Cardiac function in alcoholics with cirrhosis: absence of overt cardiomyopathy--myth or fact?

Cardiomyopathy in alcoholics is considered to be associated with a low incidence of hepatic cirrhosis. To evaluate cardiac hemodynamics in alcoholic liver disease, left ventricular function in 37 patients with hepatic cirrhosis (group II) was compared with that in 13 normal subjects (group I) matched for age, sex and cardiac size. These groups were contrasted with group III, comprising 32 alcoholics without cirrhosis who had cardiac symptoms but no cardiomegaly or heart failure. Patients with cirrhosis as a group did not differ from normal subjects (group I) in terms of left ventricular filling pressure and cardiac muscle and pump function (cardiac index). However, subgroup IIA (n = 21) had a stroke index significantly less than normal, while subgroup IIB had a significantly increased stroke index and myocardial cardial contractility with a diminished systemic arterial resistance. Similar hepatic abnormalities were present in both subgroups. In group III, left ventricular end-diastolic and aortic mean pressures were significantly elevated compared with values in normal subjects, while cardiac index and indexes of ventricular contraction and relaxation were abnormal. Further examination of patients with cirrhosis indicated that the responses to volume or pressure increments in terms of the level of stroke work for a given filling pressure were most abnormal in group IIA, approximating those of group III. Thus, although overt cardiomyopathy is infrequent in patients with cirrhosis, asymptomatic myocardial disease may assume clinical importance during volume or pressure overload.

Thiamin in the elderly--relation to alcoholism and to neurological degenerative disease.

Status of thiamin in the elderly North American population is reviewed. Most Americans eat sufficient thiamin but about 5% of those over 60 yr old show impaired thiamin status. This is more marked in the poor, those confined in institutions, or those with illness. Thiamin responsive heart disease and Wernicke Korsakoff CNS syndromes occur in the elderly but there is no increased prevalence. Minor heart or neurological syndromes related to thiamin deficiency cannot be identified. The Recommended Dietary Allowance of thiamin provides at least 50% excess thiamin for those over 60 yr old--this amount is adequate. There is no known toxicity for thiamin.

Inability of chronic alcoholics with liver disease to use food as a source of folates, thiamin and vitamin B6.

Absorption of folates, thiamin, vitamin B6, pantothenate and riboflavin from a natural food source--yeast--and their respective synthetic forms was studied in 37 patients with liver disease due to alcoholism, and 12 healthy, nonalcoholic subjects. All alcoholics absorbed riboflavin and pantothenate but had a significantly lowered absorption of thiamin and vitamin B6 from yeast. Alcoholics absorbed synthetic vitamin B6, but not thiamin. Ingested folylpolyglutamates (the predominant folates in yeast) could not serve as a source of folate for the alcoholics, but synthetic folylmonoglutamate served. We suggest that the folate, vitamin B6, and thiamin deficits so common in alcoholic liver disease ensue from inability to absorb these specific vitamins from foods.

Liver disease of the alcoholic.

Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.

Studies of nucleic acid and collagen synthesis: current status in assessing liver repair.

Much progress has been made in delineating biochemical, physiologic and morpholigic events in liver regeneration and collagen synthesis. Pharmacologic agents have been purported to be helpful in facilitating repair and preventing fibrosis. Objective indices are now available to monitor their effectiveness in man.

Disease-specific amino acid infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial.

Seventy-five patients with acute hepatic decompensation superimposed on chronic alcoholic cirrhosis were prospectively randomized for a blinded trial of the treatment of hepatic encephalopathy. The control group received 4 g of enteral neomycin daily along with 25% dextrose by a central venous catheter. The experimental group received a placebo resembling neomycin and isocaloric dextrose plus a modified amino acid mixture enriched with branched-chain amino acids to 36% and deficient in aromatic amino acids and methionine. Thirty patients in the F080 group and 29 in the control group completed the trial. The group receiving the modified amino acid mixture demonstrated a statistically significant improvement in encephalopathy as compared to the neomycin group, while maintaining nitrogen equilibrium. Survival and discharge from the hospital were statistically greater in the group treated with the modified amino acid solution and hypertonic dextrose. Treatment of hepatic encephalopathy in the presence of hepatic decompensation with an amino acid solution formulated for its treatment seems to produce faster, more complete recovery with improved capacity for nutritional support.

Hepatic disease in asymptomatic parenteral narcotic drug abusers: a Veterans Administration collaborative study.

The Veterans Administration is currently conducting a collaborative study in three hospital-based drug treatment clinics to evaluate asymptomatic parenteral drug addicts for evidence of hepatic disease. Preliminary data are presented on 347 patients who have completed at least three months of follow-up evaluation. On admission, abnormal serum transaminase values were demonstrated in one half, HBs Ag in 7 per cent, and anti-HBs in 59 per cent. The frequency of these findings increased during the follow-up evaluation, only 19 (5.5 per cent) remaining entirely free of one or more of these abnormalities. Definable hepatologic disease (acute or chronic hepatitis, alcoholic hepatitis) developed in 46 per cent of the patients. However, among 60 of them subjected to liver biopsy, a poor correlation was noted between the clinical and histologic diagnoses. In particular, routine liver function and immunologic tests did not discriminate between histologically detected chronic active and chronic persistent hepatitis. However, HBs Ag was present significantly more frequently in those with chronic active hepatitis. Wide variability of histologic diagnoses was seen among patients subjected to more than one biopsy, apparent progression and regression of the lesion being noted. This demonstrates the hazard of attempting to assign a prognosis to the disease on the basis of a single liver biopsy specimen, and suggests that repeated biopsies should be mandatory for the evaluation of chronic liver disease in drug addicts.

Erythroderma with fulminant hepatitis: a possible association.

Exfoliative dermatitis or erythroderma may be a sign of systemic disease, usually a T-cell lymphoma, although other malignancies may also be associated. We observed two patients in whom severe hepatitis and an exfoliative dermatitis occurred simultaneously. We believe that this association has not been reported previously.

Alcoholic liver disease.

Alcoholism alone, or in combination with other etiologic factors, is a common cause of liver failure because of hepatitis, cirrhosis, and/or hepatocellular cancer. Encountered morphologic and functional alterations are due to immunologic reactivity to cell injury evoked by acetaldehyde, other noxious factors, and nutrient deficits. Less than 20% of subjects who consume over 90 g/d of ethanol for years develop progressive liver damage and cirrhosis. Alcoholism should be interrupted in patients with subclinical hepatic abnormalities. Although early alcoholic hepatitis and cirrhosis respond to abstinence and symptomatic therapy, available measures have little influence on functional and morphologic abnormalities in end-stage alcoholic liver disease. Resection is desirable for localized hepatocellular cancer, and liver transplantation should be considered for cirrhosis. Transplantation is appropriate for patients with uncomplicated end-stage alcoholic cirrhosis in whom evidence of liver failure can be controlled during a 6-month period of rehabilitation. Continuous psychosocial support is required to prevent recividism in the posttransplant immunosuppressed alcoholic.

The founding and development of New Jersey Medical School.

The need to address the social and biological aspects of medicine was emphasized at the founding of New Jersey Medical School in 1954. This need has remained a major goal, as the sponsorship, name, and location of the Medical School have changed with the times.