Differences of liver membrane antibody frequency in alcoholic liver disease

The presence of liver membrane antibody in IgG and IgA was investigated by radioimmunoassay using isolated rabbit hepatocytes as target cells. This technique was more sensitive than the immunofluorescent method. IgG liver membrane antibodies were positive in 24% of patients with alcoholic liver disease. IgA liver membrane antibodies were detected in 58% of patients with alcoholic liver disease, whereas they were detected only in 21% of those with nonalcoholic liver disease, except for cases of autoimmune chronic active hepatitis. In alcoholic liver disease, IgA liver membrane antibodies were detected at a high frequency in a group of patients with alcoholic hepatitis and active cirrhosis (94%) as compared with that of fatty liver, hepatic fibrosis, and inactive cirrhosis (42%). These results suggest that alcoholic liver disease is characterized in part by a humoral immune response of IgA liver membrane antibodies.This study was supported in part by grants 59480207 and 60304058 from the Japanese Ministry of Education, Science and Culture.     

Serum procollagen III peptide in alcoholic and other chronic liver diseases

Increased levels of serum procollagen III peptide (P-III-P) have been found in patients with alcoholic hepatitis and cirrhosis. Serum P-III-P was increased (greater than 15 micrograms/l) in 38 of 44 (86%) patients with alcoholic liver cirrhosis, in 6 of 20 (30%) with fatty liver, in 1 of 13 (8%) with non-alcoholic fatty liver, and in 3 of 14 (21%) with other chronic liver diseases. Median serum P-III-P was almost three times higher in alcoholic liver cirrhosis than in alcoholic fatty liver (p less than 0.001). Serum P-III-P was increased in three of six patients with alcoholic fatty liver and periportal fibrosis. In the total material (n = 91), a statistically significant negative correlation between serum P-III-P and albumin (r = -0.71, p less than 0.001) and Normotest (r = -0.63, p less than 0.001), respectively, and a positive correlation between serum P-III-P and bilirubin (r = 0.65, p less than 0.001) were found. The serum level of P-III-P had no prognostic value concerning the mortality in patients with alcoholic cirrhosis.     

Value of serum immunoglobulins in the diagnosis of liver disease

Serum immunoglobulins were determined in 145 consecutive patients with biopsy-proven steatosis, alcoholic hepatitis, alcoholic hepatitis with fibrosis, alcoholic hepatitis with cirrhosis, inactive cirrhosis, chronic active alcoholic hepatitis, chronic active hepatitis, primary biliary cirrhosis and nonspecific hepatitis. IgM was both a sensitive (90.5%) and specific (86.2%) marker for primary biliary cirrhosis, and mean IgM levels were higher in primary biliary cirrhosis than in other diagnostic categories (p less than 0.05). IgA levels were most commonly elevated in alcoholic liver disease (p less than 0.005). IgA detected 95% of alcoholic disease, but was poorly specific (41.1%). A trend of rising IgA with increasing severity of alcoholic injury was observed, but the differences were not significant. IgG was most commonly elevated in chronic active hepatitis and alcoholic hepatitis with cirrhosis, but the IgG values did not differ significantly from those found in other diagnostic categories. Our results substantiate assertions of a diagnostic sensitivity for elevated IgA in alcoholic liver disease and IgM in primary biliary cirrhosis. With the exception of IgM in primary biliary cirrhosis, however, serum immunoglobulins are not specific markers of liver histology.     

Phenotype study of blood T lymphocytes in alcoholic hepatopathies

Peripheral blood T lymphocytes and T lymphocytes subsets have been quantified by an indirect immunofluorescence technique using monoclonal antibodies, in 10 patients with fatty liver, 8 with acute alcoholic hepatitis (AAH), 10 with inactive cirrhosis and 7 with cirrhosis and AAH. Twenty normal subjects were studied as controls. As compared to controls (1.81 +/- 0.56 10(9)/l), we found a reduced number of peripheral T lymphocytes (OKT3+) in patients with inactive cirrhosis (0.98 +/- 0.45, p less than 0.001) and in patients with cirrhosis and AAH (1.22 +/- 0.51, p less than 0.02). The OKT4 to OKT8 ratio was normal in patients with fatty liver or inactive cirrhosis, but it was significantly higher in patients with AAH with or without cirrhosis (2.83 +/- 0.79, p less than 0.01, and 2.10 +/- 0.56, p less than 0,02, respectively) than in controls (1.68 +/- 0.24). In both groups, this increased ratio was due to a decreased proportion of OKT8+ circulating lymphocytes (19.2 +/- 6.7 p. 100, p less than 0.01, and 21.8 +/- 4.6 p. 100, p less than 0.02, respectively) when compared to controls (27.1 +/- 4.1 p. 100). The T-cell imbalance observed in patients with liver cell necrosis may be of importance in the pathogenesis of alcoholic liver disease.     

Relationships between 34 HLA-A, HLA-B and HLA-DR antigens and three serological markers of viral infections in alcoholic cirrhosis

In order to study the genetic risk of alcoholic cirrhosis, the frequency of 26 HLA-A and -B antigens was compared in 184 normal controls, 175 alcoholic cirrhotic patients and 83 alcoholic patients with hepatic steatosis of carefully selected ethnic origin. Eight HLA-DR antigens were also determined in 95 subjects of the normal control group and 63 patients of the alcoholic cirrhosis group. The incidence of hepatitis B virus antibodies (anti-HBc and anti-HBs) was defined in 74 patients of the alcoholic steatosis group, 170 patients of the alcoholic cirrhosis group and 111 normal controls different from the previously mentioned normal control group. The incidence and the titers of cytomegalovirus and rubella antibodies were also determined in 93 patients of the alcoholic cirrhosis group and the 111 normal controls. Serum immunoglobulin concentrations were measured in the same 93 cirrhotic patients. Compared with the controls, the alcoholic cirrhosis group revealed a significantly higher frequency of HLA-B15 (21.7 vs. 9.8%, p less than 0.00025, corrected p less than 0.050) and HLA-DR4 (38.1 vs. 17.9%, p less than 0.005, corrected p less than 0.050) and a significantly lower frequency of HLA-B13 (2.9 vs. 11.4%, p less than 0.025, corrected p less than 0.050). As for the frequency of all other HLA antigens, there was no significant difference between the three groups (normal controls, alcoholic cirrhosis and alcoholic steatosis).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay

Plasma endotoxin concentration was measured in 85 patients with alcoholic liver disease (alcoholic cirrhosis (n = 64), alcoholic hepatitis without cirrhosis (n = 11), fatty liver (n = 10), and in patients with non-alcoholic cirrhosis (n = 15]. Endotoxin concentration was determined with an improved chromogenic substrate assay, using individual standard curves for each plasma sample. In patients with alcoholic cirrhosis the mean endotoxin concentration was significantly higher than in patients with non-alcoholic cirrhosis (p less than 0.05). In addition, distinctly higher endotoxin concentrations (greater than 20 pg/ml) were more frequently observed in patients with alcoholic cirrhosis than in non-alcoholic cirrhosis (34.4 vs. 14.3%, p less than 0.05). Mean endotoxin concentration was not significantly higher in cirrhotics with ascites or esophageal varices as compared with the subgroup without ascites or esophageal varices. The endotoxin concentration did not correlate with serum bilirubin, prothrombin concentration or serum enzyme activities. In patients with alcoholic liver disease, however, endotoxin concentration revealed a negative correlation (p less than 0.05) with the concentration of high density lipoprotein cholesterol. On admission endotoxin concentrations in alcoholics with fatty liver were similarly elevated as observed in alcoholic cirrhosis. In six out of 12 patients with fatty liver or alcoholic hepatitis, in whom a second sample of plasma was investigated after 6 to 8 days, endotoxemia was no longer detectable; in the remaining patients, the endotoxin concentration decreased markedly. The results indicate that, irrespective of the stage of liver disease, alcohol abuse favours the development of endotoxemia. They support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.     

Prevalence of HLA-A and -B antigens, anti-HBc and -HBs antibodies in alcoholic hepatopathies

The frequency of 26 HLA-A and B antigens and of antibodies to the hepatitis B core antigen (anti-HBc) and surface antigen (anti-HBs) has been studied in 150 alcoholic patients divided into 3 groups: I) n = 50, isolated hepatic steatosis; II) n = 50, acute alcoholic hepatitis +/- cirrhosis; III) n = 50, cirrhosis without acute alcoholic hepatitis. For the control group 184 blood donors were selected. In all these subjects, as in all the alcoholic patients, the Alsatian origin of four grand parents was proved. An increased frequency of HLA-B15 was observed in group III (34 p. 100) compared to the control group (9.8 p. 100) (corrected p less than 0.001). There was no significant difference between the four groups for all the other HLA antigens. In group III, the prevalence of anti-HBc and/or anti-HBs was higher in patients with HLA-B15 (64.7 p. 100) than in patients without this antigen (15.1 p. 100) (p less than 0.001). In groups I and II, there was no significant difference. These results suggest that there is a genetic predisposition to cirrhosis without acute alcoholic hepatitis, dependent on HLA-B15 antigen. This predisposition could involve the hepatitis B virus.     

Correlation between hepatic morphology and immunoglobulins and antibodies to Escherichia coli in cirrhosis.

Increased antibody production and hypergammaglobulinaemia in cirrhosis are probably to a large extent due to decreased hepatic extraction of antigens. The deceased extraction is presumably related to changed microcirculation caused by damaged anatomical structure of the liver. It is therefore to be expected that immunoglobulin and antibody levels in serum in cirrhotic patients are related to the degree of certain morphological changes of the liver. This hypothesis has been tested. In 50 patients with cirrhosis, 28 alcoholics and 22 non-alcoholics, the degree of architectural destruction, the degree of fibrosis, the degree of fatty infiltration, and the degree of "activity" were compared with immunoglobulins G, A, and M and E. coli O antibody levels. The comparison was carried out within each of the aetiological groups. Identical relationships were found in both groups. Patients with completely destroyed lobular architecture had higher levels of E. coli O antibodies than patients with partly destroyed architecture. Patients with severe fibrosis had higher IgA and E. coli O antibody levels than patients with moderate or slight fibrosis. Patients with moderate and severe steatosis and patients with no or slight steatosis had the same immunoglobulin and E. coli O antibody levels. Patients with active cirrhosis had higher IgG levels than patients with inactive cirrhosis. When architectural destruction and fibrosis were combined significantly higher IgG, IgA, IgM, and E. coli antibodies were found in the group with the most severe changes. These findings support the hypothesis that immunoglobulin and antibody levels are related to the degree of morphological changes in the liver--namely, destruction of lobular architecture, fibrosis, and "activity".     

Serum immunoglobulins (IgG, IgA, IgM) in chronic hepatitis C. A comparison with non-cirrhotic alcoholic liver disease

BACKGROUND/AIMS: Serum immunoglobulin concentrations are commonly elevated in patients with liver cirrhosis. Immunoglobulin class increase may vary depending on the cause of liver disease. Hepatitis C virus is, together with alcohol, a leading cause of chronic liver disease. The present study aimed to evaluate serum IgG, IgA and IgM levels in chronic hepatitis C. Results were compared with those of patients with non-cirrhotic alcoholic liver disease and healthy controls. Special attention was given to cases with minimal liver disease, as an approach to evaluate if the causing agent, independently of liver damage, influences serum immunoglobulin levels. METHODOLOGY: A total of 274 patients with histologically-proven chronic hepatitis C, 121 alcoholics with non-cirrhotic liver disease (steatosis or alcoholic hepatitis), and 75 healthy controls were studied. Serum IgG, IgA, and IgM were assayed by nephelometry. RESULTS: Serum IgG was increased in patients with chronic hepatitis C with respect to both alcoholics (p < 0.001) and healthy controls (p < 0.001). IgG levels were similar in alcoholics and in controls. IgA was increased in patients with non-cirrhotic alcoholic liver disease with respect to both chronic hepatitis C patients (p < 0.001) and controls (p < 0.001). IgA values were similar in subjects with chronic hepatitis C and controls. Selective IgG or IgA alteration was present in cases with minimal liver disease (chronic hepatitis C with a Knodell index equal or lower than 3, and alcoholics with liver steatosis, respectively). CONCLUSIONS: Hepatitis C virus and alcohol are linked to a selective increase of serum IgG and IgA, respectively, even in cases with mild or minimal liver disease.     

Prognosis of alcoholic cirrhosis in the presence and absence of alcoholic hepatitis

Liver biopsy specimens (178 percutaneous and 39 transjugular) were assessed from 217 consecutive patients with alcoholic liver disease, 77 noncirrhotics and 140 cirrhotics, whose cases were followed for 5 yr. Cirrhotic patients were categorized into two groups, with and without "hepatitis" using a criteria to define "hepatitis" that included only degrees of inflammation, necrosis, and Mallory bodies that had a prognostic weight in terms of mortality in 1 yr. This classification resulted in a sharp separation between a group of 42 patients with cirrhosis without "hepatitis" and with low mortality, both at 1 yr (7.1% +/- 4.0%) and at 5 yr (31% +/- 7%), and another group of 98 patients with cirrhosis and "hepatitis" and a high mortality both at 1 yr (26.5% +/- 4.5%, p less than 0.01), and at 5 yr (47% +/- 5%, p less than 0.02). Importantly, the 1-yr mortality in patients with cirrhosis and no "hepatitis" was not statistically different from that of patients with no cirrhosis or "hepatitis" (most of whom had only fatty liver) both at 1 yr (6.9% +/- 3.3%) and at 5 yr (24% +/- 6%). There were marked differences in several variables between cirrhosis with and without "hepatitis" [combined clinical and laboratory index: no "hepatitis": 4.9 +/- 0.7, with "hepatitis": 7.8 +/- 0.5, p less than 0.01; score of collagen in space of Disse: no "hepatitis": 2.1 +/- 0.4, with "hepatitis": 3.7 +/- 0.3, p less than 0.01; hepatocyte cross-sectional surface area: no "hepatitis": 682 +/- 51 micron 2, with "hepatitis": 841 +/- 31 micron 2, p less than 0.01]. These findings were more severe in the transjugular group than in the percutaneous group. Collagen in the space of Disse and hepatocyte surface area were not statistically different when cirrhosis without "hepatitis" was compared with a similar no "hepatitis" group of patients having noncirrhotic alcoholic liver disease. In this patient sample the presence of parenchymal nodules and fibrous septa, per se, did not result in an increase in mortality with respect to alcoholic patients without cirrhosis and with no "hepatitis."     

Aminoterminal propeptide of type III procollagen in serum in alcoholic liver disease

An assay of serum antigens related to the aminoterminal propeptide of type III procollagen has been suggested for monitoring fibrotic processes in the liver. These antigens were measured here in 61 alcoholics who were divided into four groups on the basis of liver histology: normal light microscopy, fatty liver, alcoholic cirrhosis with hepatitis, and inactive cirrhosis. All the subjects having alcoholic hepatitis with cirrhosis had elevated values in the assay, whereas some of those with either fatty liver or inactive cirrhosis still had normal values. It was, therefore, not possible on the basis of this method alone to distinguish fatty liver from cirrhosis or alcoholic hepatitis, although very high values were suggestive of alcoholic hepatitis. In a follow-up study, the aminopropeptide value decreased slowly during recovery from alcoholic hepatitis and increased rapidly after a new drinking bout. The antigens detected by the assay are heterogeneous in human serum. The proportions of the three main peptide forms varied during recovery from alcoholic hepatitis, the authentic propeptide being the main one at the acute stage, but almost disappearing later. The usefulness of the assay could probably be improved if distinct assays were available for the different antigen forms.     

IgA, Glomerulonephritis and Liver Disease

Abstract: Data from our Unit suggest that soluble immune complexes (IC) are responsible for the mesangial deposits of IgA and C3 in patients with IgA nephropathy. These IC are of intermediate size (9–17S) and contain IgA, IgG and less commonly IgM. Ubiquitous exogenous antigens have been implicated in some patients and primary defects in antigen exclusion or reticuloendothelial sequestration have been proposed to account for the formation and persistence of IC. The liver plays a central role in the clearance of antigens, polymeric IgA and IC, and liver disease is associated with alimentary hyper-immunization, hypergammaglobulinaemia (including IgA polymers) and circulating IC. At autopsy, mesangial (14/28), skin (10/18) and choroid plexus. (2/3) deposits of IgA were found in patients with alcoholic cirrhosis compared with 1/75, 3/10 and 2/5 respectively in controls. Raised serum antibodies to E. coli and to BSA were noted in patients with alcoholic cirrhosis but no specific antibodies have been detected in the kidney eluates. Circulating IC and mesangial deposits of IgA and C3 have also been demonstrated in rats with carbon tetrachloride-induced cirrhosis and after portacaval shunting. Measurement of reticuloendothelial function and the clearance of IgA polymers and IC is now required in patients with primary IgA nephropathy and HSP. In the meantime, IgA nephropathy is best regarded as a syndrome with primary and secondary forms, and as a clinical spectrum from isolated glomerulonephritis to systemic IC disease (HSP ).     

Cytoskeleton antibodies in chronic active hepatitis, primary biliary cirrhosis, and alcoholic liver disease

Antibodies to cytoplasmic microfilaments, intermediate filaments (vimentin filaments), and microtubules which comprise the cytoskeleton of the cell were assayed in sera from 23 patients with HBsAg-negative chronic active hepatitis and 1 with HBsAg-positive chronic active hepatitis, 15 patients with primary biliary cirrhosis, 20 patients with alcoholic liver disease, and 32 healthy controls. The cytoskeleton antibodies were assayed by indirect immunofluorescence technique using vinblastine-treated cultured human embryonic fibroblasts as substrates. There was a significantly increased incidence of cytoskeleton antibodies in patients with liver disease as compared to the control group. Antibodies to microfilaments were found frequently in sera from patients with chronic active hepatitis (67%) and primary biliary cirrhosis (53%) but were rare in sera from patients with alcoholic liver disease (25%) and in control sera (3%). On the other hand, antibodies to microtubules were found in 50% of sera from patients with alcoholic liver disease but in only 7 to 13% of sera from other groups. Intermediate filament antibodies of IgG or IgA class were found only in patient sera whereas intermediate filament antibodies of IgM class were found in the majority of sera in all groups including control sera. The highest titers of intermediate filament antibodies were seen in primary biliary cirrhosis and chronic active hepatitis. The production of cytoskeleton antibodies may be due to the reorganization or destruction of cytoskeletal structures in the liver.     

Hepatitis B virus, serological markers of viral infections and humoral immunity in alcoholic cirrhosis

In order to define the role of hepatitis B virus (HBV) in alcoholic liver disease and to study the relationship between HBV and other common viruses, the serological markers of viral disease (HBV, Rubella, Polio, Herpes, and Cytomegalovirus-CMV) were compared in 163 patients with alcoholic cirrhosis (group C), 100 patients with alcoholic steatosis (group S) and in 168 non-alcoholic control subjects (group NA). A significantly increased prevalence of HBV markers in group C was related to the presence of anti-HBc antibodies, in 10.5 p. 100 of cirrhotic patients, vs. 1.2 p. 100 in group S and 1 p. 100 in group NA (p less than 0.01). In cirrhotic patients with HBV markers (HBV +) incidence of alcoholic hepatitis was 4 times lower and the total duration of alcohol overconsumption was significantly lower than in cirrhotic patients without these markers (HBV-). Hepatic function tests were not different in HBV + and HBV- cirrhotic patients, excepted for the ASAT/ALAT ratio (1.55 +/- 0.10 vs. 1.92 +/- 0.12; p less than 0.05). Prevalence of anti-CMV antibodies, and anti-herpes greater than 1/100 antibodies, was significantly increased in S and C groups (p less than 0.01). Anti-Rubella, Polio, and CMV antibody titers were higher (p less than 0.05) in HBV + than in HBV- cirrhotic patients. In cirrhotic subjects, titers of these 3 anti-virus antibodies were not related to alcoholic hepatitis or to IgG and IgM concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased serum corrinoids correlates with disease severity and IgA levels in alcoholic cirrhosis

Relationship between increased serum cobalamin level and liver disease have been recently reported. In this work, levels of total corrinoids, cobalamin (vitamin B12) and cobalamin analogues and levels of IgA were determined by radioisotope dilution assay and nephelometric laser analyses. They all have been measured in superior vena cava, inferior vena cava and hepatic vein of controls and of alcoholic cirrhotic patients grouped according to the Child-Pugh classification. Compared with normal subjects, venous blood content of total corrinoids, of cobalamin and of IgA in alcoholic cirrhotics increased significantly with the severity of the disease (p less than 0.01). In severe, moderate, and mild alcoholic cirrhosis total corrinoids and cobalamin were, respectively, about 5-, 2-, and 1.5-fold higher than in controls, whereas IgA was 3-, 2.5- and 1.5-fold higher, respectively. The serum IgA level was significantly correlated with the level of seric saturated haptocorrin (r = 0.54; p less than 0.01) and with the seric total corrinoids (r = 0.39; p less than 0.01). In the absence of significant hepatic cytolysis, the enhanced level of seric corrinoids in cirrhosis could be partly explained by a competitive inhibition of the liver uptake of haptocorrin by circulating asialoglycoproteins, including IgA.     

Transferrin metabolism in alcoholic liver disease

The metabolism of transferrin was studied using purified 125I-labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group. There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 +/- 0.3 gm per liter vs. 2.9 +/- 0.2; p less than 0.01), resulting from diminished total body synthesis (0.9 +/- 0.2 mg per kg per hr vs. 1.8 +/- 0.2; p less than 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 +/- 0.3 mg per kg per hr) was significantly increased when compared with controls (p less than 0.05). For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = + 0.70; p less than 0.01) but the serum iron did not. These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerated.     

Histocompatibility antigens in patients with alcoholic liver disease in Scotland and northeastern England: failure to show an association.

A study of HLA-A and B antigens in 248 patients with biopsy diagnosed alcoholic liver disease was conducted to examine for a genetic predisposition to alcohol related liver injury. No statistically significant differences were established for 8 HLA-A and 16 HLA-B antigens between normal healthy controls (n = 342) and patients with alcoholic fatty liver (n = 86), alcoholic hepatitis (n = 63), active alcoholic cirrhosis (n = 64) and inactive alcoholic cirrhosis (n = 35). It is concluded that no HLA-A or B locus genetic susceptibility to alcoholic related injury could be shown.     

Serum IgA Antibodies to Human Gut Luminal Aspirates and Human Liver in Alcoholic Liver Disease

Background : Elevation of serum IgA is a characteristic feature of alcoholic liver disease. It has been proposed that this occurs partly as an antigenic response to gut-derived proteins or acetaldehyde-modified liver proteins, but the principal antigens responsible remain unknown. Aims : The goal of this study was to determine if serum IgA antibodies were present against human gut luminal antigens or liver antigens in alcoholic liver disease. Patients and Methods: Twenty-nine patients with alcoholic liver disease, 10 with primary biliary cirrhosis, 12 with "other" liver diseases, 8 alcoholics, and healthy subjects were studied. Western blotting was used to examine the reactivity of sera from these groups against human small and large bowel aspirates and liver tissue from alcoholic liver disease patients. Results: Serum IgA antibodies to a 140 kDa colonic luminal protein were found in 22 (76%) patients in the alcoholic liver disease group ( p < 0.0001), and 7 (24%) patients had serum IgA antibodies to a 40 kDa colonic luminal protein ( p = 0.04). These responses were confined to colonic aspirates and not observed in other disease groups, alcoholics or healthy subjects. There was no significant serum IgA response to human liver proteins in alcoholic liver disease. Conclusions : Serum IgA antibodies to a human 140 kDa colonic luminal protein are frequently found in alcoholic liver disease. This novel antigen may contribute to the increased levels of circulating IgA in alcoholic liver disease.     

Depressed delayed cutaneous hypersensitivity in alcoholic hepatitis

Delayed cutaneous hypersensitivity was studied in 10 patients with severe alcoholic hepatitis, 9 patients with either inactive alcoholic cirrhosis or alcoholic fatty liver, and 10 age-matched controls. The mean response of the alcoholic hepatitis group was significantly less compared to controls for SK-SD (P<0.001), mumps (P<0.001), trichophyton (P<0.025), andCandida albicans (P<0.025). Upon clinical recovery, the response of the 6 surviving patients with alcoholic hepatitis was similar to controls for 4 of the 5 antigens tested, and the improvements in response to SK-SD andCandida albicans were significant (P<0.02 and P<0.05). The mean percentage and absolute numbers of thymus-derived lymphocytes were significantly less in the alcoholic hepatitis group compared with controls. Both the alcoholic hepatitis patients and patients with less advanced alcoholic liver disease had a diminished response to concanavalin A and phytohemagglutinin. This study demonstrates a reversible depression of delayed cutaneous hypersensitivity in alcoholic hepatitis. Several mechanisms may help account for this finding. We recommend that skin tests in patients with alcoholic hepatitis be interpreted with this phenomenon in mind.This paper was presented at the 27th Annual Meeting of the American Association for the Study of Liver Disease, Chicago, Illinois, November 5, 1976.     

Endotoxin and liver diseases. High titres of enterobacterial common antigen antibodies in patients with alcoholic cirrhosis.

We have measured antibodies to the enterobacterial common antigen (ECA) in sera of 86 patients with various liver diseases. ECA is a component of the cell wall of all enteric bacteria, and ECA antibodies are a specific indication of the presence of enterobacterial components. Patients with alcoholic cirrhosis with or without signs of alcoholic hepatitis had significantly raised anti-ECA titres compared with healthy control subjects. Other groups of patients (alcoholic hepatitis and/or fatty liver, primary biliary cirrhosis, chronic active hepatitis, or liver metastases) did not differ significantly from controls in the height of their anti-ECA titres. The results support the concept that Gram-negative bacterial components may have some role in the pathophysiology of alcoholic cirrhosis.