This entry is made byGood Doctor OnlineProvide content and participate in editing.
Wang Qianyi
(Resident physician)
Hepatology Center of Beijing Friendship Hospital Affiliated to Capital Medical University
Autoimmune hepatitis is a chronic progressive liver inflammatory disease mediated by autoimmune reaction. Its clinical characteristics are elevation of serum transaminase, hypergammaglobulinemia, and positive autoantibodies to varying degrees. Its histological characteristics are interface hepatitis dominated by lymphocyte and plasma cell infiltration. Severe cases can rapidly progress tocirrhosisandhepatic failure。The disease occurs all over the world, and its incidence is relatively high in Europe and the United States. The exact incidence and prevalence rate in China are still unclear, but the number of cases reported in domestic literature shows a significant upward trend.
AIH can be divided into 3 types according to serum autoantibodies. Type I AIH is the most common, and the related antibodies are ANA and/or SMA;Type II AIH is characterized by anti LKM1 positive;Type III AIH is characterized by positive serum anti SLA/LP.Some scholars believe that type III should be classified as type I.There is no significant difference in the etiology of each type and the efficacy of glucocorticoids, so classification is of little significance for clinical guidance.
Pathogenesis
Announce
edit
The cause of disease is not completely clear
Pathogenesis
Announce
edit
Genetic susceptibility is considered to be the main factor, while other factors may cause the destruction of immune tolerance mechanism of the body on the basis of genetic susceptibility, generate immune response against liver autoantigen, thus destroying liver cells, leading to liver inflammation and necrosis, and may progress tohepatic fibrosis 、cirrhosis。
clinical manifestation
Announce
edit
The disease mostly occurs in women. The ratio of male to female is 1:4. There are two age peaks of onset, namely, 10 to 30 years old and over 40 years old.Most patients showchronic hepatitisAbout 34% of the patients had no symptoms and only went to hospital because of abnormal liver function found in physical examination;30% of patients appear at the time of visitcirrhosis；8% of patients were decompensated due to hematemesis and/or melenacirrhosisTo see a doctor;Some patients had acute or even fulminant onset (about 26%), with high levels of transaminase and bilirubin, and the clinical process was dangerous.About 17%~48% of AIH patients are complicated with other autoimmune diseasesarthritis、thyroiditisUlcerativecolitisType 1diabetesAnd even the reason for some patients' first visit.
Diagnostic differentiation
Announce
edit
1. Primary biliarycirrhosisIt is similar to AIH in clinical symptoms and laboratory tests, but it is mostly seen in middle-aged womenjaundiceSkin pruritus is the main manifestation, alkaline phosphatase and γ - glutamyltransferase in liver function test are significantly increased, serum total cholesterol, triacylglycerol and low-density lipoprotein can be increased, and IgM is the prominent immunoglobulin.The serum anti mitochondrial antibody M2 is a disease specific antibody. The pathological appearance of bile duct epithelial injury, inflammation, disappearance of bile duct and portal area granuloma is helpful to the diagnosis of this disease.
2. Primary sclerosischolangitisIt is characterized by extensive inflammation and fibrosis of the intrahepatic and extrahepatic biliary system, which is mostly seen in young and middle-aged men, often accompanied by ulcerationcolitis84% patients were ANCA positive, but not specific.Cholangiography showed beaded changes of intrahepatic and extrahepatic bile duct stricture and expansion. Secondary causes such as tumor, stone, surgery and trauma should be excluded for diagnosis. When the lesion only involved intrahepatic small bile duct, the diagnosis should rely on histological examination. The typical change was fibrouscholangitis。
3. Urgent and slowSTDToxic hepatitisHyperglobulinemia and circulating autoantibodies can also occur, but the antibody titer is low and the duration is shortSeropathyToxin antigen and antibody are very helpful for identification.
4. Alcoholic steatohepatitisWith a history of drinking, most of them had elevated serum IgA levels. Although ANA and SMA were positive, the titer was generally low, and anti LKM1 and PANCA were rarely positive.
5. Drug induced liver damageMost of them have a history of taking special drugs, and liver abnormalities can completely disappear after drug withdrawal, which generally does not develop intochronic hepatitisHistopathological examination showed necrosis of lobule or acinar zone, eosinophil infiltration, simple cholestasis, granulomatous hepatitis, hepatocyte steatosis and so on, which could indicate drug-induced liver damage.However, it should be noted that some drugs can induce autoimmune reactions, and the clinical manifestations and laboratory tests are very similar to AIH. The differentiation depends on pathology and the remission or recovery of the disease after drug withdrawal.[1]
Disease treatment
Announce
edit
medication
The main purpose of AIH treatment is to alleviate symptoms, improve liver function and pathological tissue abnormalities, and slow downhepatic fibrosis Progress.At present, glucocorticoid alone or combined with azathioprine is the standard treatment for AIH.
1. Treatment indications:
(1) Absolute indication: serum AST ≥ 10 times the upper limit of normal value, or serum AST ≥ 5 times the upper limit of normal value with γ - globulin ≥ 2 times the upper limit of normal value;Histological examination showed bridging necrosis or multilobular necrosis.
(2) Relative indications include fatigue, arthralgiajaundiceThe serum AST and/or γ - globulin levels were abnormal but lower than the absolute indication standard. Histological examination showed interfacial hepatitis.
2. Initial treatment plan
(1) Prednisone therapy alone is suitable for obvious leukopeniagestationPatients with tumor or thiopurine methyltransferase deficiency, or those who only need short-term treatment (≤ 6 months).Week 1: prednisone 60mg/d;The second week: 40mg/d;The third week: 30mg/d;The fourth week: 30mg/d;From the fifth week: 20mg/d, maintained to the end of treatment.
(2) The combination of prednisone and azathioprine is suitable formenopausePost womenosteoporosis, brittlenessdiabetes, obesityacnePsychological instability orhypertensionThe.The dose of prednisone was 30mg/d in the first week;The second week: 20mg/d;The third week: 15mg/d;The fourth week: 15mg/d;From the fifth week: 10mg/d.At the beginning of the first week, azathioprine 50mg/d was taken at the same time until the end of treatment.
3. Endpoint of initial treatment and countermeasuresAdult AIH should be treated continuously until the end points of remission, treatment failure, incomplete reaction or drug toxicity (see Table 3).The serum transaminase, bilirubin and γ - globulin levels of 90% patients improved within 2 weeks after treatment, but the histological improvement lagged behind 3 to 6 months, so it usually takes more than 12 months of treatment to achieve complete remission.Although some patients still have sustainable remission after stopping treatment, most patients need maintenance treatment to prevent recurrence.
4. Recurrence and countermeasuresRecurrence refers to the elevation of transaminase more than three times of the upper normal limit and/or the level of serum gamma globulin more than 2000 mg/dL after remission and drug withdrawal.It usually occurs within 2 years after drug withdrawal.Recurrent patients progress tocirrhosis, OccurrenceGastrointestinal bleedingAnd the risk of death from liver failure is higher.The first treatment scheme can be re selected for the first relapse, but the treatment scheme needs to be adjusted for those who have recurred at least twice. The principle is to use lower dose and longer maintenance treatment to alleviate symptoms and control transaminase below 5 times the normal value.Generally, 2.5 mg of prednisone is reduced every month after induction of remission until the lowest dose of the above indicators is maintained (the lowest average dose of most patients is 7.5 mg/d).In order to avoid the adverse effects of long-term glucocorticoid use, prednisone can also be reduced by 2.5 mg per month while azathioprine is increased by 2 mg/kg per day after remission, until the minimum maintenance dose of azathioprine alone is removed from prednisone.In addition, the lowest dose of combined treatment can also be used.
5. Alternative treatmentPatients who still have no histological remission under the treatment of high-dose glucocorticoid, or who have intolerable drug-related adverse reactions, may consider using other drugs as an alternative.For example, cyclosporine A, tacrolimus, budesonide, etc. may be effective for adult patients with glucocorticoid resistance. For those who cannot tolerate azathioprine, 6-mercaptopurine or mycophenolate mofetil may be used.In addition, ursodeoxycholic acid, methotrexate, cyclophosphamide, etc. can also be tried, but the efficacy of the above drugs still needs to be confirmed by large-scale clinical trials.[2-3]
Liver transplantation
Liver transplantation is an effective method for the treatment of end-stage AIH cirrhosis. The acute onset isFulminant hepatic failurePatients who fail to respond to hormone therapy, or whose chronic onset is in routine treatment or whose liver function is incomplete after treatment shouldLiver transplantation。The 5-year survival rate after liver transplantation was 80%~90%, and the 10-year survival rate was 75%. Most patients had negative autoantibodies within 1 year after liver transplantation, and hypergammaglobulinemia was relieved.AIH may recur after operation and before liver transplantationFulminant hepatic failurePatients, the recurrence rate is high.Prednisone alone or combined with azathioprine is still the treatment for recurrent patients. Most patients can effectively control the disease and improve the success rate and survival rate of transplantation.
Disease prognosis
Announce
edit
The prognosis of AIH varies greatly. Untreated patients can slowly progress to cirrhosis, or develop to acute, subacute, fulminant liver disease, and eventually die of various complications.Retrospective analysis showed that the 3-year survival rate of severe AIH patients without treatment was 50%, and the 5-year survival rate was 10%.After treatment, the 20-year survival rate of patients reached 80%, and there was no significant difference between their life span and that of normal healthy people matched with gender and age.Asymptomatic patients and those with HLA-DR3 have relatively good prognosis.Early diagnosis and appropriate treatment are important means to improve the prognosis.
