Autoimmune paediatric liver disease

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis（AIH）,autoimmune sclerosing cholangitis（ASC）,and de novo AIH after liver transplantation.AIH is divided into two subtypes 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 partial 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 type 1.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 normalization of biochemical parameters,and decreased inflammatory activity on follow up liver biopsies.However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies,hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH postliver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to t     

Autoimmune liver disease and rheumatic manifestations

PURPOSE OF REVIEW: To review studies that clarify the rheumatic manifestations of autoimmune hepatitis, elucidate shared pathogenic pathways, and encourage innovative site-specific therapies. RECENT FINDINGS: Autoimmune hepatitis has clinical manifestations, serological markers, pathogenic mechanisms, genetic predispositions, and therapies similar to the rheumatic diseases. The rheumatic manifestations may mask the underlying liver disease and vice versa. Variations in clinical phenotype and outcome for the autoimmune liver diseases may reflect host-specific and region-specific factors, and defects in counter-regulatory suppressor functions by regulatory T cells may facilitate cell-mediated cytotoxicity and autoreactivity. Mixed syndromes with hallmark features of one disease in another probably reflect a genetic predisposition for immune expression that is shared among the diseases. Mycophenolate mofetil, budesonide, rapamycin, and 6-thioguanine are promising treatments, and de-novo autoimmune hepatitis after liver transplantation suggests that the calcineurin inhibitors may have paradoxical effects on self-tolerance. SUMMARY: Clinical phenotypes of autoimmune hepatitis commonly include rheumatic manifestations that can mask the liver disease. Defects in counter-regulatory functions enhance cell-mediated cytotoxicity, and pharmacological interventions that promise site-specific actions affecting immunocyte differentiation and proliferation are feasible.     

Autoimmune liver disease in children

BACKGROUND AND AIM: Autoimmune liver disease (AILD) in children progresses to cirrhosis and liver failure if not diagnosed and managed in time. We prospectively analyzed our patients with liver disease for autoimmune etiology and their outcome with treatment. METHODS: All patients with liver disease were evaluated with liver function tests, abdominal ultrasonography, endoscopy, liver biopsy, viral markers and investigations for Wilson's disease. Immunoglobin (Ig)M hepatitis A virus, hepatitis E virus (HEV) and IgM hepatitis B core antibody were tested if acute viral hepatitis was suspected. Antinuclear antibody (ANA), antismooth muscle antibody (SMA), and liver kidney microsomal antibody (anti-LKM-1) were done in all cases. Autoimmune liver disease was diagnosed when one or more autoantibodies tested positive (> 1:40), and no other etiology of liver disease was identified. We also applied criteria proposed by the International Autoimmune Hepatitis Group. Cases diagnosed to have AILD were treated with immunosuppressive drugs. RESULTS: Autoimmune liver disease constituted 3.9% (6/153; median age and duration of illness 8.5 years and 3 months, respectively) of chronic liver disease cases. Four patients had acute hepatitis-like presentation. Of the six cases, two each were ANA and SMA +; one was anti-LKM-1 +, and the other was positive for both SMA and anti-LKM-1. Three of the patients achieved remission with combination therapy of oral prednisolone (OP) and azathioprine (AZT), and one with only OP. The other two patients were not treated. Two of the patients in remission have been weaned off from immunosuppressive therapy, and one is in a withdrawal phase. Another patient, while in biochemical remission developed superimposed anicteric acute HEV infection. CONCLUSION: Although AILD is uncommon in children, its search is rewarding, as remission is achieved with immunosuppressive therapy. Superimposed acute viral hepatitis can occur in endemic areas.     

Autoimmune serology in liver disease: methodology and interpretation

Abstract   Accurate measurement of levels of autoantibodies in serum is critical for the diagnosis of autoimmune hepatitis. The major reactivities include anti-nuclear antibody (ANA), smooth muscle antibody (SMA), antibody to liver kidney microsomes type-1 (anti-LKM1); other relevant reactivities include antibodies to liver cytosol 1 (anti-LC1), soluble liver antigen (anti-SLA), and neutrophil cytoplasmic antigens (ANCA). In addition to the classical indirect immunofluorescence technique, automatic assays based on recombinant antigens are now available, which allow detection of antibodies not visible on immunofluorescence, like anti-SLA, and assist in the interpretation of at times problematic immunofluorescence patterns, like anti-LKM1 or anti-LC1.     

Autoimmune liver disease in patients with neoplastic diseases

BACKGROUND: Development of de novo autoimmune liver disease has not been well documented in patients with malignant diseases. METHODS/RESULTS: In this paper we report on a series of six patients with neoplastic disorders who acquired liver disease with autoimmune features. Five patients had suffered from haematological neoplasms and one from colonic cancer. In two patients, liver disease was detected at the time of presentation with malignancy. In the remaining four, all of whom were successfully treated for malignancies, features of liver disease presented at intervals 24-72 months after the cancer diagnosis. Twelve liver specimens (11 biopsies and one hepatectomy specimen) were obtained at time intervals of 1-76 months after initial presentation of neoplastic disease. Biopsies from three patients showed features of hepatitis (one acute, one sub-acute, one chronic). Two patients had histological features suggestive of an overlap syndrome (one autoimmune hepatitis/primary biliary cirrhosis, one autoimmune hepatitis/primary sclerosing cholangitis). The sixth patient had features of autoimmune cholangiopathy. All but one responded well to steroid therapy with complete clinical and biochemical remission obtained 4 weeks to 8 months after steroid introduction. We discuss briefly possible aetiologies of autoimmune liver disease in these patients. CONCLUSIONS: Autoimmune liver disease may be precipitated by therapy for neoplastic disease or malignant disease itself. The unusually heterogeneous clinicopathological findings in this group as well as the response to treatment support the concept of a wide spectrum of manifestations of autoimmune liver disease. The results may also suggest that autoimmune liver disease may be possibly added to the list of paraneoplastic syndromes. Further prospective studies are required to confirm a causal association and to determine whether the mechanisms involved are disease- or treatment-related.     

自身免疫性肝病的基本概念和诊断思路

自身免疫性肝病指一组以肝脏病理损害和肝脏功能试验异常为主要表现的自身免疫性疾病,通常包括自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)和原发性硬化性胆管炎(PSC)。由于在国内较为少见,所以一般教科书对它们的描述较为简略,多数临床医生对此类疾病的警惕性也不高。随着国     

Autoimmune liver disease. Current standards, future directions

The diagnosis and management of autoimmune hepatitis continues to evolve as new diagnostic tests and new therapies are added to the armamentarium. Also encouraging are the advances in the understanding of the human immune system and its involvement in the origin and course of auto immune diseases in general and in the variants of autoimmune liver disease. Promising changes are expected in the next few years as new medications become available to the practicing hepatologist. New immune tests may allow therapies to be customized to patients, and antiviral therapies may also eventually be used in the management of this autoimmune liver diseases.     

Autoimmune cholangitis within the spectrum of autoimmune liver disease

Autoimmune cholangitis is an idiopathic disorder with mixed hepatocellular and cholestatic findings. Our goal was to characterize the disease prospectively by application of uniform diagnostic criteria. Twenty patients were identified and compared with 242 patients with conventional forms of autoimmune liver disease. Patients with autoimmune cholangitis were distinguished from type 1 autoimmune hepatitis (AIH) by lower serum levels of aspartate transaminase (AST), gamma-globulin, and immunoglobulin G; higher serum levels of alkaline phosphatase; and lower frequencies of autoantibodies. They were distinguished from primary biliary cirrhosis (PBC) by higher serum levels of AST and bilirubin, lower serum concentrations of immunoglobulin M, and greater occurrence of autoantibodies. Their female predominance, lower serum alkaline phosphatase levels, higher frequency of autoantibodies, and absence of inflammatory bowel disease differentiated them from primary sclerosing cholangitis (PSC). Laboratory findings ranged widely and did not characterize individual patients. HLA risk factors were similar to those of type 1 AIH and PBC, and different from those of PSC. Treatment responses to corticosteroids or ursodeoxycholic acid were poor. Composite histological patterns resembled mainly PBC or PSC. We conclude that autoimmune cholangitis diagnosed by prospective analysis cannot be assimilated into a single, conventional, diagnostic category. It may represent variant forms of diverse conditions, a transition stage, or a separate entity with varying manifestations.     

Nutritional therapy and liver disease

In terms of a general approach to these patients, the initial and most important step for the clinician is to have recognition and concern for the magnitude of malnutrition in patients with chronic liver disease. It is best to assume an inadequate diet and to have trained personnel review the individual's nutritional needs and design specific dietary regimens that supply sufficient energy and protein, perhaps in the form of frequent interval feedings. The currently available data support the use of specialized formulations only in selected patients with hepatic encephalopathy who are intolerant of an amount of protein sufficient to meet their nutritional requirements.     

酒精性肝病与非酒精性脂肪性肝病的鉴别诊断

非酒精性脂肪性肝病和酒精性肝病的鉴别诊断方面目前尚存在较多的问题和未知因素,如:过多地依赖并不可靠的饮酒史,临床表现没有特异性,缺乏有效的生物标志物,影像学检查无法鉴别,活检组织较难获取等.本文从病史、危险因素、临床表现、生化检查、影像学诊断、活检和病理组织学等方面,给出了主要的鉴别点,并且进行了相应的评论.最后,给出了鉴别诊断的基本思路和研究进展.但是,就该问题而言,这些远远不够,未来需要更多的研究来充实和完善,以促使我们对该问题的认识越来越深刻.     

Non-alcoholic fatty liver disease: The diagnosis and management

Non-alcoholic fatty liver disease(NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosisto inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease.     

Autoimmune liver diseases

The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise ＇pairs of articles＇ on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.