Various chronic diseases can affect the liver. We usually look for them if we find persistent elevations in liver function tests (LFTs), sometimes discovered by accident on a lab test done for other reasons. We’ve all heard of Hepatitis B and Hep C; there’s also Hep D (Hep A and Hep E get better on their own and don’t persist chronically – see Differences Among Hepatitis Viruses).
But there are other Liver Diseases as well; they’re all pretty rare, except for Fatty Liver at the end. The others are described here mainly FYI, if somebody is getting tests done because their LFTs were high. The blood tests we use to find them are in italics.
Hemochromatosis — Iron-overload, which can be caused by taking too much iron, but is usually a hereditary genetic condition. It’s most common among Caucasian men >40 and post-menopausal women. It affects mainly the liver, but later on other organs as well like the pancreas, heart, joints, and pituitary gland.
Once high LFTs are noted, we order blood tests for iron: ferritin, and the transferrin saturation (not just the transferrin, a common mistake). If these are very high, we look for genetic mutations, or refer the patient to Hematology specialists. Treatment involves removing a unit of blood every month or so; no problem, since the patient has way too much iron. Otherwise, the liver will gradually develop cirrhosis with failure.
Wilson’s Disease — Copper overload, also a genetic condition. It’s very rare, usually begins in childhood or by teenage years, but can occur later as well. In addition to liver disease, which can flare suddenly and lethally, the disease can cause neurological symptoms (speech and coordination difficulty, tremors, awkward movements, and sometimes psychosis (without liver manifestations).
The initial diagnostic test is a blood test finding a low ceruloplasmin level; other tests include 24-hour urine collection for copper, images, and likely a liver biopsy. Although rare, Wilson’s is worth looking for, as it’s 100% treatable, and 100% fatal otherwise (from either acute liver failure, or chronic cirrhosis).
Autoimmune Hepatitis (AIH) — Like other autoimmune diseases, our immune system mistakenly attacks the body itself, for reasons poorly understood. Liver damage progresses gradually without symptoms, until Cirrhosis and chronic liver failure develop (acute liver failure can rarely occur).
When we find elevated LFTs, we do blood tests for an elevated Antinuclear Antibody (ANA), IgG level (gamma globulin), maybe an anti-Smooth Muscle antibody. Hepatologists have many other labs to order. Eventually, diagnosis is aided by liver biopsy. Treatment includes a variety of medications to suppress the immune system.
Alpha-1 Antitrypsin Deficiency — Also a genetic condition which usually affects the lungs (causing COPD), but certain variants can damage the liver, either in early childhood, or adulthood. Diagnosis is initially made by finding a low level of blood alpha-1 antitrypsin. There’s no treatment for the liver disease, except liver transplant once liver failure progresses. Transplantation of a genetically-unaffected liver can be curative.
Primary Biliary Cirrhosis (PBC) — An autoimmune disease that destroys the liver bit by bit, without any symptoms until cirrhosis and liver failure. We usually suspect it by finding a very high blood level of Alkaline Phosphatase; the ALT and AST may even be normal. The next step in diagnosis is to order a GGT enzyme to prove we’re dealing with the liver; a normal GGT means the Alkaline Phosphatase came from bone (or pregnancy, or not having been done fasting).
An Ultrasound or other imaging is usually done, not to find PBC, but to rule out cancers of the liver or gallbladder. The main diagnostic blood test is then an Anti-Mitochondrial Antibody. If that’s high, some specialists will do a liver biopsy. But the blood test is probably so accurate that treatment can be given without biopsy. Treatment is for life, but it works very well.
Primary Sclerosing Cholangitis (PSC) — A rare disease of the gallbladder (biliary) ducts, PSC is also an autoimmune disease of unknown cause. Diagnosis is made by 1) finding an elevated Alkaline Phosphatase on a lab test, often with normal ALT and AST like PBC just above. 2) Again, a high GGT blood test proves the Alkaline Phosphatase is from the liver, not bone. Ultrasound of the liver is usually normal.
But unlike PBC above, the Anti-Mitochondrial Antibody is negative, leading to special MRI tests of the bile ducts to make the diagnosis. Also, the various treatments don’t work, until liver transplantation becomes necessary once cirrhosis develops. Since so many patients with PSC also have Ulcerative Colitis, there is a high risk of Colon Cancer, thus frequent colonoscopies are recommended.
Celiac Disease — Caused by sensitivity to gluten in foods, and more well-known for causing diarrhea, Celiac Disease can also cause ALT and AST to rise. It’s a rare cause of elevated LFTs, but we might rule it out by ordering a blood test for tissue-Transglutaminase Enzyme IgA Antibody.
Liver Cancer — Many cancers can spread to the liver, causing LFTs to rise. Ultrasound can find the metastases, and can also find primary liver cancer (one that starts in the liver itself). The latter usually only occurs in persons with chronic Hepatitis B or C infection, or with Cirrhosis from any liver disease that has advanced.
However, the vast majority of people with elevated LFTs have NONE of the above illnesses. But on ultrasound, many seem to have abnormal fat deposits, so we simply diagnose them as having “Fatty Liver”. Most of the time, nothing will happen, although some will develop end-stage cirrhosis. See the link for fuller explanation.