Clinical features of chronic hepatitis C.
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Chronic Disease↗
Biomedical subjects
S Sherlock
Publications and source records attributed to S Sherlock.
Sarcoidosis of the liver.
There are many causes of granulomas of the liver including infections, immunological aberrations, enzyme defects, drugs and other chemicals, and neoplasia (Table I). The commonest causes are tuberculosis, sarcoidosis, schistosomiasis and intrinsic liver disease. About 10 per cent of granulomas remain unidentified. In sarcoidosis, liver granulomas are usually inconspicuous and featureless. They are not associated with symptoms or abnormal physical signs. Sarcoidosis of the liver has three well-recognised clinical syndromes-chronic intrahepatic cholestasis, portal hypertension and the Budd-Chiari Syndrome.
Adult↗
Hepatitis C virus genotypes: an investigation of type-specific differences in geographic origin and disease.
Because of the nucleotide sequence diversity of different isolates of hepatitis C virus, it has become important to clarify whether distinct genotypes of hepatitis C virus vary with respect to pathogenicity, infectivity, response to antiviral therapy and geographic clustering. We assessed nucleotide sequence variability in the 5' noncoding region of hepatitis C virus, using restriction enzymes to analyze the distribution of hepatitis C virus genotypes, in 80 patients with chronic hepatitis C virus infection. Genotypes were correlated with demographic, clinical and histological features. Thirty-seven patients were infected with type 1, 10 had type 2 and 8 had type 3, and another 23 were infected with a new distinct hepatitis C virus type now classified as type 4. Two were infected with variants whose classification are uncertain. Types 1, 2 and 3 were found in patients from the United Kingdom, southern Europe, Asia, Africa and South America. Nineteen of 23 type 4 genotype isolates were from Middle Eastern patients, compared with 0 of 37 type 1 isolates (p < 0.001). Of 21 Middle Eastern patients, 19 (90.4%) had type 4 hepatitis C virus (p = 0.001, odds ratio = 9). We found no significant difference between the mean ages or mean serum aminotransferase concentrations between the various types. Types 1, 2, 3 and 4 were found in patients with mild-to-moderate disease or severe disease. However, 21 of 29 (72.4%) patients with type 1 who underwent liver biopsy had severe chronic hepatitis, cirrhosis or hepatocellular carcinoma histologically; 8 had mild or moderate chronic hepatitis without cirrhosis (p = 0.03, odds ratio = 2.6).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The kidneys in hepatic cirrhosis: victims of portal-systemic venous shunting (portal-systemic nephropathy)
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Humans↗
Niemann-Pick disease type C: diagnosis and outcome in children, with particular reference to liver disease.
The records of 52 children with Niemann-Pick disease type C were reviewed to establish whether the disease process and outcome varied with the initial clinical pattern; 34 children (65%) had cholestatic liver disease and hepatosplenomegaly in infancy; 18 were seen at a mean age of 4 years with splenomegaly or neurologic disease or both. Of the 34 children with early cholestatic liver disease, three died in the neonatal period; cholestasis and hepatomegaly subsided in the remaining 31 children, although splenomegaly persisted. Of these 31 children, 15 had persistent liver disease with elevated aminotransferase values. Serial liver biopsy specimens showed that 3 of the 15 children had normal architecture and 12 had hepatic fibrosis, with progression to cirrhosis in 5. No other significant morbidity or additional deaths were associated with the liver disease. The clinical importance of persistent liver disease was overshadowed by the subsequent development of severe neurologic disease. There was no difference in the age at onset of the disease (mean, 4.5 years) or in the pattern of neurologic disease, including supranuclear ophthalmoplegia, whether or not the child had early liver disease. Overt neurologic disease has not yet developed in seven surviving children with liver disease at onset. Sixty-seven percent of children died during the study; the main cause of death was bronchopneumonia. We conclude that the diagnosis of Niemann-Pick disease type C should be considered in patients with unexplained neonatal hepatitis, especially if splenomegaly is a persistent feature. Because liver biopsy specimens may not demonstrate storage cells, bone marrow aspiration to detect the characteristic storage cells is recommended in such patients.
Age Factors↗
Viral hepatitis management. Standards for the future. Case studies.
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.
Adult↗
Autoimmune cholangiopathy: part of the spectrum of autoimmune chronic active hepatitis.
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.
Actins↗
Clinical, biochemical and histological features in 102 patients with chronic hepatitis C virus infection.
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)
Adult↗
Development of the national radionuclide dose calibrator standardisation service.
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.
Australia↗
The pathology of hepatitis C.
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.
Adult↗
Improved diagnosis of chronic hepatitis C virus infection by detection of antibody to multiple epitopes: confirmation by antibody to synthetic oligopeptides.
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.
Antigens, Viral↗
Jaundice--the first 48 hours.
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Acute Disease↗
Pathogenesis of sclerosing cholangitis: the role of nonimmune factors.
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.
Acquired Immunodeficiency Syndrome↗