9 Rare Liver Diseases You Never Heard About

The liver is an essential organ. Its main job is to filter the blood and eliminate waste products, although over 500 unique functions have been found. 

Unfortunately, many things can go wrong with the liver. We have all heard of common liver conditions like viral hepatitis, but there are also many rare conditions. 

Here is a list of ten rare liver diseases. These conditions are divided into three categories — genetic diseases, immune-mediated and inflammatory diseases, and liver cancers. 

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Genetic liver diseases 

Genetic liver diseases are typically inherited from your parents. However, in rare cases, the mutations may be de novo “new” as well. In these cases, people are born with genetic changes leading to liver disease. However, people don’t always develop the condition early in life and may only start to experience issues during a stage of adulthood, depending on the disease.

Here are five rare genetic liver diseases you probably haven’t heard of.

1. Wilson disease 

Wilson disease is a disease of copper metabolism. It stops copper from being processed properly by the body. Wilson disease is caused by a genetic difference that stops microscopic copper transporting channels from working correctly. 

Consequently, copper cannot be released into bile and excreted, thus it builds up in the liver and other organs. This buildup causes progressive liver damage and may necessitate liver transplantation.

Though the majority of patients are diagnosed early in life, Wilson disease can emerge at any time. It has many symptoms, primarily affecting the liver and brain/nervous system. 

2. Acute hepatic porphyrias

Acute hepatic porphyrias (AHP) are a group of genetic conditions caused by genetic alterations in the heme pathway. Heme is part of a special protein that helps red blood cells carry oxygen and is important in numerous other molecules used in different metabolic pathways. As you can imagine, any disturbances of heme can cause significant issues. 

The most common type of AHP is called acute intermittent porphyria (AIP). This is also the most common of this group of diseases. This disease is inherited from one generation to the next, in a dominant manner. However, it has a low penetrance, meaning that if either of your parents have this disease, you may or may not get it. 

Symptoms of acute intermittent porphyria include widespread pain, constipation, and severe fatigue. This usually happens in episodes which may not be diagnosed immediately. Ultimately a liver transplant may be necessary for definitive management of AIP.

3. Alagille syndrome

Alagille syndrome is a genetic condition affecting multiple organs, including the liver. It is characterized by a lack of interlobular bile ducts and many other issues, including heart disease and kidney and spinal problems. Lack of bile ducts leads to chronic bile backups, resulting in jaundice. 

It can be caused by mutations in one of two different genes, both of which are important for various bodily processes.

4. Congenital hepatic fibrosis 

Congenital hepatic fibrosis is a genetic condition affecting the liver. It causes issues in the formation of the bile ducts that carry bile within the liver, leading to destruction of the liver architecture and subsequent fibrosis.  

This condition causes high blood pressure in the liver’s blood supply, an enlarged liver and spleen, and fluid buildup in the abdomen. There is often involvement of the kidney in this disease. 

5. Polycystic liver disease 

Polycystic liver disease is a condition that sometimes occurs by itself but often develops alongside another condition, polycystic kidney disease, leading to numerous cysts on the liver. 

Most of the time, people with the condition do not have symptoms. However, when they do, these can include abdominal pain, shortness of breath, heartburn, and acid reflux. 

Immune-mediated and inflammatory liver diseases 

The term “immune-mediated and inflammatory diseases” describes a range of conditions. While different, all these diseases are defined by issues with inflammatory pathways and processes. Immune-mediated means that they are related to dysfunction of the immune system. 

Here are two rare immune-mediated and inflammatory liver diseases: 

1. Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disease, meaning there is inflammation and fibrosis of the intra/extrahepatic bile ducts, leading to strictures. It is often associated with inflammatory bowel disease.¹

The underlying cause is unknown, but the presence of autoantibodies, increased association with inflammatory bowel disease (IBD), and overrepresentation of certain HLAs indicate this is an immune-mediated disorder. However, it is not a full autoimmune disease, as it does not respond to immunosuppressive therapy. Many patients remain asymptomatic for a long time, but when symptoms develop, they include extreme itching and abdominal pain. 

2. Primary biliary cholangitis 

Primary biliary cholangitis is conventionally thought to be an autoimmune liver disease. Dysfunction of the immune system causes an “attack” on the cells of the bile ducts. The result is long-term blockages in the flow of bile. Long term, this results in severe liver disease and liver failure. 

Symptoms include itching and jaundice. And if presenting with advanced-stage cirrhosis, you may also experience fluid buildup in the abdomen and bleeding from blood vessels (variceal bleeding). However, most people do not have symptoms at diagnosis. 

Rare liver cancers 

Thirty-six thousand people in the US are diagnosed with liver cancer every year. Here are two rare types of liver cancer you’ve probably never heard of: 

1. Hepatoblastoma 

Hepatoblastoma is a rare liver cancer affecting children under four years old. Although rare, it is the most common primary liver cancer in children, causing over two-thirds of liver tumors in kids. Although most cases are sporadic, certain rare genetic conditions can increase the risk of developing hepatoblastoma. 

Symptoms vary but can include a lump in the abdomen, abdominal pain, extreme tiredness, jaundice, itching, and weight loss. 

2. Cholangiocarcinoma 

Cholangiocarcinoma is cancer affecting cells that form the bile ducts. Cancers like cholangiocarcinoma have a variety of causes. But there’s a close association between infection, inflammation, and cancer, meaning some of the risk factors include chronic hepatitis B or C infections, alcoholic liver disease, HIV, or congenital liver abnormalities such as Caroli disease.

The classical presentation is painless jaundice, weight loss, and abdominal pain. However, this indicates advanced disease and most patients do not have symptoms in the early stages of the disease.  

How are rare liver diseases diagnosed? 

To diagnose rare liver disease, doctors need a detailed history of symptoms and previous health issues. Sometimes, a liver biopsy may be required, where a sample of liver tissue is taken and can be looked at under a microscope. Blood tests are often needed, for instance, liver function tests. 

In the case of genetic liver diseases, a genetic analysis may be required. Doctors can look for specific genes or mutations. Sometimes, doctors use imaging techniques to visualize your liver. 

Often, doctors use a range of techniques to form a diagnosis. 

What are the treatment options for rare liver disease? 

Treatment options are dependent on your condition and circumstances. Some people have no symptoms at all. 

In extreme cases, liver transplantation may be required, for example, with liver failure. However, depending on your condition, treatment options may be less extreme. For instance, autoimmune conditions may require long-term medications. There may also be other surgical options. 

The lowdown 

Many rare diseases affect the liver, with entirely different causes and effects. 

Rare genetic liver diseases include: 

  • Wilson disease

  • Acute hepatic porphyrias

  • Alagille syndrome

  • Congenital hepatic fibrosis

  • Polycystic liver disease 

Examples of immune-mediated and inflammatory liver diseases include: 

  • Primary sclerosing cholangitis

  • Primary biliary cholangitis

Finally, some rare liver cancers include: 

  • Hepatoblastoma

  • Cholangiocarcinoma 

Diagnosis is based on symptoms, medical history, liver biopsy, liver function tests, and imaging. Numerous treatment options are available, depending on the patient’s circumstances. If you have any concerns, speak to your doctor. 

Frequently asked questions

What does “rare disease” mean? 

Although there’s no common consensus on the definition, a rare disease is typically considered to be one that affects fewer than 200,000 people in the US.

How is PSC related to IBD? 

It isn’t 100% known why PSC is strongly related to IBD. However, there are a few theories. Autoantibodies are prototypical markers associated with both PSC and IBD, thus a common autoantibody may link both diseases.²

Furthermore, there may be issues with the resident bacteria in the gut, such as “leaky gut,” indicating chronic inflammation in the gut increasing permeability of the bacteria, or “lymphocyte-homing” model, indicating activated lymphocytes in the gut home to the liver.

  1. Primary sclerosing cholangitis – a comprehensive review (2017)

  2. Primary sclerosing cholangitis and inflammatory bowel disease comorbidity: An update of the evidence (2019)

Other sources:

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