Hepatic simple cysts are common benign liver lesions frequently encountered in clinical practice. These fluid-filled sacs are lined with epithelial cells, typically lacking solid components, and usually do not communicate with the biliary tree or vascular structures. They are characterized by a single layer of cuboidal or flattened epithelial cells, surrounded by a fibrous wall composed of collagenous tissue. The exact origin of hepatic simple cysts remains uncertain. While the majority are asymptomatic and detected incidentally during imaging, approximately 5% of patients may experience symptoms, often related to the size and location of the cysts or the development of complications.

Management of symptomatic cysts may involve percutaneous or endoscopic ultrasound (EUS)-guided aspiration with sclerotherapy, or surgical intervention, aimed at alleviating symptoms by reducing cystic volume. Solely aspirating cystic fluid tends to lead to complete cyst recurrence. Given the high recurrence rate, various management strategies have been proposed, focusing on sclerotherapy to disrupt secretory epithelial cells. Numerous protocols for aspiration sclerotherapy have been explored, varying primarily in the choice of sclerosing agent (e.g., ethanol, tetracycline, polidocanol), infused volume, and retention time. Generally, these studies indicate good symptom improvement, reduced cyst volume, and a favorable safety profile.

This review aims to revise the management approach for simple hepatic cysts by introducing two key changes based on recent practices. First, it advocates for a proactive management strategy, suggesting that intervention should not be delayed until cysts become symptomatic. Untreated growing cysts can lead to complications, making non-invasive management more challenging and increasing the likelihood of surgical intervention. Second, the review supports the use of sclerotherapy—either EUS-guided or percutaneous—as the first-line therapy for simple hepatic cysts, based on evidence demonstrating its effectiveness and safety. By addressing these changes, the review seeks to enhance current management strategies for simple hepatic cysts.

Hepatic simple cysts are frequently found as incidental findings in abdominal imaging studies. Prevalence rates vary, with United States studies reporting a prevalence of 3-5% in the general population, while computed tomography (CT) and magnetic resonance imaging (MRI) studies report rates as high as 15-18%, compared to ultrasound. The prevalence of hepatic cysts tends to increase with age, particularly among older individuals, and some studies suggest a slightly higher prevalence in women than in men. Risk factors linked to hepatic cysts include obesity, female gender, and a history of liver disease, although the precise relationship between these factors and cyst prevalence requires further investigation. The predominance of hepatic cysts in females may be influenced by hormonal factors, such as estrogen levels, warranting additional research into the underlying mechanisms.

The pathogenesis of hepatic simple cysts is not fully understood, and several theories have been proposed. One theory suggests these cysts arise from congenital malformations or developmental irregularities during embryogenesis, particularly due to abnormal dilation or budding of bile ducts [1]. Another theory posits that cysts may form from the obstruction of small intrahepatic bile ducts, leading to bile accumulation and ductal dilation. The hydrostatic pressure theory indicates that elevated pressure within the liver, caused by conditions such as venous congestion, may promote cyst formation. Additionally, some theories propose that cysts could originate from fluid extravasation from adjacent structures. While there is some evidence for a genetic predisposition to cyst development, further research is needed to clarify the genetic factors involved in cystogenesis.

Hepatic simple cysts are often asymptomatic and detected incidentally during imaging studies. However, approximately 5% of patients may present with symptoms such as abdominal pain, early satiety, nausea, vomiting, or abdominal distention due to the size or location of the cysts. Clinical examination may reveal a palpable abdominal mass or hepatomegaly. Systemic signs like hemodynamic instability, fever, or jaundice typically indicate complications related to the cyst. Although most simple hepatic cysts are benign, complications such as intracystic hemorrhage, cyst rupture, obstructive jaundice, and infection can occur in a small percentage of cases.

While there are no specific laboratory tests to definitively diagnose hepatic simple cysts, certain blood tests can help assess liver function, identify potential complications, and guide further management. Commonly requested tests include liver function tests, which are typically normal in hepatic cysts. However, elevated liver enzyme levels may indicate underlying liver disease or complications, such as infection or bile duct obstruction. Tumor markers, including carcinoembryonic antigen and CA 19-9, may also be elevated. Notably, CA 19-9 is expressed in the inner epithelial lining of a simple cyst, leading to increased levels in both cyst fluid and serum.

Various imaging modalities are utilized to diagnose and assess hepatic simple cysts, providing detailed anatomical information for accurate characterization. Abdominal ultrasound is the primary tool for identifying these cysts, revealing well-defined, round or oval anechoic lesions that often exhibit posterior acoustic enhancement. CT scans help differentiate hepatic cysts from other liver lesions, typically showing low attenuation hypodense lesions with smooth, thin walls that do not enhance with contrast. MRI provides distinct features, with cysts appearing hypointense on T1-weighted images and hyperintense on T2-weighted images, characterized by uniform signal intensity and well-defined margins. While ultrasound is highly effective for diagnosing simple hepatic cysts due to its sensitivity and cost-effectiveness, CT or MRI may be necessary for complex lesions or further characterization

A crucial step in narrowing the differential diagnosis of hepatic cysts is differentiating between simple and complex cysts, with particular attention to complex features observed on imaging studies. Simple hepatic cysts can be either solitary or multiple. The differential diagnosis for hepatic cysts includes both benign and malignant lesions. Benign conditions such as polycystic liver disease, Caroli disease, and biliary hamartoma must be considered, while malignant lesions, including biliary cystadenoma, biliary cystadenocarcinoma, and mucinous cystic neoplasms, should be excluded before making therapeutic decisions

The management of simple hepatic cysts varies based on their presentation. Asymptomatic cysts are typically managed with observation and monitoring to assess stability and detect potential complications early. However, for symptomatic or rapidly growing cysts, treatment is warranted. Treatment options include percutaneous aspiration, aspiration with sclerotherapy, and surgical intervention. Table 1 outlines the advantages and disadvantages of each treatment modality.

Percutaneous aspiration was once a common method for treating liver cysts, but its use has declined due to high recurrence rates that can approach 100% [2].

Aspiration sclerotherapy combines the percutaneous drainage of cyst fluid with the subsequent instillation of a sclerosing agent, which destroys the inner lining of the cyst [3]. Various sclerosing agents have been employed in this approach, with ethanol being the most widely utilized [4-6]. Ethanol is preferred for its safety, efficacy, and minimally invasive nature. It serves as a primary treatment option for symptomatic congenital hepatic cysts, particularly in patients at high surgical risk or those with polycystic liver disease [7].

Since Bean and Rodan [4] first reported ethanol as a sclerosing agent for treating simple hepatic cysts, it has remained the agent of choice. Studies have explored the efficacy of ethanol sclerotherapy using different concentrations (95%, 96%, and 99%) and variations in exposure time (from 10 to 240 minutes), the volume of alcohol used, and the number of treatment sessions (either single [8-10] or multiple [11,12]). Additionally, the route of cyst drainage–whether percutaneous or EUS-guided–can influence treatment outcomes for hepatic cysts [13,14]. Other sclerosing agents have also been investigated in the context of simple hepatic cyst sclerotherapy, including minocycline [15], polidocanol [16], ethanolamine oleate [17], hypertonic saline solution [18], and doxycycline [19], all of which have shown promising results.

Most studies on sclerotherapy for simple hepatic cysts have been conducted using percutaneous guidance, with only a few utilizing both percutaneous and EUS-guided techniques. In a study by Lee et al. [20], the route for either endoscopic ultrasound-guided ethanol therapy (EUS-ET) or percutaneous drainage-guided ethanol therapy (PCD-ET) was selected based on factors such as lesion size, location, and complexity. EUS-ET was predominantly used for patients with left-sided, multiple, and relatively small hepatic cysts. while PCD-ET was primarily performed for right-sided and larger cysts. Patients were considered for intervention if they exhibited symptoms related to a large simple liver cyst, such as abdominal pain, nausea, vomiting, or early satiety. Additionally, those showing a rapid increase in cyst size on imaging, even without symptoms, were also considered for intervention.

According to the approach described by Larssen et al. [21], the cyst was punctured under ultrasonographic guidance, followed by the introduction of a stiff guide wire and the insertion of a 30-cm 7 French (2.3 mm outer diameter) pigtail catheter into the cyst as far as possible. Once the cyst was fully drained, contrast material was injected, and radiographs were taken to confirm the catheter’s position and rule out communication with biliary ducts or leakage into the peritoneal cavity. Ethanol was then injected in an amount equivalent to 10% of the cyst volume, never exceeding 100 mL. To ensure optimal contact between the ethanol and the cyst wall, the patient’s position was adjusted from prone to supine and from right to left lateral decubitus position at least twice during the procedure. Finally, all ethanol was evacuated, and the cyst was irrigated with saline to prevent leakage during catheter removal, after which the catheter was withdrawn (Fig. 1).

In the study by Lee et al. [20], the EUS-guided technique proceeded as follows: using a therapeutic curved linear array EUS, the target liver cyst was identified. A 19- or 22-gauge needle was inserted to puncture the cyst, allowing for the aspiration of cystic fluid followed by ethanol injection. After needle insertion, the maximum volume of cystic fluid was aspirated, ensuring the needle tip remained within the cyst, and the aspirated volume was documented for ethanol preparation. A 99% ethanol solution, not exceeding 200 cc, was then injected into the cyst through the needle, followed by prompt re-aspiration, known as lavage. After this, both the injected ethanol and residual cystic fluid were thoroughly aspirated, and the needle was withdrawn (Fig. 2). Prior to the intervention, antibiotics were administered as a preventive measure against infection.

Based on a systematic review conducted by Wijnands et al. [22] which encompassed around 16 studies spanning from 1994 to 2015, high clinical and technical efficacy rates were observed following aspiration sclerotherapy of hepatic cysts without severe morbidity. However, due to the high risk of bias inherent in the studies reviewed, these findings underscore the necessity for larger, controlled studies to more precisely ascertain the efficacy and safety of aspiration sclerotherapy. Another systematic review, conducted by Furumaya et al. [23], aimed to assess the efficacy of percutaneous aspiration and sclerotherapy, as well as surgical management, in patients with symptomatic simple hepatic cysts. The review encompassed 736 patients from 34 studies, among whom 265 (36%) underwent percutaneous aspiration and sclerotherapy, 348 (47%) laparoscopic cyst deroofing, and 123 (17%) open surgical management. The primary outcomes assessed included symptom relief, symptomatic recurrence, and quality of life. The review concluded that the outcome of percutaneous aspiration and sclerotherapy for symptomatic simple hepatic cysts appears to be excellent, with symptoms persisting in less than 4% of patients, and complication and recurrence rates each less than 1%.

In a systematic review conducted by Wijnands et al. [22], thirteen studies reported on safety outcomes. The most commonly reported adverse event was pain, which was documented in eight studies. Ethanol or ethanolamine oleate was utilized in these studies. Among them, three studies reported cases of ethanol intoxication, characterized by signs such as drunkenness, headache, nausea, and flushing. The highest frequency of intoxication was noted in a study with a sclerotherapy duration of 120–240 minutes and a median volume of ethanol of 138 mL [10], the highest among all included studies. Additionally, a few other symptoms were reported, including fever, postprocedural cyst hemorrhage, and cyst infection. However, no mortality was reported across the studies.

Two common surgical options for hepatic simple cysts are fenestration (cyst unroofing or deroofing) and hepatic resection.

Typically performed using minimally invasive laparoscopic or robotic techniques, fenestration is occasionally enhanced by argon beam coagulation or the insertion of the greater omental flap into the former cavity. This approach offers advantages such as shorter recovery times, reduced postoperative pain, and improved cosmesis compared to open surgery. It is effective in relieving symptoms, reducing cyst size, and preventing recurrence in the majority of cases, with low rates of complications [24,25].

Hepatic resection should be reserved for cases of recurrence after deroofing, diffuse hepatic involvement, and multiple hepatic cysts due to the increased risk of morbidity [26]. The approach to hepatic resection may involve open surgical techniques or minimally invasive approaches, depending on factors such as the size and location of the cysts and the extent of liver resection required. While hepatic resection provides definitive treatment by completely removing the cyst, it carries risks such as bleeding, bile leak and infection, Additionally, hepatic resection is associated with longer operative times, hospital stays, and recovery periods compared to fenestration [27].

Simple hepatic cysts are common in the general population and are usually asymptomatic. Management is typically indicated when cysts are symptomatic or rapidly growing. However, given the safety and efficacy of available non-invasive management options, it may be more beneficial to adopt a proactive approach, especially in cases involving large or rapidly growing cysts. Even in the absence of symptoms, early intervention could prevent potential complications and reduce the need for more invasive treatments in the future

Recent systematic reviews analyzing multiple studies have highlighted the high clinical and technical efficacy rates associated with aspiration sclerotherapy for hepatic cysts, demonstrating promising outcomes without severe morbidity [22,23]. with lower rate of recurrence compared to surgical deroofing [23] Additionally, sclerotherapy is associated with a lower incidence of complications compared to surgical intervention [28]. Erdogan et al.’s [29] study revealed a 20% recurrence rate in the sclerotherapy group, attributed to potential factors like inadequate sclerosant instillation or insufficient exposure of the cyst lining to the sclerosant, especially in larger cysts. Conversely, the surgical group demonstrated a higher recurrence rate at 27%. The review by Moorthy et al. [28] compared aspiration sclerotherapy to surgical deroofing, suggesting that the efficacy of alcohol sclerosis and laparoscopic deroofing is nearly equivalent, with the added benefit of fewer adverse events associated with aspiration sclerotherapy. However, due to differences in study endpoints and the absence of randomization, determining the safest and most effective treatment remains inconclusive. The recent European Association for the Study of the Liver Guidelines and the American College of Gastroenterology Clinical Guideline does not favor one treatment over others due to the lack of high-quality randomized controlled trials directly comparing these volume-reducing therapies. They advised to treat simple hepatic cysts based in the best locally available volume-reducing therapy with emphasized that volume reduction after aspiration sclerotherapy is slow in onset and may take at least 6 months. They advise against reintervention during the initial 6 months following aspiration sclerotherapy. They reported good volume reductions ranging between 76% and 100% after aspiration sclerotherapy, with symptom relief achieved in 72% to 100% of cases and symptom disappearance occurring in 56% to 100% of cases [1-30]. Given the available evidence, we propose aspiration sclerotherapy as the first-line treatment option due to its minimally invasive nature and good safety profile. Laparoscopic cyst deroofing should be reserved as a secondary approach for cases of cyst recurrence, atypical simple cysts, or suspicious pre-malignant cyst features on imaging.

The time may be ready to adopt a more proactive approach in therapeutic decision-making for simple hepatic cysts and to consider aspiration sclerotherapy as the preferred initial treatment for simple hepatic cysts, given its minimally invasive nature, good clinical success rates, and favorable safety profile. Laparoscopic fenestration should be reserved as a second-line treatment for cases of cyst recurrence. Open hepatic resection would serve as a final option for recurrent cysts or if sclerotherapy and/or laparoscopic cyst deroofing are not feasible.