Clinical features
Autoimmune hepatitis (AIH) is characterized by predominantly female, borderline hepatitis, hyperglobulinemia and autoantibodies. The disease generally responds well to glucocorticoid therapy, with 65% of patients achieving clinical, laboratory test and histological remission within 18 months.
Most patients with type II AIH contain anti-LKM-1 that reacts with the short linear sequence described above, and this reactivity is distinct from anti-LKM-1 in patients with chronic hepatitis C. The susceptibility of type II AIH is clearly associated with DRB1*0701, however, it is also associated with HLAB14, DR3 and C4A-Q0. The prognosis of type II AIH is not necessarily worse than that of type I AIH, and the type I and II The response to glucocorticoids is also comparable in type I and type II AIH. Both types can have acute or even fulminant attacks, and timely recognition and treatment is necessary to control inflammatory activity.
Diagnosis
I. Diagnosis
The diagnostic criteria for AIH have been clearly defined by an international panel (Tables 2 and 3). A definitive diagnosis requires the exclusion of viral, drug, alcoholic, and hereditary liver disease. Laboratory features must confirm essential immunoreactivity, and liver tissue must reveal at least a mononuclear cell infiltrate in the confluent area and bounding plate hepatitis. No 6 months are required to establish a chronic course, and clinical, laboratory, and histologic changes of a stasis nature preclude this diagnosis. a probable diagnosis of AIH requires the same histologic findings as the definitive diagnosis, but possibly a weaker immune reactivity or some degree of exposure to potentially hepatotoxic drugs or alcohol.
Furthermore, confirmation of the presence of anti-salivary glycoprotein receptor antibodies, liver-specific cytoplasmic antigen type I, anti-SLA/LP, and/or perinuclear anti-neutrophil cytoplasmic antibodies supports the probable diagnosis. The point system facilitates the diagnosis of patients with complex presentations, and it provides a mechanism to assess the strength of the diagnosis in a diverse population. By measuring each component of the syndrome, conflicting features can be accommodated, avoiding the errors associated with isolated inconsistent features. Summarizing the data from six studies containing 983 patients, the diagnostic accuracy of the scoring system was calculated to be 89.8%.
I. Immunosuppressive therapy
The combination of prednisone and azathioprine has fewer side effects than high-dose prednisone alone (10% vs. 40%) and is indicated for those who cannot tolerate high doses of hormones, such as postmenopausal women, osteoporosis, diabetes mellitus, hypertension, and the emotionally unstable; whereas high-dose single hormone therapy is commonly used for those who cannot tolerate high doses of hormones. High-dose monohormone therapy is often used for those who cannot tolerate azathioprine, such as those with severe hematocrit, pregnancy, coexisting tumors, or short courses of experimental therapy.
Treatment endpoints are defined as discontinuation of treatment after
(i) Significant remission (disappearance of symptoms, AST£2 times normal and return of normal or only slightly abnormal liver histology);
(ii) Incomplete response (treatment extended to 3 years without remission);
③Toxic drug reactions (such as exogenous obesity, full-moon face, acne, diabetes, mood disorders and hirsutism, etc.);
(iv) Treatment failure (worsening of disease during treatment, AST and/or serum bilirubin ³ 67% of the previous value and progression of active hepatic histological lesions, such as the development of ascites or hepatic encephalopathy, etc.).
Improvement in liver tissue with immunosuppressive therapy often lags behind clinical and biochemical improvement by 3 to 6 months, so liver tissue biopsy must be performed to determine histologic remission and prevent premature discontinuation of the drug. The course of hormone therapy should be at least 2 years, and treatment may be discontinued if significant remission is still not achieved. Hormone therapy can achieve remission in 65% of patients with severe AIH within 2 years.
Ursodeoxycholic acid (Usfer)
Ursodeoxycholic acid (UDCA) was early used to treat chronic hepatitis. In a Japanese study of 8 patients with AIH treated with UDCA (600 mg/day) for 2 years, improvement in clinical manifestations and hepatic biochemical parameters, significant reduction in serum IgG, g-globulin, decrease in ANA titers, and negative SMA were observed. Histological examination saw improvement in inflammatory but not fibrotic indices in the four patients who underwent post-treatment liver biopsy, suggesting that UDCA is an effective therapeutic agent for type I AIH.
Recently, Czaja et al. treated patients with treatment failure, multiple relapses and incomplete response with corticosteroids combined with UDCA for 6 months and showed that the addition of UDCA to corticosteroids during the treatment of patients with refractory AIH improved some laboratory findings, but had no significant effect on corticosteroid tapering or withdrawal, clinical regression or histological changes The two studies have in common that both of them have a significant effect on the reduction or withdrawal of corticosteroids. Common to both studies was the beneficial effect of UDCA on liver function parameters observed in both studies.
The difference in efficacy may be due to the difference in the subjects treated in the two groups. The Japanese group observed patients with milder AIH, while Czaja et al. observed patients with refractory AIH. In our clinical work, we generally treat AIH patients with UDCA in combination with immunosuppressive therapy, and after the patients show response, the dosage of corticosteroids is gradually reduced to the point of discontinuation, and UDCA therapy is still maintained for a period of time, which may help to prevent relapse of the disease.
III. Liver transplantation
End-stage liver disease (portal hypertension and decompensated cirrhosis) due to AIH is one of the best indications for liver transplantation. patients with AIH have a slightly higher risk of developing liver cancer than those without chronic liver disease, but routine follow-up with liver ultrasound or alpha-fetoprotein is not yet recommended. Patients who undergo liver transplantation have a 5-year survival rate of up to 96%, with good long-term survival and quality of life.
However, 20% of AIH patients have postoperative recurrence. However, recurrence is more difficult to distinguish from acute or chronic rejection. Eosinophilia, bile duct injury and intrahepatic phlebitis are signs of rejection, and borderline hepatitis with plasma cell infiltration strongly suggests AIH recurrence. treatment of AIH recurrence and rejection is similar.