Autoimmune Hepatitis: Clinical features, Diagnosis And Treatment

Last Updated on June 4, 2020

Autoimmune hepatitis is a disease in which the immune system of the body attacks the liver and results in inflammation and liver damage.

Read more about Liver Anatomy, Structure and Function

It is a chronic disease whose exact cause is unknown. The interaction of genetic and environmental factors is thought to trigger the disease.

The disease more commonly affects women. About 70%-80% of patients are women.

It has a bimodal age distribution. The first peak of incidence is at age 10-20 years while the second peak occurs at age 45-70 years. Approximately half of the affected individuals are younger than 20 years. However, autoimmune hepatitis may occur in people of any age. In older people, the disease may affect men more commonly than women.

If left untreated, autoimmune hepatitis can lead to end-stage liver disease – cirrhosis; that is characterized by scarring of the liver and ultimately to liver failure.

However, early diagnosis and adequate treatment can usually control the disease and produce symptomatic relief. In patients who don’t respond to medicines or those having advanced liver disease, a liver transplant may be considered.

Causes of Autoimmune Hepatitis

In autoimmune diseases, the immune system of the body mistakenly identifies certain parts of one’s own body as foreign invaders. In response, it releases special antibodies, called autoantibodies that attack a person’s own cells and tissues.

In the case of autoimmune hepatitis, these autoantibodies attack healthy liver tissue, ultimately causing damage to the liver.

The exact cause of what causes the body to turn against itself is not known.

It is thought that a combination of genetic and environmental factors (such as medications or viral infections) usually triggers the disease.

Genetic factors

The presence of HLA haplotypes B8, B14, DR3, DR4, and Dw3 has been associated with increased susceptibility to develop autoimmune hepatitis. The presence of C4A gene deletions leads to increased chances of developing the disease in younger patients.

People having some other autoimmune disease or a family history of autoimmune disease are more likely to develop autoimmune hepatitis.

Environmental factors

Several factors (eg, viral infection, drugs, environmental agents) may trigger an autoimmune response in an already genetically susceptible person. Most common of these include:

Viral infections: Rubella, Epstein-Barr, hepatitis A, B, and C, cytomegalovirus

Drugs: Minocycline, methyldopa, nitrofurantoin, hydralazine, adalimumab, infliximab, etc

Clinical Features

Symptoms of autoimmune hepatitis range from mild to severe. The disease may present as acute hepatitis, chronic hepatitis, cirrhosis, or fulminant hepatic failure.

Patients may be asymptomatic in the early stages. In the later stages, symptoms may appear suddenly or may develop slowly over time.

Many patients present with symptoms of acute hepatitis such as fever, jaundice, and pain in the upper abdomen. Some patients present with signs and symptoms of chronic liver disease, while others rapidly progress to acute liver failure, as marked by an increased tendency for bleeding and jaundice.

Common symptoms include the following:

Fatigue
Jaundice (yellowish discoloration of skin and eyes)
Nausea
Vomiting
Loss of appetite
Upper abdominal pain or discomfort
Diarrhea
Weight loss

Other symptoms may be present depending on the stage and presentation of the disease.

Dark-colored urine
Pale or gray-colored stools
Pruritus or itchy skin
Skin rashes (including acne)
Myalgia
Joint pains
Cushingoid features
Hirsutism
Amenorrhea (absence of menstrual periods in women)
Chest pain due to pleuritis
Abnormal blood vessels on the skin (spider angiomas)
Abdominal distention (swelling)
Hepatic encephalopathy (loss of brain function)
Ascites (fluid in the abdomen)
Swelling of the legs (edema)
Easy bruising and bleeding.
Splenomegaly
Hepatomegaly

Failure to diagnose the disease and provide adequate therapy carries a risk of disease progression resulting in liver fibrosis. Over a period of time there may occur scaring of the liver (cirrhosis) that can ultimately cause liver failure or even cancer of the liver.

Complications of Autoimmune Hepatitis

Liver failure
Complications due to chronic liver disease (increased blood pressure in the portal vein, esophageal varices, gastrointestinal bleeding, ascites, etc)
Cirrhosis of the liver
Liver cancer

Types of Autoimmune Hepatitis

Type 1 autoimmune hepatitis

It is the most common type of the disease accounting for about 96% of all the patients of autoimmune hepatitis in North America. It can occur at any age and is more common in females. It is characterized by the presence of antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA).

Type 2 autoimmune hepatitis

It accounts for about 4% of all autoimmune hepatitis cases in North America. It is most commonly seen in children and young people. About 80% of patients of type 2 disease are children.

It is more severe as compared to type 1 disease. Also, it doesn’t show a good response to corticosteroids and has a greater tendency to relapse.

It is characterized by the presence of anti-liver kidney microsomal antibody type 1 (anti LKM1) and/or anti liver cytosol type 1 (anti LC1) autoantibodies.

Diagnosis

Diagnosis of autoimmune hepatitis is made after careful analysis of clinical features and laboratory findings.

Liver function tests

These tests may be abnormal depending upon the stage of the disease or the type of presentation of liver disease.

Serum aminotransferase levels (ALT and AST): These may be elevated 1.5-50 times the normal range.
Alkaline phosphatase (ALP): Levels are usually normal. Very high levels which are disproportionate to aminotransferase elevation usually indicate other liver diseases such as drug-induced disease, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).
Gamma-glutamyltranspeptidase (GGT): Levels are usually elevated
Albumin levels: It is a protein synthesized by the liver. Low levels indicate severe liver dysfunction as seen in active disease or cirrhosis.
Prothrombin time (PT) and international normalized ratio (INR): These tests measure the ability of blood to clot. Damage to the liver can result in reduced levels of various clotting factors leading to increased PT and INR.
Bilirubin: Increased level may occur due to severe inflammation of the liver or reduced liver function.

Low levels of albumin and prolongation of the prothrombin time are markers of severe hepatic dysfunction, which may be seen in active disease or decompensated cirrhosis.

Read more about Liver Function Tests or LFTs

Gamma globulin level and Serum protein electrophoresis (SPEP)

There is a polyclonal rise of gamma globulins (IgG levels) in the majority of the cases.

Elevated levels of liver transaminases and gamma globulin are important indicators for the diagnosis of disease as well as disease activity. Levels of IgG may also be used to measure the responsiveness of the disease to treatment.

Autoimmune markers

Antinuclear antibody (ANA)
Anti smooth muscle antibody (ASMA)
Anti liver kidney microsomal antibody (anti LKM)
Anti liver cytosol 1 antibody (anti LC1)

Elevated levels of ANA and IgG are present in many autoimmune diseases. So increased levels don’t imply the presence of AIH but only increase the likelihood of an autoimmune disease. Increased levels of ASMA and LKM are more specific for AIH especially when liver enzyme tests are also elevated.

Liver biopsy

It helps to confirm the diagnosis and to assess the severity of the disease. It can detect liver damage and the amount of fibrosis present.

The hallmark of AIH on biopsy is interface hepatitis characterized by lymphocytic infiltrate in the portal triad. This inflammation extends beyond the limiting plate and reaches the bordering hepatocytes. The bile ducts remain intact.

Fibroscan

Fibroscan is a specialized ultrasound of liver. It helps to quantify the amount of liver fibrosis and fat in the liver. It also gives an idea of the overall health of the liver.

Imaging studies

These are not required for diagnosing autoimmune hepatitis.

However, certain features may indicate a liver abnormality. Heterogeneous echotexture of the liver on ultrasound or abnormal contrast enhancement on an abdominal CT scan suggests the presence of active inflammation or necrosis of the liver. An irregular nodular liver is suggestive of cirrhosis.

Imaging studies may also be helpful to rule out the hepatocellular carcinoma, which can occur as a complication of autoimmune hepatitis.

All children with autoimmune hepatitis should undergo magnetic resonance cholangiopancreatography (MRCP) to rule out autoimmune sclerosing cholangitis.

Other causes of liver disease and chronic hepatitis should be excluded. These include alcohol-induced hepatitis, drug-induced hepatitis, viral hepatitis, Wilson disease, hemochromatosis, alpha-1 antitrypsin deficiency, nonalcoholic steatohepatitis, etc. The following tests may be performed.

Tests for viral hepatitis
Ceruloplasmin level: to rule out Wilson disease
Alpha 1-antitrypsin levels: to rule out alpha1-antitrypsin deficiency
Serum ferritin: to rule out hemochromatosis
Complete blood count (CBC)
Anemia panel

Treatment

The main aim of treatment is to stop or slow down liver damage. In case significant liver damage has occurred, treatment may also reverse the damage to some extent.

People who are asymptomatic or have a very mild disease do not require treatment.

Corticosteroids, either alone or in combination with immunosuppressive drugs are the mainstay of treatment for patients with autoimmune hepatitis.

About 65 to 80% of patients respond to treatment and go into remission (meaning their symptoms improve and liver function tests show improvement in liver functioning). Remission, however, may take up to two to three years. Such patients can taper off their medications.

Majority of the patients relapse once the drug treatment is withdrawn and may need long-term treatment.

Corticosteroids

These drugs have anti-inflammatory properties and also modify the body’s immune response. Treatment with high-dose corticosteroids prevents progression to fulminant hepatic failure or cirrhosis. It also significantly improves the chances of survival.

The most commonly used corticosteroid is prednisolone. It should be taken for a minimum period of 18-24 months. In some patients, the drug needs to be taken throughout life to prevent the disease from recurring.

When taken for a long time, corticosteroids can produce a wide range of serious side effects, such as thinning of bones (osteoporosis), high blood pressure, cataracts, glaucoma, weight gain, diabetes, etc.

Immunosuppressive agents

These drugs inhibit the immune system of the body. Commonly used drugs are azathioprine, cyclosporine or 6-mercaptopurine.

When taken along with prednisone at the beginning of treatment, azathioprine allows the dose of prednisone to be reduced quickly.

Cyclosporine has steroid-sparing effects (reduces the requirement of steroids) when given for several months before corticosteroids and azathioprine.

Since these drugs inhibit the body’s immune mechanism, they reduce the ability of the body to fight other infections.

Liver transplantation

Liver transplantation is required in the following conditions

In patients who do not respond to treatment
Those who can’t continue medical treatment due to the side effects of drugs
Those having progressive liver disease causing fulminant liver failure or cirrhosis

About 10%-20% of patients of autoimmune hepatitis require liver transplantation.

During a liver transplant, the diseased liver is removed and is replaced with a healthy liver from a donor. The liver used for transplantation can be obtained from deceased organ donors or living organ donors. In the case of living organ donors, only a portion of healthy liver tissue is transplanted. Both the donor and the recipient’s liver start regenerating new cells soon after the transplantation.

Even after a successful liver transplant, the disease can sometimes recur.

Prognosis of Autoimmune Hepatitis

Without treatment, the patient may develop any of the above-mentioned complications and about half of the individuals with severe disease will die within 6 months to 5 years.

Treatment with steroids and immunosuppressive drugs has brought about a significant change in the course of the disease. Most patients respond to medical therapy and the 10-year survival rate is more than 80 %. Thus prompt recognition of the disease and initiation of proper treatment is of utmost importance.

Patients with autoimmune hepatitis induced cirrhosis should undergo ultrasonography every 6 months to monitor for liver cancer (hepatocellular carcinoma)

References

Sebode M, Hartl J, Vergani D, Lohse AW, for the International Autoimmune Hepatitis Group (IAIHG). Autoimmune hepatitis: From current knowledge and clinical practice to future research agenda. Liver Int. 2018 Jan. 38(1):15-22.
Reich DJ, Fiel I, Guarrera JV, et al. Liver transplantation for autoimmune hepatitis. Hepatology. 2000 Oct. 32(4 Pt 1):693-700.
Fernandes NF, Redeker AG, Vierling JM, et al. Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis. Am J Gastroenterol. 1999 Jan. 94(1):241-8.
Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999 Nov. 31(5):929-38.
Gregorio GV, Portmann B, Reid F, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology. 1997 Mar. 25(3):541-7.
Oettinger R, Brunnberg A, Gerner P, Wintermeyer P, Jenke A, Wirth S. Clinical features and biochemical data of Caucasian children at diagnosis of autoimmune hepatitis. J Autoimmun. 2005 Feb. 24(1):79-84.