Autoimmune hepatitis K75.4

Autoimmune hepatitis is a rare, acute or chronic, recurrent inflammatory autoimmune disease of the liver that leads to liver cirrhosis within a few years if left untreated (Schmeltzer PA et al. 2018). A familial clustering is possible (Grønbæk L et al. 2018).

• Type 1: classical (lupoid) autoimmune hepatitis (80% of cases)
• Type 2: LKM-positive autoimmune hepatitis (rare; 50% occur already in childhood) Note: LKM-antibody=liver kidney microsome-Ak against cytochrome P450 2D6.

0.1-1.0/100,000 persons

w:m=8:2; there are 2 manifestation peaks: 20-30 years; 40-40 years.

Tiredness, exhaustion, nausea, joint problems (usually in several joints, without redness and swelling), signs of liver skin (e.g. erythema of the palms), in some cases icterus.

In acute cases: general feeling of illness, drowsiness, distinct jaundice, darkening of the urine.

Type 2 autoimmune hepatitis is characterized by an early age, a poor prognosis and frequent association with other autoimmune diseases.

Liver values (GOT, GPT) increased, synthesis capacity of the liver decreased (albumin, Quickwert), usually only slight increase in cholestasis parameters (AP, gamma-GT), increased gamma globulins (especially IgG). In 90% detection of autoantibodies(ANA, SMA, SLA/LP). In 20% of cases SLA/LP antibodies can be detected.

For type 1 autoimmune hepatitis, high-titer detection of ANA and ASMA (smooth muscle antigen) is characteristic. Furthermore, high-titer SLA/LP antibodies are characteristic of type1 AIH (usually in combination with high-titer ANAs). They have a high specificity but only a low sensitivity (Böhm O 2018).

For autoimmune hepatitis type2, LKM antibodies(anti-LKM antibodies, subclass LKM-1) are pathognomonic. LKM is the acronym for "Liver Kidney Microsomes. Serologically, viral markers are negative. Also AIH type2 associated are LC -(Liver Cytosol) 1 antibodies (Eckardstein A of 2017).

Association with HLA haplotypes B8, DR3, and DR4.

Liver histology typically shows the picture of a chronically active hepatitis (interface hepatitis). Cirrhosis of the liver is already detectable in every 3rd - 4th patient at the time of diagnosis.

Therefore, liver puncture is always part of the diagnostic procedure if autoimmune liver disease is suspected.

The diagnosis is based on the clinical picture, the laboratory findings (autoimmune parameters, early reduction of the liver's ability to synthesize) and the results of the tissue examination (liver histology). If autoimmune hepatitis is suspected, an immunosuppressive therapy with glucocorticoids is initiated. Since autoimmune hepatitis responds surprisingly well and promptly to immunosuppression, this good responsiveness can confirm the suspected diagnosis.

Immunosuppression with prednisolone and azathioprine. Patients have a normal life expectancy if therapy is started early enough. The disease responds promptly to steroid treatment, so that the success of the therapy can be an important diagnostic criterion.

As an alternative to prednisolone, budesonide can be used, also in combination with azathioprine. Budesonide is broken down very quickly in the liver but is only used if there is no liver cirrhosis (Rizvi S et al. 2018).

If the laboratory values (GOT, GPT, IgG) are within the normal range under low-dose immunosuppressive therapy (no disease activity), an attempt can be made to balance the drugs after 4 years at the earliest (control of the inflammatory activity by renewed liver biopsy). However, the majority of patients (>80%) require lifelong therapy. In case of therapy failure, liver transplantation may be necessary.

The appearance of autoimmune hepatitis is not uniform. Many patients have no symptoms over a long period of time. In this phase of the disease, the disease is usually noticed during a routine examination, e.g. by elevated liver values. In addition, there are also highly acute courses of the disease, which can very quickly lead to acute liver failure and require immediate intensive medical care.

Without therapy, the prognosis is poor.

Under controlled immunosuppressive therapy, the prognosis is good with almost normal life expectancy. Risk factors for unfavourable progression: Type 2-AIH, late diagnosis, high inflammatory activity, young age at diagnosis.

Autoimmune hepatitis is often associated with extrahepatic autoimmune diseases:

• Chronic lymphocytic thyroiditis (autoimmune thyroiditis
• Rheumatoid Arthritis
• Chronic inflammatory bowel diseases (e.g. ulcerative colitis)
• Autoimmuncholangitis overlap syndrome
• Sjögren's syndrome (Zhu LL et al. 2018)
• Hepatocellular carcinoma: the frequency of occurrence of hepatocellular carcinoma in autoimmune hepatitis is given as 1-9% (Czaja AJ 2013).

1. Böhm O (2018) Autoantibody diagnostics. In: Neumeier B et al. (Eds) Clinical guide to laboratory diagnostics. Elsevier GmbH S. 425
2. Czaja AJ (2013) Hepatocellular carcinoma and other malignancies in autoimmune hepatitis. Dig Dis Sci 58(6):1459-76. doi: 10,1007/s10620-012-2525-5.
3. Eckardstein A of (2017) Pathological laboratory findings. In: Battegay E (Ed.) Differential diagnosis of internal diseases. Georg Thieme Publishing House. Stuttgart New York S 1202-1238
4. Grønbæk L et al (2018) Family occurrence of autoimmune hepatitis: A Danish nationwide registry-based cohort study. J Hepatol 6. pii: S0168-8278(18)32120-2.
5. Rizvi S et al (2018) Autoimmune hepatitis in the Elderly: Diagnosis and Pharmacologic Management. Drugs Aging 35:589-602.
6. Schmeltzer PA et al. (2018) Clinical narrative: autoimmune hepatitis. Am J Gastroenterol 113:951-958.
7. Zhu LL et al. (2018) Clinicopathological Analysis of Autoimmune Hepatitis with Sjögren's Syndrome. Sichuan Da Xue Xue Bao Yi Xue Ban 49:183-187.