Inflammatory Liver Histology Research Articles

Clinical management of autoimmune hepatitis.

Autoimmune hepatitis is a rare and chronic liver disease that is characterised by increased serum transaminases and immunoglobulin G, inflammatory liver histology and presence of circulating autoantibodies. An autoimmune hepatitis diagnosis justifies life-long treatment in most patients in order to prevent development of cirrhosis and end-stage liver disease. The cornerstone of treatment is steroid induction therapy followed by maintenance therapy with azathioprine, which is effective in most cases. For patients who do not respond to standard treatment, second-line treatment with other immunosuppressants can be effective. Treatment should be aimed at biochemical remission of the disease, which is defined as normalization of transaminases and immunoglobulin G. Patients should be monitored intensively during the first months of treatment in order to monitor side-effects, assess symptoms and individualise treatment. Specialist consultation should be sought in difficult-to-treat patients. Future studies and networking initiatives should result in optimization of current treatment strategies in autoimmune hepatitis.

Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement.

Paediatric autoimmune liver disease is characterized by inflammatory liver histology, circulating autoantibodies, and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis, and de novo AIH after liver transplantation. Two types of pediatric AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibodies (AIH-2).Pertinent issues addressing the diagnosis, treatment, and long-term follow-up were formulated by a core group of ESPGHAN members. They have commissioned the first authors with execution of this project. Initially, they have performed a systematic literature search on MEDLINE, ResearchGate, and Mendeley databases during the last 30 years and produced a document focusing on prospective and retrospective studies in children. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique.

Parameters of ventricular repolarization in patients with autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a liver disorder that affects both children and adults. It is characterized by inflammatory liver histology, elevated transaminase level, circulating nonorgan-specific autoantibodies, and increased level of immunoglobulin G in the absence of known etiology. Ventricular repolarization has been evaluated using T wave and QT interval measurements in patients with hepatic cirrhosis. Ventricular repolarization may be defined using QT interval, QT dispersion, and T wave measurements. Recently, it has been demonstrated that peak and end of the T wave (Tp-e) interval, Tp-e/QT, and Tp-e/corrected QT interval (QTc) ratios can be novel indicators for prediction of ventricular arrhythmias and mortality. In this study, an investigation of ventricular repolarization using Tp-e interval and Tp-e/QT ratio in patients with AIH was performed. Total of 31 patients with AIH and 31 controls were enrolled in the present study. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were measured on 12-lead electrocardiogram. QT interval (378.9±41.4 vs. 350.0±22.7; p=0.001), QTc interval (396.8±46.7 vs. 367.3±34.9; p=0.039), Tp-e interval (68.2±12.3 vs. 42.5±6.8; p<0.001), Tp-e/QT ratio (0.18±0.02 vs. 0.12±0.01; p<0.001) and Tp-e/QTc ratio (0.17±0.02 vs. 0.11±0.01; p<0.001) were significantly higher in patients with AIH than control patients. The results of the present study indicated that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were greater in patients with AIH.

Double Trouble Bubble: Autoimmune Overlap Syndrome Causing Portal Gastropathy, with Review of Current Literature

A 57 year old female with a past medical history of cirrhosis and high elevation of SM-Ab titer, elevated actin IGG, and anti-mitochondrial antibody significantly increased presented to the emergency department with hematemasis and bright red blood per rectum. After admission to the ICU she received 2 units packed red blood cells and was started on intravenous antibiotics, protonix, and octreotide. An esophagogastroduodenoscopy revealed esophageal and gastric varices extending into the stomach with gastropathy, not amenable to banding. A Trans-Jugular Intrahepatic Portosystemic Shunt (TIPS) was performed after resolution of bleeding. The patient was discharged with follow up for transplant evaluation while being treated with ursodiol, rifaximin, lactulose, pantoprazole, and diuretics. Autoimmune hepatitis (AIH) is a liver disease characterized by inflammatory liver histology, elevated transaminase levels, circulating autoantibodies, and increased levels of immunoglobulin G in the absence of a known etiology. Two types of AIH are recognized according to seropositivity: smooth muscle antibody and/or antinuclear antibody (AIH type 1) and antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 (AIH type 2). There is mounting evidence that genetic susceptibility, molecular mimicry, and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4 T-cells. The histological findings of lymphocytes, plasma cells, and macrophages is non-specific but consistent with the diagnosis of AIH. A massive recruitment of activated inflammatory cells is likely to cause damage and eventually leads to portal hypertension; this prolonged elevated portal pressures then can lead to progressive congestion and eventually gastropathy. Due to large heterogeneity of the disease AIH may be unrecognized, and the clinical manifestation of AIH can range from mild or severe symptoms to fulminant hepatic failure. Growing insights into the clinical presentation of AIH highlights the importance of evaluation of the current diagnostic criteria and development of new treatment strategies to identify patients who would benefit from more efficient therapy. We present a patient in which liver transplant would be the only viable option for long term therapeutic benefit due to the untreated progression of her disease.

Update on Autoimmune Hepatitis.

Autoimmune hepatitis (AIH), a liver disorder affecting both children and adults, is characterized by inflammatory liver histology, elevated transaminase levels, circulating nonorganspecific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of AIH are recognized according to seropositivity: smooth muscle antibody and/or antinuclear antibody define AIH type 1 and antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 define AIH type 2. AIH type 1 affects both adults and children, while AIH type 2 is mainly a paediatric disease, though it does occasionally affects young adults. AIH should be considered during the diagnostic workup of any patient with increased liver enzyme levels. AIH is exquisitely responsive to immunosuppressive treatment with prednisolone with or without azathioprine, with symptom free long-term survival for the majority of patients. For those who do not respond to standard treatment, or who are difficult-to-treat, mycophenolate mofetil and, in the absence of a response, calcineurin inhibitors should be tried in addition to steroids. The pathogenesis of AIH is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4 T-cells, although recent studies support the involvement of diverse populations, including Th17 cells. A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigenspecific regulatory T-cells, which ultimately aim at restoring tolerance to liver-derived antigens.

Autoimmune Hepatitis

Autoimmune hepatitis is characterized by inflammatory liver histology, circulating nonorgan-specific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of juvenile autoimmune hepatitis (AIH) are recognized according to seropositivity for smooth muscle and/or anti-nuclear antibody (AIH type 1) or liver kidney microsomal antibody (AIH type 2). There is a female predominance in both. AIH type 2 presents more acutely, at a younger age and commonly with immunoglobulin A deficiency, whereas duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the 2 groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. Differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. In this article we review the state of the art of diagnosis, monitoring, and treatment for children with AIH.

Autoimmune Hepatitis in Children: What is Different from Adult AIH?

Autoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the two groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. The differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis, liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress.

Autoimmune Liver Disease in Children

Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.