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Interleukin-32 (IL-32), a multiple pro-inflammatory cytokine, played a vital role in immune-related diseases and infectious diseases. The promoter region of IL-32, which showed functional polymorphism, could regulate IL-32 expression. Although IL-32 rs28372698 polymorphism was related to a lot of inflammatory diseases, the association of IL-32 rs28372698 polymorphism with hepatic flare of chronic HBV infection was not been reported. In the present study, IL-32 rs28372698 polymorphism was genotyped in 104 chronic HBV carriers and 151 active chronic hepatitis B (CHB) patients. The frequency of IL-32 T/T genotype in patients with active CHB was significantly higher than that in chronic HBV carriers. Furthermore, the frequency of the T allele at IL-32 rs28372698 in active CHB patients was also higher than that in chronic HBV carriers. Serum level of IL-32 in active CHB patients was higher than that in chronic HBV carriers. Our results imply that IL-32 T/T polymorphism might be associated with hepatic flare of chronic HBV infection. This article is protected by copyright. All rights reserved.

Background Chronic HBV infection presents weak or no virus-specific T-cell responses, implying to an exhausted phenotype, characterized by overexpression of several inhibitory receptors. In the present study, it was aimed to characterize the panel of inhibitory molecules on the CD8+ T cells in patients with active chronic HBV infection. Methods In this study, 31 active and 32 inactive individuals with chronic HBV infection were recruited. Peripheral blood mononuclear cells were isolated and a multicolor flow cytometry was applied to evaluate the surface inhibitory molecules of TIM3, PD-1, and CD39. Results CD8+ T cells expressing TIM3 were significantly higher in cases with active chronic HBV infection compared to inactive chronic HBV group (8.43 ± 1.4 vs. 5.15 ± 1.43; P Conclusion It appears that CD8+ TIM3+ T cells are the major exhausted phenotype of T cells during the active state of HBV infection.

Although available therapies can effectively inhibit hepatitis B virus (HBV) replication in patients with active chronic hepatitis B (CHB) infection, therapeutic efficacy is limited because of potential drug resistance, and an inability to mediate viral clearance and to rectify immune impairment in CHB patients. This review will summarize the state-of-the-art for anti-HBV drugs and focus on potential drugs and targets under development and evaluation.New developing drugs are evaluated for their antiviral effects in the areas of interference with the viral replication cycle, elimination of covalently closed circular DNA, modulation of host immunity and identification of the La protein and its regulator casein kinase as possible targets for the development of anti-HBV therapies.These novel compounds and targets have showed great inhibitory effects on HBV replication in vitro and in animal models. Several novel therapies are promising in early clinical trials. Potentially, combination of newly developing and current antiviral drugs may cure CHB in the clinic.

The progression of chronic hepatitis B (CHB) is associated with single-nucleotide polymorphisms (SNPs). In this study, we demonstrated the association between immune-related SNPs and delayed spontaneous HBeAg seroconversion in immune-active CHB patients. In addition, we investigated the impact of delayed spontaneous HBeAg seroconversion-related SNPs on HBeAg seroconversion within 3 years during antiviral treatment. We enrolled 332 CHB patients and genotyped 124 SNPs associated with HBV-infected clinical outcomes, including 32 interleukin-related genes, 62 HLA genes, 9 CD marker genes, 7 NK cell receptor genes, and 14 other genes, using ABI OpenArray as a platform. Comparing the immune-active CHB patients with delayed spontaneous HBeAg seroconversion (persistent HBeAg seropositivity, older than 40 years) to those with early inefficient HBeAg seroconversion (HBeAg seroconversion with high viremia, younger than 40 years), logistic analysis revealed that rs3820998 (TANK), rs2621377 (HLA-DOB), rs3130215 (HLA-DPB2), rs2255336 (KLRK1), and rs11614913 (MIR-196A2) were significantly associated with delayed spontaneous HBeAg seroconversion. Using multivariate analysis, we determined that high serum HBV DNA levels (OR = 1.66, 95% CI = 1.33–2.08), rs3820998 (CA, OR = 3.37, 95% CI = 1.24–9.12), rs2621377 (TC, OR = 4.96, 95% CI = 1.85–13.3), rs2255336 (TT, OR = 0.09, 95% CI = 0.01–0.86), and rs11614913 (TT, OR = 2.53, 95% CI = 1.05–6.11) were five independent risk factors for delayed spontaneous HBeAg seroconversion. After patients received nucleos(t)ide analogue treatment, rs3820998 heterozygous CA variant conversely became the only independent favorable factor for treatment-induced HBeAg seroconversion within 3 years (OR = 0.21, 95% CI = 0.06–0.78). These results indicate that distinct immune-related SNPs play a vital role in regulating HBeAg status in immune-active CHB patients with or without antiviral treatment.

The aim of this erratum is to clearly state the individual author's contribution which was erroneously mentioned as "Tianyu He, Yuqing Bai, Wei Yi, and Jidong Jia contributed equally to this work."

Background Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment. Aim To assess the efficacy of mycophenolate mofetil as second line treatment after AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes. Methods Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients, with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-nonresponse and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression. Results Forty-five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse group and 63% and 25% of the AZA-intolerance group (N.S.); 33% had side effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA-nonresponse group (P

A retrospective study of 29 patients with active chronic hepatitis treated over 38 different periods with azathioprine was carried out with particular attention to the effects of high (above 1.5 mg/kg) and low (below 1.5 mg/kg) doses. Early side-effects (within 4 weeks) occurred in 7 of 10 patients using above 2 mg/kg and in 6 of 11 patients on 1.5–2 mg/kg azathioprine. Of the patients treated with the low azathioprine dose only 4 of 17 had early side-effects. Eighteen patients were treated up to 2 years, among whom 2 of 12 on low dose and 3 of 6 on high dose had late side-effects. Of 9 patients treated for more than 2 years (average 2 3/4 years) on a low azathioprine dose late side-effects occurred in 2. The clinical course of the liver disease in these patients showed that 5 of 8 treated on high dose were unchanged or improved compared to 15 of the 21 on the low dose. Serum γ-globulin and SGPT decreased significantly in the patients on the low azathioprine dose concomitantly with a non-significant increase in serum albumin. These changes were not less marked on low than on high dose. Our experiences thus favor doses below 1.5 mg/kg when azathioprine is used in active chronic hepatitis.

Analysis of the enzyme pattern in 34 patients with liver histology indicating porto-periportal inflammation showed two statistically well differentiated groups: 20 patients with clinical suspicion of early chronic active hepatitis and 14 patients with suspected chronic destructive cholangitis. The course of the disease and the response to immunosuppressive treatment were quite different in the two groups. For differentiation of the early stages of chronic active hepatitis and chronic destructive cholangitis correct interpretation of the enzyme pattern is of great importance. It is also relevant for the decision to use long term immunosuppressive treatment.

Las manifestaciones clínicas de la hepatitis viral tipo B tienen un amplio abanico de presentaciones, dependiendo de muchos factores, algunos desconocidos y otros, perfectamente identificables: subtipo del virus, características genéticas del huésped, estado inmunológico en el momento de la inoculación, carga viral y vía de entrada de dicha inoculación, entre los más importantes. La clínica de la hepatitis viral por virus B tanto aguda como crónica puede ser desde síntomas inespecíficos sin ictericia, a un cuadro severo con ictericia y encefalopatía. La hepatitis B que se manifiesta por primera vez, se clasifica como hepatitis aguda y hepatitis fulminante. La hepatitis B no aguda se clasifica en hepatitis subaguda o prolongada, hepatitis crónica persistente y hepatitis crónica activa. The clinical manifestations of hepatitis B has a wide spectrum of presentations that depend on many factors, some are unknown and others very well identifiable: virus subtypes, genetic characteristics of the host, immunological status at the time of inoculation, viral burden, and entrance pathway of such inoculation, among others. The clinical case of acute and chronic hepatitis type B, can show either unspecific symptoms without jaundice or a severe case of jaundice and encephalopathy. The hepatitis B that manifests for the first time is classified as acute hepatitis and fulminant.

The authors wish to add the following grant support to the funding information: "National Natural Science Foundation of China (No. 30771912)".

Item does not contain fulltext BACKGROUND: Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment. AIM: To assess the efficacy of mycophenolate mofetil as second line treatment after AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes. METHODS: Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients, with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-nonresponse and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression. RESULTS: Forty-five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse group and 63% and 25% of the AZA-intolerance group (N.S.); 33% had side effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA-nonresponse group (P < 0.001). CONCLUSIONS: Mycophenolate mofetil induced response or remission in a majority of patients with autoimmune hepatitis and azathioprine-intolerance and with overlap syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune hepatitis with azathioprine nonresponse mycophenolate mofetil is less often effective.

Partial splenic embolization (PSE) was introduced as an alternative to splenectomy to avoid the risk of post-splenectomy sepsis and to reduce the number of situations in which surgery would be dangerous or not feasible [5]. PSE is an accepted therapy for the treatment of secondary hypersplenism in various disorders, including oesophageal variceal haemorrhage [3], thalassaemia major [5], portal hypertension [1], painful splenomegaly [2], Gaucher disease [9], hypersplenism in cirrhosis [5], and prior to myelosuppressive treatment in hepatocarcinoma and active chronic hepatitis [2, 3].

Tonder, M, Nordoy, A. & Elgjo, K. Sulfonamide-induced chronic liver disease. Scand. J. Gastroent. 1974, 9, 93–96.A case with development of a clinical picture of active chronic hepatitis and biopsy...

肝炎の慢性化に関し最近注目されている機序の一つは,肝細胞膜抗原に対する抗体依存性細胞障害作用(ADCC)である.著者らはこの前提となる抗肝細胞膜抗体(AHMA)の詳細を検討するため,Meyerらの肝細胞膜由来の特異抗原で家兎を免疫し,得られたAHMAの臓器特異性を明らかにした.またこの抗体を対照抗体として肝疾患69例につき遊離ラット肝細胞を用い膜蛍光抗体法で血中のAHMAを検索した.慢性活動性肝炎37例中17例,ルポイド肝炎11例中6例で陽性成績を得たが,陽性頻度は血中HBsAgとは無関係であった.しかしその他の肝疾患ではAHMAは全例陰性であった.また肝細胞膜と反応する抗体にはlinear patternおよびgranularpatternを示す2種類があり,前者はAHMA,後者は肝細胞膜上の収縮性蛋白に対する抗体と考えられた.したがって慢性活動性肝炎やルポイド肝炎では,AHMAを介するADCCによる細胞障害の持続がその病因に大きな要因を占めるものと推定された.

Ten cases of active chronic hepatitis in Sri Lanka patients are presented. Their clinical and biochemical findings were in no way different from previously published cases. Two followed an attack of v

SUMMARY In thirty-four patients with porphyria cutanea tarda treated with small doses of chloroquine, liver biopsies were performed before and after treatment. In seventeen cases (50%) the morphological patterns before treatment corresponded to unstabilized fibrosis, while in eleven (32.4%) there were non-specific changes in the form of focal fatty change, haemosiderosis, and a mild fibrosis of the portal tracts. Active chronic hepatitis was found in three patients (8.8%), and cirrhosis also in three cases. Although in all patients a clinical and metabolic remission of porphyria cutanea tarda occurred during treatment, the morphological patterns in the liver parenchyma remained on the whole unchanged. Only in five cases was there an increase in the inflammatory changes, while in two patients these changes tended to disappear.

SummaryTracer quantities of colloidal 198Au were used to estimate the hepatic blood flow in normal children and in children with active or progressive chronic hepatitis and also to obtain scintigrams of the liver.In active chronic hepatitis a significant decrease in HBF values was observed, suggesting that the method may be used as a diagnostic criterion which is superior to hepatic scintigraphy.In progressive chronic hepatitis HBF values even lower than those in active hepatitis were observed. Together with more characteristic clinical findings and abnormal results of biochemical function tests, they underline the value of the method in estimating the severity and the evolution of the disease.

A case of chronic hepatitis with ultrastructural changes resembling alterations usually occurring in Wilson's disease is presented in an elderly man. At the time of the diagnosis, the patient did not show clinical and laboratory data consistent with the diagnosis of Wilson's disease. Subsequently, the patient developed neurologic symptoms similar to that resulting from hepatolenticular degeneration. The possibility that such lesions are caused by an abnormal copper metabolism in consequence of acquired liver disease is considered.

The first observation of “in vivo activated lymphocytes” [IVAL] in cases of active chronic hepatitis is reported. Lymphocytes with an elevated metabolism were observed in about 30% of patients with this disease. The persistence of such active lymphocytes was associated with a bad prognosis. The role of these cells as mediators of specific immunity comparable to the graft rejection is discussed.

Summary Changes characteristic of focal postneerotic cirrhosis and of active chronic hepatitis were found in high incidence among 17 cases of advanced hepatic schistosomiasis. Focal cirrhotic changes may have been induced by repeated ischemic insults tolerated f or a long time, and by "piecemeal necrosis", possibly an expression of a chronic immunologic response, either to schistosomal antigens or to liver cell breakdown products, or to both.

True arthritis is very much less common than arthralgia in patients suffering from active chronic hepatitis and only scanty information is available about the joint changes in this disease. We report here the case of a young woman with active chronic hepatitis complicated by a painless, erosive small joint arthropathy.

It is believed that active chronic hepatitis in most cases is a sequela of liver damage caused initially by the hepatitis virus and that this sequela occurs in persons with a genetically based anomaly of immune tolerance. The auto-immune response, once established, tends to be perpetuated because self-reactive immunocytes continue to be stimulated by antigens released from liver cells damaged initially by nonimmune agents but damaged thereafter by the autoimmune reaction itself.

Another member of a previously described kindred is reported in whom active chronic hepatitis with cirrhosis led to hepatocellular carcinoma with pulmonary metastases. The patient and his relatives did not show serological evidence of Australia antigen.

1. The metabolic and hormonal responses to intravenous glucose (0·5 g/kg body wt.) were studied in ten normal subjects and thirteen patients with active chronic hepatitis. Untreated patients showed a decreased initial insulin response and glucose intolerance (KG, 0·89 ± 0·10%/min compared with 2·34 ± 0·24%/min), together with a paradoxical rise in growth hormone. 2. Fasting blood lactate and pyruvate were normal but both metabolites showed a diminished rise after glucose. The rate of rise of lactate was directly related to initial insulin secretion in both hepatitis subjects and controls. 3. Fasting blood ketone bodies, blood glycerol, plasma triglycerides and free fatty acids were all significantly elevated in the patient group. Results were similar to those found in mild diabetes mellitus. 4. In two patients with a more severe cirrhosis fasting values of serum insulin, growth hormone, blood lactate, pyruvate and glycerol were raised. 5. After corticosteroid therapy hyperinsulinism was found together with a return towards normal of glucose tolerance (KG, 1·49 + 0·10%/min), ketone bodies, free fatty acids and triglycerides; blood glycerol remained elevated and lactate response to glucose was excessive. 6. It is suggested that in active chronic hepatitis there might be pancreatic dysfunction on an autoimmune basis.

Summary: Humoral immunity has been investigated in 39 first-degree and 12 second-degree relatives of patients with ACH. A significant increase was shown in the number of abnormal immunological findings, especially hyperglobulinaemia and the presence of tissue antibodies. It is considered that these results support the hypothesis that a genetic factor is involved in the pathogenesis of ACH.

Summary: Immunological changes and liver disease associated with alpha-1 -antitrypsin deficiency. A female aged 60 years with heterozygous alpha-1-antitrypsin deficiency developed a progressive and ultimately fatal liver disease with the clinical, biochemical, immunological and histological characteristics of active chronic hepatitis. It is suggested that the hepatic disease of A-AT deficiency be included among the types of liver disease which may initiate a progressive immuno-pathic response.