Portal hypertension--25 years of progress.
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Biomedical subjects
Publications and source records attributed to B R MacDougall.
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Enprostil, a prostaglandin E2 analogue, is effective in healing acute duodenal ulcer but its value in preventing recurrence, when given daily for maintenance therapy, is uncertain. In this three-centre study we compared enprostil and ranitidine maintenance therapy; the latter is known to reduce duodenal ulcer relapse rates. Patients whose duodenal ulcers had been healed by treatment with an H2-receptor antagonist were randomized to receive single-blind treatment with either 35 micrograms enprostil (n = 64) or 150 mg ranitidine (n = 64) at bedtime for periods of up to 1 year. Endoscopy was routinely performed at 3 months at one centre, and at 6 and 12 months at all three centres, or whenever ulcer symptoms recurred. Clinical assessment and laboratory investigations were performed every 3 months. Relapse, defined as recurrent ulcer with or without pain, or erosions with pain, was significantly greater in patients on enprostil, the comparative rates at 3, 6 and 12 months were: enprostil 23, 31 and 36% ranitidine 6, 12 and 17% (P = 0.013; P = 0.03 and P = 0.03, respectively). Thirty-one patients reported adverse events, the most common being headache (enprostil = 6, ranitidine = 2) and mild diarrhoea (enprostil = 6, ranitidine = 0). Four patients on enprostil were withdrawn for adverse events, although none terminated because of diarrhoea. There were no clinically significant changes in haematology or biochemistry. Enprostil may reduce duodenal ulcer relapse but at a dose of 35 micrograms nightly, it is less effective than 150 mg ranitidine nightly.
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.
In a prospective study of emergency endoscopy in patients with portal hypertension and oesophageal varices referred to King's College Hospital with acute upper gastrointestinal bleeding, initial endoscopic examination on 90 separate consecutive hospital admissions carried out within 24 h of clinical haemorrhage showed active variceal bleeding in only 21 (23.3%) cases. Coexisting upper gastrointestinal lesions were present in 38.8% of examinations, but active bleeding from these sites was seen in only five cases (5.6%). Of the 64 cases in which no active bleeding was seen at initial endoscopy, 39 (60.9%) rebled during that admission, and repeat endoscopy in 27 of these, carried out within 1 h of this episode, revealed active variceal haemorrhage in 20 (74.1%) cases. These results indicate that variceal haemorrhage is intermittent, and, although bleeding may often stop spontaneously, a high proportion of patients subsequently rebleed, and this is invariably from varices rather than from coexisting upper gastrointestinal lesions. In addition, these findings confirm the importance of emergency endoscopy in making the correct decision about acute management.
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The use of cyclosporin A (CyA) with a protocol designed to avoid the effects of nephrotoxicity resulted in a one-year survival of 86% in recipients of renal allografts from unmatched cadaveric donors. The drug also controlled rejection of liver and pancreatic allografts. It was possible to change patients initially treated with CyA to azathioprine and corticosteroids and vice versa, thus enlarging the potential value of CyA in organ allografting. Of 34 recipients of renal allografts, 29 were currently receiving only CyA as immunosuppressive treatment. Twelve patients never required any adjuvant steroid treatment. These results suggest that CyA is an effective immunosuppressant, and if used with care side effects need not be severe.
The selection of 200 consecutive patients who underwent liver biopsy as a day-case procedure and subsequent complications were reviewed, In 59 patients a diagnosis of cirrhosis was confirmed by histological examination. Six patients developed minor complications attributable to the procedure and had to stay longer in hospital, and another returned with abdominal pain the evening after the biopsy. With careful selection of patients, liver biopsy may be safely undertaken on a day-case basis.
The overall indications for liver transplantations are becoming clearer. Patients with decompensated cirrhosis are poor risks and grafting should be done earlier. Results of transplants for primary biliary cirrhosis and well compensated cirrhosis are more encouraging. Transplantations for hepatocellular carcinoma is faced with the problem of high recurrences postoperatively. The presence of hepatitis B in a recipient is no longer a contraindication to grafting since this can be adequately treated with specific immunoglobulin. The latest introduction of Cyclosporin as an immunosuppressant may be of real benefit in liver transplantations.
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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.
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