B.R.D. Macdougall

INCREASED LONG-TERM SURVIVAL IN VARICEAL HAEMORRHAGE USING INJECTION SCLEROTHERAPY: Results of a Controlled Trial

Analysis of 107 patients with cirrhosis and recent variceal haemorrhage included in a prospective randomised trial of endoscopic injection sclerotherapy showed that in the sclerotherapy group 22 (43%) of the 51 patients had episodes of haemorrhage during the period of treatment, but in only 4 did bleeding occur after the varices had been obliterated. This contrasts with episodes of bleeding in 42 (75%) of the 56 patients receiving standard medical management-a highly significant difference. The overall risk of bleeding per patient-month of follow-up was reduced threefold with sclerotherapy. Of 22 patients followed up for at least one year after obliteration of varices, 14 had no evidence of reappearance of varices within this period and, by means of cumulative life-analysis tables, survival was shown to be significantly improved in the sclerotherapy group.

Recurrence of Primary Biliary Cirrhosis after Liver Transplantation

Three patients who had undergone orthrotopic liver transplantation for primary biliary cirrhosis and were being maintained on immunosuppressive therapy were investigated 31/2 to 41/2 years later because of the redevelopment of pruritus and mild jaundice. In one patient pigmentation was again evident, and all three had a rise in the titer of serum mitochondrial antibody after an initial fall. Liver histology showed features of primary biliary cirrhosis with non-suppurative destructive cholangitis, lymphoid aggregates, and increased deposition of copper-binding protein in the absence of cholestasis. None of these features was found in patients who had received grafts for other conditions and had lived for comparable periods, nor were they found in patients who had had rejection with bile-duct abnormalities. The overall findings indicate a recurrence of primary biliary cirrhosis in the donor organ.

H2-receptor antagonists and antacids in the prevention of acute gastrointestinal haemorrhage in fulminant hepatic failure. Two controlled trials.

In two controlled trials, involving 75 patients, on the prevention of bleeding from gastric erosions in fulminant hepatic failure, antacids given four-hourly had no significant effect. Only 35% of intragastric pH recordings taken at two-hourly intervals in the treated group were maintained above 5 with the doses used, whereas this could be consistently achieved with the histamine H2-receptor antagonists, metiamide and cimetidine. In the group receiving these drugs only 1 patient out of 26 bled, compared with 13 (54%) of the controls, a highly significant difference. Blood-transfusion requirements were significantly less in those treated with H2-receptor antagonists.

PROSPECTIVE CONTROLLED TRIAL OF INJECTION SCLEROTHERAPY IN PATIENTS WITH CIRRHOSIS AND RECENT VARICEAL HÆMORRHAGE

64 patients with cirrhosis and recent variceal haemorrhage were studied in a prospective randomised trial of injection sclerotherapy by means of a flexible oesophageal sheath. 12 (33%) of the 36 patients in the sclerotherapy group, suffered further bleeds from varices compared with 19 (68%) of the 28 patients receiving standard medical treatment. The risk of bleeding per patient-month of follow up decreased more than threefold with sclerotherapy and the number of patients rebleeding after 2, 6, and 12 months was significantly reduced (p < 0.05). 1-year survival without further bleeding improved significantly with sclerotherapy (46% compared with 6%, p < 0.02), although the difference in overall survival assessed by cumulative life-table analysis was not statistically significant. The main complication of the technique was the development of oesophageal ulcers in some patients.

SURVIVAL AND REHABILITATION AFTER ORTHOTOPIC LIVER TRANSPLANTATION

Between May, 1968, and April 27, 1980, 94 patients have been treated by orthotopic liver transplantation. During this time operative techniques and the management and selection of patients have changed. Healing of the biliary-tract anastomoses has been better since the introduction of a gallbladder conduit procedure and early irrigation of the donor biliary tract largely prevents damage to biliary-tract mucosa and sludge formation. Partial cardiopulmonary bypass in selected cases can provide control of the circulation during surgery. Many patients have been operated on too late, and an earlier selection is indicated. Of the 94 patients, 18 lived for over one year and 11 for two years, with 2 surviving for more than five years. 13 patients are currently alive. Rehabilitation of long-term survivors has been excellent, and although tumour recurred in more than 60% of patients grafted for primary hepatoma, worthwhile palliation can still be achieved.

B1 selective adrenoreceptor blockade for the long term management of variceal bleeding. A prospective randomised trial to compare oral metoprolol with injection sclerotherapy in cirrhosis.

Oral metoprolol, in a dose sufficient to reduce resting pulse rate by 25%, was compared with repeated injection sclerotherapy for the long term management of variceal bleeding. The prospective, randomised study was undertaken in 32 patients with biopsy proven cirrhosis and variceal bleeding who were Grade A or B on a modified Childs classification. In the 15 patients receiving metoprolol, portal pressure showed a mean fall of 3.7 mmHg (17.3 +/- 1.2 to 13.6 +/- 1.2 mmHg, p less than 0.01) after four weeks of continuous therapy, as compared with pretreatment levels. Nine of the 15 patients taking metoprolol had further bleeding (total of 21 episodes) compared with six of 17 in the sclerotherapy group (nine episodes). The risk of bleeding per patient/month of follow up was three times higher in the metoprolol group compared with those treated by sclerotherapy (0.14 and 0.04 respectively, p less than 0.025). Rebleeding in the metoprolol group occurred in six of the patients who had a fall in portal pressure of 10% or more.

[1-14C] Ethanol breath test in alcoholic liver disease

The activity of ethanol metabolising enzymes was assessed in 51 patients with alcoholic and non-alcoholic liver disease using tracer doses of [1-14C]ethanol and measuring 14CO2 excretion in the breath. Alcoholic patients with only fatty infiltration of the liver showed significantly increased activity compared with controls. Comparing alcoholic patients with cirrhosis and a serum albumin greater than 28 g/l, activity in those with a recent history of continued heavy drinking was significantly greater than in patients who had abstained from alcohol. In addition, both groups of alcoholic cirrhosis showed significantly more activity than patients with non-alcoholic cirrhosis. The activities of patients with acute alcoholic or viral hepatitis were normal when their prothrombin times were less than 7 sec prolonged, but were reduced when prolongation exceeded 7 sec. These results demonstrate that in chronic alcoholic liver disease, even with cirrhosis, alcohol can still increase the activity of ethanol oxidising enzymes provided hepatic function remains adequate. However, this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction.

UPPER GASTROINTESTINAL HÆMORRHAGE

of a family history of congenital adrenal hyperplasia. There was spontaneous onset of labour at 40 weeks, but delivery was by cxsarean section because of fetal distress. At birth, clinical examination was entirely normal. Serum-17-OHP concentrations, determined by radioimmunoassay, were: mixed cord blood 183 nmol/1 and 2, 8, and 16 h and 5 day values 4

Improved survival following injection sclerotherapy for esophageal varices: Final analysis of a controlled trial

, 42, 15, and 3 nmol/1, respectively. The raised concentrations in cord blood and during the first few hours of life presumably reflect the placental production of 17-OHP. Thereafter, the concentrations fell rapidly to normal, thus excluding a diagnosis of congenital adrenal hyperplasia secondary to C21-hydroxylase deficiency. These results are in striking contrast to those obtained from a male infant with congenital adrenal hyperplasia. Mixed cord serum-17-OHP concentration was 225 nmoi/1, and at 2, 8, and 16 h and 5 days age the levels were 109, 188, 488, and 188 nmol/1, respectively. The raised 17-OHP concentrations persisted after birth; subsequently, biochemical confirmation of congenital adrenal hyperplasia was further substantiated by increased urinary excretion of 17-oxosteroids and pregnanetriol. The 17-OHP assay should be of value in the early diagnosis of congenital adrenal hyperplasia due to C21-hydroxylase deficiency, especially in newborn males in whom clinical examination is usually entirely normal.