So, an autoimmune disease is this special sort of disease, where your own immune cells have gone rogue and start to attack your own cells, right? Hepatitis happens to mean inflammation of the liver, so it’s reasonable to say that autoimmune hepatitis is this resulting inflammation of your liver tissue, because they’re being attacked by your own immune cells. Like many autoimmune diseases, the root cause of autoimmune hepatitis is, ultimately, not super clear, but some researchers think it’s a combination of environmental triggers and genetic predisposition. It tends to occur most often in young women, and the female to male ratio is about 4:1. Also though, an important piece of the genetic puzzle is the Human Leucocyte Antigen system, shortened to HLA, which is this location of genes on chromosome 6 that regulate our immune functions. Specifically, these genes control the proteins that are encoded and used on the cell’s surface to present foreign molecules to the immune system. But, although they present antigens, they’re also a form of antigen themselves. They aren’t, though, the same type of antigen as one on an infectious molecule, but actually alloantigens that vary from person to person, and are, actually, specific “self-proteins”. Usually, our thymus makes sure that the T-cells that attack these self proteins aren’t allowed to survive. In autoimmune disease, there may be some abnormality associated with specific self-proteins that lets the T-cells attack them. Based on studying people with autoimmune hepatitis, they often have HLA-DR3 and -DR4, which are both MHC class II surface receptors, The DR part refers to its location on the chromosome. For example, depending on the location, you could have HLA-A, HLA-B, HLA-C or HLA D, and HLA-D has three subregions: P, Q and R. So, this one is HLA-DR. So, specifically with autoimmune hepatitis, there seems to be some sort of connection between these particular “self-proteins”, the HLA-DR, and mounting an attack against your own liver. Autoimmune hepatitis also tends to be associated with other diseases, like Hashimoto’s thyroiditis, where your immune cells attack your thyroid, and Grave’s disease, where your thyroid overproduces thyroid hormones. Clinically, autoimmune hepatitis patients can sit anywhere on a spectrum from completely asymptomatic, to cirrhosis and fulminant hepatitis, also known as acute liver failure, or they might be somewhere in-between with debilitating symptoms like fever, jaundice, and hepatosplenomegaly, a condition where both the spleen and the liver are way larger than their normal size, probably caused by inflammation due to immune cell attack. Also, for symptomatic patients, there’ll be this increase in blood transaminases. Usually, there’s only a small amount of transaminases in the blood, which are these enzymes that help metabolise amino acids. Alanine aminotransferase, or ALT, is mostly found only in the liver, and aspartate aminotransferase, or AST, is found in both the liver as well as other tissues. So, if the liver cells are damaged by immune cells, both ALT and AST start leaking out into the blood from the liver, but typically since ALT is more associated with the liver, ALT will be higher than AST, even though they both will likely be elevated. Autoimmune hepatitis can be split into two types: Type 1 is the most common, accounting for about 80% of autoimmune hepatitis cases, and is characterised by several lab findings. First, we’ll look for antibodies to your own nuclei that are floating around in your blood. We also call these antinuclear antibodies, or ANAs, and these antibodies have failed to be able to tell the difference between self and non-self, and so they end up being against the proteins in the nuclei of your own cells. Also, along the same lines, we might find antibodies that are targeting your own smooth muscle proteins as well. Decreased serum albumin is also a marker for autoimmune hepatitis and damage to the liver. Usually, serum albumin is produced in the liver, but if the liver becomes damaged, serum albumin production may decrease. Finally, an elevated or prolonged prothrombin time, which is the time it takes your blood to clot, is a typical lab finding in more severe cases. Type 2 autoimmune hepatitis is way less common, and is defined by the presence of antibodies to the microsomes of the liver or your kidney, ALKM-1, or to a liver cytosol antigen, ALC-1. This type is most common in young girls, and usually happens alongside another autoimmune disease. As to treatment, initially, patients can be given immunosuppressant medications. They may be given corticosteroids, which help inhibit the immune responses that are mediated by both B- and T-cells. Another drug, azathioprine, has a similar immunosuppressing action and inhibits an enzyme that we need to synthesise DNA, and so it strongly inhibits cells, like T-cells and B-cells, that proliferate a lot during an immune response. If patients are resistant to these drug therapies, they might have to undergo a liver transplant.