While the role of nutrition in the pathogenesis of cirrhosis of the liver in man has not been elucidated in its entirety, evidence from many sources suggests a relationship between a deficient intake of protein and the development of fatty infiltration, cellular necrosis and fibrosis of the liver. The dietary history of many patients with cirrhosis indicates a low intake of protein and of B-complex vitamins. The institution of a diet rich in protein has been followed by improvement in the clinical condition of the patient and in liver function tests. Eckhardt and associates found that provision of a diet adequate in protein resulted in a decrease in liver fat and a return of the size and appearance of liver cells to normal.
In patients with untreated cirrhosis in whom biopsy specimens showed fatty infiltration of the liver, administration of a large single dose of methionine or choline has been shown to increase phospholipid turnover. Studies of Kirsner (41) suggest that in patients with cirrhosis, amino acids other than methionine may be metabolized adequately although less efficiently than normal. In acute severe hepatitis, concentrations of methionine in plasma are greatly increased. A high protein intake is contraindicated under these circumstances and in impending hepatic coma.
A detailed discussion of the diagnosis of cirrhosis is not warranted here but it seems pertinent to emphasize the importance of searching for evidence of liver dysfunction in the presence of serious dietary deficiency of protein. A palpable liver, abnormal liver function tests and histologic changes in liver tissue obtained by biopsy will establish the presence of liver disease. Measurement of enzyme activity in biopsy specimens may prove useful in studying many of the syndromes associated with protein deficiency. Certain other changes in cirrhosis of the liver which are of nutritional import may be mentioned, al-though they are not related directly to protein nutrition. An increased loss of fat in the stools has been observed that has been postulated to be due to defective formation of bile salts. In decompensated alcoholic cirrhosis, serum concentrations of sodium, potassium, calcium and phosphorus have been found to be lower than normal, while pyruvic acid concentration in the blood has been elevated. The low calcium and phosphorus levels may have been due to an increase in fecal fat.
In hepatic coma, concentrations of pyruvate and a-keto glutarate have been found to be high in both blood and spinal fluid. Since thiamine administration does not influence these levels, it has been postulated that the liver may be unable to assimilate pyruvic acid to form the carboxylic acids of the Krebs cycle or that a partial deficiency of cocarboxylase may be responsible. High blood ammonia concentrations have been observed, also, in hepatic coma. It has been suggested that high concentrations of keto acids in hepatic coma may represent a defect in intermediary metabolism due to impaired utilization of ammonia and faulty removal from the blood by the diseased liver.