Autoantibodies against liver cell membrane antigens detected by enzyme-linked immunosorbent assay in acute and chronic liver disease

An enzyme-linked immunosorbent assay was developed to detect serum antibody binding to liver membrane antigen derived from human hepatoma cell line SK-Hep-1. When we tested sera from 214 patients with this assay, IgM antibodies were detected in 100% of patients with acute type A, but not with type B or non-A, non-B hepatitis. IgM antibodies were also found in highest frequency (76%) and titer in patients with autoimmune chronic active hepatitis (CAH) among chronic liver disease groups. IgG antibodies occurred in over 50% of patients with acute type A hepatitis, type B chronic active liver disease (CALD), and autoimmune CAH. IgA antibodies were present in 43% of the patients with alcoholic liver disease, but were also seen in other patient groups. When freshly isolated rat hepatocytes were used as target cells, prevalences and titers similar to those obtained with SK-Hep-1 were found. The levels of serum membrane binding antibody were significantly reduced by the addition of human liver-specific membrane lipoprotein in all patient groups. In particular, IgM antibodies became negative in over 50% of patients with CALD (both type B and non-A, non-B) and autoimmune CAH, whereas in acute hepatitis over 50% lost their positivity for IgG antibody. These results indicate that circulating liver membrane binding autoantibodies are heterogeneous, occurring in hepatitis virus-induced acute and chronic liver disease as well as in autoimmune CAH.     

Symptomatic anti-HBe positive chronic hepatitis B in Taiwan with special reference to persistent HBV replication and HDV superinfection

Ninety-four patients, who were admitted with symptoms of liver disease and found to be positive for hepatitis B surface antigen and antibody to hepatitis B e antigen (anti-HBe), were examined for hepatitis B virus (HBV) DNA in serum and immunoglobulin antibody to hepatitis B core antigen and liver biopsies were stained for hepatic hepatitis B core antigen. Of 94 patients, 34 (36%) had evidence of HBV replication and 35 (37%) evidence of hepatitis D virus (HDV) superinfection. Most of the latter two groups of patients (greater than 70%) had evidence of chronic active hepatitis or active cirrhosis in their liver biopsies. The majority of these patients (greater than 80%) also had high levels of serum alanine aminotransferase (greater than 200 U/L) during the acute stage of their illness, and suffered from prolonged hepatic inflammation (greater than 1 year). Many of the patients (59%) also experienced frequent (1-6 episodes) relapsing exacerbations during a two-year follow-up period. Thus, persistent replication or reactivation of HBV and HDV superinfection were the two major causes of clinical exacerbations in anti-HBe-positive chronic HBV carriers in Taiwan, and also played an important role in the progression of their liver diseases and unfavorable outcomes.     

DNA-binding antibodies and hepatitis B markers in acute and chronic liver disease.

A Farr technique has been used to assay antibodies to double-stranded DNA in the serum of patients with acute and chronic liver disease and carriers of HBsAg from the United Kingdom and Iraq. These antibodies were found in all groups from both countries. The highest levels were found in chronic active hepatitis and cirrhosis. In the Iraqi patients there was a strongly positive correlation between DNA-binding antibody levels and the presence of hepatitis B markers but not with disease activity. In the patients from the United Kingdom there was little correlation with disease activity and none with autoantibodies. Ninety-five per cent of asymptomatic carriers of HBsAG had elevated DNA-binding antibodies. It is suggested that hepatitis B-specific DNA might be one trigger to DNA antibody formation, though in liver disease a variety of factors are clearly operative.     

Detection of antibodies to Chang liver cell in sera from patients with chronic liver diseases by 125I-labelled protein A binding assay and the effect of prednisolone and 6-mercaptopurine treatment on the level of the antibodies

Antibody binding to living Chang liver cell was measured in sera from 71 patients with various chronic liver diseases using 125I-labelled protein A binding assay. The level of antibody binding to Chang liver cell was significantly elevated in sera from patients with chronic active hepatitis (CAH), chronic persistent hepatitis (CPH) and liver cirrhosis as compared to those from healthy donors, but not in sera from patients with fatty liver. There was no detectable antibody binding to HeLa cells in those sera. The antibody binding to Chang liver cell was blocked by a human liver specific protein (LSP) preparation. The levels of antibody binding to Chang liver cell were significantly higher in patients with CAH than patients with CPH. On the other hand, the level of antibody binding to Chang liver cell was significantly decreased in sera from patients with CAH after a treatment with prednisolone (PSL) for 2 months and a subsequent combined administration of 6MP and a maintenance dose of PSL for 1 month. These results suggest that antibodies to Chang liver cell are closely correlated with the activity of chronic liver disease and that PSL and 6MP treatment can reduce the level of the antibodies.     

Hepatitis B virus DNA in liver, serum, and peripheral blood mononuclear cells after the clearance of serum hepatitis B virus surface antigen

The integration of hepatitis B virus (HBV) DNA in the liver of chronic HBV carriers has been documented extensively. However, the status of the viral genome during acute infection has not been assessed conclusively. While HBV DNA sequences are detected often in serum, liver, and peripheral blood mononuclear cells (PBMCs) after the clearance of serum the hepatitis B virus surface antigen (HBsAg), the precise status of the viral genome, and in particular the possible persistence of integrated genomes in PBMCs, has not been established. A highly sensitive PCR-derived assay (Alu-PCR) was employed to re-examine liver and PBMC specimens obtained from patients with acute (n = 19) and chronic (n = 22) hepatitis in whom serum HBsAg was present (n = 12) (HBV-related chronic active hepatitis) or absent with anti-HCV (n = 10) (HCV-related chronic active hepatitis). Viral integration was demonstrated in 3 out of 19 liver specimens from patients with acute hepatitis and 12 out of 12 specimens from patients with chronic hepatitis. Viral integration was also observed in 4 out of 7 PBMC samples from HBV-related chronic active hepatitis patients and 2 out of 10 liver and PBMC samples from HCV-related chronic active hepatitis patients. In one liver specimen from an acute hepatitis patient, HBV DNA was found integrated in the intronic sequence of the tumour necrosis factor (TNF)-induced protein gene; viral integration into cellular sequences was also found in the PBMCs of four HBV-related chronic active hepatitis and two HCV-related chronic active hepatitis. The results demonstrate the early integration of HBV genome during acute viral infections and the persistence of the viral genome in an integrated form in PBMCs.     

Autoimmune implications of immune complexes in clinical variants of hepatitis B.

Immune complexes (IC) were investigated in sera from 208 individuals with various clinical types of viral hepatitis diagnosed by clinical and laboratory criteria, including liver biopsy. Immune complexes were assessed by platelet aggregation (PI A) and by radioimmunoassay (RIA). The data were related to autoimmune phenomena (especially rheumatoid factors) and to the role that the IgM class of hepatitis B (HB) antibody might have in IC formation. Although the highest frequency of P1 A was in the few sera from patients with cirrhosis or hepatoma, the next highest was in sera from acute hepatitis patients (71%), and the lowest in sera from chronic active (57%) and chronic persistent (46%) hepatitis patients. A proportional number of patients with IC's were positive for hepatitis B surface antigen (HBs). A parallel prevalence was noted between P1 A and autoantibodies, with anti-Ig's being found more frequently in sera from acute hepatitis and chronic active hepatitis patients. The relationship between RIA results for complexes and RIA results for anti-IgG was inverse, as though anti-IgG interfered with IC reactivity by RIA. Anti-IgM pre-incubated with sera increased the amount of P1 A in sera from patients with acute hepatitis as well as in those from patients with chronic persistent hepatitis, suggesting a more frequent IgM involvement in IC's in these diseases than in chronic active hepatitis. Whereas liver cell damage in acute and active hepatitis may reflect elevated autoantibodies, the IgM class of HBs antibody may be involved in acute as well as chronic persistent hepatitis.     

Hepatitis B virus concentrations in serum determined by sensitive quantitative assays in patients with established chronic hepatitis delta virus infection.

To clarify the correlation between hepatitis B virus (HBV) DNA levels and serum alanine aminotransferase (ALT) levels in patients with established chronic hepatitis delta virus (HDV) infection, sensitive HBV quantitative assays were used for the study. Thirty-four consecutive patients with chronic liver disease who were positive for both hepatitis B surface antigen (HBsAg) and antibody to HDV (anti-HDV), including 19 patients with chronic hepatitis, 8 patients with liver cirrhosis and 7 patients with hepatocellular carcinoma. All were negative for hepatitis Be antigen (HBeAg) and positive for antibody to HBeAg. HBV DNA was detected in 25 (73.5%) of the 34 patients using real-time detection PCR, and the HBV DNA levels of these patients were significantly lower compared with HBeAg status and ALT level-matched patients with chronic liver disease positive for HBsAg but negative for anti-HDV. There was no correlation between serum HBV DNA and ALT levels among the 34 patients with chronic liver disease positive for anti-HDV. Whereas serum ALT levels in anti-HDV-positive HBsAg carriers with HDV RNA were significantly higher than those without HDV RNA. Liver damage in patients with established chronic HDV infection may be caused mainly by ongoing HDV infection not by HBV replication.     

慢性乙型肝炎急性发作与血清HBN DNA含量关系

目的 研究慢性乙型肝炎急性发作与血清ＨＢＶ ＤＮＡ含量的关系。方法 采用荧光ｍｐｌｉＳｅｎｓｏｒ）定量方法。测定一组自发性反复发作的慢性乙型肝炎患者发作前,中和后的血清ＨＢＶ ＤＮＡ含量的变化。结果 （１）１１例患者中有９例（８２％）血清ＨＢＶ ＤＮＡ含量的高峰值是在最大肝损害之前出现或与丙氨酸转氨酶（ＡＬＴ０同时达到高峰。     

Characteristics of the early phase of chronicity in acute hepatitis B infection

The mechanism of development of chronicity after acute hepatitis B infection has not been elucidated fully. Following a single source outbreak of hepatitis B among 79 adult women, three patients (4%) became chronic carriers of hepatitis B virus (HBV). We compared features of the virus and antibody response of the latter three patients with those of 12 HBeAg-positive cases with resolving infection. The virus genotype was D, antigenic subtype ayw2. Base sequence analysis of S- and C-gene regions revealed no differences between the two groups. During the acute illness the three patients who developed chronicity had a remarkable transient reduction of HBsAg, HBeAg, and HBV DNA levels at 14-20 weeks after infection, the time of HBeAg seroconversion in the patients who cleared the infection. One HBeAg-specific monoclonal antibody (HBOT.95A) used as solid-phase antibody in a sandwich enzyme immunoassay detected an increased HBeAg signal in 2 of the 3 patients that developed chronicity and in 1 of the 12 patients who recovered. The latter patient had an exceptional long period of HBsAg antigenemia. Standard HBeAg assays detected HBeAg in all cases. HBeAg and anti-HBe-positive serum samples from the patients who recovered could inhibit the HBOT.95A response. The results suggest that chronic hepatitis B develops after an interruption of immune clearance. Differentiation of the antibody response to HBeAg may help to find patients with an increased risk for this interrupted immune clearance who might be candidates for an early intervention therapy.     

Diagnostic significance of anti-HBc IgM (RIA) in healthy HBsAg carriers and in chronic hepatitis B

The diagnostic significance of IgM antibody against hepatitis B core antigen (anti-HBc) in healthy hepatitis B surface antigen (HBsAg) carriers and in subjects affected by chronic hepatitis B was evaluated. IgM anti-HBc was sought and found in all nine patients examined who were affected by acute HBsAg-positive hepatitis. It was also detected in 2 out of 18 patients with HBsAg-positive chronic persistent hepatitis and in 12 out of 42 patients affected by HBsAg-positive chronic active hepatitis. The absence of this marker was noted in all 26 HBsAg healthy carriers and in the subjects with HBsAg-positive cirrhosis. No relationship was found between the presence of IgM anti-HBc and the degree of inflammatory activity in the patients with HBsAg-positive chronic active hepatitis. A correlation was not found between the presence of IgM anti-HBc and the presence of hepatitis B e antigen (HBeAg) in the same patients. These data show that the absence of IgM anti-HBc may be useful in identifying healthy carriers of HBsAg. The presence of this antibody may be a suitable indication of acute HBsAg-positive hepatitis. In patients with chronic active hepatitis B the presence of IgM anti-HBc cannot be used as diagnostic tool in predicting the severity of liver disease.     

Detection of antibodies directed against a liver-specific membrane lipoprotein in patients with acute and chronic active hepatitis

A specific and sensitive radioimmunoassay was used to measure the levels of antibody to a liver-specific membrane lipoprotein in patients with acute and chronic liver disease. Antibody was detected in 29 of 30 patients with chronic active hepatitis (all of 15 HBsAg-negative and 14 of 15 HBsAg-positive cases), and in 10 of 17 patients with chronic persistent hepatitis but at significantly lower titer. The titer of antibody to the lipoprotein showed a significant correlation with activity of disease as judged histologically and biochemically. Transiently elevated levels were found in 20 of 21 patients with acute viral hepatitis, but there was no correlation with the degree of liver damage. Antibody to liver-specific membrane protein may be part of the final common pathway of liver-cell damage in both HBsAg-positive and HBsAg-negative chronic activite hepatitis, whereas other immune mechanisms determine the liver-cell injury in acute viral hepatitis.     

Detection of a liver-membrane autoantibody in HBsAg-negative chronic active hepatitis.

Investigation of humoral immunity against hepatocellular membrane antigens in patients with chronic active hepatitis and other liver diseases showed two different immunofluorescence patterns of IgG on hepatocyte membranes. A linear pattern was seen in HBsAg-negative hepatitis, but HBsAg-positive cases and some of protracted, acute hepatitis B had a granular pattern. In patients with IgG bound to hepatocytes, continuing necrosis of parenchymal liver cells was seen. Conversely, hepatocytes without bound IgG were found in cases of chronic active hepatitis in remission, acute viral hepatitis without HBsAg and chronic persistent hepatitis, in "healthy" HBsAg-carriers and in patients with fatty liver or alcoholic cirrhosis. A liver-membrane autoantibody in serum, proved by fixation on membranes of isolated rabbit hepatocytes, could be demonstrated only in HBsAg-negative chronic active hepatitis with elevated IgG-concentrations. The results support the existence of different pathogenetic types of chronic active hepatitis, a so-called autoimmune type and a hepatitis virus-B-induced type.     

HBcAg‐Specific IL‐21‐Producing CD4+ T Cells are Associated with Relative Viral Control in Patients with Chronic Hepatitis B

Function exhaustion of specific cytotoxic CD8+ T cell in chronic virus infection partly results from the low levels of CD4 help, but the mechanisms by which CD4 help T cell required to control hepatitis B virus infection are not well understood. In this study, we investigated the role of interleukin‐21‐producing CD4+ T cell response in viral control of hepatitis B virus infection. HBcAg‐specific interleukin‐21‐producing CD4+ T cells in blood were detected in patients with hepatitis B virus infection. Patients with acute hepatitis B had greater HBcAg‐specific interleukin‐21‐producing CD4+ T cells in blood compared with chronic hepatitis B patients, and there was no statistical significance between immune active chronic hepatitis B patients and inactive healthy carrier patients for these cells, whereas frequencies of these cells negatively correlated with HBV DNA levels but positively correlated with HBc18‐27‐specific IFN‐γ‐producing CD8+ T cells. Moreover, interleukin‐21 sustained HBc18‐27‐specific CD8+ T cells in vitro, and interleukin‐21 production by HBcAg‐specific IL‐21‐producing CD4+ T cells of acute hepatitis B patients enhanced IFN‐γ and perforin expression by CD8+ T cells from chronic hepatitis B patients. Our results demonstrate that HBcAg‐specific interleukin‐21‐producing CD4+ T cell responses might contribute to viral control by sustaining CD8+ T cell antiviral function.     

Monoclonal antibody recognizing pre-S(2) epitope of hepatitis B virus: characterization of pre-S(2) epitope and anti-pre-S(2) antibody

A hybrid cell line producing monoclonal antibodies recognizing an epitope encoded by the pre-(S)2 region of hepatitis B virus (HBV) genome was obtained by fusion of mouse myeloma cells with lymphocytes from mice immunized with HBV. The monoclonal antibody Mo-F124 secreted from the hybrid line reacted with the pre-S(2) epitope expressed on the surface of both viral and recombinant HBsAg particles--pre-S(2) and S gene product--localised on 34 kD glycoprotein of the viral envelope. The pre-S(2) epitope was sensitive to digestion with V8 protease from Staphylococcus aureus. The enzyme abolished reactivity with Mo-F124 and polymerized human serum albumin (pHSA) binding activity of recombinant particles. Mo-F124 antibody was used to develop highly sensitive radioimmunoassays for determination of pre-S(2) epitope and anti-pre-S(2) antibody in sera of hepatitis B patients. Detection of a pre-S(2) epitope by the monoclonal antibody-based assay in the early phase of acute HBV infection correlated well with the presence of markers of active viral replication (HBeAg, HBV DNA). The appearance of anti-pre-S(2) antibody, usually in the third month after onset of symptoms, was followed by elimination of circulating HBsAg and seroconversion to anti-HBs in all tested cases of uncomplicated acute hepatitis followed by recovery. Anti-pre-S(2) response was not observed in patients with chronic hepatitis B or acute HBV infection progressing to chronic disease. The observed correlation of anti-pre-S(2) response with recovery suggests that the pre-S(2) epitope may represent one of the epitopes inducing antibodies that neutralize the hepatitis B virus.     

Morphologic and immunohistochemical features of fulminant delta hepatitis

Recent studies have indicated that some cases of fulminant hepatitis that were ostensibly type B were actually acute viral hepatitis, types B and delta, or persistent hepatitis, type B with superimposed acute delta infection. Histologic characterization of the various types has not yet been undertaken. Within ten to 37 days of the onset of initial symptoms, liver tissues from a total of 16 patients who had acute delta hepatitis with fulminant clinical courses were examined. Tissues were from biopsies in nine cases and from autopsies in seven. Based on the serologic absence of IgM hepatitis B core antibody, chronic forms of hepatitis B with acute delta infection were diagnosed in five of the 16 patients. The underlying liver disease in three of these five patients was identifiable as chronic active hepatitis with fibrosis, and that in the others was apparently persistent hepatitis B. Coded liver tissues from these seven autopsies were evaluated without the knowledge of serologic diagnosis for qualitative and quantitative light microscopic features, together with autopsy liver tissues from five patients with fulminant B hepatitis without serologic evidence of delta infection and five patients with fulminant non-A, non-B hepatitis. No specific features that would allow discrimination among these three types of hepatitis were found.     

Liver-infiltrating T helper cells in autoimmune chronic active hepatitis stimulate the production of autoantibodies against the human asialoglycoprotein receptor in vitro.

Autoantibodies against the human asialoglycoprotein receptor (ASGPR) occur in the sera of patients with autoimmune liver disorders. Liver-infiltrating T cell clones that specifically recognize the ASGPR have been described in patients with autoimmune chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with AI-CAH or PBC but not chronic viral hepatitis secreted anti-ASGPR antibodies in vitro. In this study we characterized the influence of liver-infiltrating T cells on the secretion of ASGPR-specific autoantibodies by autologous B cells in cell culture supernatants. T cell clones from liver biopsies of three patients with chronic autoimmune liver disorders (one with AI-CAH, two with PBC) were isolated and investigated for their proliferative response to soluble ASGPR and their helper function provided to autoantibody-secreting B lymphocytes. PBMC from these patients secreted autoantibodies spontaneously in their cell culture supernatants and showed a proliferative response to ASGPR. T cell-depleted PBMC, however, lacked spontaneous antibody secretion. Four CD4+CD8- liver-infiltrating T cell clones showed a proliferative response to ASGPR and also induced spontaneous anti-ASGPR antibody production in cell culture supernatants when added to autologous T cell depleted PBMC. Activated supernatants of these T cell clones failed to induce antibody production. None of seven CD4+CD8- and two CD4-CD8+ T cell clones non-responding to ASGPR provided this help for antibody secretion. Anti-ASGPR secretion in vitro could not be inhibited by the addition of MoAbs raised against monomorphic determinants on HLA class II molecules. The addition of purified ASGPR or polyclonal-activating pokeweed mitogen showed no influence on the production of autoantibodies in these cultures. These data show that B lymphocytes require T cell help for the production of ASGPR-specific antibodies. This help can be provided by ASGPR-responsive T helper cells via cellular interactions.     

Significance of anti-HBc IgM in the differential diagnosis of viral hepatitis

IgM antibody to hepatitis B core antigen (anti-HBc IgM) as determined by IgM capture immunoassay is generally present in high titer during acute hepatitis B infection. A strong positive reaction for anti-HBc IgM during acute hepatitis is indicative of an acute HBV infection even in hepatitis B surface antigen (HBsAg)-negative patients. With the help of anti-HBc IgM otherwise unidentified HBV infection can be diagnosed in HBsAg-negative patients and an optimal combination of diagnostic tests for acute hepatitis B infection would therefore include assays for both HBsAg and anti-HBc IgM. In the HBsAg carrier with or without chronic liver disease the presence and meaning of anti-HBc IgM is still a matter for discussion. Detection of a weak positive result for anti-HBc IgM in HBsAg-positive patients without a recent history of acute hepatitis cannot always be regarded as a definite marker of recent hepatitis B infection. However. quantitation of the anti-HBc IgM results seems to improve the clinical value of the test. Comparison of the available anti-HBc IgM assays is needed and may well establish a reliable cut-off level that would differentiate acute from chronic hepatitis B and ongoing from resolving hepatitis B in HBsAg-positive patients.     

TT virus infection in patients with chronic hepatitis B or C: influence on clinical, histological and virological features

Concomitant infection with TT virus and hepatitis B virus (HBV) or hepatitis C virus (HCV) is common. However, the effect of TTV infection on chronic hepatitis B or C is unknown. The prevalence of TTV infection, the effect of TTV infection on the clinical, histological and virological features of patients with chronic hepatitis B or C, and the influence of TTV infection on the HCV response to interferon alfa therapy were studied. A total of 100 asymptomatic hepatitis B surface antigen carriers, 220 patients with HBV-related chronic liver diseases, and 110 patients with chronic hepatitis C treated with interferon alfa (3 million units subcutaneously three times a week for 24 weeks) were enrolled. Serum HCV RNA and serum TTV DNA were detected by the polymerase chain reaction (PCR). Serum HBV DNA and serum HCV RNA level were quantified by branched DNA assays. Infection with TTV was detected in 21.5% of HBV carriers and 37% of HCV carriers. TTV infection had little effect on the clinicopathological course of chronic HBV infection. In chronic hepatitis C, clinical features, histological severity, serum HCV RNA levels, and the response to interferon alfa therapy did not differ between those with and without TTV infection. The loss of serum TTV DNA did not correlate with the biochemical response as did in the loss of serum HCV RNA. In conclusion, TTV infection is found frequently in patients with chronic hepatitis B or C in Taiwan; however, coinfection with TTV does not affect the clinicopathological course of chronic hepatitis B or C and the response to interferon alfa therapy.     

Serum levels of soluble Tac peptide in acute and chronic hepatitis B virus infection

Serum-soluble Tac peptide was measured by an enzyme-linked immunosorbent assay in 12 patients with acute type B hepatitis, 33 patients with chronic type B hepatitis, and 15 age- and sex-matched controls. All 12 patients with acute type B hepatitis had elevated levels of soluble Tac peptide with a mean (+/- SD) of 1527 +/- 432 U/ml, significantly higher than that of normal controls (264 +/- 74 U/ml) or patients with chronic type B hepatitis (646 +/- 399 U/ml). Serial follow-up showed that serum levels of soluble Tac peptide tended to return to normal 2-4 months after onset of acute hepatitis along with the normalization of alanine aminotransferase and seroconversion of hepatitis B surface antigen (HBsAg) to anti-HBs. Patients with chronic type B hepatitis also had significantly higher levels of soluble Tac peptide than normal controls, although only 63.6% (21/33) of them had a level greater than the upper limit of normal. Serum levels of soluble Tac peptide in patients with chronic type B hepatitis varied considerably with the inflammatity in liver. The hepatitis B e antigen (HBeAg)-positive patients with chronic active liver disease had significantly higher levels of soluble Tac peptide (928 +/- 424 U/ml) than HBeAg-positive (412 +/- 146 U/ml) or anti-HBe-positive (424 +/- 175 U/ml) patients with chronic persistent hepatitis or minimal histological change. In addition, there was a significant positive correlation between serum levels of soluble Tac peptide and alanine aminotransferase. These findings suggested that activation of T cells might play an important role in the pathogenesis of acute and chronic type B hepatitis. Assay of serum-soluble Tac peptide might provide a simple and useful means to better understand the immune mechanisms of acute and chronic hepatitis B virus infection.     

Platelet-associated IgG in hepatitis and cirrhosis

Increasing evidence is accumulating which indicates that immunological abnormalities contribute to the development of liver disease and its signs and symptoms. Platelet-associated IgG (PAIgG) levels were quantified in 42 patients with biopsy-proven liver disease of various etiologies to determine the relationship of thrombocytopenia to immunologic abnormalities in these disorders. Five of six nonthrombocytopenic patients with acute viral hepatitis B had elevated PAIgG. Six of ten patients with chronic active hepatitis had elevated PAIgG and thrombocytopenia. In contrast, only one of six patients with chronic persistent hepatitis had elevated PAIgG. Nine of ten patients with alcoholic hepatitis had elevated PAIgG; seven of the nine were thrombocytopenic. Seven of ten alcoholic patients with cirrhosis had elevated PAIgG; six of seven were thrombocytopenic. Thus the increase in PAIgG may be present without thrombocytopenia in acute liver injury, while patients with chronic persistent hepatitis do not usually exhibit this abnormality. Severe chronic active liver disease is accompanied by thrombocytopenia and an increase in PAIgG levels.