Soluble interleukin 2 receptors in autoimmune chronic active hepatitis.

Children with uncontrolled autoimmune chronic active hepatitis have increased numbers of activated T lymphocytes expressing interleukin 2 receptors (IL2R). A soluble form of IL2R has recently been described whose proposed role is to downregulate T cell activation by competing for interleukin 2. We investigated whether a deficiency of soluble IL2R could account for the high concentrations of IL2R positive T lymphocytes in autoimmune chronic active hepatitis. Soluble IL2R was measured by enzyme-linked immunosorbent assay in the serum of 16 children with autoimmune chronic active hepatitis, eight with chronic liver disease due to hepatitis B virus infection, seven with Wilson's disease, nine with alpha 1 antitrypsin deficiency, and 15 healthy age matched controls. Soluble IL2R concentration was significantly higher in patients with autoimmune chronic active hepatitis than in healthy controls (mean (SEM) 475 (75) U/ml, 145 (8) U/ml respectively, p less than 0.01). Eleven patients who had active disease had significantly higher soluble IL2R concentrations (590 (89) U/ml) than the five cases with inactive disease (220 (36) U/ml, p less than 0.01). No difference was found between the controls and the patients with chronic liver disease due to hepatitis B infection, Wilson's disease, and alpha 1 antitrypsin deficiency. Percentages and absolute numbers of surface IL2R positive T cells as detected by immunofluorescence were significantly higher in the patients with autoimmune chronic active hepatitis (11.8% (1); 274/microliters (31)) than in controls (0.2% (0.1); 5/microliters (2), p less than 0.001), the highest values being found in those with uncontrolled disease. A significantly positive correlation was observed between concentrations of soluble IL2R and the percentage of T cells expressing IL2 receptors (r=0.67, p<0.001). These results indicate that the high levels of IL2R positive T lymphocytes characteristic of autoimmune chronic active hepatitis are not due to a deficiency of soluble IL2 receptors.     

Soluble interleukin 2 receptor (sIL-2R) in chronic polyarthritis

An ELISA was used to measure soluble interleukin-2 receptor (sIL-2R) in the sera and synovial fluid (SF) of patients with rheumatoid arthritis (RA). Patients with seropositive, as well as seronegative RA had raised levels of sIL-2R in serum and SF compared to patients with osteoarthritis and sex-age matched healthy subjects. According to literature, sIL-2R levels in the sera of RA-patients may be a useful marker of disease activity. Increased sIL-2R levels in SF show new aspects in pathophysiology of RA.     

Serial observation of lymphocyte subpopulations and interleukin 2 production of T cells from patients with acute viral hepatitis and chronic active hepatitis

T cell subpopulations and interleukin 2 (IL-2) production of T cells in peripheral blood from patients with acute viral hepatitis (AVH) and chronic active hepatitis (CAH) were studied to elucidate the change of T cells functions during the exacerbation of viral hepatitis. The ratio of the number of CD4-positive cells to CD8-positive cells (CD:CD8 ratio) was increased in many patients with AVH. During exacerbation of CAH, the CD4:CD8 ratio was higher than that during remission (p less than 0.01), due to a decrease in the number of CD8-positive cells. IL2 production of T cells in AVH and CAH with bridging necrosis was higher than that of T cells in normal controls (p less than 0.01, p less than 0.05, respectively). T cells from patients with CAH produced more IL2 during exacerbation than during remission (p less than 0.01). IL2 production of T cells and the CD4:CD8 ratio (p less than 0.005, p less than 0.01). The change in T cell subpopulations in AVH and during exacerbation of CAH was found to induce an immunological condition, in which T cells easily produce IL2, which induces a proliferation of cytotoxic T cells.     

Paraproteins with antibody activity in acute viral hepatitis and chronic autoimmune liver diseases

Of 27 patients with liver disease and cryoglobulinaemia 18 proved to have paraproteins. Six of these monoclonal immunoglobulins were shown to have antibody activity, directed to human gamma globulin, alpha₁-fetoprotein, smooth muscle, and mitochondria.

Eight of the patients suffered from acute viral hepatitis, five of whom were HB Ag positive; in all these cases the monoclonal spikes were transient and their antibody activities were directed against IgG in two cases and alpha₁-fetoprotein in one.

Seven of the patients had active chronic hepatitis and in these the paraproteinaemia persisted, though remaining quantitatively unchanged over several years. One of them had a cryoprecipitable monoclonal smooth muscle antibody. Three patients had primary biliary cirrhosis and in two of them monoclonal IgM mitochondrial antibodies were demonstrated.

In three out of the 18 cases there was a double M-component.

Since these monoclonal antibodies are directed to autoantigens not unlike the polyclonal ones usually seen in autoimmune hepatic diseases, it is suggested that the factor which triggers the uncontrolled plasma cell proliferation to produce paraproteins must meet cells from an already expanding clone.

     

Increased serum soluble interleukin 2 receptor levels in patients with viral liver diseases

Soluble interleukin 2 receptors (sIL 2R) in the sera of patients with viral liver diseases were quantified with a solid-phase enzyme immunoassay using two monoclonal antibodies against the receptors. The sIL 2R levels in patients with acute hepatitis, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were significantly higher than those in control subjects. In acute hepatitis patients, the high levels of sIL 2R observed during the florid stage returned to normal during remission. Levels in patients with chronic active hepatitis were significantly higher than in those with chronic persistent and lobular hepatitis, and levels observed during the exacerbation phase of chronic hepatitis were higher than they were during remission. Thus, in chronic hepatitis, sIL 2R levels increased in proportion to the inflammatory activity, and correlated well with serum transaminase (glutamic oxaloacetic transaminase: SGOT, glutamic pyruvic transaminase: SGPT) activities, but not with blood urea nitrogen or creatinine concentrations. In patients with a high degree of focal and piecemeal necrosis, serum sIL 2R levels increased further during recombinant interleukin 2 therapy. In post-hepatitic liver cirrhosis and hepatocellular carcinoma, sIL 2R levels correlated with serum cholinesterase and creatinine concentrations, but not with transaminase activities. Measurement of serum sIL 2R levels in patients with liver disease but without renal injury, may help in the diagnosis of inflammation in hepatitis, a process in which interleukin 2 may participate.     

Pregnancy-associated acute liver disease and acute viral hepatitis: differentiation, course and outcome

BACKGROUND/AIMS: Pregnant women with acute viral hepatitis (VH) and those with pregnancy associated acute liver disease (PAALD) including acute fatty liver disease of pregnancy, hemolysis elevated liver enzyme and low platelet syndrome present with similar clinical features and liver tests abnormalities. Accurate differentiation between the two groups is critical to expedite early delivery in the latter and prevent progressive liver damage. There is scant data in the literature to differentiate between PAALD and VH. METHODS: We studied the clinical variables, hematological, biochemical and viral serological tests of 87 consecutive pregnant patients with jaundice from 2000 to 2003. RESULTS: There were 46 and 41 patients in PAALD and VH group, respectively. Two-thirds in VH group were due to hepatitis E. Univariate analysis identified hypertension, encephalopathy, oliguria, ascites, serum creatinine, and low platelets as significantly more common in the PAALD group. Multivariate analysis and recursive partitioning identified hypertension and ascites as predictors of PAALD with excellent predictive ability and c value of 0.92. Mortality was 41% in PAALD and 7.5% in VH. Increased bilirubin and oliguria were predictors of mortality in PAALD. CONCLUSIONS: Presence of ascites and hypertension differentiates PAALD from VH and should prompt early delivery. Mortality due to hepatitis E is low.     

Interleukin-6 production by peripheral blood monocytes in patients with chronic liver disease and acute viral hepatitis.

The in vitro production of the acute-phase mediator interleukin-6 by peripheral blood monocytes derived from patients with various liver diseases was studied. Compared with healthy controls (n = 45; 860 +/- 92 U/ml, mean +/- SEM), monocytes from patients with chronic hepatitis B produced significantly lower amounts of interleukin-6 (n = 14; 424 +/- 126 U/ml) after stimulation with lipopolysaccharide (p = 0.02), whereas monocytes from patients with chronic hepatitis non-A, non-B secreted normal amounts of interleukin-6 (n = 13; 672 +/- 151 U/ml; n.s.). In contrast, monocytes of patients suffering from alcoholic liver cirrhosis (n = 22; 1310 +/- 153 U/ml) or primary biliary cirrhosis (n = 6; 1450 +/- 186 U/ml) produced higher amounts of interleukin-6 than healthy control individuals (p = 0.03, respectively). Lipopolysaccharide-stimulated monocytes derived from patients with acute hepatitis A, B and non-A, non-B showed an interleukin-6 production not different from that seen in healthy control individuals and did not experience a discernible change during the course of the acute disease. These results suggest that the production of the acute-phase mediator interleukin-6 varies in chronic liver disease in accordance with various etiologies with a reduced lipopolysaccharide-inducible interleukin-6 response in chronic hepatitis B and an enhanced response in alcoholic liver cirrhosis and primary biliary cirrhosis.     

Treatment of acute and chronic viral hepatitis

Over the 12 years since the first introduction of interferon for the treatment of chronic hepatitis B, progress has apparently been slow. Nevertheless, it now appears that at least one third of chronic hepatitis virus carriers, particularly those with more severe disease, and a similar, perhaps greater, proportion of those with chronic parenteral non-A, non-B hepatitis, can be successfully treated with alpha-interferon. In the not too distant future, controlled trials of alpha-interferons in these situations will be complete and they will be a yardstick by which other future therapies can be judged. Already a number of trials are in progress to determine which agents might, in addition to interferon, augment the response rates. The situation clinically is analogous to that for tuberculosis in the 1950s and for cancer chemotherapy only a decade or so ago. The prospects of prevention of the progression to cirrhosis, and perhaps in the long term reduction in the incidence of hepatocellular carcinoma, are exciting, and with the introduction of a number of new cytokines available through recombinant technology, each with novel antiviral activities, the future prospects are exciting indeed.     

Effect of pregnancy on pre-existing liver disease: chronic viral hepatitis

Women with viral chronic hepatitis generally do quite well during pregnancy, providing that they have not progressed to decompensated cirrhosis. As a general rule, a stable liver equals a safe pregnancy. However, concern is about how pre-existing chronic liver disease may affect the pregnancy and the unborn baby. This review plans to answer some key questions regarding this issue in order to provide to healthcare professionals updated information of the current knowledge in this field. Besides, a synopsis of the following subject matters are reviewed, for instance, the main risk factors associated with vertical transmission of HBV and HCV in pregnant women chronically infected, the influence of pregnancy on HBV and HCV viral load and the effect of pregnancy on the clinical course of chronic hepatitis. Lastly, it is included a list of recommendations to decrease vertical transmission rates of chronic viral hepatitis as well as some information for the reproduction team.     

Chronic liver disease after acute non-A, non-B viral hepatitis.

We have analyzed the frequency of chronicity and its distribution according to epidemiologic background following acute non-A, non-B hepatitis. Eighteen of 45 cases (40%) developed chronic liver disease. The incidence of chronicity was significantly higher following transfusion and among drug addicts (54% and 58%) than among patients without obvious source of infection (20%). Chronic active hepatitis developed in 4 of 13 patients (31%) with posttransfusion hepatitis. This lesion was not observed among the addicts or the patients without obvious source for the acute hepatitis.     

急性病毒性心肌炎患者可溶性白细胞介素-2受体和肿瘤坏死因子

目的 :了解病毒性心肌炎 (VM)患者血清可溶性白细胞介素 - 2受体 (s IL- 2 R)和肿瘤坏死因子 (TNF)的改变 ,并探讨其发病机制。方法 :检测 30例 VM患者血清 s IL- 2 R和 TNF水平及与临床关系。结果 :VM患者血清 s IL- 2 R和 TNF水平明显增高。VM患者中 s IL- 2 R水平高者 ,临床病情亦较重。结论 :s IL- 2 R和 TNF在 VM发病机制中可能起作用 ,其血清学检测有助于临床病情分析。     

Liver transplantation for acute and chronic viral hepatitis

Summary. Hepatotrophic viruses are responsible for a substantial proportion of cases of both end-stage chronic liver disease and of acute liver failure which are treated by liver transplantation. We review here current practice in transplantation for viral-induced liver disease addressing, in particular, the selection of patients for transplantation and the increasingly recognized problem of recurrent disease in liver grafts.     

自身免疫性肝病与慢性乙型病毒性肝病超声影像对比分析

探讨自身免疫性肝病与慢性乙型肝病的超声表现的异同点,通过单因素、非条件Logistic回归测得AIH与CHB在性别、肝脏大小方面,存在明显差别(P<0.001);中晚期PBC与乙肝肝硬化超声表现在肝脏大小、肝脏回声(P<0.001、P=0.047)方面存在明显差异。AIH与CHB,PBC与乙肝肝硬化超声表现不同。     

代谢综合征、非酒精性脂肪性肝病与慢性乙型病毒性肝炎

非酒精性脂肪性肝病(nonalcoholic falty liver disease,NAFLD)是一种胰岛素抵抗和遗传易感性相关的代谢应激性肝损伤,为肥胖和代谢综合征累及肝脏的病理表现.肥胖和代谢综合征除可导致NAFLD外,还可促进慢性丙型病毒性肝炎(丙肝)、慢性乙型病毒性肝炎(乙肝)等其他肝病的进展并影响其疗效.本文主要综述代谢综合征、NAFLD和慢性乙肝之间关系及其机制.     

Serum levels of soluble interleukin-2 receptors in acute and chronic viral hepatitis

To analyze interleukin-2-dependent immunoregulatory function in hepatitis B virus infection and in other forms of viral hepatitis, levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked assay in sera from patients with acute and chronic viral hepatitis of different etiology. Increased sIL-2R levels were detected in the early phase of acute hepatitis type A and type B, but not during acute non-A, non-B hepatitis. Among 46 patients with chronic hepatitis B virus infection, levels of sIL-2R were significantly increased only in cases with chronic active hepatitis, while they were about normal in chronic persistent hepatitis or in healthy carriers of the infection. These differences were independent of virus replication, being maintained when patients were stratified according to HB_eAg/anti-HB_e status and to serum HBV-DNA. Nine patients with chronic active hepatitis type B and high sIL-2R levels at presentation were followed prospectively for two to eight years, and in HB_eAg -positive patients, the behavior of receptor levels closely paralleled disease activity. These results, which may reflect increased shedding of IL-2R by activated T lymphocytes in patients with active destruction of HBV infected hepatocytes, indicate the usefulness and potential prognostic importance of serum slL-2R determination in patients with chronic viral hepatitis. Patients with chronic non-A, non-B hepatitis had much lower sIL-2R levels, although their liver disease was similar to hepatitis B cases, suggesting that different pathogenetic mechanisms operate in these patients.     

Superimposed acute hepatitis E infection in patients with chronic liver disease.

BACKGROUND: The natural history of infection with hepatitis E virus (HEV) in patients with chronic liver disease (CLD) is not well described. Our study aims to document the presentation, course and outcome of HEV superinfection in patients with CLD. METHODS: Over an 18-month period, ten patients with CLD were diagnosed to have HEV superinfection by detection of anti-HEV IgM antibodies in a setting of acute worsening. These patients were tested for HBsAg, IgM anti-HBc, anti-hepatitis C virus antibodies and IgM anti-hepatitis A virus antibodies, and were followed-up. RESULTS: The etiology of underlying CLD in the 10 patients (9 men; mean [SD] age 42.4 [10.3] years) was alcohol in five patients, hepatitis B in two, hepatitis C in one and cryptogenic in two. Seven patients presented for the first time with recent-onset liver decompensation (median duration 27 days, range 7-45). All 10 had ascites and 7 had hepatic encephalopathy. Four patients developed renal failure during the course of illness. The median (range) bilirubin, ALT and albumin levels at presentation were 18.6 (4.9-32.6) mg/dL, 105 (28-6610) IU/L and 32 (29-41) g/L, respectively. At 8 weeks, only one patient had normalization of serum bilirubin or ALT levels. Three patients (30%) died, including two of renal failure and one of massive upper GI bleed. CONCLUSIONS: Superinfection with HEV in patients with CLD causes severe liver decompensation, which is frequently complicated with hepatic encephalopathy and renal failure. Acute hepatitis E in these patients has a protracted course with high morbidity and mortality.