Prognosis

Standard treatment

Untreated autoimmune hepatitis (AIH) has a poor prognosis, with a 5-year survival rate of 50% and 10-year survival rate of 10%.[45] Immunosuppressive therapy significantly improves survival.[63]​​

The majority of patients with moderate to severe AIH respond to treatment within 2 weeks and achieve remission, with serum aminotransferases falling into the normal range after 12 or more months of treatment.[36][64][65]

The aim of treatment is for patients to achieve sustained remission without the need for medication. Guidance recommends an attempt at withdrawal of treatment for patients who have been in remission for at least 24 months.[1][26]​ However, sustained remission without treatment is only achieved in a minority of patients, and 50% to 90% of patients who achieve remission relapse within 12 months of drug withdrawal.[1][36]​​

The risk of relapse can be predicted based on histological findings prior to withdrawing treatment. The American Association for the Study of Liver Diseases suggests that a liver tissue examination (via biopsy) prior to drug withdrawal is useful.[1]

The overall 10‐ and 20‐year survival rates of treated AIH in a non-transplant centre are 91% and 70%, respectively. The standardised mortality ratio is 1.63 for all-cause death and 1.86 after inclusion of liver transplant as ‘death’.[64]

AIH should not be treated when risks clearly outweigh the benefits or in those with chronic cirrhosis in the absence of an inflammatory component.[45]

Liver transplantation

The 5-year patient and graft survival rate is approximately 75% to 90%.[66] The 10-year survival rate is approximately 75%.[66] Immunosuppression post-liver transplant has usually consisted of tacrolimus alone or with mycophenolate or azathioprine. The use of corticosteroids remains controversial.

Recurrent AIH is a challenge post-transplant and may be related to greater disease severity in the recipient liver before transplantation, as well as the type of immunosuppression used, or the human leukocyte antigen (HLA) status of the donor. Some reports implicate weaning of patients off corticosteroids. Successful management of recurrent disease relies on early detection with liver biopsy. In most cases, increased immunosuppression is successful. The 5-year survival in this population still approaches >78%.[54]

De novo AIH can arise in patients who have received a transplant for other liver diseases and may be a form of late cellular rejection. This generally responds to modification of immunosuppression.[1]​​

Special clinical challenges in the prognosis of AIH

AIH can present in a variety of ways. This diversity of presentation can impede the diagnosis. For example, serological markers can be variably expressed in some patients. In addition, different ethnic groups can have non-classical clinical presentations, and sex may affect treatment response and outcome. Debate remains regarding therapy in asymptomatic patients, older patients, and pregnant women.[67]

Older patients

Twenty percent of adults develop AIH after 60 years of age and generally have a greater degree of hepatic fibrosis, ascites, and cirrhosis, indicating that they have an aggressive disease.[68][69] The frequency of comorbidities such as osteoporosis, hypertension, diabetes, and active malignancy may preclude the use of corticosteroids.

Post-menopausal women were found not to have a statistically different frequency of drug-related adverse effects compared with pre-menopausal women.[67] However, older patients can be managed successfully with a combination of prednisone and azathioprine, and may respond more quickly than younger counterparts and fail treatment less often. Initial therapy has been shown to be well tolerated. Re-treatment after relapse, however, was associated with a higher cumulative frequency of drug-related complications such as vertebral compression in the post-menopausal group. Bone maintenance and densitometry monitoring regimens can reduce complications.

Older patients should not be denied liver transplantation simply on the basis of age because the 5-year survival rates after liver transplantation in this age group have been shown to be the same as those in younger adults, and older patients had lower rates of acute rejection.[70]

Males

Because AIH is rare in males, the diagnosis might be delayed or missed. Men tend to be younger than women at presentation, relapse more commonly after treatment withdrawal, and more frequently express the HLA-A1-D8-DRB1*03 allele.

Men have a better long-term survival rate than women, which may be related to the fact that women often have other autoimmune disorders concomitantly.[71]

Pregnancy

AIH during pregnancy is a complicated clinical state. However, experience indicates that both pregnancy and liver disease can be successfully managed when they co-exist. The major risk of pregnancy in these cases is premature delivery of the fetus, which has been estimated to occur in 16% to 20% of pregnancies.[72][73] The fetal loss and stillbirth rate of 27% is higher than that for the general population (7% to 15%) but similar to that for women with chronic disease (24% to 29%).[1][73]​ Antiphospholipid antibodies are strongly associated with AIH, and may be a separate, but related, cause of preterm delivery.​​​​[1]

AIH may improve during pregnancy because oestrogen mediates a cytokine shift from a T-helper type 1 (Th1) to a T-helper type 2 (Th2) anti-inflammatory profile. Unfortunately, AIH is frequently exacerbated after delivery, when oestrogen levels can fall dramatically.[74]

Azathioprine and mercaptopurine appear to be relatively safe in prospective cohort studies and retrospective reviews of pregnant patients with inflammatory bowel disease.[75][76][77]

US and European guidance states that azathioprine can be continued throughout pregnancy.[1][26]

Acute, severe, or fulminant AIH presentation

Acute, severe, or fulminant AIH is rare. Overall, the reported response to corticosteroids in severe AIH has fluctuated from 36% to 100%.[78]​ One study found that Model for End-stage Liver Disease (MELD) scores of >12 at presentation had sensitivity of 97% and specificity of 68% for treatment failure; MELD scores may therefore be a useful tool in identifying patients who warrant more urgent consideration for liver transplantation.[79]

Non-white patients

Black North American patients more commonly have cirrhosis at presentation than white North American patients, whereas Japanese patients typically have mild, late-onset disease. South American patients are more frequently younger than white North American counterparts and have less severe laboratory abnormalities at presentation. Alaskan natives have icteric disease more frequently than non-native patients, while African, Asian, and Arab patients have a higher frequency of cholestatic features and greater occurrence of biliary changes on histology than white Northern European patients.[67]

The variations in these phenotypes indicate that genetic background and geographical location may affect presentation and occurrence of the disease.[67]

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