D.R. Triger

ANORECTAL VARICES, HAEMORRHOIDS, AND PORTAL HYPERTENSION

In a prospective study of 100 consecutive patients with cirrhosis, 44% had anorectal varices. The prevalence of anorectal varices rose with progression of portal hypertension; it was 19% in cirrhotic patients without portal hypertension compared with 59% in those who had bled from oesophageal varices. There was no evidence that endoscopic sclerotherapy directly increased the prevalence of anorectal varices. Haemorrhoids occurred independently of anorectal varices and their presence was unrelated to the degree of portal hypertension. These data provide further evidence that haemorrhoids and anorectal varices are separate and distinct entities. However, both can bleed and careful examination is essential to prevent misdiagnosis and inappropriate treatment.

Natural history of autonomic neuropathy in chronic liver disease

To determine the natural history of autonomic neuropathy in chronic liver disease we used standard cardiovascular autonomic tests to evaluate prospectively 60 patients (33 male, 27 female) with initially well-preserved hepatic function. On initial testing, 27 patients (45%; median [range] age 56 [32-67] years) had vagal neuropathy. Autonomic dysfunction was equally common in patients with alcohol-related and nonalcoholic-related liver disease. The cumulative 4-year mortality rate in patients with vagal neuropathy was 30% compared with 6% in those with normal autonomic function. Multiple logistic regression analysis showed that presence of vagal neuropathy and severity of hepatic damage were independent predictors of mortality. Serial testing showed that whereas disease progression occurred in some patients, in others mild abnormalities in autonomic function were reversible. Vagal dysfunction is common in well-compensated chronic liver disease and its presence identifies a subgroup of patients with a substantially worse outlook.

Peripheral and cardiovascular autonomic impairment in chronic liver disease: prevalence and relation to hepatic function.

We have evaluated autonomic function using standard cardiovascular tests and a test of peripheral autonomic denervation, the acetylcholine sweatspot test, in 104 patients with biopsy proven chronic liver disease and 35 age- and sex-matched controls. Cardiovascular autonomic dysfunction was significantly more frequent in advanced liver disease compared with early liver disease (71.8% Child B or C vs. 39.7% Child A; p < 0.0006), and a strong correlation between the number of abnormal tests and Child-Pugh score could be demonstrated (Rs = 0.5; p < 0.0001). On multiple logistic regression analysis, cardiovascular autonomic dysfunction was related to age and to Child-Pugh score and occurred independently of the aetiology of liver disease. Peripheral autonomic denervation was found in 39% of patients, was significantly associated with cardiovascular abnormalities (p < 0.009) and correlated with the number of abnormal cardiovascular tests in each patient (Rs = 0.48; p < 0.0001). In chronic liver disease, the prevalence and severity of cardiovascular autonomic dysfunction is related to the severity of hepatic dysfunction and is independent of aetiology, suggesting a common pathogenetic basis related to hepatic damage; the association with peripheral autonomic denervation indicates that at least some of the abnormalities may be due to a true autonomic neuropathy. The possible significance of these findings to the complications of cirrhosis is discussed.

Autonomic and peripheral neuropathy in primary biliary cirrhosis

Autonomic and peripheral nerve function was examined in a group of patients with primary biliary cirrhosis using standard cardiovascular reflex tests and peripheral nerve conduction studies. Sixty-three percent had cardiovascular autonomic dysfunction with predominantly parasympathetic abnormalities. Symptoms of peripheral neuropathy were rarely volunteered spontaneously but occurred frequently when specifically sought; 40.7% had definite peripheral neuropathy, with symptoms and/or signs plus peripheral neurophysiological abnormalities. A close association between autonomic and peripheral nerve function was found with correlation between the heart rate variation on deep breathing and both peroneal nerve conduction velocity (r = 0.67, P < 0.001) and sural nerve conduction velocity (r = 0.52, P < 0.008). Correlations were also noted between other autonomic tests and peripheral nerve function. Both autonomic and peripheral nerve function correlated with serum bilirubin and albumin; no significant association was noted with vitamin E deficiency or hyperlipidaemia. A generalised neuropathy with peripheral and autonomic abnormalities is common in primary biliary cirrhosis and could be related to hepatic damage. Although rarely clinically disabling, the autonomic impairment associated with this neuropathy may be of prognostic significance.

A randomised prospective trial comparing daily paracentesis and intravenous albumin with recirculation in diuretic refractory ascites

We report a randomised trial in 40 consecutive patients with diuretic refractory ascites comparing our standard therapy of ascites recirculation (Rhodiascit apparatus) with the newly proposed method of daily paracentesis (3-4 litre) and intravenous albumin infusion. A mean of five (range 2-13) paracenteses removed 13.3 (2.0-36.0) l of ascites. 12 (5-32) h of recirculation produced 6.0 (2.0-12.0) l of waste. A significant diuresis occurred in 14 recirculation patients compared to four treated by paracentesis. No significant changes in electrolyte levels or renal function occurred. Complications were commoner with paracentesis (12) than with recirculation (5). Following recirculation, 18 patients were discharged after 7 (2-21) days; significantly (p less than 0.04) shorter than after paracentesis (11 (4-34) days, 16 discharges). Ascites reaccumulation and survival were identical in both groups. Fewer complications, shorter hospital stay and lower consumables costs (recirculation 240 pounds, paracentesis 400 pounds) make ascites recirculation an attractive therapeutic option to daily paracentesis and intravenous albumin in diuretic refractory ascites.

Portal hypertensive gastropathy

There is now substantial clinical evidence to suggest that portal hypertensive gastropathy is an important source of gastrointestinal bleeding in patients with portal hypertension. Although a relatively uncommon presenting feature in such patients, it appears to become progressively more frequent and important the longer such patients with bleeding oesophageal varices survive after treatment by endoscopic sclerotherapy. It is now being increasingly recognized as the most important cause of haemorrhage after oesophageal varices in such patients. The endoscopic and histological characteristics of the condition are now well established but from a clinical point of view it is important to distinguish it from a number of other disorders. The pathogenesis of portal hypertensive gastropathy is poorly understood; venous congestion secondary to portal hypertension undoubtedly plays an important role but this is not thought to account entirely for the condition since abnormalities in the arterial blood supply are also observed. Many abnormalities in gastric mucosal function have been reported but it is unclear whether these are secondary disturbances or whether they play an important primary role in the development of the condition. Animal studies to date have not been helpful due to the lack of a satisfactory experimental model. Portocaval shunt surgery cures portal hypertensive gastropathy but propranolol has been shown to be highly effective in controlling haemorrhage from this condition and should now be considered the treatment of choice. The mechanism of action is unclear, and it remains to be shown whether other beta-blockers, or indeed any other drugs, are useful in treating this disorder.

Coagulation disturbances following ascites recirculation

To investigate the effects of extra-corporeal ascites recirculation on coagulation, several coagulation variables were measured in ascitic return fluid and plasma before, during and after this procedure in 16 patients with diuretic resistant ascites. Small but significant reductions in plasma fibrinogen levels and platelet counts and increases in plasma X-oligomer were observed during and after the procedure compared with before. These findings are consistent with the view that ascites recirculation induces disseminated intravascular coagulation although this would appear to be only mild and of no clinical significance in the majority of patients. Although increased levels of activated factor VII were observed in ascitic fluid indicating activation of the extrinsic pathway of coagulation, a significant increase in plasma activated factor VII during the procedure was not demonstrated. Increased fibrinolytic activity was observed in ascitic fluid due to the presence of tissue plasminogen activator. Increased X-oligomer levels were observed in ascitic fluid indicating that lysis of cross-linked fibrin is also an active process within ascites.

Phagocytic function in the isolated perfused rat liver: An experimental model

An experimental model for measuring the phagocytic function of the isolated perfused rat liver is described. A progressive rise in phagocytosis was observed with increasing liver blood flow. This is due to an increase in total particle uptake by the liver with no alteration in the rate constant for phagocytosis except at the highest flow rate. Phagocytosis is substantially greater in the livers of 100-day-old rats than in 21-day-old rats, but the number of particles ingested per unit weight by the older rats is significantly less. Liver phagocytosis is shown to be both temperature- and oxygen-dependent, but independent of nutritional status and animal gender. This model may be useful for assessing the effects of drugs and toxins on hepatic phagocytosis.

Autoimmune chronic active hepatitis and primary biliary cirrhosis

Autoimmune CAH is important to recognize, since it is highly responsive to treatment which undoubtedly prolongs life. Autoimmune CAH can rarely be cured; complete withdrawal of treatment leads to relapse in over 80% of patients. Prednisolone and azathioprine are the major drugs of choice, the former inducing remission while the latter maintains remission, either alone or in combination with prednisolone. Since both drugs are associated with substantial side-effects which tend to be dose-related, the object of treatment must be to induce and maintain remission with the minimum risk of relapse together with an acceptably low incidence of complications. Although PBC shares many features in common with autoimmune CAH, treatment of the underlying disease is generally unsuccessful. To date no drug has been shown to induce remission or to prolong survival. The main aim of treatment should be directed towards the complications of PBC, of which pruritus and osteoporosis are the two major complaints. Cholestyramine and antihistamines are the drugs of choice, but when these fail a variety of other therapies are also available, although many have only been shown to be effective on an anecdotal basis. No treatment has yet been shown to reverse the bone demineralization which occurs in PBC, but early calcium supplementation is recommended in this disorder. Osteomalacia is uncommon and can be prevented by prophylactic calcium and vitamin D supplementation in jaundiced patients. Liver transplantation is effective in treating PBC, and when successful leads to complete restoration of health with the prospects of increasingly long survival. Recurrence of PBC does not appear to be a significant problem.