Mitochondrial and other tissue antibodies in relatives of patients with primary biliary cirrhosis.
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Biomedical subjects
Publications and source records attributed to S Sherlock.
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In a series of 64 cases of elective end-to-side portacaval shunts performed for liver disease the success rate-in that the patient survived with a patent shunt, free of subsequent haemorrhage and severe encephalopathy-was 48%.The early postoperative death rate was 12.5% and the five-year survival 65%. Bleeding from oesophagogastric varices after blockage of the shunt was responsible for at least half of the early postoperative deaths, and most late deaths were due to liver failure. A decreased chance of late survival was associated with age over 40 years, active chronic hepatitis, and with a preoperative history of hepatocellular jaundice.Shunt blockage occurred in 16% of patients, and all bled again from oesophagogastric varices. Shunt block is more likely if the portal vein is calcified or thrombosed, and may be more likely if the portal vein diameter, as shown by splenic venography, is 1.5 cm or less.In survivors with a patent shunt the most serious late complication was chronic, severe portal-systemic encephalopathy, which occurred in 38%. Severe encephalopathy was associated with age over 40 years, a preoperative history of any degree of encephalopathy, diabetes mellitus, and with continued drinking in the alcoholic. Most patients who had portal-systemic encephalopathy in the first year postoperatively developed chronic disabling encephalopathy.A preoperative history of transient mild or moderate ascites did not seem adversely to influence the outcome.
The diagnosis of primary cancer of the liver was reviewed in 75 patients. A definitive diagnosis was made during life in 63% and in a further 20% this condition was suspected though histological confirmation was obtained only at necropsy. The most common presenting complaints were abdominal pain and weight loss and the most frequent findings hepatomegaly and ascites. Less than one-half of the patients were jaundiced and when present it was usually mild. An arterial bruit was heard over the liver in 25% of the patients. A sudden and unexplained deterioration in a patient known to have cirrhosis or haemochromatosis should raise the possibility of a primary hepatic tumour; this occurred in 24% of our patients.Alpha-fetoprotein was found in the serum of 11 out of 18 cases. The presence of a mass in the liver was frequently confirmed by liver scan, portal venography, or hepatic arteriography, but these showed no features diagnostic of a primary tumour. Liver scan also proved useful in localizing the lesion for biopsy purposes. Definitive diagnosis is dependent on the histological demonstration of the features of the tumour. This can frequently be achieved by percutaneous needle biopsy, which was positive in 38 out of 57 patients. Wedge biopsies were positive in a further nine patients.
In 8 out of 20 patients with chronic liver disease ascites was controlled with metolazone, 10 required additional amiloride or spironolactone to achieve control, and 2 were resistant to all diuretic therapy. An initial dose of 5 mg daily is suggested, though much higher doses may be required ultimately. When metolazone is used alone the high incidence of hypokalaemia (80%), hypochloraemia (35%), and encephalopathy (35%) compared with the results of other series is a major disadvantage and indicates that this drug should be used with caution in patients with liver disease. Hypokalaemia can usually be prevented by the simultaneous administration of amiloride or spironolactone. The low incidence of azotaemia (5%) suggests that this diuretic may be useful if renal function is particularly impaired.
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Evidence of portal hypertension was found in 50 out of 109 patients (47%) with primary biliary cirrhosis, and of these 32 bled from oesophageal varices. In four patients portal hypertension was the initial manifestation of the disease and this complication was recognized in a further 17 within two years of the first symptom of primary biliary cirrhosis. The development of portal hypertension was associated with a poor prognosis and death could frequently be attributed to variceal bleeding; the mean duration of survival from the time that portal hypertension was recognized was 14.9 months. Portal decompression operations may have improved the immediate prognosis in some patients but did not otherwise influence the progression of the disease. In 47 patients the histological findings in wedge biopsy or necropsy material were correlated with the presence or absence of varices. An association between nodular regeneration of the liver and varices was confirmed, but, in the absence of nodules, no other histological cause for portal venous obstruction could be found.