Biomedical subjects
Publications and source records attributed to S Sherlock.
These four case studies were presented by Professor Sheila Sherlock to a panel of four expert hepatologists and a mixed audience of specialists. The response of the audience to a number of questions was monitored using an interactive key pad system. This response is presented in the form of bar graphs and is accompanied by comments from the expert panel.
We describe four patients with features overlapping those of primary biliary cirrhosis and autoimmune chronic active hepatitis. Three were female and one was male; only one was symptomatic. Serum biochemical study showed increases in alkaline phosphatase and alpha-glutamyltranspeptidase levels. Markers of hepatitis B and C viruses were absent. In all four patients, serum mitochondrial antibodies could not be detected on immunofluorescence study and serum M2 antibodies were absent. All four patients had high titers of serum antinuclear antibody of diffuse type. Serum actin antibodies were detected in all four patients. Liver biopsy specimens showed histological features of primary biliary cirrhosis, with marked cellular infiltration of the portal areas and bile duct damage. Intralobular inflammation and piecemeal necrosis were mild. Three patients were treated with prednisolone and showed rapid clinical and biochemical remission. Serial liver biopsy specimens showed reduced inflammation, but bile duct lesions persisted. These patients probably form a subgroup of autoimmune chronic active type 1 with predominant bile duct damage. The subgroup might be termed autoimmune cholangiopathy.
The clinical, biochemical and histological features of 102 consecutively referred patients with chronic hepatitis C virus infection were analysed. Demographic, epidemiological, biochemical, haematological and histological details were catalogued for each patient. The mean follow-up was 49 +/- 6 months. Liver biopsies were obtained from 92 patients; a second biopsy was obtained from 35 patients. The average known duration of infection was 8.6 +/- 0.7 years. The most common risk factors that could be identified were past blood transfusion, surgery or intravenous drug abuse. Twenty-four of the 27 patients (85%) with past blood transfusion had received blood in countries outside of northern Europe. In contrast, 12 of the 16 former drug users were northern European. Patients were frequently diagnosed incidentally; one-quarter had no symptoms of liver disease and were generally asymptomatic or had presented with non-specific complaints and were found to have abnormal serum aminotransferase levels after routine screening. The mean serum aminotransferase levels were not significantly different in those presenting with fatigue compared to those diagnosed incidentally. The most common physical sign in these patients was a palpable liver, which was present in 52%. The mean serum albumin concentration in patients older than 40 years was significantly lower than that in younger patients. Splenomegaly and endoscopic evidence of varices was also more common in older patients. Cirrhosis was present in 37% of patients at presentation: 20% showed progression on rebiopsy, and 5% developed cirrhosis within 4 years of initial presentation. Of those treated, 27% showed histological improvement. Histological severity did not correlate with duration of disease, but did correlate with age.(ABSTRACT TRUNCATED AT 250 WORDS)
The Australian Nuclear Science and Technology Organisation, acting as agent for the CSIRO Division of Applied Physics, maintains the Australian standard of measurement for activity. The standard includes all nuclear medicine gamma emitters and a new standard for pure positron emitters. Under Section 10 of the National Measurement Act 1960, if a measurement is made for a legal purpose, or if the legality of a measurement is in dispute, it can only be confirmed if the following two conditions are fulfilled: (a) that the measurement be in terms of the prescribed Australian legal units of measurement. (b) that it can be proven to be traceable to an Australian primary standard of measurement. To satisfy these requirements, radionuclide dose calibrators require a calibration report determined by Ansto. For this reason, Ansto has developed the national radionuclide dose calibrator standardisation service.
To determine the histologic pattern of hepatitis C, 54 liver biopsy specimens from 45 patients with a clinicopathological diagnosis of hepatitis C were studied. All patients were seropositive for antibody to hepatitis C virus by second-generation testing. Both transfusion-related and sporadic cases were included. More than half the samples showed chronic hepatitis without cirrhosis, whereas 44% showed developing or fully established cirrhosis. A histological pattern of mild chronic hepatitis with portal lymphoid follicles and varying degrees of lobular activity was found in many of the patients. Lymphoid aggregates or follicles were seen in 78% of biopsy specimens, but aggregates, less prominent than in hepatitis C, were also seen in 14 of 27 samples (52%) from patients with hepatitis B. We conclude that a characteristic histological pattern exists in chronic hepatitis C, that this pattern is not always found and that prominent lymphoid follicles, though not unique to hepatitis C, provide a useful diagnostic clue.
Serum samples from 226 patients covering a wide spectrum of liver disease were tested for antibodies to hepatitis C virus (HCV) using both first and second generation enzyme linked immunosorbent assays. Selected sera were also tested by peptide immunoassays, by the four-antigen recombinant immunoblot assay (RIBA II), and for viral genome by the polymerase chain reaction. Antibody to c100-3 was detected in 61% of patients with chronic non-A, non-B (NANB) hepatitis and/or 46.5% with presumed NANB-related cirrhosis by the first generation test. These figures increased to 77% and 58% when antibodies to recombinant structural and non-structural HCV antigens were sought by the second generation assay. Supplemental testing against peptide Sp75 and Sp65/sp67 confirmed that reactivity of sera by second generation assays was due to antibodies to the additional structural and non-structural antigens. Samples negative by the first generation assay were not confirmed by the supplemental assay using peptides Sp75 and Sp65/Sp67. HCV RNA was detected in 60% of the anti-HCV positive sera tested, most of which were also RIBA II positive. Our findings confirm that the introduction of the structural and non-structural antigens, especially the putative nucleocapsid protein, improves sensitivity of detection of antibodies to HCV, and facilitates diagnosis in patients with "cryptogenic" chronic hepatitis.
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The diagnosis of primary sclerosing cholangitis is made on cholangiographic appearances supported by liver histologic findings. Clinical features may be compatible but are not diagnostic and there is no specific diagnostic test. Immunologic mechanisms have been proposed as pathogenetic, but the evidence is far from conclusive. Similar cholangiographic and histologic changes are found in other diseases of known etiology, including infections with intestinal bacterial organisms and with cryptosporidiosis. Primary sclerosing cholangitis has a strong association with ulcerative colitis and possible mechanisms are discussed. Gut-derived toxic bacterial products may be implicated in the biliary damage. Vascular damage to the hepatic arterial tree by cytotoxic drugs, or after hepatic transplantation, also may produce the picture of sclerosing cholangitis. If the syndrome of sclerosing cholangitis can have so many possible causes, it seems likely that the "primary" type eventually may be found to have a known etiology (possibly infectious). At that point, it will no longer be considered primary.
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Hepatitis B virus (HBV) is carried by approximately 300 million people in the world. The natural history of the disease in an individual patient depends on the method by which the infection was acquired, whether perinatal, in childhood, as a result of drug abuse, or in the course of health care work. Other important factors determining the course of the disease include an individual's sex and immunological status. Geographic factors also contribute. Changing lifestyles and the use of prophylactic hepatitis B vaccination affect the prevalence in various groups in the community. The clinical course of the disease, possible complications, and a recent classification system for chronic HBsAg carriers are discussed.
Bleeding from esophageal varices is related to the size and pressure of varices, endoscopic danger signs, and severity of liver failure. Prevention of bleeding with propranolol has given conflicting results in controlled trials, but is a safe treatment. Prophylactic sclerotherapy has been shown to reduce bleeding in European studies, but this has not been confirmed by studies in the United States. Acute variceal bleeding can usually be controlled by sclerotherapy, which may be supplemented by pharmacotherapy with vasopressin, nitroglycerin, or somatostatin. Recurrent bleeding is prevented initially by sclerotherapy, with surgery reserved for patients who have not responded to this treatment. Once bleeding has been controlled, the suitability and timing of hepatic transplantation must be considered.
Alcoholic hepatitis is a serious consequence of alcohol misuse and the usual precursor of cirrhosis. Risk factors, histology, pathogenesis, clinical features, prognosis and treatment are discussed in this review.
To investigate the basis of subclinical alveolitis in patients with primary biliary cirrhosis, 10 primary biliary cirrhosis patients were studied by bronchoalveolar lavage. Both bronchoalveolar lavage lymphoid and non-lymphoid cell populations were analysed using immunocytological methods to determine their proportions and phenotypic features in an attempt to gain information as to possible immune mechanisms active in the lung of these patients. Six of the 10 patients in our study showed evidence of an alveolitis (raised lymphocyte count: 27.6 (4.3)% of total count) on lavage. The results were compared with control groups of normal volunteers and patients with active pulmonary sarcoidosis. The six primary biliary cirrhosis patients with lymphocytosis had a raised CD4/CD8 T-cell ratio (4.13:1), similar to the sarcoid patients (5.60:1). A proportion of these T-lymphocytes expressed markers of activation (HLA-DR+ 7.5 (2.1)%); CD25 + 2.3 (0.9)%; CD7 + 5.8 (1.5)%. This increased T-cell activation was also seen in the sarcoid groups (HLA-DR+ 10.0 (1.9)%; CD25 + 3.0 (1.1)%; CD7 + 5.0 (0.2)%). This was not seen in the primary biliary cirrhosis patients without lymphocytosis and the normal volunteers. Within the non-lymphoid cell population, an increase in dendritic (RFD1+) cells was seen in primary biliary cirrhosis patients with lymphocytosis (31.2 (1.9)%) and sarcoid patients (46.3 (5.1)%) in contrast with the normal and primary biliary cirrhosis group without lymphocytosis. The primary biliary cirrhosis patients without lymphocytes had a relatively greater proportion of mature phagocytes (RFD7+). We postulate that these observations suggest the emergence in the lung of a granuloma producing mechanism similar to that occurring in the liver. By comparison, the alveolitis found in primary biliary cirrhosis is consistent with that observed in interstitial granulomatous lung disorders such as sarcoidosis.