Autoimmune liver disease is a disease that occurs when the immune system attacks the cells of the liver. It is estimated that about 5% of the population suffer from autoimmune diseases. They are usually associated with rheumatoid arthritis, multiple sclerosis, or Crohn's disease. However, inflammatory processes resulting from a malfunction of the immune system also affect other organs, including the liver.
Autoimmune liver diseaseis defined as an abnormal response by the immune system that causes the body to produce antibodies against its own liver cells. "The causes of such disorders are not fully understood," says Dr. Iwona Kozak-Michałowska, medical director of Synevo Laboratories. - They can be genetic, environmental, infectious and many other factors. "
Liver diseases are also among autoimmune diseases. They are:
- autoimmune hepatitis (AIH)
- primary biliary cirrhosis (PBC)
- primary sclerosing cholangitis (PSC)
" Autoimmune liver diseasesare not common diseases. However, there are groups of people for whom their occurrence should be taken into account - emphasizes Dr. Kozak-Michałowska. - These include patients with unexplained elevations of AST and ALT transaminases, HCV or HBV qualified for interferon therapy, with symptoms of inflammation, cirrhosis or liver failure, and patients with other autoimmune diseases. "
Autoimmune Hepatitis (AIH)
It is a chronic, inflammatory disease of the liver parenchyma. It is estimated that the incidence in Western European countries is 0.1–1.2 cases per 100,000 people per year .¹ Untreated autoimmune hepatitis leads to liver cell necrosis, chronic or acute liver failure, and consequently to cirrhosis. Then, the only method of treatment and saving the patient's life is liver transplantation. Autoimmune hepatitis accounts for 2.6% of hepatitis transplants in Europe².
It is a disease of unknown etiology. It is believed to be caused by misplaced class II histocompatibility (HLA II) antigens on the surface of hepatocytes. It is not knownwhat it is caused by, maybe a genetic factor plays a role, viral infection (e.g. hepatitis A or B, also EBV infection), toxic agents (interferon, melatonin, methyldopa, nitrofurantoin) as well as autoantigens such as hepatic receptor asioglycoprotein and cytochrome P-450 IID6. On the other hand, more than 85% of patients are not exposed to any of these factors.
Initially, it was thought to affect young women who also have other autoimmune diseases. It is now known that autoimmune hepatitis is a multi-organ disease, it can affect both genders at any age, although women account for 70-80% of all patients. Two age peaks are observed. Most often they occur between 10-20. year and 45-70. year Over 50% of patients are patients over 40 years of age
There are three types of autoimmune hepatitis:
- type I (AIH1) - classic - the most common (affects about 80% of all patients)
- type II (AIH2) - diagnosed mainly in children, adults get sick less often (10% of all patients)
- type III (AIH3) - characterized by the presence of antibodies other than type I and II
The course of autoimmune hepatitis can be mild or asymptomatic, or very severe, with periods of remission and exacerbation. Approximately 20% of patients experience spontaneous remission, but the most common diagnosis is the mildly symptomatic form of the disease. Then the dominant symptom, and sometimes the only one, is fatigue, which increases during the day and hinders proper functioning. This symptom is so uncharacteristic that it is often underestimated by the patient. Other symptoms include:
- lack of appetite
- weight loss
- pains in the right hypochondrium
- itchy skin
- bone and joint pains
- nose bleeds
In women, menstrual disorders, intensification of acne, increased hair, which indicates accompanying hormonal disorders. Symptomatic autoimmune hepatitis develops jaundice and symptoms resembling acute viral hepatitis.
At diagnosis, 25% of patients have cirrhosis, another 30% will develop cirrhosis despite treatment and normalization of laboratory test results, and untreated patients will develop cirrhosis in more than 80% of cases.
Characteristic for AIH is the coexistence of other autoimmune diseases, such as: thyroiditis, ulcerative inflammationcolon, rheumatoid arthritis, diabetes or celiac disease.
Laboratory tests show a 5-10 fold increase in the activity of AST and ALT transaminases, a slight increase in the activity of GGT (gammaglutamyltransferase) and AP (alkaline phosphatase), hypergammaglobulinemia with hypoalbuminemia, prolonged prothrombin time.
The presence of autoantibodies is important for diagnosis. Antibodies against mitochondrial ANA and anti-smooth muscle ASMA (86-91% of patients) are of great importance mainly in type I AIH. In type II, anti-LKM-1 (hepatorenal anti-microsomal antibodies) and anti-LC-1 ( anti-cytosolic). The presence of SLA / LP antibodies (against soluble antigens of the liver and pancreas cells) and the lack of antibodies characterizing the previous two types is a different type of type III. In addition, most patients with AIH have antibodies to the ASGPR asialoglycoprotein receptor.
In order to differentiate AIH from other disease entities (e.g. chronic hepatitis C, drug-induced or alcohol-induced damage, and primary sclerosing cholangitis) and make the final diagnosis, it is necessary to perform a liver biopsy and histopathological evaluation.
Primary biliary cirrhosis (PBC)
It is a chronic liver disease with an immune background, in the course of which the small intrahepatic bile ducts are destroyed. It is more common in women, mainly between the ages of 30 and 60. It is manifested by chronic fatigue (about 60% of patients), breathing problems and itching of the skin (50% of patients), which may appear months or years before other symptoms. Jaundice is present when the disease is advanced. The features of portal hypertension, cholestasis (cholestasis), hyperlipidemia, and osteoporosis are less common.
Laboratory tests that allow for the diagnosis of cholestatic syndrome are helpful in the diagnosis of PBC. It is characterized by:
- increase in alkaline phosphatase activity (50% of patients)
- increase in GGTP (gamma-glutamyltranspeptidase enzyme)
- increase in total bilirubin
Increased bilirubin at diagnosis and its progression indicate advanced disease and worsen prognosis. With time, the levels of immunoglobulins, mainly of M class (IgM), and cholesterol (50-90% of patients) increase.
Another important diagnostic criterion is the identification of characteristic inflammatory changes in the bile ducts on the histopathological examination of the liver. Relevant forconfirmation of the diagnosis is the presence of AMA anti-mitochondrial antibodies (35-95% of patients), including:
- AMA M2 (in 95% of patients) - PBC-specific marker
- AMA M4 (up to 55% of patients)
- AMA M8 (up to 55% of patients)
- AMA M9 (35-85% of patients)
as well as ANA antinuclear antibodies (50% of patients) and / or ASMA (20-30% of patients).
PBC is often associated with other autoimmune diseases, e.g. Sjögren's syndrome, rheumatoid arthritis, scleroderma, thyroiditis, Raynoud's disease, lichen planus, systemic lupus erythematosus, pernicious anemia, pemphigus.
Primary sclerosing cholangitis (PSC)
It is a chronic autoimmune disease that causes damage to the intra and extrahepatic bile ducts. It occurs mainly in young men. 50-70% of patients are additionally diagnosed with ulcerative colitis, less often diabetes, autoimmune thyroiditis, Sjögren's syndrome, and pancreatitis.
Clinical symptoms, as in other inflammatory diseases of the liver, are often non-specific. These include chronic fatigue, weight loss, and itchy skin. About 50% of patients have no symptoms. In laboratory tests, an increase in the activity of ALP and GGTP is observed, AST and ALT increase to a lesser extent.
There is also hypergammaglobulinemia - it mainly affects IgM and IgG immunoglobulins (45-80% of patients). About 80% of patients have pANCA antibodies against the cytoplasm of granulocytes (depending on the method used, they are also referred to as MPO - against granulocyte myeloperoxidase), and 20-50% of patients have ANA and ASMA antibodies.
Source:
1. David C Wolf, MD, FACP, FACG, AGAF, FAASLD et al., Autoimmune Hepatitis, updated September 25, 2017 https://emedicine.medscape.com/article/172356-overviewa6, accessed October 15, 2017
2. Francque, Sven et al. "Epidemiology and Treatment of Autoimmune Hepatitis." Hepatic Medicine: Evidence and Research 4 (2012): 1-10. PMC. Web. 15 Oct. 2022