Hepatic Cysts

Simple cysts

The cause of simple liver cysts is not known, but they are believed to be congenital in origin. The cysts are lined by biliary-type epithelium (see the image below), and perhaps result from progressive dilatation of biliary microhamartomas. Because these cysts seldom contain bile, the current hypothesis is that the microhamartomas fail to develop normal connections with the biliary tree. Typically, the fluid within the cyst has an electrolyte composition that mimics plasma. Bile, amylase, and white blood cells are absent. The cyst fluid is continually secreted by the epithelial lining of the cyst. For this reason, needle aspiration of simple cysts is not curative, and recurrence is the norm.

Polycystic liver disease

Adult PCLD (AD-PCLD) is congenital and is usually associated with autosomal dominant polycystic kidney disease (AD-PKD). Mutations in these patients have been identified in PKD1 and PKD2 genes. Occasionally, PCLD has been reported in the absence of polycystic kidney disease (PKD). In these patients, a third gene, protein kinase C substrate 80K-H (PRKCSH), has been identified. Despite these differences in genotype, patients with PCLD are similar phenotypically.[2]

In patients with PKD, the kidney cysts usually precede the liver cysts. PKD often results in renal failure, whereas liver cysts only rarely are associated with hepatic fibrosis and liver failure.

Neoplastic cysts

Liver tumors with central necrosis visualized on imaging studies are often misdiagnosed as liver cysts. True intrahepatic neoplastic cysts are rare. The cause of cystadenomas and cystadenocarcinomas is unknown, but they may represent proliferation of abnormal embryonic analogs of the gallbladder or biliary epithelium. These cystic tumors are lined with biliary-type cuboidal or columnar cells and are surrounded by ovarianlike stroma. Cystadenoma is a premalignant lesion with neoplastic transformation to cystadenocarcinoma confirmed by tubulopapillary architecture and invasion of the basement membrane.

In a retrospective study, Kim et al investigated the value of quantitative color mapping of the liver’s arterial enhancement fraction (AEF) in the detection of hepatocellular carcinoma (HCC).[3] The investigators determined that when the color maps were analyzed in combination with multiphasic computed tomography (CT) scans, the mean sensitivity for HCC detection reached 88.8%, in comparison with 71.7% sensitivity for HCC detection using the multiphasic CT scans alone.

Hydatid cysts

Hydatid cysts are caused by infestation with the parasite Echinococcus granulosus. This parasite is found worldwide, but it is particularly common in areas of sheep and cattle farming.

The adult tapeworm lives in the digestive tract of carnivores, such as dogs or wolves. Eggs are released into the stool and are inadvertently ingested by the intermediate hosts, such as sheep, cattle, or humans. The egg larvae invade the bowel wall and mesenteric vessels of the intermediate host, allowing circulation to the liver.

In the liver, the larvae grow and become encysted. The hydatid cyst develops an outer layer of inflammatory tissue and an inner germinal membrane that produces daughter cysts. When carnivores ingest the liver of the intermediate host, the scolices of the daughter cysts are released in the small intestines and grow into adult worms, thus completing the life cycle of the worm.[4, 5]

Hepatic abscesses

Hepatic abscesses can be amebic or bacterial in origin. Entamoeba histolytica is the causative agent in amebic abscesses. It is contracted by ingestion of food or water contaminated by the cyst stage of the parasite. Amebiasis generally only involves the intestine but can invade the mesenteric venules resulting in liver abscesses. Its only host is the human. Pyogenic abscesses can be a result of instrumentation but are most often caused by ascending cholangitis in the setting of biliary obstruction. Microorganisms isolated are most often bowel flora. Other routes of contamination include the portal vein and hepatic artery.

Patients with intra-abdominal infections may present with liver abscesses with extension of bacteria through the portal venous system. Hematogenous spread via the hepatic artery in patients with septicemia is rare.

The precise prevalence and incidence of liver cysts are not known, because most do not cause symptoms; however, liver cysts have been estimated to occur in 5% of the population. No more than 10-15% of these patients have symptoms that bring the cyst to clinical attention. Hepatic cysts are usually found as an incidental finding on imaging or at the time of laparotomy. Most series in the literature are relatively small, reporting fewer than 50 patients each.

Several small series of patients undergoing laparoscopic unroofing of simple hepatic cysts have reported cure rates of 90% or higher. Kneuertz et al reported improvements in quality of life.[6]

Patients with PCLD have lower cure rates (see Table 1 below).

Table 1. Series of Patients Undergoing Laparoscopic Unroofing of Liver Cysts (Open Table in a new window)

Investigating optimal treatments for nonparasitic hepatic cysts, Mazza et al analyzed the outcomes associated with various surgical procedures used to treat these lesions.[17] The study involved the evaluation of data from 131 patients (78 with simple cysts, 53 with PCLD) treated at an institution where the authors practiced.

Mazza et al reported that laparoscopic unroofing or marsupialization (66 patients) completely relieved symptoms from either simple lesions or PCLD, with the procedure's morbidity, mortality, and recurrence rates being, respectively, 2%, 0%, and 2% for patients with simple cysts, and 25%, 0%, and 5% for patients with PCLD.[17] For infected cysts, the investigators' procedure of choice was percutaneous drainage (19 patients), the morbidity, mortality, and recurrence rates for this procedure being, for simple cysts, 0%, 0%, and 75%, respectively, and for PCLD, 0%, 0%, and 20%, respectively.

Simple cysts

Simple cysts generally cause no symptoms but may produce dull right-upper-quadrant pain if large in size. Patients with symptomatic simple liver cysts may also report abdominal bloating and early satiety. Occasionally, a cyst is large enough to produce a palpable abdominal mass. Jaundice caused by bile duct obstruction is rare, as are cyst rupture and acute torsion of a mobile cyst. Patients with cyst torsion may present with an acute abdomen. When simple cysts rupture, patients may develop secondary infection, leading to a presentation similar to a hepatic abscess with abdominal pain, fever, and leukocytosis.

Polycystic liver disease

Polycystic liver disease (PCLD) rarely arises in childhood. These cysts are observed at the time of puberty and increase in adulthood. They occur as part of a congenital disorder associated with polycystic kidney disease (PKD). Women are more commonly affected, and an increase in cyst size and number is correlated with estrogen level. In PCLD, hepatomegaly may be prominent, and patients occasionally progress to hepatic fibrosis, portal hypertension, and liver failure. Complications (eg, rupture, hemorrhage, and infection) are rare. However, patients do present with abdominal pain as the cysts enlarge.

Neoplastic cysts

Cystadenoma most often occurs in middle-aged women. However, cystadenocarcinoma equally affects both men and women. Most patients are asymptomatic or have vague abdominal complaints of bloating, nausea, and fullness. These patients, like all those with hepatic cysts, eventually present with abdominal pain. Rarely, they present with evidence of biliary obstruction.

Hydatid cysts

Patients with hydatid cysts, like those with simple cysts, are most often asymptomatic, but pain may develop as the cyst grows. Larger lesions typically cause pain and are more likely to develop complications than simple cysts. At presentation, patients generally have a palpable mass in the right upper quadrant.

Cyst rupture is the most serious complication of hydatid cysts. Cysts may rupture into the biliary tree, through the diaphragm into the chest, or freely into the peritoneal cavity. Rupture into the biliary tree may result in jaundice or cholangitis. Free rupture into the peritoneal cavity may cause anaphylactic shock. As with simple cysts, patients with hydatid cysts may develop secondary infection and subsequent hepatic abscesses.

Hepatic abscesses

Patients with hepatic abscesses present with abdominal pain, fever, and leukocytosis. Typically, symptoms are vague and relatively nonspecific, and as a result, diagnosis is often delayed. Clinical history is important because of associated illnesses. Those patients with amebiasis can have a history of diarrhea and weight loss, though some may be asymptomatic. Pyogenic abscesses often present with cholangitis, abdominal infections, or sepsis. Rarely, abscesses will rupture, and patients present with peritonitis.

The evaluation of a patient with a simple liver cyst involves carefully recording the patient history and performing a physical examination plus an imaging study (eg, abdominal computed tomography [CT]) to define the anatomy of the cyst. The clinician can minimize the cost of evaluation by obtaining only key studies that may alter the treatment plan.

Before the widespread availability of abdominal imaging techniques, including ultrasonography and CT, liver cysts were diagnosed only when they grew to an enormous size and became apparent as an abdominal mass or as an incidental finding during laparotomy. Today, imaging studies often reveal asymptomatic lesions incidentally.

Little preoperative laboratory workup is required for these patients. Liver function test (LFT) results, such as transaminases or alkaline phosphatase, may be mildly abnormal, but bilirubin, prothrombin time (PT), and activated partial thromboplastin time (aPTT) are usually within the reference range.

In the setting of polycystic liver disease (PCLD), greater abnormalities in LFT results are found, but liver failure is uncommon. Renal function test results, including blood urea nitrogen (BUN) and creatinine levels, are often abnormal and should be performed on initial evaluation.

In the presence of hydatid cysts, eosinophilia is noted in approximately 40% of patients, and echinococcal antibody titers are positive in nearly 80% of patients.

With cystic tumors, as with simple cysts, LFT results are normal. There may be mild abnormalities in some patients. Carbohydrate antigen (CA) 19-9 levels are elevated in some patients. Cyst fluid can be sent for CA 19-9 testing at the time of surgery as a marker for cystadenoma and cystadenocarcinoma.

Patients with hepatic abscesses can usually be easily identified on the basis of the clinical presentation. Leukocytosis is generally present.

The enzyme immunoassay (EIA) test detects specific antibodies to E histolytica.

The clinician has a number of options for imaging the liver in patients with hepatic cysts. Ultrasonography is readily available, noninvasive, and highly sensitive. CT (see the image below) is also highly sensitive and is easier for most clinicians to interpret, particularly for treatment planning. Magnetic resonance imaging (MRI), nuclear medicine scanning, and hepatic angiography have a limited role in the evaluation of hepatic cysts.

Simple cysts have a typical radiographic appearance. They are thin-walled with a homogenous low-density interior.

PCLD is confirmed by means of ultrasonography or CT (see the image below), with multiple liver cysts identified at the time initial of evaluation.

Hydatid cysts can be identified by the presence of daughter cysts within a thick-walled main cavity (see the image below).

In patients who are jaundiced with hydatid disease, endoscopic retrograde cholangiopancreatography (ERCP) should be performed to determine whether the cyst has ruptured into the bile duct.

Central necrosis of large solid neoplasms can mimic cystic hepatic tumors, in that this area of necrosis appears cystic.

Cystadenoma (see the image below) and cystadenocarcinoma usually appear multiloculated with internal septations, heterogeneous density, and irregularities in the cyst wall. Unlike many tumors, cystadenoma and cystadenocarcinoma are rarely associated with calcifications.

A practical problem in the evaluation of a patient with a cystic hepatic lesion is differentiating cystic neoplasms from simple cysts. Cystic neoplasms tend to have thicker, irregular, hypervascular walls, whereas simple cysts tend to be thin-walled and uniform. Simple cysts tend to have homogenous low-density interiors, whereas neoplastic cysts usually have heterogeneous interiors with septa and papillary extrusions.

Abscesses of the liver appear cystic on imaging studies (see the image below) but can usually be diagnosed from the overall clinical presentation.

Other tests are generally not necessary in the evaluation of hepatic cysts. Percutaneous aspiration should be avoided because the laboratory and cytologic evaluation of the simple cyst fluid is nondiagnostic, and a small risk exists of inducing anaphylaxis from leakage from the hydatid cyst or of causing abscess formation in a previously sterile cyst.

Histologic assessment of the excised cyst wall should be routinely undertaken to identify the presence of an unsuspected neoplasm, such as cystadenoma. In simple cysts, histology of the cyst wall generally reveals a layer of simple cuboidal epithelium.

Treatment of polycystic liver disease (PCLD) or solitary nonparasitic cysts of the liver is indicated only in symptomatic patients. Asymptomatic patients do not require therapy, because the risk of developing complications related to the lesion is lower than the risk associated with treatment.

Patients with hydatid cysts should be treated to prevent complications related to cyst growth and rupture. If cysts on imaging studies show abnormalities suggestive of cystic tumors, resection is indicated. Abscesses should be treated at the time of identification, but percutaneous drainage and antibiotics are usually adequate treatment.

Contraindications to treatment of symptomatic liver cysts relate mainly to underlying comorbid illnesses that increase surgical risk. In particular, congestive heart failure and liver failure with portal hypertension and ascites increase operative risk. Symptoms suggestive of angina or transient ischemic attacks should lead to further preoperative diagnostic studies to identify significant coronary or carotid arterial stenoses.

Guidelines for the management of cystic liver disease have been developed by the European Association for the Study of the Liver (EASL).[18] (See Guidelines.)

Simple cysts

No medical therapy has proved effective in reducing the size of simple hepatic cysts. Percutaneous aspiration guided by ultrasonography or computed tomography (CT) is technically simple but has been abandoned because the recurrence rates are nearly 100%. Aspiration combined with sclerosis with alcohol or other agents has been successful in some patients but has high failure and recurrence rates. Successful sclerosis depends on complete decompression of the cyst and apposition of the cyst walls. This is not possible if the cyst wall is thickened or if the cyst is large.

Percutaneous catheters should not be placed to drain simple cysts, because the cavity becomes contaminated, leading to the development of hepatic abscess. Unlike the typical pyogenic hepatic abscess, this problem is difficult to resolve with repeated catheter placements because of continued secretion from the cyst epithelium.

Polycystic liver disease/neoplastic cysts

No options are available for the medical treatment of PCLD or cystadenocarcinoma. Because of the malignant potential of cystadenoma, a role also does not exist for medical therapy for this lesion.

Hydatid cysts

Medical therapy with antihydatid agents (albendazole and mebendazole) is relatively ineffective. These drugs are used as adjuvant treatment, but they do not replace surgical or percutaneous therapy. In surgically treated patients, the use of antihydatid agents is generally given perioperatively; continuation is limited to those who have spillage of cyst fluid at the time of operation or to those with cyst rupture. Antihydatid agents are used in conjunction with percutaneous treatment. Medical therapy should be started 4 days before percutaneous treatment and continued either for 1 month (albendazole) or for 3 months (mebendazole), according to the World Health Organization (WHO) recommendations.

PAIR (puncture, aspiration, injection, reaspiration) is a percutaneous treatment technique for hydatid disease. In this minimally invasive method, a needle is introduced into the cyst under ultrasonographic guidance. Cyst fluid is aspirated and analyzed. Hypertonic saline or ethanol is then injected and reaspirated. PAIRD (puncture, aspiration, injection, reaspiration, drainage) is similar to PAIR except that a catheter is left in place after completion of the procedure. PAIRD is most often used for large cysts.

This percutaneous treatment with sclerosing agents was introduced in the 1980s. Since that time, its use in the treatment of hydatid cysts has been somewhat controversial. However, as this technique has become more common and its safety and efficacy have been reported in the literature, it has been increasingly accepted as a treatment option for hydatid disease. The WHO has supported PAIR as an effective alternative to surgery, though its use is limited.

The WHO recommendations for indications for PAIR are as follows[19] :

• Nonechoic lesion greater than or equal to 5 cm in diameter
• Cysts with daughter cysts and/or with membrane detachment
• Multiple cysts if accessible to puncture
• Infected cysts
• Patients who refuse surgery
• Patients who relapse after surgery
• Patients in whom surgery is contraindicated
• Patients who fail to respond to chemotherapy alone
• Children older than 3 years
• Pregnant women

The WHO recommendations for contraindications for PAIR are as follows[19] :

• Noncooperative patients
• Inaccessible or risky location of the liver cyst
• Cyst in spine, brain, and/or heart
• Inactive or calcified lesion
• Cyst communicating with the biliary tree

Patients should be followed clinically after PAIR treatment. Recurrence is increased in more complicated cysts, including those with multiple daughter cysts.

PAIR should only be performed in highly specialized centers with appropriately trained and experienced staff. In addition, an anesthesiologist should be present for monitoring and treatment in the event of anaphylactic shock. Surgeons should be notified immediately in case of complication.

Hepatic abscesses

Patients with liver abscesses are immediately started on antibiotics/amebicides. If abscesses are small, patients may respond to medications alone. More likely, these patients will require the addition of percutaneous drainage for eradication.

Simple cysts

Most patients with simple cysts are asymptomatic and require no treatment. When the cysts become large and cause symptoms, such as pain, treatment is warranted. Surgical treatment of simple liver cysts involves "unroofing" the cyst by excising the portion of the wall that extends to the surface of the liver. Excision of this portion of the cyst wall at the liver surface produces a saucer-type appearance in the remaining cyst so that any fluid secreted from the remaining epithelium leaks into the peritoneal cavity where it can be absorbed.

Although ablating the remaining epithelium with electrocautery or an argon beam coagulator is possible, this generally is not required because the volume of fluid secreted each day can be absorbed by the peritoneum without any consequence. Furthermore, ablation of the cyst wall can lead to bleeding or bile leak secondary to injury to underlying vessels and bile ducts. The cyst wall should be sent to pathology to confirm the diagnosis and exclude cystadenoma or cystadenocarcinoma as these lesions require enucleation or formal resection in the setting of cancer.

Historically, treatment of symptomatic hepatic cysts required laparotomy, but today, cyst unroofing can be successfully performed laparoscopically.[20] Anecdotal reports of laparoscopic treatment became common by the mid-1990s, and the laparoscopic approach is currently considered the standard of care.[21] As compared with laparotomy, this technique is associated with less postoperative pain and disability, shorter duration of hospital stay, and superior cosmetic results.

Polycystic liver disease

In adult PCLD (AD-PCLD), enlargement of the liver occurs slowly and only rarely compromises liver function. Only those patients with clearly disabling pain should be considered for surgery. In patients with PCLD, the surgical goal is to decompress as much of the cystic liver as possible. This can be accomplished by a combination of unroofing and fenestration or, in selected patients, by resection of the involved portion of the liver (see the image below). Recurrence of symptoms with either procedure is high as new cysts replace those that have been resected. Small numbers of patients have been treated with liver transplantation.[22]

Neoplastic cysts

Several surgical methods for treatment of cystadenoma and cystadenocarcinoma have been described. Regardless of surgical technique, all surgical options should result in complete ablation of the tumor. Enucleation and formal resection have been accepted as appropriate treatment options. Fenestration and complete fulguration have also been implemented, although, in this method, complete ablation cannot be confirmed by pathology.

Hydatid cysts

All patients with hydatid disease should be considered for percutaneous or surgical treatment because of the risk of life-threatening complications of untreated disease. More complicated cysts are better managed surgically. Treatment of hydatid cysts is associated with two technical problems: (1) risk of anaphylaxis from spillage of cyst fluid containing eggs and larvae into the peritoneal cavity and (2) recurrence caused by residual eggs in incompletely removed germinal membranes.[23]

To prevent these problems, most surgeons use a technique in which the cyst contents are aspirated and replaced with a hypertonic saline solution to kill residual daughter cysts in the germinal membrane before unroofing and pericystectomy.[24] The goal of the latter procedure is to excise the germinal membrane, leaving the inflammatory and fibrous components of the cyst wall in situ. Attempts to excise the entire cyst wall or to perform formal hepatectomy for hydatid cysts have largely been abandoned because of increased surgical morbidity.

Hepatic abscesses

In general, abscesses are adequately managed by means of antibiotics and percutaneous drainage. If abscesses persist despite attempted percutaneous drainage, surgical drainage is indicated. Other surgical indications include large cysts at risk of rupture and abscesses not anatomically amenable to percutaneous treatment.

Surgical procedure

Prepare patients for general endotracheal anesthesia. Prophylactic antibiotics are not necessary. The patient is positioned supine, with placement of orogastric and bladder catheters to decompress the stomach and bladder. The abdomen is prepared and draped in a sterile fashion.

The operation is begun by inducing pneumoperitoneum with carbon dioxide gas via placement of a Veress needle or Hasson trocar. Generally, three laparoscopic ports are required: one for the telescope with camera, one for retraction, and one to carry out the dissection. The extent of the cyst is usually readily apparent on laparoscopic inspection, but, if not, laparoscopic ultrasonography can be performed to define the cyst anatomy.

The line of the intended unroofing is marked with an electrocautery device, and the cyst excision itself is undertaken with an electrocautery or an ultrasonic or bipolar scalpel. These steps are shown in the images below. Excision of the entire cyst wall is neither necessary nor desired; if attempted, it carries the risk of injury to portal or hepatic venous vessels that may be stretched over the cyst wall.

In cases where the proportion of the cyst wall that can be excised easily is small, omentum should be positioned on a pedicle into the cyst cavity to prevent closure of the roof defect and cyst recurrence. The omentum should be sutured or clipped to the edges of the excision margin. After ensuring that hemostasis is complete, the pneumoperitoneum is desufflated and the trocar sites closed. Waterproof dressings are applied.[25]

Technical points

Expose the entire target area (mobilize the liver if necessary), and mark the intended excision line. Begin unroofing at the dependent margin (see the video below).

The ultrasonic scalpel produces less smoke and achieves better hemostasis than the monopolar cautery does.

Saucerize the large cysts (see the video below).

Fill the intraparenchymal cavities with omentum (see the video below).

In patients undergoing laparoscopic unroofing of simple hepatic cysts, the orogastric and bladder catheters can be removed before the patient awakens from anesthesia. A light diet is offered the evening of surgery, and most patients can be discharged home the following day.

Generally, recovery is rapid, and most patients resume full activity within 1 week. Patients can shower with the waterproof dressings in place the day after surgery. The dressings can be removed after 2-3 days.

Complications of laparoscopic unroofing of simple liver cysts are uncommon. Trocar-site infection is a rare occurrence. Unexpected leakage of bile from the cut edges of the cyst can lead to a subhepatic or subphrenic fluid collection or, rarely, bile ascites.

In patients with PCLD, unroofing and fenestration procedures should be performed with care to avoid injury to biliary or vascular structures in the compressed hepatic parenchyma between the cysts.

In patients with hydatid cysts, spillage of cyst contents into the peritoneal cavity, which may cause anaphylaxis, is best avoided.

After successful laparoscopic unroofing of a simple liver cyst, the patient is seen at a follow-up visit within 2 weeks and again 6 weeks after surgery to assess symptomatic relief and to identify complications, such as wound infection or ascites. Routine radiographic studies are not obtained unless symptoms recur.

In June 2022, the European Association for the Study of the Liver (EASL) published guidelines on management of cystic liver disease.[18] Recommendations included the following.

Hepatic cysts

The number of lesions (solitary vs multiple) and architecture (simple vs complex cyst) are essential in the characterization of hepatic cyst(s).

Use ultrasonography (US) as the first imaging modality for diagnosing simple hepatic cysts and polycystic liver disease (PCLD), with additional imaging for hepatic cysts with complex features such as atypical cyst wall or content, either solitary or in patients with PCLD. For diagnosis of biliary hamartomas, use magnetic resonance imaging (MRI) with heavily T2-weighted sequences and MR cholangiography sequences.

Do not use the tumor markers carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9) in blood or cyst fluid to distinguish between hepatic cysts (solitary or in PCLD) and mucinous cystic neoplasms (MCNs) of the liver.

Patients with symptomatic simple hepatic cysts without biliary communication should receive the best volume-reducing therapy available locally.

Hepatic cyst infection should be viewed as definite when accompanied by neutrophil debris and/or microorganisms in cyst aspirate with evidence of infection, and it should be viewed as likely when accompanied by features including fever for more than 3 days with no other detectable source, gas in a cyst found on computed tomography (CT) or MRI, tenderness near the liver, and increased C-reactive protein (CRP).

Fluoroquinolones and third-generation cephalosporins should be used for empiric first-line antibiotic therapy for hepatic cyst infection; antibiotics should be given for 4-6 weeks.

CT should not be used for diagnosis of cyst hemorrhage.

Temporarily stop anticoagulants in patients with hepatic cyst hemorrhage.

Polycystic liver disease

Stop exogenous estrogen in female patients with PCLD.

Treatment for PCLD should be given to symptomatic patients only.

Before pregnancy, patients with PCLD should be counseled about the risk of giving PCLD to the newborn but should not be advised against pregnancy.

Caroli disease

Patients with multiple segmental cystic or saccular dilatations of bile ducts should be evaluated for congenital hepatic fibrosis to distinguish Caroli disease from Caroli syndrome.

Consider referral for liver transplantation in patients with Caroli disease or Caroli syndrome who have recurrent cholangitis and either bilobar involvement or monolobar involvement with liver fibrosis or portal hypertension when liver resection is not possible.