Biomedical subjects
Publications and source records attributed to S Sherlock.
Plasma calcium and magnesium fractions were measured in 51 patients with either hepatocellular or biliary disease. The fractions were found to be only minimally deranged. Plasma albumin correlated with total calcium and with the protein bound and ionized fractions. Abnormalities of plasma calcium or magnesium fractions are unlikely to play a role in the pathogenesis of the osteomalacia seen in chronic biliary disease.
Despite regular long-term parenteral vitamin D2 treatment, four patients with biliary cirrhosis had multiple symptoms of bone disease and bone biopsy specimens showed osteomalacia without osteoporosis. Three patients also had a proximal myopathy. Plasma calcium values (after correction for albumin), phosphorus, magnesium, and serum 25-hydroxy-vitamin D were within normal limits. Treatment with 1,25-dihydroxy-cholecalciferol (1,25-(OH)2D3) relieved symptoms in three of the four patients and improved those in the fourth. Histological examination of bone showed improvement in all four patients, but serum and urinary biochemical changes were not pronounced. We conclude that 1,25-(0H)2D3 treatment has a beneficial effect on bone and muscle in hepatic osteomalacia, either because vitamin D 1-hydroxylation fails in biliary cirrhosis or because hepatic osteomalacia is resistant to vitamin D2 metabolites.
Two cases of liver abscess are reported in whom the diagnosis was suggested by a combination of liver scanning, ultrasonography, arteriography, and liver biopsy. The diagnosis was confirmed by ERC which showed intrahepatic extravasation of contrast from the biliary tree, a characteristic of liver abscess. The value of ERC in the search for an underlying cause as well as in delineating certain features of the absceses is shown.
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The enzyme collagen proline hydroxylase has been measured in liver biopsies from fourteen patients with primary biliary cirrhosis. The activity was elevated in ten of the patients, but not to the degree previously found in patients with active cirrhosis. There was no correlation between the enzyme activity and the liver copper concentration, which was elevated in all except one of those measured. This suggests that excessive collagen synthesis in PBC is not directly related to the high liver copper concentrations.
Different methods of performing the (14C) aminopyrine breath test have been assessed. A tracer dose of 2 muCi without a loading dose and with a single breath collection at two hours was the method selected, since it gave the best discrimination between patients with hepatocellular diseases and normal subjects (5.2 +/- 0.2%, mean +/- SEM). Reduced values occurred in patients with chronic active hepatitis (with and without cirrhosis) (1.5 +/- 0.2%), alcoholic cirrhosis (1.7 +/- 0.4%) and hepatitis (2.5 +/- 0.3%), and late primary biliary cirrhosis suggesting defective microsomal function with respect to demethylation. Normal results were common in early primary biliary cirrhosis. Two weeks of prednisolone therapy caused some improvement in the breath test in nine of 10 patients with chronic active hepatitis. It is concluded that the (14C) aminopyrine breath test is a simple test for detecting hepatocellular dysfunction, but has no obvious diagnostic advantage over the determination of serum aspartate transaminase and two hour post-prandial bile-acids.
During the last 25 years, there have been important developments in visualising the portal vein, in examining its contents, and in measuring the pressure of blood flowing within it. Radiologists have set the scene and now is the time of the scanner. These technical advances have been applied to the diagnosis and treatment of patients with portal hypertension, and many ingenious surgical techniques have been proposed. The problem of successful treatment of the patient with bleeding oesophageal varices and cirrhosis of the liver, however, has not yet been solved. This report discusses the portal vein in terms of pressure, flow, and regeneration factors. Portal hypertension is classified and methods of relief are discussed.
Liver biopsies in nine of 70 male alcoholics seen during a 12 month period showed predominantly portal fibrosis with fatty change, but little or no alcoholic hepatitis. None of the 30 female alcoholics seen during the same period showed this appearance. The nine men were younger and of lower socioeconomic class than the other male alcoholics, but had similar alcoholic history. Seven of the nine had chronic pancreatitis, diagnosed in six patients on the results of the pancreatic scan, Lundh meal and endoscopic retrograde pancreatography and in one because of pancreatic calcification and steatorrhoea. Serum tests for hepatitis B surface antigen were negative but five showed hepatitis B antibody. Four had serological evidence of previously treated or active syphilis compared with only one of the remaining 61 male alcoholics. Two had pulmonary tuberculosis and both had received isoniazid. Four of the other 61 alcoholics gave a history of tuberculosis similarly treated. At least one cause for the portal fibrosis other than primary alcoholic liver disease was found in all nine patients. Portal fibrosis in an alcoholic in the absence of severe alcoholic hepatitis should lead to a search for other causal factors. In particular, chronic pancreatitis should be excluded even if the patient is asymptomatic.
The molar ratio valine + leucine + isoleucine/phenylalanine + tyrosine was determined in the plasma of patients with liver disease of varying aetiology and severity and in an age and sex matched control group. In the control group of 58 subjects the mean ratio was 3.3 +/- 0.5 (ISD). The mean ratio was significantly lowered in groups of 25 patients with alcoholic cirrhosis (P less than 0.001), 25 patients with chronic active hepatitis (P less than 0.001), 23 patients with primary biliary cirrhosis (P less than 0.001), and 11 patients with cryptogenic cirrhosis (P less than 0.001). In a group of 50 patients with cirrhosis, the ratio was significantly lowered (P less than 0.001) irrespective of the presence of hepatic encephalopathy. A good correlation existed between the value of the ratio and the severity of the liver disease as judged histologically, with values of the ratio appearing to reflect histological change irrespective of the patient's clinical condition. There was no significant diurnal variation in the value of the ratio. Lowering of this plasma amino acid ratio appears to be secondary to liver disease and quite independent of the presence of hepatic encephalopathy.
Twenty of 32 patients with either chronic cholestatic or hepatocellular liver disease had bone pain or recent fractures. On bone biopsy five patients had normal bone, 15 had osteomalacia, five had osteoporosis, and seven had a combination of osteomalacia and osteoporosis. In the presence of osteoporosis, osteomalacia was minimal or absent. There was no biochemical, radiological, or histological evidence of excess parathyroid activity. No significant correlations were demonstrated between the plasma and urinary biochemical findings and the presence of either osteoporosis or osteomalacia and bone biopsy was essential for correct diagnosis. There was no statistical relationship between low serum 25-hydroxy vitamin D values and the presence of osteomalacia. Bone disease was not prevented by regular intramuscular vitamin D2, although biochemical changes were improved. Drugs such as corticosteroids and cholestyramine may be important aetiological factors in hepatic osteodystrophy.
Serum immunoreactive prolactin was measured in 150 patients with liver disease of varying aetiology and severity and in 45 control subjects. The upper limit of the reference range for serum prolactin was 331 mU/l. Eighteen patients with liver disease (12%) had unexplained hyperprolactinaemia. No relationship existed between the prolactin value and the sex of the patient, the aetiology of the liver disease, the severity of the liver disease, or the presence of gynaecomastia. The cause of the hyperprolactinaemia in patients with liver disease and its clinical implications need further investigation.
Liver copper concentrations in percutaneous biopsy specimens were measured by neutron activation analysis and compared with histological staining for copper by rubeanic acid and rhodanine, and with copper-associated protein stained by orcein. Liver copper concentrations were elevated in 31 of 35 biopsies from patients with primary biliary cirrhosis (PBC), and discrimination between normal and elevated liver copper was correct in 32 of the 35 biopsies by staining with rubeanic acid, and 31 of the 35 by staining with rhodanine. Orcein staining of copper-associated protein was positive in 33 of the 35 biopsies. All 17 biopsy specimens from patients with Wilson's disease had high liver copper concentrations, but only nine had positive staining for copper, and six were orcein positive. Similarly, histological stains gave little indication of the liver copper concentrations in tissue from 16 patients with chronic active hepatitis. Staining of liver sections can be useful in detecting elevation of liver copper in PBC, but not in Wilson's disease, where the absolute concentration must be measured. Excess copper appears to accumulate in the liver in different chemical forms in PBC and Wilson's disease.
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Three alcoholic patients are described who presented with acute cholestasis and liver cell failure. In each patient the liver biopsy showed severe fatty change with cholestasis, but without typical alcoholic hepatitis. There was no evidence of extra-hepatic biliary obstruction, although one patient had chronic pancreatitis. Two of the three patients died of hepatic failure, but the third recovered and has remained well while abstaining from alcohol.
The value of the serum ferritin assay in the management of idiopathic haemochromatosis has been examined in groups of patients at diagnosis, during venesection therapy, and following completion of therapy. At diagnosis, serum ferritin levels were elevated in all 16 patients studied, including 10 with precirrhotic disease. Venesection resulted in a gradual fall in serum ferritin which commenced shortly after the start of treatment in 5/8 patients. In 3/8 the fall was preceded by a transient rise in ferritin levels. In three patients serum ferritin fell to normal before liver iron stores had been restored to normal. After therapy serum ferritin proved unreliable in detecting early re-accumulation of hepatic iron stores. Serum ferritin does provide valuable information in patients with idiopathic haemochromatosis, particularly at diagnosis and during therapy. A normal value does not exclude iron storage disease.
The serum aspartate transaminase, 2-h post-prandial bile acids and the aminopyrine breath test were measured in 14 alcoholics with histologically proved minimal liver damage. A raised aspartate transaminase value was found in 64% (9/14) of the patients and was the commonest abnormality found. In three patients all three tests were normal. Six patients stopped abusing alcohol and, when reassessed a mean of 33 days later, showed significant changes in the mean aspartate transaminase value and the mean value for the aminopyrine breath test. There was no significant change in the mean post-prandial bile acids value. The remaining eight patients continued to drink alcohol and, when reassessed at a mean of 118 days, showed no significant change in any of these indices. Of the methods assessed, the serum aspartate transaminase appeared to be the most useful for detecting and monitoring patients with minimal alcoholic liver disease. However, all three tests failed to detect an unacceptably high percentage of the patients, and liver biopsy therefore remains a more certain diagnostic method.