Polycystic Liver Disease

What is Polycystic Liver Disease?

Polycystic liver disease, or PLD for short, is a rare genetic condition where certain gene mutations cause changes in essential liver proteins. These proteins are normally responsible for managing fluid transport and cell growth in your liver. This disorder leads to normal liver tissue being replaced by liver cysts, which are pockets filled with fluid. There are two types of PLD: one that occurs by itself and another tied to a condition called polycystic kidney disease (PKD).

Many people with PLD do not show any symptoms. In fact, the condition is usually discovered by accident when a person gets an ultrasound, CT scan, or MRI for another reason. However, a small number of people with PLD experience an enlarged liver, which can cause abdominal discomfort, a bloated feeling, and put pressure on nearby organs, potentially impacting their quality of life.

For those who have symptoms caused by PLD, the main treatment goal is to decrease the size of the liver. Do note that there are a few surgical options available, including removing fluid from the cysts (cyst fenestration), surgically removing a part of the liver (hepatic resection), or in severe cases, a liver transplant. Interestingly, there are medications under investigation that might help treat PLD in the near future. It’s therefore extremely important to get regular medical check-ups and follow up on your PLD diagnosis and management plans regularly.

What Causes Polycystic Liver Disease?

Polycystic liver disease (PLD) is caused by changes, or mutations, in several genes. In some cases, this happens in genes known as PRKCSH and SEC63. These genes carry instructions for proteins which help to move fluids and aid in the growth of cells in the liver’s lining. We aren’t sure exactly how these genes are involved in the formation of cysts, which are fluid-filled sacs that can cause complications.

A second type of PLD is linked to polycystic kidney disease (PKD). There are two kinds of PKD – one that is commonly passed from parent to child (autosomal-dominant PKD or ADPKD) and another that is less common and more severe (autosomal recessive PKD or ARPKD). In these cases, the kidneys are the organ most affected. Many people with this disease eventually need treatments like dialysis or a kidney transplant, as their kidneys stop working properly over time.

The genes involved in ADPKD are called PKD1 and PKD2. They are in charge of creating proteins that control fluid movement and cell growth. When these genes have mutations, they can cause problems with fluid control and unusual growth, resulting in the formation of cysts.

Most individuals with ARPKD, unfortunately, don’t survive long after birth due to lung complications. Those who do survive often develop liver fibrosis, which involves scarring of the liver, rather than cysts.

Risk Factors and Frequency for Polycystic Liver Disease

Polycystic liver disease (PLD) was originally thought to only develop in patients with polycystic kidney disease (PKD). However, in the 1950s, it was recognized as a separate condition, and this was confirmed genetically in 2003 through the study of eight Finnish families. In the general population, PLD affects between 1 to 10 people per million, while PKD affects between 1 in 400 to 1 in 1000 people. Interestingly, about 80 to 90% of all PLD patients also have PKD.

Because PLD is inherited in an autosomal pattern, it should affect males and females equally. But, studies have found that PLD is about six times more common in females than in males. This is due to higher levels of estrogen in females, which can stimulate the production of cysts. Consequently, women tend to experience more symptoms and a more severe form of PLD than men.

Signs and Symptoms of Polycystic Liver Disease

Most individuals with Polycystic Liver Disease (PLD) don’t experience any symptoms and are typically diagnosed by chance during imaging tests. However, those who do experience symptoms tend to have many large cysts that cause issues by pressing against structures inside the liver. Some commonly reported symptoms include abdominal bloating, shortness of breath, a feeling of fullness after eating, acid reflux, stomach pain, and back pain. In some cases, these symptoms can lead to problems like malnutrition.

When these cysts press on blood vessels in the liver, it can lead to a condition called portal hypertension. Some people with this condition show symptoms such as internal bleeding, yellowing of the skin and eyes (jaundice), fluid accumulation in the abdomen (ascites), and mental confusion (encephalopathy). This condition can be caused by either disruption of blood flow out of the liver or by compression of blood flow into the liver. Typical symptoms associated with obstruction of blood flow into the liver include abdominal pain, enlargement of the liver, and fluid buildup in the abdomen.

In some instances, liver cysts can cause symptoms similar to Budd-Chiari syndrome, a condition where the veins that drain blood from the liver are blocked. This presents with abdominal pain, fluid buildup in the abdomen, and an enlarged liver. If PLD progresses, it can lead to serious complications such as cyst infection, twisting of the cysts, cyst rupture, and bleeding. In severe cases, the liver can become cirrhotic, which is a condition characterized by the buildup of scar tissue that replaces healthy liver tissue. Patients with advanced PLD who undergo significant liver enlargement may not meet the standard criteria for a liver transplant but can be considered for transplant due to failure to thrive and malnutrition.

Testing for Polycystic Liver Disease

The diagnosis of Polycystic Liver Disease (PLD, a condition where numerous cysts form on the liver) usually relies on imaging studies like ultrasound, MRI, and CT scans, though there aren’t any universal criteria for diagnosing it through these methods as of now. Typically, this condition is identified in people in their 40s or 50s. In an ultrasound, the liver would show areas that are brighter than the surrounding tissue, while in CT and MRI scans, cysts would appear as dark, well-defined areas.

Doctors often use the ‘Reynolds criteria’ to diagnose PLD. This takes into consideration the patient’s family history, age, and the appearance of the liver in medical imaging. The initial test recommended is an ultrasound to identify cysts in the liver and kidney. It’s important to rule out another disease called ADPKD before diagnosing PLD, this is where the ‘Ravine criteria’ comes in handy.

However, diagnosing between these two diseases can sometimes be complicated as up to a third of people with PLD can also have a few kidney cysts. For people with kidney cysts, ADPKD is diagnosed based on age and the number of kidney cysts: three or more cysts for ages 15-39, two or more cysts for ages 40-59, and four or more cysts for those over 60.

In some cases, PLD is diagnosed even when simply 15-20 cysts are found and the person has no family history of the disease. According to Reynold’s criteria, though, patients need to have a family history of the disease and ruled out for ADPKD to be diagnosed with PLD. If these conditions apply, they are further categorized based on age and liver appearance in imaging; people under 40 with one or more liver cysts, or people over 40 with four or more liver cysts, then meet the criteria for PLD.

As of now, there is no laboratory test designed to specifically diagnose PLD, and most of these patients have a normal functioning liver. Some, however, might show a slight increase in the levels of GGT (a protein involved in processing drugs and toxins) and alkaline phosphatase (an enzyme found in several tissues throughout the body). On the contrary, people with ADPKD often show signs of kidney dysfunction, such as changes in levels of creatinine (a waste product in the blood), blood urea nitrogen (a waste product in the blood), and glomerular filtration rate (a test of kidney function).

Treatment Options for Polycystic Liver Disease

Many people with Polycystic Liver Disease (PLD) don’t experience any symptoms and may not require any treatment at all. However, for those who do have symptoms, there are several treatment options available with the main goal being to reduce the size of the liver and the cysts to relieve any discomfort. These treatments range from medication to surgery and even potentially a liver transplant as a last resort.

Medical treatment for PLD is still being explored in research studies, so the options may not be as plentiful. Here are a few under consideration:

An option being studied is Octreotide, a treatment that has shown potential in positively impacting those with PLD. It works by blocking the production of a substance in the body called cAMP, which contributes to cell growth and fluid secretion. Clinical trials have shown that Octreotide can reduce the volume of the liver and improve patient symptoms. It’s important to note that these medications are usually well-tolerated, with side effects such as diarrhea, stomach discomfort, and gallstones being generally temporary.

Another drug being researched is Sirolimus, which is found to be overactive in patients with PLD and contributes to cyst growth. Some studies have shown that Sirolimus can successfully inhibit cyst growth, but the use of this drug in patients with PLD is not routinely recommended and requires further testing in larger clinical trials.

Researchers are also looking into Vasopressin-2-receptor antagonists that work to slow down cyst growth. In one large study, a drug named Tolvaptan slowed kidney growth in patients but its effect on liver cysts is not yet fully understood. Further research is underway to better understand the benefits of this drug in patients with PLD.

There is also a belief that the female hormone estrogen contributes to cyst growth, hence the disease affects women at a higher rate than men. There have been anecdotal reports about the use of estrogen receptor antagonists in PLD, but no formal studies as of yet.

Asides from medications, there are also surgical options available. Percutaneous Cyst Aspiration and Sclerotherapy is a procedure where doctors remove fluid from a cyst under imaging guidance and then inject an agent that destroys the cyst lining to prevent fluid from building up again. This procedure can relieve symptoms in many patients, most especially those with cysts larger than 5 cm in size.

Laparoscopic Cyst Fenestration is another surgical technique where multiple cysts can be treated at once. The cysts are aspirated and then the top is removed, preventing further fluid accumulation. However, after the operation, patients may experience complications such as abnormal fluid buildup, bleeding, or bile leaks.

A Segmental Hepatic Resection may be recommended for patients that have cysts confined to certain areas of their liver. In this procedure, the cyst-ridden segments of the liver are removed, however, this is typically reserved for those patients with severe symptoms and large liver size where a liver transplant would not be the first option. Post-surgery complications can include bleeding or bile leaks.

Lastly, a liver transplant may be an option for some patients, notably those with widespread cystic disease making resection unfeasible or those with impaired liver function. This process involves a thorough assessment of the patient’s general health and nutritional status. Despite it being a drastic measure, liver transplant survival rates are promising with the majority of liver grafts and patients surviving past five years.

When thinking about Polycystic Liver Disease (PLD), there are other possible causes that need to be excluded. This encompasses:

Cancers (neoplasm)
Infections
Trauma or injuries

Medical imaging helps to separate PLD from liver-related issues like metastases (cancer spread) or an abscess (swelling filled with pus). Other possible conditions that are related to the biliary tree (channels in the liver that make bile) are Caroli disease and Caroli syndrome. Both these conditions are:

Born with (congenital) genetic disorders affecting bile ducts within the liver
Usually seen in children, while PLD appears often in adults
Associated with congenital hepatic fibrosis, a rare liver disease from birth

What to expect with Polycystic Liver Disease

PLD, or Polycystic Liver Disease, is a condition that tends to worsen over time. However, only a small group of patients actually experience severe symptoms. The first step in treating PLD, especially in patients with acute or chronic abdominal pain, is pain management with medication taken as necessary. The main goal of treating PLD is reducing the size of the liver to help relieve symptoms and improve the patient’s quality of life.

There are several more invasive procedures that have been shown to help improve patient outcomes. These include aspiration sclerotherapy (a procedure that involves draining and then sealing off cysts in the liver), laparoscopic cyst fenestration (a minimally invasive surgery that creates openings in the cysts to drain them), liver resection (removing part of the liver), or liver transplantation. However, it’s important to keep in mind that while these procedures can offer significant benefits, they also come with the risk of serious complications. Therefore, these risks and benefits need to be carefully considered before proceeding.

Possible Complications When Diagnosed with Polycystic Liver Disease

People with PLD (Polycystic Liver Disease) may face several complications. We can divide these complications into two categories: those taking place within the liver cysts (intra-cystic complications) and those related to the overall size of the liver (liver volume complications).

Intra-cystic Complications

Hemorrhage in Liver Cyst
A patient can have a bleed inside their liver cyst, which usually comes on as sudden pain in the right upper part of the abdomen. This pain may get worse in the first few days before it subsides on its own. This may happen due to high pressure inside the cyst, fast growth, or a direct injury. Doctors can identify these bleeds using ultrasound, and sometimes CT scans or MRI may be needed to tell the difference between a bleed and a cancer. All three health issues – adenocarcinoma (a type of cancer), adenoma (a type of benign tumor), and a bleed inside a cyst – look similar on ultrasound.

Liver Cyst Infections
Liver cyst infections are rare and are believed to occur when bacteria move from the intestines to infect a cyst. The common symptoms are pain in the right upper part of the abdomen, fever, and a general feeling of discomfort. An image of an infected cyst may show thickened walls and complex fluid inside it, meaning it is suggestive of infection but not accurate for diagnosis. The best method of diagnosis is aspiration, or drawing out cyst fluid and checking for presence of inflammatory cells and bacteria. Two bacteria that commonly cause these infections are E. coli and Klebsiella species. A specific scan named FDG-PET can help identify infected cysts, but it is not always accurate, particularly in the early stages of infection.

Treatment usually includes broad-spectrum antibiotics, which are then tailored according to the type of bacteria identified from cultures. Antibiotics fail to treat infection adequately in about 64% of cases, and in these instances, cyst drainage is recommended. A type of protein named C-reactive protein can help monitor the effect of treatment.

Liver Cyst Ruptures
When a liver cyst bursts, it’s an extremely rare event that’s been discussed only in specific case reports. This happens due to an increase in cyst size that may happen suddenly or be caused by a bleed. Imaging will show free fluid around the liver and what’s left of the burst cyst. This leads to severe belly pain, which is usually managed with supportive care and rest. However, if the patient’s vital signs become unstable, drainage of fluids from the belly or from other liver cysts may be required, or even a surgical evaluation and intervention.

Liver Volume Complications

Complications from the size of the liver are also very unusual. They happen when large cysts or an enlarged liver press on nearby organs. The consequences can be a blockage of the flow of bile causing yellowing of the body (jaundice), portal vein blockage, an increase in blood pressure in the vessel leading to the liver (portal hypertension) with swollen veins in the spleen, narrowing of the vessels draining blood from the liver (Budd-Chiari syndrome), and pressure on the main blood vessel carrying blood from the lower half of the body to the heart (inferior vena cava), causing fluid buildup in the belly (ascites). Treatment should be personalised according to the specific complications.

The last relatively rare complication found is liver cyst cancer which usually presents as belly pain and weight loss, typically seen in patients with advanced liver disease.

Preventing Polycystic Liver Disease

PLD, or polycystic liver disease, is a condition that gets worse over time. However, only a small number of those with the disease experience severe symptoms. If the symptoms are mild, doctors typically suggest managing them with supportive care. In more serious cases, surgery may be required. The only way to completely cure PLD is through a liver transplant.

Sadly, there aren’t many effective treatments for PLD right now. Scientists are studying possible new treatments in clinical trials. Certain factors can increase a person’s risk of developing a severe form of PLD. These include: age, being female, using hormone therapy in the past (exogenous estrogens), and having multiple pregnancies.

PLD is typically passed down through families, with a 50% chance of a parent with PLD passing it to their children. Therefore, people severely affected by PLD are advised to seek genetic counseling. This service can help understand the difference between PLD and another similar condition called ADPKD.

Screening for PLD in everyone is not recommended, as the disease is not very common. Thus, widespread screening would not be beneficial.

Frequently asked questions

Polycystic Liver Disease (PLD) is a rare genetic condition where gene mutations cause changes in essential liver proteins, leading to the replacement of normal liver tissue with fluid-filled cysts. It can occur by itself or be tied to a condition called polycystic kidney disease (PKD).

Polycystic liver disease affects between 1 to 10 people per million in the general population.

Some signs and symptoms of Polycystic Liver Disease (PLD) include: - Abdominal bloating - Shortness of breath - Feeling of fullness after eating - Acid reflux - Stomach pain - Back pain In some cases, PLD can lead to complications such as malnutrition. When the cysts press on blood vessels in the liver, it can cause portal hypertension, which may result in symptoms like internal bleeding, jaundice (yellowing of the skin and eyes), ascites (fluid accumulation in the abdomen), and encephalopathy (mental confusion). Obstruction of blood flow into the liver can cause symptoms such as abdominal pain, liver enlargement, and fluid buildup in the abdomen. PLD can also cause symptoms similar to Budd-Chiari syndrome, including abdominal pain, fluid buildup in the abdomen, and an enlarged liver. If PLD progresses, it can lead to serious complications such as cyst infection, twisting of the cysts, cyst rupture, and bleeding. In severe cases, the liver can become cirrhotic, characterized by the buildup of scar tissue that replaces healthy liver tissue. Patients with advanced PLD who experience significant liver enlargement may not meet the standard criteria for a liver transplant but can be considered for transplant due to failure to thrive and malnutrition.

Polycystic Liver Disease (PLD) is caused by changes, or mutations, in several genes, including PRKCSH and SEC63.

The doctor needs to rule out the following conditions when diagnosing Polycystic Liver Disease: - Cancers (neoplasm) - Infections - Trauma or injuries - Metastases (cancer spread) - Abscess (swelling filled with pus) - Caroli disease (congenital genetic disorder affecting bile ducts within the liver) - Caroli syndrome (congenital genetic disorder affecting bile ducts within the liver) - Congenital hepatic fibrosis (rare liver disease from birth)

The types of tests needed for Polycystic Liver Disease (PLD) include: 1. Imaging studies: Ultrasound, MRI, and CT scans are commonly used to diagnose PLD. These imaging tests can help identify the presence of cysts on the liver and determine their appearance. 2. Reynolds criteria: Doctors use the Reynolds criteria, which takes into account family history, age, and liver appearance in medical imaging, to diagnose PLD. 3. Ravine criteria: The Ravine criteria are used to rule out another disease called ADPKD before diagnosing PLD. This criteria considers age and the number of kidney cysts to differentiate between the two conditions. 4. Laboratory tests: Currently, there is no specific laboratory test designed to diagnose PLD. However, some patients with PLD may show slight increases in the levels of GGT and alkaline phosphatase, which are proteins and enzymes found in the liver. It's important to note that the diagnosis of PLD is based on a combination of these tests and criteria, and the presence of symptoms.

Polycystic Liver Disease (PLD) can be treated through various methods depending on the severity of symptoms. For individuals without symptoms, treatment may not be necessary. However, for those experiencing discomfort, the main goal of treatment is to reduce the size of the liver and cysts. Treatment options include medication, such as Octreotide and Sirolimus, which have shown potential in reducing liver volume and improving symptoms. Vasopressin-2-receptor antagonists, like Tolvaptan, are also being researched to slow down cyst growth. Surgical options, such as Percutaneous Cyst Aspiration and Sclerotherapy, Laparoscopic Cyst Fenestration, and Segmental Hepatic Resection, can provide relief for larger cysts or cysts confined to specific areas of the liver. In severe cases or when liver function is impaired, a liver transplant may be considered.

When treating Polycystic Liver Disease (PLD), there may be some side effects associated with the different treatment options. Here are the potential side effects for each treatment: - Medications: - Octreotide: Side effects may include diarrhea, stomach discomfort, and gallstones, but these are generally temporary. - Sirolimus: The use of this drug in patients with PLD is not routinely recommended, and further testing in larger clinical trials is required. - Vasopressin-2-receptor antagonists: The side effects of drugs like Tolvaptan on liver cysts are not yet fully understood, and further research is underway. - Surgical options: - Percutaneous Cyst Aspiration and Sclerotherapy: This procedure can relieve symptoms, but there may be complications such as abnormal fluid buildup, bleeding, or bile leaks. - Laparoscopic Cyst Fenestration: After the operation, patients may experience complications such as abnormal fluid buildup, bleeding, or bile leaks. - Segmental Hepatic Resection: Post-surgery complications can include bleeding or bile leaks. - Liver transplant: While the survival rates are promising, there can be complications associated with the transplant surgery. It's important to note that these side effects may vary from person to person, and it's essential to consult with a healthcare professional for personalized information and guidance.

The prognosis for Polycystic Liver Disease (PLD) varies depending on the individual. Many people with PLD do not show any symptoms and have a normal life expectancy. However, for those who experience symptoms, the main treatment goal is to decrease the size of the liver to relieve symptoms and improve quality of life. There are surgical options available, such as cyst fenestration, hepatic resection, or liver transplant, but these procedures come with the risk of serious complications.

A hepatologist or a gastroenterologist.

Gut Health Liver Disease