Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

that occurs when the body's immune system attacks

liver cells A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...

, causing the liver to be inflamed. Common initial symptoms may include fatigue,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, muscle aches, or

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...

or signs of acute liver inflammation including fever, jaundice, and right upper quadrant abdominal pain. Individuals with autoimmune hepatitis often have no initial symptoms and the disease may be detected by abnormal

liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...

and increased protein levels during routine bloodwork or the observation of an abnormal-looking liver during abdominal surgery. Anomalous

presentation A presentation conveys information from a speaker to an audience. Presentations are typically demonstrations, introduction, lecture, or speech meant to inform, persuade, inspire, motivate, build goodwill, or present a new idea/product. Presenta ...

MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial ce ...

receptors on the surface of liver cells, possibly due to

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

tic predisposition or

acute Acute may refer to: Science and technology * Acute angle ** Acute triangle ** Acute, a leaf shape in the glossary of leaf morphology * Acute (medicine), a disease that it is of short duration and of recent onset. ** Acute toxicity, the adverse eff ...

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...

, causes a cell-mediated

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

against the body's own liver, resulting in autoimmune hepatitis. This abnormal immune response results in inflammation of the liver, which can lead to further symptoms and complications such as fatigue and

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...

. The disease is most often diagnosed in patients in their late teens or early 20s and between the ages of 40 and 50. It affects women more commonly than men.

Signs and symptoms

Autoimmune hepatitis may present completely asymptomatic (12–35% of the cases), with signs of chronic liver disease, or acute or even fulminant hepatic failure. People usually present with one or more nonspecific, long-lasting symptoms such as fatigue, general ill health, lethargy, weight loss, mild right upper quadrant abdominal pain, malaise, anorexia,

itch Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

ing, nausea, jaundice or

joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...

especially affecting the small joints. Rarely,

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, c ...

or unexplained fever may appear. In women, the absence of menstruation (

amenorrhoea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of mense ...

) is a frequent feature. Physical examination may be normal, but it may also reveal signs and symptoms of chronic liver disease. Many people have only laboratory abnormalities as their initial presentation, as unexplained increase in

transaminase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α- keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid ...

s and are diagnosed during an evaluation for other reasons. Others have already developed

at diagnosis. Of note, alkaline phosphatase and bilirubin are usually normal. Autoimmune hepatitis may overlap with other autoimmune conditions, mainly

type 1 diabetes mellitus Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...

ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...

, lupus,

celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused ...

, and

autoimmune thyroiditis Autoimmune thyroiditis, is a chronic disease in which the body interprets the thyroid glands and its hormone products T3, T4 and TSH as threats, therefore producing special antibodies that target the thyroid's cells, thereby destroying it. It may ...

Cause

The prevailing theory for the development of autoimmune hepatitis is thought to be the interplay of genetic predisposition, an environmental trigger (virus, drugs, herbs, immunizations), and failure of the native immune system resulting in chronic inflammation of hepatocytes and subsequent fibrosis of the liver. There is no specific evidence of the cause. Sixty percent of patients have findings associated with chronic hepatitis but without serologic evidence of a viral infection. The disease is strongly associated with anti-smooth muscle autoantibodies. The exact genes and triggers responsible remain undefined, but studies show association of early-onset, severe disease with the HLA-DR3 serotype and late-onset disease with the

HLA-DR4 HLA-DR4 (DR4) is an HLA- DR serotype that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world. Serology The serological identification of DR4 is ...

serotype.

Diagnosis

The diagnosis of autoimmune hepatitis is best achieved with a combination of clinical, laboratory, and histological findings after excluding other etiological factors (e.g. viral, hereditary, metabolic, cholestatic, and drug-induced liver diseases). The requirement for histological examination necessitates a

liver biopsy Liver biopsy is the biopsy (removal of a small sample of tissue) from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment. Medica ...

, typically performed with a needle by the

percutaneous {{More citations needed, date=January 2021 In surgery, a percutaneous procedurei.e. Granger et al., 2012 is any medical procedure or method where access to inner organs or other tissue is done via needle-puncture of the skin, rather than by using ...

route, to provide liver tissue.

Autoantibodies

A number of specific antibodies found in the blood ( antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti-liver kidney microsomal antibodies (LKM-1, LKM-2, LKM-3), anti soluble liver antigen (SLA), liver–pancreas antigen (LP), and

anti-mitochondrial antibody Anti-mitochondrial antibodies (AMA) are autoantibodies, consisting of immunoglobulins formed against mitochondria, primarily the mitochondria in cells of the liver. The presence of AMA in the blood or serum of a person may be indicative of the pres ...

(AMA)) are of use, as is finding an increased immunoglobulin G level. The presence of

is more suggestive of

primary biliary cholangitis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build ...

. Hypergammaglobulinemia is also of diagnostic value.

Histology

Autoimmune hepatitis can be characterized histologically by the following nonspecific findings: * Portal mononuclear cell infiltrate that invades the boundary surrounding the portal triad and infiltrates the surrounding lobule. * Periportal lesions, also known as interface hepatitis, that spare the biliary tree (may include centrizonal necrosis). * Bile duct abnormalities (cholangitis, ductal injury, ductular reaction) can be seen and should prompt evaluation for primary biliary cholangitis or sarcoidosis if granulomas are observed. * Plasma cell infiltrate, rosettes of hepatocytes, and multinucleated giant cells. * Varying degrees of fibrosis (except in the mildest form of autoimmune hepatitis). Bridging fibrosis that connects the portal and central areas can distort the structure of the hepatic lobule and result in cirrhosis.

Diagnostic scoring

The Internal Autoimmune Hepatitis Group developed a standardized scoring system for clinical diagnosis in population studies but lacks value in individualized cases. A simplified scoring system for clinical use incorporates titers of autoantibodies, total IgG levels, liver histology, and the exclusion of viral hepatitis for diagnostic scoring.

Classification

On the basis of detected autoantibodies, autoimmune hepatitis can be classified into three subtypes but have no distinct clinical presentations. * Type 1 autoimmune hepatitis. Positive antibodies include: ** Antinuclear antibody (ANA) ** Anti-smooth muscle antibody (ASMA) - 65% of people ** Anti-actin antibodies ** Anti-mitochondrial antibodies - rare except for overlap syndromes with

** Anti-soluble liver antigen/liver pancreas antibody antigen - 20% of people ** Anti-double stranded DNA - 30% of people ** Atypical perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) * Type 2 autoimmune hepatitis. Positive antibodies include: ** Liver Kidney Microsomal antibody (LKM-1) ** Anti-liver cytosol antibody-1 (SLC-1) * Autoantibody negative autoimmune hepatitis. ** Lack positive ANA, ASMA, LKM-1, etc. antibody panels but present with clinical features of autoimmune hepatitis that resolve with standard treatment.

Differential diagnosis

Other diagnoses to consider include conditions that may cause acute hepatitis or chronic liver inflammation that may be accompanied by cirrhosis: * Other autoimmune diseases that involve the liver: ** Primary biliary cholangitis - the presence of isolated elevated AMA antibodies usually signifies primary biliary cholangitis rather than autoimmune hepatitis and further diagnostic evaluation is needed. ** Overlap syndromes - autoimmune hepatitis may present similarly to primary sclerosing cholangitis but people with primary sclerosing cholangitis have stricturing and dilatation of intra/extra-hepatic ducts while people with autoimmune hepatitis generally have a spared biliary tree. * Other causes of hepatitis: ** Viral hepatitis - it is necessary to distinguish autoimmune hepatitis from acute hepatitis caused by Hepatitis A/B/C/D/E, herpes simplex, varicella zoster, EBV, CMV virus ** Drug-induced liver injury - portal neutrophils are more prevalent in drug-induced liver injury on liver biopsy and can help distinguish the two ** Nonalcoholic steatohepatitis - related medical history and liver biopsy showing fatty infiltration and the presence of neutrophils and central fibrosis can distinguish the two ** Lupus-associated liver disease - rarely presents with elevated ASMA or AMA antibodies ** Acute liver failure - people with acute liver failure may have elevated autoantibodies but the antibodies alone are not enough for the diagnosis of autoimmune hepatitis ** Iron overload - elevated iron in the body can cause liver inflammation

Treatment

The choice for medical treatment should be based on the individual's severity of symptoms, quantitative elevation of liver enzymes and antibody levels, findings on liver biopsy, and ability to tolerate side effects of medical therapy. Generally, treatment is not required in asymptomatic patients with normal liver enzyme and antibody levels and liver biopsies that do not demonstrate inflammation because these patients are at a low risk of disease progression. In symptomatic individuals with evidence of interface hepatitis and necrosis on liver biopsy, it is recommended to offer treatment especially if the patient is young and can tolerate the side effects of medical therapy. The mainstay of treatment involves the use of immunosuppressive

glucocorticoids Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...

such as

prednisone Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and ad ...

during acute episodes and resolution of symptoms can be achieved in up to 60–80% of cases, although many will eventually experience a

relapse In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or ...

. In individuals with moderate to severe disease who may not tolerate glucocorticoids, lower dose prednisone monotherapy or combination with azathioprine is a reasonable alternative.

Budesonide Budesonide, sold under the brand name Pulmicort among others, is a medication of the corticosteroid type. It is available as an inhaler, nebulization solution, pill, nasal spray, and rectal forms. The inhaled form is used in the long-term mana ...

has been shown to be more effective in inducing remission than

, but evidence is scarce and more data is needed before it can be routinely recommended. Those with autoimmune hepatitis who do not respond to glucocorticoids and azathioprine may be given other immunosuppressives like mycophenolate,

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

, or methotrexate. Liver cirrhosis can develop in about 7% to 40% of treated patients. People with the highest risk for progression to cirrhosis are those with incomplete response to treatment, treatment failure, and multiple relapses. Once cirrhosis develops, management of liver cirrhosis in autoimmune hepatitis is standard regardless of etiology. Liver transplantation is the standard of care in people presenting with fulminant liver failure or those with the progression of disease despite multiple lines of therapy.

Prognosis

Without treatment, the ten-year survival rate for individuals with symptomatic autoimmune hepatitis is 50%. However, with treatment, the ten-year survival rate is above 90%. Despite the benefits of treatment, people with autoimmune hepatitis generally have a lower transplant-free survival than the general population. Outcomes with liver transplant are generally favorable with a five-year survival greater than 80 percent. Presentation and response to therapy may differ according to race. African Americans appear to present with a more aggressive disease that is associated with worse outcomes. There has been strong evidence that patients with autoimmune hepatitis can develop mental health disorders like

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

and bipolar disorder later in their life.

Epidemiology

Autoimmune hepatitis can develop in people of any race or age but occurs most frequently in women. Eighty percent of cases are the type 1 subtype with women being affected 4 times more often than men; for the type 2 subtype, women are affected 10 times more often than men. European studies suggest a disease incidence of 1 to 2 people affected per 100,000 population with a prevalence of 10 to 25 people per 100,000 population. The disease has a bimodal peak occurring between the ages of 10 to 20 and then later in life between the ages of 40 to 50.

History

Autoimmune hepatitis was previously called "lupoid" hepatitis due to people having an associated autoimmune disease like system lupus erythematosus at time of diagnosis, which was believed to be its cause. It was originally described in the early 1950s.

References

External links

{{DEFAULTSORT:Autoimmune Hepatitis Hepatitis Steroid-responsive inflammatory conditions Articles containing video clips