relative increase of IgA rather than IgG corresponds to the degree of inflammatory activity of a liver process.