Cytodiagnosis of gastric ulcer penetration of the liver by examination of endoscopic brushings

The penetration of a gastric peptic ulcer into the liver was initially diagnosed by the cytologic examination of endoscopic brushings and later confirmed by an endoscopic biopsy of the stomach. One of the smears of the gastric brushing contained sparse groups of liver cells with mild atypia. The endoscopic biopsy specimen included liver parenchyma with signs of peptic hepatitis. The differential diagnostic considerations for a gastric brushing containing hepatoid cells are discussed.     

The intrahepatic immune response during chronic hepatitis B infection can be monitored by the fine-needle aspiration biopsy technique

Frequent analysis of the intrahepatic cellular immune response during chronic hepatitis B infection is not feasible with the liver tissue biopsy technique, due to its risk profile and patient discomfort. We investigated whether the relatively safe and patient-friendly cytological fine-needle aspiration biopsy (FNAB) technique is suited for this purpose. FNABs taken during hepatitis flares in three chronic hepatitis B patients treated with interferon-alpha, showed significant increments of CD8(+)-lymphocytes compared with the FNABs taken before and after the flares. No increments were observed in peripheral blood. The increments of intrahepatic CD8+ lymphocytes detected by the FNAB were related to anti-viral immune reactivity, since they coincided with significant serum hepatitis B virus DNA level reductions and in two of three patients with HBeAg seroconversion. In conclusion, the FNAB technique is suited to investigate the intrahepatic immune response during chronic hepatitis B infection on a frequent basis.     

Prolyl hydroxylase activity in normal and diseased human liver.

Prolyl hydroxylase activity was determined in liver biopsy samples obtained from 10 patients. The liver prolyl hydroxylase values in patients with active hepatitis distribute into two numerical populations based on the extent of elevation over control. The first of these groups includes those with enzyme levels elevated approximately 2.5-fold over normal. Included in this group are patients with active (but nonagrressive) hepatitis and patients where advanced portal fibrosis is already established. The second group where prolyl hydroxylase is elevated approximately nine-fold is comprised of two patients with advanced clinical symptoms of active alcoholic hepatitis with evidence of aggressive cirrhosis but with only early minimal evidence of existing fibrosis.     

Assessing liver fibrosis with serum marker models

Chronic liver disease is characterised by liver fibrosis, which may lead to cirrhosis. Conventional serum-based liver function tests do not give information on either the presence or the rate of progress of liver fibrosis. The reference diagnostic test to detect fibrosis is liver biopsy, a procedure subject to various limitations, including risk of patient injury and sampling error.Serum markers have been evaluated for the determination of fibrosis either singly or combined as a panel of markers, however diagnostic accuracy is greatest in studies using a panel together with an algorithm, which generates a predictive score. Serum marker models, especially those targeted at hepatitis C, have multiplied in spectacular fashion over the last five years, with most models regularly achieving a median area under the receiver operating characteristic curve (ROCC) of 0.80 versus liver biopsy. Five years after publication of the first major serum marker model, the first study to document clinical outcomes reported that applying the model to hepatitis C patients improved prediction of decompensated cirrhosis and survival compared to liver biopsy.An obstacle to widespread adoption of serum marker models has been the lack of uniform performance indicators, such as diagnostic odds ratios and likelihood ratios. At present, serum marker models are not considered sufficiently reliable to replace liver biopsy in patients with chronic liver disease. However with continued evaluation in parallel with liver biopsy rapid advances are being made.     

Glomerular lesions in HIV-infected patients: a Yale University Department of Medicine Residency Peer-Teaching Conference.

HIV-associated nephropathy (HIVAN) is a clinicopathologic entity characterized by heavy proteinuria, absence of edema and an irreversible decline in renal function. Findings on renal biopsy include: collapsed glomerular capillaries; visceral glomerular epitheliosis; microcystic tubules; mesangial prominence; and endothelial tubuloreticular inclusions. Early in the AIDS epidemic, HIVAN was the predominant glomerular lesion observed in HIV-infected patients. It is being increasingly recognized, especially in Caucasian populations, that a variety of immune complex-mediated lesions such as membranoproliferative glomerulonephritis, proliferative glomerulonephritis and IgA nephropathy are associated with HIV infection. In this review we present two cases: one patient whose first presentation of AIDS was end-stage renal disease, who on biopsy was found to have HIVAN, and the second, who was infected with HIV, and on biopsy was found to have hepatitis C-related hepatitis C related membranoproliferative glomerulonephritis. We also review the current literature on HIVAN and HIV-associated immune complex diseases (HIVICDs). Each case illustrates an important clinical point. The first that renal disease can be the first manifestation of HIV infection and the second that HIV-infected patients may develop immune complex related renal diseases, some of which may be potentially treatable.     

A technique for liver biopsy performed in Pekin ducks using anesthesia with Telazol.

Infection of Pekin ducks with duck hepatitis B virus is a useful model for studying the hepadenoviruses, of which human hepatitis B virus is the prototype. The utility of this model has been limited, however, by the difficulties associated with anesthetizing and obtaining liver biopsies from ducks. We developed a technique using Telazol (13 mg/kg) to anesthetize ducks before surgical biopsy of the liver in ducks infected with duck hepatitis B virus. Eight Pekin ducks infected with duck hepatitis B virus underwent serial biopsies at 4- to 5-week intervals. There was one perioperative death in 34 surgical procedures with no evidence on intra-abdominal sepsis or wound complications. Telazol can be used safely and humanely to anesthetized ducks without the need for general endotracheal anesthesia.     

Drug metabolism in drug-induced liver diseases: pathogenetic role of active metabolites

Three cases with drug-induced liver diseases (hepatitis caused by hydralasine, steatosis caused by methimazole, choletasis caused by birth control pill) were investigated with respect to their drug metabolising ability. Clinical diagnoses were based on the exclusion of other pathogenetic factors, on histological findings of liver biopsy specimens and on the clinical chemical tests. Investigation of biotransforming ability was carried out using test materials (menthol loading, antipyrine, sulfadimidine, caffeine, indocyanine green kinetics) and measurement of D-glucaric acid excretion. In all cases the results show a defective capacity in some respect of drug metabolism. Possible pathogenetic role of reactive metabolites is discussed in the pathomechanism of genesis of drug-induced liver diseases.     

Effect of chronic CCl4 poisoning in the rat and of partial hepatectomy of the pathologically altered organ on glycogen levels of hepatocytes

A cytofluorometric study was made of total glycogen in rat liver cells in the norm and upon the chronic intoxication with CCl4. The liver cells were obtained from rats by means of intravital needle aspiration biopsy at the beginning of the experiment, after 3, and 6 months, and 1 month after partial hepatectomy of control and cirrhotic livers. Glycogen contents in liver cells were attributed to dry weight measured interferometrically. Upon the long-term chronic intoxication of rats with the hepatotropic poison the glycogen content increased by 1.4-2.5 times, and in some cells of cirrhotic livers even by 5-5.5 times compared to the normal level. 1 month after the resection both glycogen content and rat liver cell morphology were seen almost close to the normal. The data are discussed in terms of results earlier reported elsewhere on the increase of glycogen content in liver cells of patients with chronic hepatitis.     

Mesenchymal reaction and serum glycoprotein concentration in chronic hepatitis and liver cirrhosis.

In liver biopsy specimens of 45 patients with chronic persistent hepatitis, chronic aggressive hepatitis and liver cirrhosis the number of lymphoid cells and fibroblasts as well as in the sera of the same patients the concentration of IgG, IgA, IgM, alpha-2-macroglobulin and coeruloplasmin have been studied. The number of lymphoid cells and fibroblasts, was significantly elevated in chronic aggressive hepatitis and liver cirrhosis; a close correlation could be demonstrated between the number of the lymphoid cells and the IgG concentration; the serum alpha-2-macroglobulin level changed parallel to the number of liver fibroblasts in chronic aggressive hepatitis and liver cirrhosis.     

NEEDLE BIOPSY OF THE LIVER—General Considerations

Needle biopsy of the liver provides concrete diagnostic information that cannot be as readily obtained in any other way. This report reviews 401 liver biopsies in 312 patients.The major indications for use of this procedure are: To determine the cause of an obscure liver enlargement; to establish the cause of jaundice; to distinguish between malignant disease and cirrhosis of the liver; to determine when hepatitis has subsided; and to evaluate the results of treatment. At times, systemic disease that has not been recognized by other means may be diagnosed by this technique. There is risk in performing this test, and the 0.25 per cent mortality in this series compares favorably with that reported from other clinics. Where the diagnosis by biopsy could be compared with observations at operation or autopsy, the correct diagnosis was made by biopsy in 85 per cent of cases. Greater accuracy was obtained by two or more biopsic examinations in one case then by single biopsy.In several cases in which surgical operation was considered, biopsic information made it unnecessary, and vice versa.     

Hepatitis B virus surface and core antigens in the liver of primary hepatocellular carcinoma cases in Virginia

Zenker-fixed paraffin-embedded sections of biopsy liver tissue from 64 cases of primary hepatocellular carcinoma (PHC) were stained for hepatitis B surface antigen (HBsAg) and for hepatitis B core antigen (HBcAg) by histochemical and/or immunohistochemical techniques in a retrospective study. PHC arose in livers with postnecrotic cirrhosis in 30 (46.9%) cases. Controls included liver biopsy sections from 123 miscellaneous liver disorders and from 67 randomly selected autopsy specimens, none of which were known to be associated with hepatitis B virus (HBV) infection. HBsAg was detected in tumorous hepatocytes in only one of the 64 cases of PHC. HBsAg was identified in nontumorous hepatocytes of 8 (20%) of 40 specimens that contained adequate nontumorous liver tissue. All of these HBsAg positive cases of PHC were associated with cirrhosis. Thus HBsAg was detected in 8 (33.3%) of 24 cases of PHC with cirrhosis, but in none of the remaining 16 cases without cirrhosis. HBcAg was not detected in the hepatocytes of those HBsAg positive PHC cases tested. Our results suggest that HBV infection may successively lead to chronic hepatitis, cirrhosis and ultimately PHC.     

Spread of hepatitis virus as a threat to national security

Information on viral hepatitis A, B and C morbidity in Russia is presented. A distinct trend to decreased viral hepatitis B and C morbidity in 2001-2002 in comparison with the 1990-ies is noted. Nevertheless, there is still unfavorable prognosis regarding high hepatitis B morbidity among the population of reproductive age, as well as among adolescents, which increases the risk for children at an early age. In addition, a new specific feature of hepatitis A spread is observed: morbidity in this infection is shifted to older age groups. The role of vaccinal prophylaxis in the decrease of hepatitis A and B morbidity, virus safety of blood and its components, the quality of the diagnostics of chronic hepatitis, especially hepatitis C, are discussed. The complex of measures for the prophylaxis of viral hepatitis is proposed.     

A technique for liver biopsy in Pekin ducks

The duck hepatitis B virus (DHBV), a member of the hepadna-virus group, has become a useful animal model for exploring important aspects in this family of viruses such as viral replication, course of infection, and the response to antiviral therapy. In chronically DHBV infected ducks, repeated analyses of liver tissue are important in defining the degree of viral replication and liver injury. We describe a technique for repeated liver biopsy using a Keyes skin punch biopsy. This technique provided sufficient quantities of liver tissue for serial analyses with minimal hemorrhage in 18 Pekin ducks. This procedure offers a safe and reliable method of obtaining serial liver biopsies.     

Molecular mimicry of trifluoroacetylated human liver protein adducts by constitutive proteins and immunochemical evidence for its impairment in halothane hepatitis.

A monospecific antibody (anti-CF3CO antibody) was obtained by affinity chromatography on a N epsilon-trifluoroacetyl-L-lysine (CF3CO-Lys) matrix of a rabbit polyclonal antiserum, directed against trifluoroacetylated protein adducts (CF3CO-proteins). The anti-CF3CO antibody recognized distinct CF3CO-proteins on immunoblots of a liver biopsy obtained from a human individual 10 h after halothane anaesthesia. Cross-reactive proteins of 52 kDa and 64 kDa were recognized on immunoblots of livers obtained from human individuals not exposed to halothane. Recognition of both CF3CO-proteins and the 52-kDa and 64-kDa cross-reactive proteins was abolished in the presence of 1 mM CF3CO-Lys. Anti-CF3CO antibody, affinity-adsorbed to the 52-kDa or the 64-kDa cross-reactive proteins of human liver, recognized the majority of target CF3CO-proteins on immunoblots of the human liver biopsy of an individual exposed to halothane. Liver biopsies of 5 out of 7 (71%) patients with halothane hepatitis exhibited an absence or low amounts of immunorecognizable 52-kDa and/or 64-kDa cross-reactive proteins. In contrast, of 22 control human individuals tested, all liver tissue samples were positive for the 52-kDa and/or the 64-kDa cross-reactive proteins. These data indicate that epitopes on the cross-reactive proteins of 52 kDa and 64 kDa of human liver bear strong immunochemical resemblance to epitopes on human liver CF3CO-proteins. Low-level expression of the cross-reactive proteins of 52 kDa and 64 kDa is discussed as one possible factor in human susceptibility to halothane hepatitis.     

Structure of replicating hepatitis C virus (HCV) quasispecies in the liver may not be reflected by analysis of circulating HCV virions.

We have analyzed the population of hepatitis C virus (HCV) sequences in paired liver and serum samples from four patients with chronic hepatitis C. Sequences from three different biopsy specimens from a liver explant from one patient were compared with each other and with the circulating sequences. Our results demonstrate that the circulating quasispecies does not necessarily reflect the viral population replicating in the liver and that this is not due to a macroscopic anatomic compartmentalization of HCV replication. This finding has important implications for the pathogenesis and natural history of chronic HCV infection.     

The nuclear dry weight of liver cells from patients with virus hepatitis and from controls.

Interferometric investigations were performed at liver cell nuclei isolated in 70 per cent glycerol. In 11 patients with virus hepatitis and seven patients without liver disease the nuclear dry weight of liver cells obtained by liver biopsy was determined by interferometry. The average nuclear dry weight of diploid liver cells from controls was 39.9 pg while an average value of 45.4 pg was found for patients with hepatitis. The corresponding nuclear volumes were 241 and 274mu3 respectively. The dry mass and volume of tetraploid nuclei was twice as big as that of diploid nuclei in both materials. The nuclear water content was neither significantly different between diploid and tetraploid nuclei nor significantly different between nuclei from controls and patients with hepatitis.     

Cytofluorimetric study of glycogen fractions of the liver cells of patients with chronic viral and alcoholic hepatitis

A cytofluorometric study was made of total glycogen and two glycogen fractions--the one easily soluble (ES) and the other hard soluble (HS) in isolated liver cells (needle aspiration biopsy) of patients in the norm and with chronic viral hepatitis (CVH) and chronic alcoholic hepatitis (CAH). The amount of LS in hepatocytes of patients with CAH was lower than that in patients with the norm or with CVH. This distinction was shown already at the beginning of chronic disease, and then, in spite of a considerable increase in the total glycogen content in hepatocytes, with progression of the disease did not change. The quantitative analysis of glycogen fraction contents in liver cells may be an additional differential diagnostic marker for the etiological distinction of chronic hepatitis.     

Current Concepts of Viral Hepatitis and A Peek into the Future

New information has prompted revision of the conceptual framework for considering the epidemiology and virology of viral hepatitis. The means are now at hand to identify infections due to either Hepatitis A or B, as well as to implicate other etiologic agents in hepatitis. Immunologic evidence of variation in the antigens associated with Hepatitis B, and possibly in Hepatitis A, may explain some well known epidemiologic phenomena and has important implications in immune serum globulin prophylaxis. The ambiguous relationship of antigenemia and viremia in Hepatitis B is explored in relation to the hepatitis hazard of blood products, to trials of immune serum globulin, and to the potential role of the carrier-health worker in hepatitis transmission. The emerging concept of non-parenteral transmission of Hepatitis B is reviewed and future developments in the production of hepatitis vaccines and in experimental viral hepatitis in non-human primates is briefly discussed.     

Management of chronic hepatitis C: clinical audit of biopsy based management algorithm.

OBJECTIVE: To assess the attendance, outcome, compliance with treatment, and response to interferon alfa in patients with chronic hepatitis C who attended during 1995 and were treated according to a biopsy based algorithm. DESIGN: Retrospective audit of all patients with chronic hepatitis C attending outpatient clinics over one year. SETTING: The liver unit at a London teaching hospital. SUBJECTS: 255 patients with chronic hepatitis C. MAIN OUTCOME MEASURES: Patient survival, attendance, and compliance with diagnostic and therapeutic regimens. Response to interferon alfa treatment, based on loss of viraemia three months after cessation of treatment. RESULTS: A large proportion of patients (39%) with newly diagnosed chronic hepatitis C infection do not want to undergo further investigation. Of those patients who do attend for further treatment, a large proportion with severe hepatic fibrosis (42%) do not want to undergo currently available treatment. The response rate to interferon (21%) in treated patients was similar to that previously reported in a trial setting. There was no significant difference in response rates in patients with or without severe fibrosis not amounting to cirrhosis. In patients with cirrhosis there was a high incidence of hepatocellular carcinoma (18%) over a follow up period of 20 months. CONCLUSION: Current strategies aimed at investigating and treating patients with chronic hepatitis C are not acceptable to a large proportion of patients. Many patients with cirrhosis related to hepatitis C infection develop hepatic neoplasms, and management strategies to deal with this problem are urgently required.