I.M. Murray-Lyon

CHARCOAL HÆMOPERFUSION IN THE TREATMENT OF FULMINANT HEPATIC FAILURE

Abstract Twenty-two patients with fulminant hepatic failure who deteriorated to grade-IV coma despite full supportive therapy were treated by repeated periods of haemoperfusion through columns containing activated charcoal. The procedure was well tolerated clinically. Eleven of the patients regained consciousness and ten left hospital. Follow-up liver biopsies in the first three patients at around six months after discharge from hospital showed restitution of the normal lobular architecture. Of the eleven treatment failures, haemorrhage was responsible for death in three, and in six brain herniation secondary to cerebral œdema was an important contributory factor. The column extracted most aminoacids from plasma, and during perfusion arterial concentrations of phenylalanine, tyrosine, and methionine-aminoacids known to be involved in the pathogenesis of the encephalopathy—fell significantly. The charcoal was coated with a biocompatible polymer, and there was no evidence for removal of coagulation factors. The extraction of platelets was below 30% in most instances, and in only two patients was there evidence that bleeding may have been precipitated by the haemoperfusion. These survival figures are to be compared with a previous survival figure of 10% in a series of ninety-two cases with fulminant hepatic failure and grade III or IV encephalopathy treated by full supportive measures.

INDUCTION OF REMISSION IN HEPATOCELLULAR CARCINOMA WITH DOXORUBICIN

Doxorubicin (60 mg/m2 at 3-weekly intervals to a maximum total of 550 mg/m2) induced clinical remission in 14 (32%) of 44 patients with hepatocellular carcinoma. In 3 of those who responded, hepatic arteriography showed clearing of the previously extensive tumour circulation, and in a 4th there was disappearance of the tumour on serial ultrasound examinations. A fall in serum-alpha-fetoprotein level after the initial injection of doxorubicin predicted a favourable clinical response, whereas the level continued to rise in patients who did not respond.

Quadruple chemotherapy versus radiotherapy in treatment of primary hepatocellular carcinoma.

Although there have been many therapeutic trials of chemotherapy for primary hepatoma, few have been controlled and the results of treatment have been disappointing. The present report is concerned with a controlled trial of chemotherapy alone versus radiotherapy followed by chemotherapy in 18 patients with primary hepatoma. Ten patients received quadruple chemotherapy (5‐flurouracil, cyclophosphamide, methotrexate, and vincristine). These patients survived considerably longer (21 weeks) than eight patients who received radiotherapy followed by the same chemotherapy regime (12 weeks). Further analysis of these results suggested that length of survival in both treatment groups was related to age, length of history, levels of serum bilirubin and aspartate transaminase, and to the presence of cirrhosis or ascites. According to these criteria, patients were subdivided into two grades of disease. For patients with less severe disease (grade A), median survival after chemotherapy alone (54 weeks) was longer than after radiotherapy followed by chemotherapy (24 weeks). Survival of patients with severe disease (grade B) was equally poor in both treatment groups (5 weeks, chemotherapy; 7.5 weeks radiotherapy followed by chemotherapy). In conclusion, these results show that quadruple chemotherapy alone is a valuable form of therapy for grade A patients. Neither form of therapy, however, was of any benefit for grade B patients. Cancer 40:609–614, 1977.

Quantitative immunoelectrophoresis of plasma proteins in acute viral hepatitis, extrahepatic biliary obstruction, primary biliary cirrhosis and idiopathic haemochromatosis

Abstract The concentration of 12 plasma proteins were measured in patients with acute viral hepatitis (12), extrahepatic biliary obstruction (12), primary biliary cirrhosis (20) and idiopathic haemochromatosis (20). In the first three diseases the changes were broadly similar, there being a fall in the concentration of prealbumin and haemopexin and a rise in easily precipitable glycoprotein, α 1 -antitrypsin and caeruloplasmin. Raised levels of α 2 -macroglobulin were found only in primary biliary cirrhosis and haemochromatosis. Transferrin was reduced in extrahepatic biliary obstruction and haemochromatosis. It is suggested that the pattern of changes represents the “acute phase reaction” which is modified in part by the limitations on protein synthesis imposed by the underlying liver disease. The most marked changes were found in the diseases with the greatest disturbance in liver function, and there were numerous statistically significant correlations between the levels of individual proteins and the clinical data.

The use of cysteamine and dimercaprol.

Introduction It has been suggested that hepatic damage following a paracetamol* overdose might be prevented by the administration of compounds containing sulphydryl groups (Mitchell et al 1973) which would either increase the amount of glutathione available in the liver or substitute for the action of this compound. One such substance, cysteamine is effective in preventing hepatic necrosis in laboratory animals (Mitchell et a/ 1974, Gazzard et a/ 1974). A preliminary uncontrolled study suggested that it was effective in man (Prescott et al 1974) but recently it was found in a controlled clinical trial not to give significant protection against hepatic damage (Douglas, Hamlyn & James 1976). This study was undertaken in patients following paracetamol overdose to compare the protective effect ofcysteamine with that of dimercaprol, another sulphydryl group donor, found to be of some protective effect in laboratory animals (Mitchell et al 1974) and which had the advantage of being commercially available for human use. We present here the results of the thirty-five patients treated in the trial to date.