R.G. Long

Presentation and Course of Asymptomatic Primary Biliary Cirrhosis

Twenty patients without symptoms of hepatobiliary disease were diagnosed as having asymptomatic primary biliary cirrhosis. In every patient liver histology was diagnostic of, suggestive of, or compatible with the diagnosis. Eighteen had a positive serum mitochondrial antibody, 18 had raised serum immunoglobulin M, and 17 had markedly raised serum alkaline phosphatase values. A mean of 4.5 years after diagnosis, 10 of the patients had not developed hepatobiliary symtoms; 4 of these 10 patients have survived 6 to 10 years. Ten patients developed symptoms after a mean of 2.2 years from initial diagnosis; 7 are still alive but 3 have died of liver failure. The development of symptoms could not be predicted by either serum biochemical tests or hepatic histology. It is concluded that the diagnosis of asymptomatic primary biliary cirrhosis is compatible with 10 or more asymptomatic years.

25-Hydroxylation of vitamin D in primary biliary cirrhosis.

The ability to 25-hydroxylate vitamin D was investigated in thirty-nine patients with symptomatic primary biliary cirrhosis (P.B.C.). In seven previously untreated patients serum-25-hydroxy-vitamin-D (25-OHD) concentration increased after regular monthly injections of vitamin D. After a single injection of vitamin D in eight P.B.C. patients serum-25-OHD did not change significantly over 12 days; in contrast there were significant increases in eight normal subjects and in seven patients with nutritional osteomalacia. Twenty-three of twenty-five P.B.C. patients on regular vitamin-D therapy had normal serum-25-OHD values. These results indicate that serum-25-OHD concentrations become normal in P.B.C. if adequate amounts of vitamin D are presented to the liver as substrate.

SERUM-25-HYDROXY-VITAMIN-D IN UNTREATED PARENCHYMAL AND CHOLESTATIC LIVER DISEASE

Serum-25-hydroxy-vitamin-D (25 OHD) concentration has been measured in 106 patients with untreated parenchymal and cholestatic liver disease. Low mean values were found in groups of patients with alcoholic hepatitis and cirrhosis, non-cirrhotic active chronic hepatitis, lupoid and cryptogenic cirrhosis, symptomatic primary biliary cirrhosis, and acute and chronic biliary disease. In a group of patients with presymptomatic biliary cirrhosis the mean value was not significantly different from normal. It is concluded that in the presence of significant parenchymal or cholestatic liver disease serum-25-OHD concentrations are usually low. The mechanisms for the reduction remain to be clarified, but low serum-25-OHD values may play a contributory role in the aetiology of osteomalacia in chronic liver disease.

PERCUTANEOUS TRANSHEPATIC OBLITERATION OF GASTRO-ŒSOPHAGEAL VARICES

Percutaneous transhepatic portal-vein catheterisation was attempted to obliterate the major variceal venous supply in 13 decompensated cirrhotic patients, who continued to bleed after conservative therapy. Obliteration was achieved and bleeding stopped in 7 patients. In 5 patients obliteration was technically unsuccessful. The remaining patient had an unsuspected portal-vein block diagnosed by the transhepatic technique. 1 patient with successfully obliterated varices died after a haemothorax and haemorperitoneum developed. Follow-up splenic venography at three to six months in the 6 successfully thrombosed patients showed that 4 had persistent obliteration and had not re-bled. 2 patients re-bled from incompletely obliterated varices. It is concluded that selective obliteration of the major variceal supply is effective in stopping acute gastro-oesophageal variceal bleeding, but that greater experience is necessary before the long-term effectiveness of the procedure can be determined.

POLYMYALGIA RHEUMATICA AND LIVER DISEASE

Abstract In a case of polymyalgia rheumatica with hepatic involvement, liver-function tests returned to normal after treatment with steroids. Liver biopsy revealed portal inflammation, liver-cell necrosis, and a granuloma. It seemed likely that these biopsy findings were associated with the polymyalgia rheumatica, rather than a second coincident liver disease, since other investigations of liver disease were negative. It is suggested that polymyalgia rheumatica may be another rare cause of liver granulomas.

Percutaneous transhepatic cholangiography using the “Chiba” needle—80 cases*

Using the Chiba needle for percutaneous transhepatic cholangiography, bile ducts have been visualized radiographically in 80% of 80 patients with cholestatic jaundice. The success rate was 94.4% in the 54 patients with dilated bile ducts due to an extrahepatic bilary obstruction, and 50% of the 20 patients with undilated ducts. Four patients developed ascending cholangitis with septicaemia on the same day as the procedure, and early surgery after visualization of obstructed bile ducts is recommended. The technique was successful in three of five patients with sclerosing cholangitis. Percutaneous cholangiography using the Chiba needle is a convenient method of opacifying the biliary system in patients with severe large bile duct obstruction.

Plasma calcium and magnesium fractions in liver disease.

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.

Formation of vitamin D metabolites from 3H- and 14C-radiolabelled vitamin D-3 in chronic liver diseases

Four of the eight patients studied were vitamin D replete and 4 vitamin D depleted as judged by serum 25-hydroxy vitamin D (25-OHD) concentration. Three of the 4 vitamin D depleted patients (including 2 with histological osteomalacia) formed radioactive 1,25-dihydroxycholecalciferol. One of the four vitamin D replete patients formed 1,25-dihydroxycholecalciferol but all formed 24,25-dihydroxycholecalciferol. This study suggests that patients with liver disease form dihydroxy vitamin D metabolites in an appropriate manner.

Phosphate metabolism in chronic liver disease

Phosphate metabolism was investigated in 26 patients with a spectrum of liver diseases and mean fasting plasma phosphate concentrations were in the low normal range. A standard oral load of phosphate was used to test absorption and was subnormal in the majority of patients with large bile-duct obstruction and alcoholic liver disease. Subnormal results were also seen in patients with primary biliary cirrhosis and cirrhosis secondary to chronic active hepatitis. These abnormalities appeared to be related to vitamin-D deficiency. Tubular reabsorption of phosohate was markedly reduced in 3 of 14 patients. The therapeutic implications of phosphate status in liver disease are important.

The use of small endoscopic biopsies in the measurement of disaccharidase activities and the effect of duodenal ulceration

Objectives To define a reference range for disaccharidase (sucrase, maltase, lactase) activities for duodenal biopsy specimens taken by small (3.7mm and 2.5 mm open bite) forceps; to determine inter-patient, inter-biopsy and intra-assay variation, and to investigate whether duodenal ulcers affect disaccharidase activities. Design The reference range was derived retrospectively from biopsy specimens from 186 patients undergoing duodenal biopsy for gastrointestinal symptoms (52 with abnormal histology were excluded). Prospective studies compared 2.5 with 3.7mm forceps data and measured inter-patient, inter-biopsy and intra-assay variation. Method The reference range was defined by analysis of probit plots; 2.5 mm forceps specimens were compared with those taken with 3.7 mm forceps in 20 patients biopsied with both forceps. Eight patients with duodenal ulceration had disaccharidase activities measured before and after a course of treatment. Results The reference range for lactase was 3–58 U/g protein, for maltase 58–531 U/g protein and for sucrase 10–114.5 U/g protein. Three clusters of lactase activity were seen: a normal group, a profoundly hypolactasic group and an intermediate group. Biopsy specimens taken by 2.5 and 3.7 mm forceps produced similar results. The intra-assay and inter-biopsy variation observed was acceptable for disaccharidase activities. Duodenal ulceration does not affect disaccharidase activities obtained from the second part of the duodenum. Conclusions Endoscopic biopsies, performed with 2.5 and 3.7 mm forceps, from the second part of the duodenum are valid for disaccharidase activity assays. An appropriate reference range should be used. Subjects with lactase activity less than 3 U/g protein represent patients with phenotypic variation and may have a mosiac pattern of lactase expression. Duodenal ulcers do not affect disaccharidase activity results.