Liver disease is a medical term referring to any condition that affects and potentially damages your liver. It accounts for approximately two million deaths per year worldwide.¹ Cholestatic liver diseases have distinct features that set them apart from other types of liver disease.
In this article, we’ll cover what cholestatic liver diseases are, the symptoms, causes, and complications, and how doctors diagnose and treat these types of liver diseases.
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Cholestasis is where bile doesn’t form properly or flow out of the liver.² Bile is the digestive fluid your liver produces to break down food, especially fats.
Bile usually flows into your gut. When it doesn’t leave the liver properly, this leads to a build-up of bilirubin, which can cause jaundice (yellowing of the skin and eyes).
Factors both inside and outside the liver can cause cholestasis.
Common intrahepatic cholestatic liver diseases include:
Primary biliary cholangitis (PBC)
Primary sclerosing cholangitis (PSC)
Cholangiopathy due to COVID-19.
These are typically slow, progressive liver diseases where your body attacks your cells, causing bile duct destruction. However, the mechanisms that cause this in both diseases differ.
You may notice numerous signs and symptoms of cholestatic liver disease. In some cases, specific symptoms may be present in certain types of cholestasis. For an accurate diagnosis, it’s best to get your symptoms checked by a healthcare professional.
Symptoms may include:
Itchiness (anywhere on the body)
Light-colored stools (poop)
Deficiency in fat-soluble vitamins
Loss of appetite
Apart from cirrhosis, several other complications can arise from chronic cholestasis.
Metabolic bone disease can occur, resulting in osteoporosis, osteopenia, and overall low bone mineral density. This is especially evident after liver transplants, for about 4–6 months.
Itching is a common symptom of cholestatic liver disease that can decrease your quality of life. It can cause decreased mood, concentration, appetite, and sleep.
Unhealthy fat levels in your blood (dyslipidemia) can also be a potential complication. When this occurs, yellow plaques may collect around your eyelids, palms, and soles.
Fat-soluble vitamin deficiency can also occur due to lacking bile to digest fats.
Depending on whether the disease is acute or chronic, several things can cause cholestasis:
Common bile duct stones or cholangitis
Drug-induced liver injury
Intrahepatic cholestasis of pregnancy (ICP)
Primary sclerosing cholangitis (PSC)
Causes can also depend on whether it is intrahepatic or extrahepatic.
Intrahepatic cholestasis is due to an impairment of bile formation. Extrahepatic cholestasis is due to irregular bile flow after bile forms.
Causes of intrahepatic cholestasis include:
Drugs and toxins
Hepatitis (viral and alcoholic)
Infiltrative diseases (amyloidosis, lymphoma, etc.)
Causes of extrahepatic diseases include:
Parasites (liver flukes, Ascaris lumbricoides)
Bile duct tumors (benign and malignant)
Cholecoholithiasis (a gallstone in your bile duct)
A specific cholestatic liver disease called intrahepatic cholestasis of pregnancy (ICP) can occur during the late second or third trimester of pregnancy. This condition can have potential complications for the health of the mother and the baby, so it’s best to be monitored by a doctor.
The causes and risk factors vary depending on the person. However, people with a personal or family history of developing cholestasis of pregnancy or a history of liver damage have an increased risk. Causes can include anything from genetics to pregnancy hormones.
Symptoms of cholestasis of pregnancy include:
Without a rash
Often starting at night
On the palms of hands and feet
Progressing to the rest of the body
Loss of appetite
The last two symptoms are common in most pregnancies, so it's important to watch out for the first two symptoms in particular.
Because cholestatic liver diseases can be complex, clinical evaluation of cholestasis usually occurs in several steps.
This will include telling your doctor about your medications and any illnesses. In most cases, providing your family history is vital, as genetics can play a role in liver cholestasis development.
Your doctor will look for physical signs, such as jaundice, dark urine, and pale stools.
Your doctor will check for an enlarged spleen and liver, jaundice, skin pigmentation, and scratch marks.
If necessary, your doctor will order an abdominal ultrasound, CT, and similar imaging, such as MRCP. Ultrasound imaging of the liver is crucial to determine whether the disease is intrahepatic or extrahepatic. These are non-invasive tests.
In most cases, these tests will investigate the extent of liver dysfunction and check bilirubin levels and serum albumin. Your doctor may also check your levels of vitamins A, D, E, and K, as deficiency can be present in long-standing cholestasis.
If you still present with unexplained and persistent cholestasis, your doctor may recommend liver biopsies to determine the cause.
Treatment of liver cholestasis usually depends on the type of liver disease present (PBC or PSC) and whether it’s intrahepatic or extrahepatic.
For PBC, the risk of developing cirrhosis is high if you don't seek treatment. When cirrhosis occurs, the median time to death is 6–10 years without intervention.
While no cure for PBC is available yet, treatment includes ursodeoxycholic acid (UDCA).³ This medication significantly delays the progression of liver cirrhosis.
The second-line treatment for PBC is obeticholic acid (OCA). This was FDA-approved in 2016 and is suitable for people who don’t respond well to UDCA. Other treatment options for PBC include fibrates and liver transplantation.
Multiple clinical trials have been investigating treatment options for PSC. For now, no drugs have shown promise in improving long-term outcomes. The mainstays of treatment are lifestyle changes and management of itching.
Cholestatic liver diseases can have long-term complications on health. It's best to get a diagnosis and treatment plan as soon as possible.
Common signs and symptoms include jaundice, itchiness, and fatigue, all of which can greatly affect your quality of life.
While no cures for the various types of cholestatic liver disease are available yet, medications may slow disease progression and eventual cirrhosis.
At present, no cure exists for PBC, a common cholestatic liver disease. However, your doctor should monitor the disease progression and treat you accordingly. Scientists generally accept that drug therapy is effective at delaying the course of the disease.
In some cases, a liver transplant is necessary, highlighting the importance of early diagnosis and intervention.
Drugs such as antibiotics, NSAIDs, and psychotropic agents typically cause drug-induced cholestatic liver disease. However, almost all types of drugs, herbal products, and supplements can cause liver injury.
Risk factors that increase your susceptibility to drug-induced issues include:
Using multiple medications (comedication)
Depending on the type of cholestatic liver disease you have, the causes may be different. These include:
Infections, such as COVID-19
Blockages, such as gallstones, cysts, or tumors
Ursodeoxycholic acid (2022)
Cholestasis | MSD Manual Version