Annual progress of autoimmune liver disease

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China Medical TribuneAuthor: Jia Jidong, Beijing Friendship Hospital affiliated to Capital Medical University liver disease research center,


China Medical Tribune

Author: Jia Jidong, Beijing Friendship Hospital affiliated to Capital Medical University liver disease research center, Duan Weijia

In recent years, scholars at home and abroad have made some progress in the pathogenesis, diagnosis and treatment of autoimmune liver disease. In 2010, the organization of foreign society guidelines for autoimmune liver disease was updated, such as the American Association for the study of liver diseases (AASLD): the primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) guidelines, published in primary biliary cirrhosis (PBC) experimental design conference file. The International Working Group on autoimmune hepatitis (IAIHG) also issued a position paper on overlap syndrome in 2010.

In this paper, the main progress of domestic and foreign scholars in the field of autoimmune liver disease in 2010 is reviewed.

Primary sclerosing cholangitis

In 2010, AASLD published a guideline for the diagnosis and treatment of PSC

Diagnosis of PSC

In the presence of alkaline phosphatase (ALP) and gamma glutamyltransferase (gamma -GT). Patients with cholestasis and biochemical characteristics, if cholangiography [magnetic resonance cholangiopancreatography (MRC) and endoscopic retrograde cholangiopancreatography (ERC), percutaneous transhepatic cholangiography] showed multifocal stenosis and section dilatation of the bile duct and the typical change, except for secondary sclerosing cholangitis, which can diagnose PSC (Figure 1).

Although ERC is the gold standard for the diagnosis of PSC, but the examination record, can lead to bacterial cholangitis, pancreatitis, perforation, bleeding and other complications. Because MRC has good accuracy and security, it is the first choice for diagnosis.

Recent meta-analysis showed that the sensitivity and specificity of MRC in diagnosing PSC were 0.86 and 0.94, respectively. For most patients suspected of PSC, the diagnosis can be diagnosed by MRC, thus avoiding complications that may occur due to ERC.

Therefore, in 2009 the European Association for the study of the liver (EASL) guidelines cholestatic liver disease guidelines and AASLD 2010 are recommended, for suspected PSC patients, should first check MRC, can not be diagnosed can be examined by ERC.

Treatment of PSC

At present, there is no effective drug for the treatment of PSC, the main goal of the treatment is for its complications, including fat soluble vitamin deficiency, osteoporosis, bold stenosis, bile duct cancer.

Liver transplantation is the only effective treatment for end-stage PSC. The main drug treatment of PSC prior to ursodeoxycholic acid (UDCA), but recent meta-analyses have shown that UDCA treatment can reduce the mortality of PSC patients, also can not reduce the needs of patients for liver transplantation. In addition, the use of large doses of UDCA[28 ~ 30 mg/ (kg * d)] increased the number of serious adverse events.

In one study, 56 patients with PSC received high-dose UDCA therapy. Compared with baseline values, UDCA, total bile acid (TBA) and total bile acid (LCA) levels were significantly increased in patients treated with high-dose UDCA. It is suggested that the cause of the increase in adverse events caused by high dose of UDCA may be the effect of the bacteria in the colon on the non absorbed UDCA, which leads to the increase of bile acids (such as LCA).

On the applicability of UDCA in PSC patients, AASLD recommendations that, for adult PSC patients, does not recommend the use of UDCA as a drug treatment; the recommendations of the EASL, because of the limited data, currently not on UDCA for PSC are given specific recommendations.

Primary biliary cirrhosis

The survival rate of UDCA patients with better biochemical response of PBC was similar to that of healthy controls, but the survival rate of patients with UDCA was significantly lower than that of healthy controls. Patients with poor response should be explored.

Treatment of poor response to UDCA

Methotrexate (MTX) in 91 patients with poor response to UDCA patients received colchicine treatment for 6 months, if the ALP is not improved, with MTX (0.25 mg/kg, 1 times / week). ALP, aspartate aminotransferase (AST), pathological fibrosis and inflammatory index were significantly improved from MTX to the last 1 visits.

The 1 study evaluated the budesonide budesonide (6 mg/d) combined with mycophenolate mofetil (1.5 g/d) and UDCA[13 ~ 15 mg/ (kg - D)] treatment of poor efficacy in patients with PBC in response to UDCA. In 15 patients, the biochemical parameters of all the 7 patients were reduced to normal, and some of the 6 patients had partial response. After 3 years of treatment, patients with histological inflammatory activity and fibrosis were significantly improved than before treatment.

Fenofibrate, recently, the United States and Europe have reported the application of PBC in fenofibrate in poor biochemical response to UDCA. In 20 patients receiving fenofibrate 160 mg/d combined with UDCA after 48 weeks of treatment, ALP, AST and IgM were significantly decreased, while the level of bilirubin and albumin before and after the treatment, no difference. 10 patients with suboptimal response in patients with PBC were randomly divided into two groups, 4 patients continued to receive UDCA treatment, 6 patients received fenofibrate for 8 weeks (200 mg/d) and UDCA (600 mg/d) combined treatment. The levels of ALP, gamma -GT and alanine aminotransferase (ALT) in the combined treatment group were significantly lower than those in the baseline group, but there was no significant improvement in the biochemical indexes in the UDCA group.

There is no uniform treatment for patients with poor response to UDCA. The 2009 EASL guidelines, for without cirrhosis (histological staging of the 1 ~ 3 period), may be treated with UDCA combined with budesonide (6 ~ 9 mg/d) treatment (/C2). Further clinical studies in the treatment of immunosuppressive schemes have to be combined with UDCA and other treatments.

PBC clinical trial design

PBC patients are less, it is difficult to carry out large sample study. In addition, the disease progresses slowly, limiting the effectiveness of drug treatment in terms of survival rate, liver transplantation rate, etc.. In addition, there are a number of factors that increase the complexity of the design, including the severity of the disease and the biochemical response to UDCA.

Therefore, the design and the end point AASLD experts on the PBC clinical trial is discussed, and each part of the test gives specific recommendations, including test criteria, test duration, according to the clinical, biochemical and histological features of portal vein hypertension disease were stratified, the application of UDCA in clinical trials of new drugs the primary end point, the secondary end point, histological study end point, end point of symptoms, thus establishing the feasible criteria for clinical trials of PBC.

Autoimmune hepatitis and overlap syndrome

Autoimmune hepatitis

In 2010, AASLD published guidelines on the diagnosis and treatment of AIH. The guidelines have been given specific recommendations in terms of AIH's diagnosis, treatment indications, treatment options, initial treatment endpoints and strategies for treatment, and relapse after withdrawal.

Diagnostic criteria as early as 1992, the international expert group meeting on the development of AIH diagnostic criteria. In 1999, IAIHG revised descriptive criteria and diagnostic scoring systems for AIH diagnosis. In 2008, IAIHG proposed a simplified AIH scoring system. Although the simplified criteria are simple and feasible, and a number of retrospective studies have shown that it has good specificity and sensitivity, further studies are needed to verify its diagnostic efficacy.

Therefore, the AASLD guidelines recommend the use of a revised diagnostic scoring system for evaluation of clinical, laboratory, serological, or histologic findings in less or atypical cases in the 1999.

AIH autoantibodies can occur in patients with a variety of autoantibodies, including the common anti nuclear antibody (ANA), anti smooth muscle antibody (SMA) and anti liver kidney microsomal antibody type 1 (LKM-1), anti liver cytosolantibody type 1 (LC-1), the other antibody also includes perinuclear anti neutrophil cytoplasmic (pANCA) antibody, anti soluble liver antigen (SLA) and anti liver kidney microsomal antibody type 3 (LKM-3), anti asialoglycoprotein receptor (ASGPR) antibody and anti liver kidney microsomal antibody type 2 (LKM-2). AASLD presents a flow chart for the diagnosis of unexplained liver injury by detecting autoantibodies (Figure 2).

Overlap syndrome

There is no AIH-PBC and AIH-PSC for the diagnosis and treatment of uniform standards, 2010 IAIHG issued a position paper overlap syndrome, that overlap syndrome is not an independent disease, autoimmune liver disease should be divided into AIH, PBC and PSC/ in bile duct PSC; not recommended IAIHG scoring system in diagnosis of overlap syndrome; characteristic of AIH or PBC PSC can be considered immunosuppressive therapy; put forward the flow chart of diagnosis and treatment.

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