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1.
Clin Perinatol ; 28(1): 91-136, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11265513

ABSTRACT

In critical congenital heart lesions, the ultimate outcome depends on timely and accurate diagnosis of the structural anomaly, the evaluation and resuscitation of secondary organ damage, effective lesion-specific preoperative management, and the appropriate timing and type of surgery. Crucial to this process is continuous communication among medical, surgical, and nursing disciplines.


Subject(s)
Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/surgery , Intensive Care, Neonatal/methods , Neonatal Screening/methods , Perinatal Care/methods , Perioperative Care/methods , Critical Illness , Delivery, Obstetric , Diagnosis, Differential , Echocardiography , Heart Defects, Congenital/complications , Heart Defects, Congenital/epidemiology , Humans , Infant Mortality , Infant, Newborn , Patient Selection , Resuscitation/methods , Risk Factors , Time Factors , Treatment Outcome , Ultrasonography, Prenatal
2.
Liver ; 19(6): 509-18, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10661685

ABSTRACT

AIMS/BACKGROUND: The integrin alpha4beta7 and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) are involved in normal recirculation of lymphocytes between the blood and the tissues of the gastrointestinal tract. In this study we have examined the expression of MAdCAM-1 in human liver. METHODS: MAdCAM-1 expression was determined in archival human liver tissues by immunohistochemistry. RESULTS: While MAdCAM-1 was not detected in normal fetal or adult human liver, expression was observed in association with portal tract inflammation in a variety of liver diseases. Detailed analysis of liver biopsies from patients with hepatitis C showed a positive correlation between the portal/periportal component of the histological activity index (HAI) grade and the presence or absence of MAdCAM-1 expression. CONCLUSION: MAdCAM-1 expression may be important in the recruitment of lymphocytes to the liver during inflammation.


Subject(s)
Hepatitis/metabolism , Immunoglobulins/metabolism , Liver/metabolism , Mucoproteins/metabolism , Receptors, Lymphocyte Homing/metabolism , Animals , Antibody Specificity , Antigens, CD34/metabolism , Binding Sites, Antibody , Cell Adhesion Molecules , Enzyme-Linked Immunosorbent Assay , Fetus/metabolism , Hepatitis/pathology , Humans , Immunoenzyme Techniques , Liver/pathology , Rabbits , Receptors, Complement 3d/metabolism
3.
J Hepatol ; 28(2): 194-8, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9514531

ABSTRACT

BACKGROUND/AIMS: Calcium channel blockers have a hepatoprotective action in animal models of alcohol-induced liver injury but their effect in alcoholic liver disease in humans has not been previously investigated. We have conducted a randomised, placebo-controlled trial to investigate the possible benefit of the calcium channel blocker amlodipine in terms of 4-week survival in hospitalised patients with severe acute alcoholic hepatitis. METHODS: Sixty-two patients with acute alcoholic hepatitis were randomised to receive 5-10 mg amlodipine each day for 1 year or an identical capsule containing placebo. In 36 (58%), acute alcoholic hepatitis was confirmed on biopsy and in the remainder on clinical and laboratory criteria. There were no statistically significant differences in clinical characteristics and disease severity in the treated and placebo groups. RESULTS: Of the 32 patients receiving amlodipine, there were six deaths (19%) in the first 4 weeks compared with seven (23%) of the placebo patients (p=0.329). Causes of death were similar in the amlodipine and control groups, with liver failure predominant. Analysis by the Cox proportional hazards model after adjustment for other prognostic factors showed survival was not significantly influenced by active treatment (p=0.07). One patient in each group was withdrawn because of the development of hypotension, but this did not recur on reintroduction of the capsules. CONCLUSIONS: This study shows that calcium channel blockers are well tolerated with few side effects in advanced alcoholic liver disease, but there is no conclusive evidence from this study that calcium channel blockers are helpful in the treatment of alcoholic hepatitis.


Subject(s)
Amlodipine/therapeutic use , Calcium Channel Blockers/therapeutic use , Hepatitis, Alcoholic/drug therapy , Liver Failure/drug therapy , Acute Disease , Amlodipine/adverse effects , Amlodipine/pharmacokinetics , Biological Availability , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/pharmacokinetics , Double-Blind Method , Female , Hepatitis, Alcoholic/metabolism , Hepatitis, Alcoholic/mortality , Humans , Liver Failure/mortality , Male , Middle Aged , Prognosis , Proportional Hazards Models , Survival Rate
4.
Clin Chim Acta ; 253(1-2): 171-80, 1996 Sep 30.
Article in English | MEDLINE | ID: mdl-8879847

ABSTRACT

Serum alpha-glutathione S-transferase (alpha-GST) has been shown to be a sensitive marker of liver injury. We compared the relationship of both serum alpha-GST and alanine transaminase (ALT) with liver biopsy inflammatory activity in patients who had chronic hepatitis C infection (HCV), and examined the effects of alpha-interferon therapy on serum alpha-GST and ALT concentrations. Of 32 patients with chronic HCV infection studied, 17 received alpha-interferon 4.5 MU three times per week for 3 months and 15 acted as controls. Liver biopsy just prior to treatment was scored for the grade of inflammation (Scheuer histological activity index). Serum alpha-GST and ALT were assayed just prior to biopsy and 3 months later. Neither serum alpha-GST nor ALT levels showed any correlation with baseline inflammation on liver biopsy. alpha-Interferon significantly reduced serum alpha-GST concentration at 3 months (P = 0.01). ALT fell with treatment but not significantly (P = 0.05). Small falls in alpha-GST and ALT were noted in the control group, and when these were considered the significance of the changes in alpha-GST and ALT with treatment was lost (P = 0.35 and P = 0.09, respectively). This study shows that serum alpha-GST is not a useful marker of the degree of liver inflammation in chronic HCV infection, though it may be of more value than ALT in monitoring response to treatment with alpha-interferon.


Subject(s)
Antiviral Agents/therapeutic use , Glutathione Transferase/blood , Hepatitis C/enzymology , Hepatitis C/therapy , Interferon-alpha/therapeutic use , Isoenzymes/blood , Alanine Transaminase/blood , Chronic Disease , Genotype , Hepacivirus/genetics , Humans , Interferon alpha-2 , Recombinant Proteins
5.
J Hepatol ; 24(4): 385-90, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8738723

ABSTRACT

BACKGROUND/METHODS: Hepatocyte growth factor is thought to be important in stimulating growth of the liver following injury. In this study we have measured serum levels of hepatocyte growth factor together with hepatocyte proliferation in liver biopsies, by detection of the Ki-67 antigen, in 23 patients with alcoholic hepatitis. RESULTS: Serum hepatocyte growth factor was elevated in all patients (median 0.9 ng/ml; range 0.6-7.7 ng/ml; normal < 0.5 ng/ml) and there was a positive correlation between hepatocyte growth factor levels and hepatocyte proliferation in the biopsies. CONCLUSIONS: These results demonstrate that in acute alcoholic hepatitis the liver proliferates in response to injury and suggest that hepatocyte growth factor may be one of the growth factors responsible for this proliferative activity.


Subject(s)
Hepatitis, Alcoholic/blood , Hepatitis, Alcoholic/pathology , Hepatocyte Growth Factor/blood , Liver/pathology , Adult , Aged , Antibodies, Monoclonal , Cell Division , Female , Hepatitis, Alcoholic/physiopathology , Humans , Ki-67 Antigen/analysis , Liver/physiopathology , Liver Function Tests , Male , Middle Aged
6.
J Med Virol ; 47(4): 429-34, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8636714

ABSTRACT

Paired serum and saliva specimens were collected on a regular basis from 18 asymptomatic blood donors participating in a controlled clinical trial of interferon alpha 2a (IFN) treatment of chronic hepatitis C virus (HCV) infection. Nine patients were randomised to receive interferon and nine to observation only. Serum and salivary HCV RNA was detected by a "nested" polymerase chain reaction (PCR) assay. Complete follow-up data were available for 14 patients (7 treated and 7 untreated). Serum ALT levels declined to normal in five of the seven IFN-treated patients by the twelfth week. Of these five, loss of hepatitis C viraemia was observed in three. Of the seven treated patients, the three responders had a lower viraemia level than the partial or nonresponders. Both nonresponders had infection with type 1 HCV, but the complete and partial responders were infected with types 2 or 3. HCV RNA was detected in the saliva of all seven observation patients during the follow-up period. HCV was also detected in the saliva of the two patients who did not respond to IFN treatment. No correlation was shown between the level of HCV RNA in serum and the presence of HCV RNA in saliva. A role for noninvasive salivary investigations in monitoring treatment is possible, but further refinement of the methodology is required.


Subject(s)
Hepacivirus/genetics , Hepatitis C/drug therapy , Interferon-alpha/therapeutic use , RNA, Viral/analysis , Saliva/virology , Adult , Biomarkers/analysis , Biomarkers/blood , Chronic Disease , Female , Follow-Up Studies , Hepacivirus/isolation & purification , Hepatitis C/blood , Hepatitis C/physiopathology , Hepatitis C/virology , Humans , Interferon alpha-2 , Male , Middle Aged , RNA, Viral/blood , Recombinant Proteins , Viremia/blood
7.
Alcohol Clin Exp Res ; 19(6): 1537-40, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8749823

ABSTRACT

To investigate whether complement pathway activation contributes to the clinical and histological features of acute alcoholic hepatitis, we studied the activation of the classical and alternative pathways in patients with alcoholic hepatitis (n = 20), inactive alcoholic cirrhosis (n = 8), heavy drinkers without alcoholic liver disease (n = 10), patients with liver disease of nonalcoholic etiology (n = 11), and healthy control subjects (n = 18). Complement activation was evaluated in the alcoholic hepatitis patients by its correlation with a number of clinical and laboratory features indicative of the severity of liver injury, as well as by comparison of the patient groups. There was no significant difference in circulating C3 [1.02 g/liter, confidence interval (CI) = 0.76-1.28] or C4 (0.25 g/liter, CI = 0.17-0.33) in patients with alcoholic hepatitis when compared with the four control groups. Factor B levels (0.24 g/liter, CI = 0.21-0.27) were higher in the alcoholic hepatitis patients than the control groups (p < 0.01). However, activation of complement (given by the ratios C3d/C3, C4d/C4, and Ba/factor B) was not different in alcoholic hepatitis patients when compared with the control groups. Univariate analysis of a wide range of clinical and laboratory features in the alcoholic hepatitis subjects showed a positive correlation between plasma C3 and serum alkaline phosphatase (r = 0.68, p = 0.0014), AST (r = 0.55, p = 0.015), and gamma-glutamyltranspeptidase (r = 0.47, p = 0.035), but no correlation with clinical or laboratory features associated with high morbidity or mortality. There is no relationship between clinical or laboratory indicators of disease severity and complement activation, and it is unlikely that complement activation contributes to the clinical and histological features of alcoholic liver disease.


Subject(s)
Alcohol Drinking/adverse effects , Complement Activation/drug effects , Hepatitis, Alcoholic/immunology , Acute Disease , Adult , Alcohol Drinking/pathology , Complement Activation/immunology , Female , Hepatitis, Alcoholic/pathology , Humans , Immune Tolerance/drug effects , Immune Tolerance/immunology , Liver/immunology , Liver/pathology , Liver Cirrhosis, Alcoholic/immunology , Liver Cirrhosis, Alcoholic/pathology , Liver Function Tests , Male , Middle Aged , Prognosis
8.
Scott Med J ; 40(2): 53-4, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7618070

ABSTRACT

Radiological features of sclerosing cholangitis are an uncommon but well recognised complication of HIV infection in homosexual males. In this report we document the clinical features and course of the disease in four patients. Four homosexual males with established AIDS were referred in 1990-92. Three of the four had intractable upper abdominal pain which was poorly responsive to opiates. Three of the patients had diarrhoea and all had weight loss. The diagnosis of AIDS related cholangitis was confirmed by endoscopic retrograde cholangiography in three cases, but in only one patient was there no evidence of biliary disease on ultrasound scanning. In the two cases with cholangiographic features of papillary stenosis, endoscopic sphincterotomy was carried out and there was subsequently a dramatic improvement in the abdominal pain. Three of the patients had evidence of gastrointestinal infection with Microsporidia (1) or Cryptosporidia (2). All the patients died within 2-9 months of the diagnosis of cholangitis, but none of the deaths resulted from hepatobiliary disease.


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , Cholangitis, Sclerosing/diagnosis , AIDS-Related Opportunistic Infections/blood , AIDS-Related Opportunistic Infections/surgery , Adult , Cholangiopancreatography, Endoscopic Retrograde , Cholangitis, Sclerosing/blood , Cholangitis, Sclerosing/surgery , Cholangitis, Sclerosing/virology , Fatal Outcome , Homosexuality, Male , Humans , Liver Function Tests , Male , Sphincterotomy, Endoscopic
9.
J Gen Intern Med ; 10(3): 133-7, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7769469

ABSTRACT

OBJECTIVE: To test the hypothesis that profoundly deaf persons would have better preventive care compliance and improved physician communication if enrolled in a primary care program providing American Sign Language (ASL) interpreters. DESIGN: A case-cohort community-based study. The authors had ASL-fluent research assistants interview 90 randomly selected patients (the cases) enrolled in a unique primary care program for the deaf (Deaf Services Program), which provided full-time ASL interpreters and subsidized health care costs for some patients. Eighty-five deaf controls were friends of the cases drawn from the community. RESULTS: The cases were poorer and less often married than were the controls, but other baseline characteristics were similar. The cases were more likely (p < 0.05) to report receiving within the preceding three years Pap tests (90% vs 72%), mammography (86% vs 53%), and rectal examinations (72% vs 25%), but not breast examinations (76% vs 71%, p = 0.7). The cases were more likely than the controls to report receiving counseling in ASL for psychiatric and substance abuse problems (49% vs 5%, p < 0.001). Although only 18% of the controls were fluent in written English, 67% of them used written notes to communicate with their physicians. Twenty percent of the controls used ASL interpreters compared with 84% of the cases (p < 0.001). More cases than controls were moderately or extremely satisfied with communication with their physicians (92% vs 42%, p < 0.001). CONCLUSION: Deaf persons enrolled in a primary care program that included full-time interpreters were more likely to use ASL, were more satisfied with physician communications, and had improved preventive care outcomes.


Subject(s)
Communication , Deafness , Primary Health Care/organization & administration , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Patient Compliance , Patient Satisfaction , Physician-Patient Relations , Random Allocation , United States
10.
Eur J Gastroenterol Hepatol ; 7(2): 161-3, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7536113

ABSTRACT

OBJECTIVE: To test the hypothesis that many patients with alcoholic liver disease have coexisting hepatitis C virus (HCV) infection which promotes the development of cirrhosis. DESIGN: Prospective, two-centre study comparing patients with alcoholic liver disease with HCV-positive blood donors identified by the Regional Blood Transfusion Service. SETTING: Two teaching hospitals in Glasgow, UK. PATIENTS: Sixty patients admitted to hospital with a diagnosis of alcoholic liver disease on the basis of clinical and histological tests. For comparison, a group of 50 anti-HCV-positive subjects identified from 305,012 blood donors during the same period (1991-1993) were questioned about their alcohol consumption and liver biopsy specimens are taken. MAIN OUTCOME MEASURES: The prevalence of HCV infection was determined by a second generation enzyme-linked immunosorbent assay (ELISA) for anti-HCV and by liver histology. RESULTS: No patients with alcoholic liver disease were anti-HCV-positive. Of the blood donors with chronic HCV infection, 11 (22%) reported previous or continuing consumption of more than 80 g alcohol daily for at least 2 consecutive years but liver histology in all 50 cases showed features characteristic of chronic HCV. There was no difference in liver histology between donors with a history of high alcohol consumption [mean grade 2.6 (range, 1-5), stage 0.4 (range, 0-2)] and abstinent, anti-HCV-positive donors [grade 2.8 (0-5), stage 0.5 (range 0-1)]. CONCLUSIONS: The absence of anti-HCV in this population of patients with alcoholic liver disease shows that HCV is not a necessary or a common cofactor in the development of alcoholic liver disease in the west of Scotland.


Subject(s)
Hepatitis C/complications , Liver Diseases, Alcoholic/etiology , Adult , Aged , Aged, 80 and over , Alcoholism/pathology , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Female , Hepatitis Antibodies/analysis , Hepatitis C/epidemiology , Hepatitis C/pathology , Hepatitis C Antibodies , Humans , Liver/pathology , Liver Diseases, Alcoholic/pathology , Male , Middle Aged , Prospective Studies , Scotland/epidemiology , Seroepidemiologic Studies
11.
J Viral Hepat ; 2(5): 261-5, 1995.
Article in English | MEDLINE | ID: mdl-8745319

ABSTRACT

Since blood donor screening for the hepatitis C virus (HCV) began in 1991 a large number of seropositive subjects have been detected and several reports have suggested a high prevelance of liver disease. The aim of this study was to evaluate the severity of liver disease in HCV-positive blood donors in terms of the clinical, biochemical and histological abnormalities and to investigate the relationships between these features and the mode of transmission, duration of infection and viral genotype. We evaluated 54 consecutive blood donors who were positive for HCV both on serological testing and polymerase chain reaction. Twenty-three (43%) had a history of intravenous drug abuse and 17 (31%) had received blood transfusions. In only two (4%) was no risk factor identified. The mean duration of infection in those with a clear history of HCV exposure was 12 years. Eighty-three percent were HCV genotypes 1 or 3. All had abnormal liver biopsies with chronic hepatitis and several patients had periportal or portal-portal fibrous septa, but there was none with architectural distortion or cirrhosis. There was no correlation between severity of liver disease and duration of HCV infection, mode of transmission or viral genotype. In the majority of HCV carriers detected at donor screening there is a chronic hepatitis with bridging necrosis in one third, but the degree of fibrosis is minimal and cirrhosis was not present in our patients. The long period of infection of many patients suggests that irreversible liver injury does not necessarily develop at an early stage despite persistent infection.


Subject(s)
Blood Donors , Hepacivirus/genetics , Hepatitis C Antibodies/analysis , Hepatitis C/epidemiology , Hepatitis C/genetics , Female , Genotype , Hepacivirus/immunology , Hepatitis C/immunology , Hepatitis C/pathology , Hepatitis C/transmission , Humans , Liver/pathology , Male , Polymerase Chain Reaction , Risk Factors , Scotland/epidemiology
12.
Lancet ; 343(8901): 820-3, 1994 Apr 02.
Article in English | MEDLINE | ID: mdl-7908077

ABSTRACT

To determine whether clinical outcome in patients with acute alcoholic hepatitis is related to the regenerative capability of the liver, liver biopsy specimens from 25 prospectively recruited patients with acute alcoholic hepatitis were studied for hepatic expression of mRNA for two proliferation markers, proliferating cell nuclear antigen and human histone, and for transforming growth factor alpha (TGF alpha) and TGF beta 1 and hepatocyte growth factor (HGF), which regulate hepatocyte proliferation. Proliferation markers were detected to varying degrees in 0-80% of hepatocytes and occasionally in sinusoidal cells and bile-duct epithelium in 19 patients (76%). Patients who survived for 6 months had greater expression of proliferation markers than those who did not survive (p < 0.01). TGF alpha was detected in hepatocytes and bile-duct epithelium, whereas TGF beta 1 was detected mainly in sinusoidal cells and was associated with perivenular fibrosis. Patients who survived for 6 months had greater expression of TGFs than non-survivors (p < 0.02). HGF was detected in sinusoidal cells in 7 patients and correlated with survival (p < 0.01). These data indicate that hepatocyte proliferation, which is possibly related to the pattern of hepatotrophic factor expression, is a good indicator of outcome in acute alcoholic hepatitis.


Subject(s)
Hepatitis, Alcoholic/pathology , Liver/pathology , Acute Disease , Adult , Aged , Cell Division , ErbB Receptors/analysis , Female , Hepatitis, Alcoholic/metabolism , Hepatocyte Growth Factor/analysis , Histones/analysis , Humans , Immunohistochemistry , Liver/chemistry , Male , Middle Aged , Nuclear Proteins/analysis , Prognosis , Proliferating Cell Nuclear Antigen , Prospective Studies , Transforming Growth Factor alpha/analysis
13.
J Hepatol ; 20(3): 359-63, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8014447

ABSTRACT

Heat shock proteins are known to be immunogenic in a number of diverse conditions and can be induced by hypoxia, tumour necrosis factor and alcohol--all potential triggers in patients with acute alcoholic hepatitis. In the present study, sera from 23 patients with acute alcoholic hepatitis, 18 liver disease controls, ten patients with inactive alcoholic liver disease and six alcoholics without liver damage were screened for the antibody to a 65 kDa heat shock protein using an ELISA technique. IgA antibody was found to be closely associated with alcoholic hepatitis; 20/23 patients were seropositive compared to 5/18 liver disease controls and 4/10 with inactive alcoholic cirrhosis. IgM and IgG antibodies to the 65 kDa heat shock protein were less closely associated with alcoholic hepatitis and were positive in nine and eight of the 23 patients, respectively, compared with six and seven of 18 liver disease controls. Neither antibody was detected in alcoholics without liver damage or normal controls. These data indicate that an IgA immune mediated response to the 65 kDa heat shock protein is characteristic of patients with acute alcoholic hepatitis and may be one mechanism underlying observed persistence of liver damage after cessation of alcohol consumption.


Subject(s)
Heat-Shock Proteins/immunology , Hepatitis, Alcoholic/immunology , Immunoglobulin A/blood , Acute Disease , Adult , Antibody Formation , Enzyme-Linked Immunosorbent Assay , Female , Heat-Shock Proteins/analysis , Hepatitis, Alcoholic/blood , Humans , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Molecular Weight
14.
Baillieres Clin Gastroenterol ; 7(3): 663-82, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8219405

ABSTRACT

In heavy drinkers with clinical evidence of liver disease, routine investigations should exclude the possibility of other chronic liver diseases of non-alcoholic aetiology requiring specific therapy--these include chronic viral hepatitis, autoimmune diseases of the liver, Wilson's disease and genetic haemochromatosis. If abnormalities in liver biochemistry persist despite abstinence, or if the diagnosis of alcoholic liver disease is in doubt, a liver biopsy should be carried out. Studies evaluating the role of liver biopsy in alcoholic liver disease suggest that without histological confirmation the diagnosis will be inaccurate in 10-20% of patients. Serum biochemistry and the currently available imaging modalities have severe limitations in determining the relative contributions of fatty liver, alcoholic hepatitis and cirrhosis to the overall picture in alcoholic liver disease. Histological examination is therefore of additional value in determining the prognosis, which is worst in patients with a combination of alcoholic hepatitis and cirrhosis. There are a number of indices available, based on clinical and laboratory information, for evaluating the short-term prognosis, but these can only be used with accuracy if the histological pattern of damage has initially been evaluated.


Subject(s)
Liver Diseases, Alcoholic/diagnosis , Biopsy , Humans , Liver Diseases, Alcoholic/metabolism , Prognosis
15.
Hepatology ; 17(6): 1047-51, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8514253

ABSTRACT

The precise mechanism of the pathogenesis of alcoholic hepatitis is unknown, but immune involvement may perpetuate and exacerbate the process. Heat-shock proteins, normally protective, may be immunogenic and have been shown to induce antibody formation in some inflammatory conditions. Alcohol, cellular hypoxia and tumor necrosis factor, all involved in alcoholic hepatitis, are potent inducers of heat-shock protein. In this study, we sought 60-kD heat-shock protein in liver tissue with a murine monoclonal antibody and measured circulating antibody to 60-kD heat-shock protein on ELISA. Fourteen of 20 livers from patients with acute alcoholic hepatitis expressed 60-kD heat-shock protein in hepatocyte cytoplasm in a diffuse pattern with superimposed clusters; other cell types were occasionally positive. Twelve of these patients had high-titer IgA 60-kD heat-shock protein antibody in serum. In contrast, 60-kD heat-shock protein was identified in only 2 of the 10 patients with alcoholic cirrhosis without hepatitis (p = 0.013). These two patients had severe liver disease, and one patient in this group was seropositive for IgA 60-kD heat-shock protein antibody. Eight alcoholic patients with fatty liver alone were negative for antigen, and all but one were negative for antibody. The 10 patients without liver damage were negative for antigen and antibody. The findings that 60-kD heat-shock protein is present in liver tissue of patients with acute alcoholic liver damage and that circulating IgA 60-kD heat-shock protein antibody levels are increased may point to one pathogenetic mechanism underlying development and progression of liver damage in alcoholic hepatitis.


Subject(s)
Heat-Shock Proteins/metabolism , Hepatitis, Alcoholic/metabolism , Liver/metabolism , Adult , Aged , Cytoplasmic Granules/metabolism , Fatty Liver/metabolism , Fatty Liver/pathology , Female , Heat-Shock Proteins/immunology , Hepatitis, Alcoholic/pathology , Humans , Immunoglobulin A/blood , Immunohistochemistry , Liver/pathology , Liver Cirrhosis, Alcoholic/metabolism , Liver Cirrhosis, Alcoholic/pathology , Male , Middle Aged
16.
Clin Invest Med ; 16(3): 226-36, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8365050

ABSTRACT

To determine the effect of immunosuppressive therapy on hepatic expression of hepatitis B virus (HBV) DNA and antigens in vivo, serial biopsies from 12 patients with chronic active hepatitis B who had been given immunosuppressive therapy (prednisolone 10-15 mg +/- azathioprine 75-125 mg daily) in an earlier period were studied using immunohistochemistry and non-isotopic in situ hybridization. Four out of the 12 patients were positive for hepatic HBcAg/HBeAg/HBV DNA before immunosuppressive therapy. In these 4 patients positive for HBcAg, there was an increase in staining intensity and the proportion of liver cells positive for both HBcAg/HBeAg/HBV DNA and HBsAg during therapy. Of the 8 patients negative for hepatic HBcAg/HBeAg/HBV DNA before immunosuppressive therapy, hepatic HBcAg, HBeAg, and HBV DNA were detected in 2 patients, along with stronger and more diffuse hepatic expression of HBsAg. The other 6 patients also had an increase in hepatic HBsAg expression but without HBcAg. These data provide in vivo evidence that in some patients, immunosuppressive therapy enhances hepatic expression of both HBV genome and gene products.


Subject(s)
DNA, Viral/genetics , Gene Expression/genetics , Hepatitis B Antigens/genetics , Hepatitis B virus/genetics , Hepatitis B/immunology , Immunosuppressive Agents/therapeutic use , Liver/immunology , Liver/microbiology , Adult , Aged , Azathioprine/therapeutic use , Biopsy , Gene Expression/drug effects , Genome, Viral , Hepatitis B Antigens/immunology , Humans , Liver/pathology , Male , Middle Aged , Prednisolone/therapeutic use
17.
Dig Dis Sci ; 38(5): 888-95, 1993 May.
Article in English | MEDLINE | ID: mdl-7683263

ABSTRACT

To determine the relationship between hepatitis B virus (HBV) replication and HLA antigen display at a cellular level, the hepatic expression of HLA antigens and HBV genome (HBV-DNA)/gene products (HBsAg/HBcAg) was studied in 24 patients with chronic HBV infection using simultaneously immunohistochemistry and nonisotopic in situ hybridization. The effect of interferon-alpha and interferon-gamma on hepatocyte HLA antigen expression was also evaluated using primary hepatocyte culture in eight patients with chronic HBV infection. HLA class I antigens were detected on hepatocyte membrane in 23 patients (95.8%). Hepatocytes positive for HBcAg and HBV-DNA (cytoplasmic +/- nuclear) were either negative or only faintly positive for HLA class I antigens, while hepatocytes positive for HBsAg showed similar levels of HLA class I antigen expression compared with those hepatocytes with no HBsAg expression. In contrast, hepatocytes adjacent to inflammatory infiltrates, whether positive for HBV-DNA or HBV antigens or not, were always strongly positive for HLA class I antigens. Furthermore, active liver histology (N = 12) was associated with a higher overall level of hepatic HLA class I antigen expression as compared with inactive histology (N = 12, P = 0.003). Both interferon-alpha and interferon-gamma treatment in vitro enhanced hepatocyte HLA class I antigen expression. These data indicate that expression of HLA class I antigens is not enhanced on the membrane of hepatocytes with HBV replication, and this may be one factor that permits the development of viral persistence.


Subject(s)
Genome, Viral , HLA Antigens/analysis , Hepatitis B virus/genetics , Hepatitis B/immunology , Hepatitis B/microbiology , Hepatitis, Chronic/immunology , Hepatitis, Chronic/microbiology , Liver/pathology , Viral Proteins/analysis , Adult , Cells, Cultured , DNA, Viral/analysis , Female , Hepatitis B/pathology , Hepatitis B Antigens/analysis , Hepatitis B virus/isolation & purification , Hepatitis, Chronic/pathology , Histocompatibility Antigens Class I/analysis , Humans , Immunohistochemistry , Interferons/pharmacology , Male , Middle Aged
18.
Gastroenterology ; 103(6): 1860-7, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1451979

ABSTRACT

Considerable clinical and experimental evidence points to the importance of immune responses in the development of alcoholic liver disease. In the present study it was investigated whether circulating antibodies from patients with alcoholic liver disease recognize acetaldehyde-liver protein adducts. Cytosolic and microsomal fractions from livers of Wistar rats or from normal human liver were incubated with acetaldehyde (0.5-2.5 mmol/L) and/or cyanoborohydride (100 mmol/L) then analysed by immunoblotting. Cytosolic fractions that had been incubated with acetaldehyde and cyanoborohydride expressed a 200-kilodalton protein antigen not present in untreated fractions or fractions incubated with acetaldehyde or cyanoborohydride alone. The 200-kilodalton antigen was recognized by immunoglobulin (Ig)A antibodies in a large proportion of sera from patients with alcoholic hepatitis (70%, n = 23), but in significantly smaller proportions of sera from patients with alcoholic cirrhosis without hepatitis (30%, n = 10; P < 0.05), heavy drinkers without overt liver disease (20%, n = 10; P < 0.02), patients with nonalcoholic liver disease (35%, n = 17; P < 0.05), or normal control subjects consuming moderate quantities of alcohol (25%, n = 20%; P < 0.005). These results indicate that IgA antibodies to a 200-kilodalton acetaldehyde-protein adduct are present in a large proportion of patients with alcoholic liver disease and in a significantly smaller proportion of other individuals.


Subject(s)
Acetaldehyde/metabolism , Cytosol/metabolism , Hepatitis, Alcoholic/immunology , Immunoglobulin A/analysis , Proteins/metabolism , Acetaldehyde/immunology , Animals , Antigens/analysis , Humans , Immunoglobulin A/immunology , Male , Rats , Rats, Wistar
19.
Alcohol Alcohol ; 27(1): 55-61, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1580929

ABSTRACT

The relationship between levels of coagulation Factors V and VIII and disease severity was evaluated in 33 patients with alcoholic liver disease, and related to outcome in the 23 with severe acute alcoholic hepatitis. Factor V levels in acute alcoholic hepatitis were significantly lower than in inactive alcoholic liver disease (median 28% vs 74%), and both results were lower than values in 10 control subjects (median 101%; P less than 0.001 and P less than 0.002, respectively). Plasma Factor VIII concentrations were not significantly higher in alcoholic hepatitis than in inactive alcoholic liver disease, although both results significantly exceeded control values (median 163% and 151% vs 104%; P less than 0.005 and P less than 0.05, respectively). In the 18 in-patients with alcoholic hepatitis who survived, admission factor V (median 32%) was higher, and admission serum bilirubin (65 mumol/l) and discriminant function score (derived from prothrombin time and bilirubin: median 31) were lower than in the four who died and one who received a liver transplant (median 16%, 527 mumol/l and 113; P less than 0.005, P less than 0.005, P less than 0.05, respectively). An admission Factor V level less than 15% correctly predicted outcome in a greater number (87%) of cases than admission discriminant function greater than 100 (83%), bilirubin greater than 300 mumol/l (83%) or prothrombin ratio greater than 1.5 (78%). This predictive accuracy increased to 100% for minimum Factor V less than 15% and was again superior to maximum discriminant function greater than 100 or greater than 300 mumol/l (both 83%) or maximum prothrombin ratio greater than 1.5 (78%).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Factor VIII/metabolism , Factor V/metabolism , Hepatitis, Alcoholic/blood , Liver Cirrhosis, Alcoholic/blood , Adult , Aged , Biopsy , Female , Follow-Up Studies , Hepatitis, Alcoholic/pathology , Humans , Liver/pathology , Liver Cirrhosis, Alcoholic/pathology , Liver Function Tests , Male , Middle Aged , Prothrombin/metabolism
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