Sheila Sherlock

Liver biopsy today. The Royal Free Hospital experience.

Experience of needle liver biopsy at the Royal Free Hospital London between 1960 and 1983 has been reviewed with regard to selection of patients, techniques, complications and indications.

Effect of Pitressin on the Splanchnic Circulation in Man

The effects of 20 units of pitressin administered intravenously on the splanchnic circulation in four patients without liver disease, 10 patients with cirrhosis and a patent portal vein, 11 patients with cirrhosis and an end-to-side portacaval anastomosis and two patients with an extrahepatic portal vein obstruction and a normal liver structure, were observed. Estimated hepatic blood flow and wedged hepatic venous and intrasplenic pressures were measured in all groups, and the splanchnic, hepatic arteriolar, and hepatic postsinusoidal resistances were calculated. Pitressin reduced the portal pressure by an average of 39 per cent for 1 hour. Estimated hepatic blood flow was reduced by 40 per cent. Splanchnic resistance was increased by 87 per cent and hepatic arteriolar resistance by 77 per cent. Postsinusoidal resistance was not affected. The drop in portal pressure could be related to the increases in splanchnic resistance. There was no difference in the response to pitressin between patients with cirrhosis and patients with normal liver structure and function. It is suggested that the fundamental lesion causing portal hypertension in cirrhosis is an obstruction to the hepatic venous outflow and that mesenteric and hepatic arteriolar venous anastomoses are not operative in the genesis of portal hypertension in cirrhosis. This obstruction to hepatic venous outflow is not alterable pharmacologically and any attempts to lower portal pressure by medical means must be achieved by alterations in the splanchnic resistance. Pitressin appears to be the most potent splanchnic vasoconstrictor available.

Portal hypertension in chronic hepatitis: relationship to morphological changes.

Various anatomical factors were examined which might provide passive resistance to portal venous flow and so cause portal hypertension. Methods included the measurement of portal pressure (WHVPG) in cirrhotic and non-cirrhotic patients, morphological assessment by semiquantitative grading of severity of disease, calculation of hepatocyte size indices, and assessment of volume density of hepatocytes, sinusoids, Disses space and Disses space collagen by electron microscopy. The wedged hepatic venous pressure gradient increased with progression of disease and portal hypertension was present before histologically detectable cirrhosis had developed. With increasing progression of disease towards cirrhosis, the relationship between individual and aggregated features and the WHVPG diminished and lost statistical significance. Hepatocyte size increased with progression of histological changes and correlated significantly with increase of WHVPG, both in non-alcoholic and alcoholic patients. Disses space collagen was increased significantly in non-alcoholic chronic active hepatitis compared with patients with near-normal liver. No significant decrease of sinusoidal space was found. Multiple factors rather than any single feature influence the development of portal hypertension.

What is hepatic coma

The pic ture is character is t ica l ly f luetuant and (lifters in acuteuess and in symptoma to logy ; the p rogress to coma may be a matter of hours or years? . 4..~. 2~,. 3~, 3o Dis tu rbed consciousness wi th d isorder of steeI) is a cons tant feature . Reduc t ion of spontaneous movement , apathy, slowness, and brev i ty of response are ear ly signs. De te r io ra t ing fur ther , the pa t ien t reacts only to in tense or noxious s t imuli unt i l coma develops, resembl ing a deep sleep. Deter iora t ion m a y be a r re s t ed at any level, wi th e i ther regress ion or pers is tence of symptoms , t~.apid changes in the level of consciousness are accompanied by del ir ium. Persona l i ty changes are most conspicuous in associat ion with chronic liver disease. I n t e r m i t t e n t ehanges include childishness,

Virus hepatitis B, A, non-A, non-B

Hepatitis B vaccine is safe and effective. Its impact on the prevention of the disease, however, has been limited. In high risk areas, such as the Far East, mass vaccination of all babies is recommended. Even in low risk areas, such as Northern Europe and the United States, vaccination as part of a routine childhood immunisation programme might be effective so that protection is given before the adult becomes at risk of drug abuse or becoming a promiscuous homosexual or has joined the Health Care Service. A booster injection is probably necessary 5-7 years after primary vaccination. Hepatitis A still causes enormous epidemics. In Western Europe, large numbers of adults are at risk and the economic consequences are considerable. Vaccines which will replace serum immune globulin prophylaxis are under development. Epidemic non-A, non-B hepatitis is caused by a 27-34 nm virus, enterically transmitted. An antibody can be detected in the serum of sufferers from the epidemic but not the sporadic disease. Parenteral non-A, non-B hepatitis is associated with a viral genomic clone, isolated from infected chimpanzee liver and plasma. An antibody to it has been shown in serum of infectious blood donors and in haemophiliac patients previously exposed to blood products.

Chronic active hepatitis. Definition, diagnosis and management.

The manifestations of chronic active hepatitis mark it as a systemic rather than only a hepatic disease. Many of the patients, most of whom are young women, look remarkably well, an appearance that belies the presence of a disease likely to be fatal within five years, possibly within months. Associated diseases are many, and immunologic changes are striking. Treatment with prednisolone seems to prolong the lives of some patients but does not cure the disease or prevent eventual cirrhosis.

FACTORS DETERMINING THE HEPATIC REACTIONS TO DRUGS

Whenever a new drug is introduced into clinical practice, the question of hepatotoxicity is always raised. In every instance, despite extensive preliminary testing in animals, some doubt remains concerning the effect on the human liver. This uncertainty is related t o many factors. Species vary in their reactions to drugs, and genetic factors must also be considered. The effect of drugs at various ages and in the pregnant and malnourished must also be noted, and the status of the patient in respect to previous drug therapy and underlying liver function is of great significance.