OVERVIEW
常染色体基因突变导致的遗传病，引起肝脏多发囊性病变
大多数患者无症状，少数因肝脏增大出现腹胀、右上腹痛、营养不良等症状
主要与PRKCSH、SEC63等常染色体基因突变有关
手术治疗为主，辅以药物治疗
Definition
Polycystic liver is an inherited disease caused by an autosomal gene mutation that results in multiple cystic lesions of the liver during embryonic development due to disorders of intrahepatic bile ducts or lymphatic vessels.
Polycystic liver can exist either on its own as an isolated polycystic liver or in combination with polycystic kidneys.
Staging and Classification
Hepatic cysts are categorized according to their size, number and volume of liver parenchyma, generally Gigot typing and Schnelldorfer typing [2].
Gigot分型
Gigot type I: It refers to the number of hepatic cysts <10 and the diameter of the largest cyst >10 cm.
Gigot type II: refers to a large number of medium-sized cysts diffused in the liver parenchyma, and the remaining liver parenchyma volume is larger than the total cyst volume.
Gigot type III: A large number of medium-sized cysts diffuse in the liver parenchyma, and the remaining liver parenchyma volume is smaller than the total cyst volume.
Schnelldorfer分型
Type A: Patients are asymptomatic or mildly symptomatic with a small number of cysts, normal liver parenchyma > 3 lobes, and no portal or hepatic vein occlusion in the reserved lobes.
Type B: Patients presenting with moderate or severe symptoms, small number and large size of cysts, normal liver parenchyma ≥ 2 liver lobes, and reserved liver lobes without portal or hepatic vein occlusion.
Type C: Patients presenting with severe symptoms, a high number and small size of cysts, normal hepatic parenchyma > 1 hepatic lobe, and preserved hepatic lobes without portal or hepatic vein occlusion.
Type D: Patients presenting with severe symptoms, an uncountable number of cysts, normal hepatic parenchyma < 1 liver lobe, and portal or hepatic vein occlusion in the preserved liver lobes.
Morbidity
Prevalent in people with a family history of polycystic liver.
Etiology
Polycystic liver is generally associated with autosomal gene mutations.
Causes
The exact cause of polycystic liver is not yet clear, but current research suggests that it is mostly related to autosomal gene mutations, such as PRKCSH, SEC63, PKD1, PKD2, GANAB and so on. Gene mutation can cause the developmental disorder of intrahepatic bile ducts during embryonic development, leading to the accumulation of cystic fluid and the formation of cysts, which in turn causes polycystic liver.
Risk factors
Family history of polycystic liver, elderly women and those with multiple pregnancies are at high risk for polycystic liver.
Symptoms
Most patients do not have any clinical symptoms. A few patients with polycystic liver may have gastrointestinal symptoms such as abdominal distension, right upper abdominal pain, nausea, vomiting, etc., due to the enlargement of the liver, and in severe cases, symptoms of hepatic insufficiency such as jaundice and malnutrition may occur.
Main Symptoms
Digestive tract symptoms
Manifested as abdominal distension, abdominal pain, early satiety, acid reflux, nausea, vomiting.
Sometimes patients may have anorexia symptoms.
Liver insufficiency
Manifested by skin pigmentation, emaciation, decreased appetite, anorexia, malnutrition, dyspnea.
Symptoms become more severe when the cysts spread throughout the liver and the liver parenchyma shrinks.
Other symptoms
Kidney damage
Patients with polycystic liver are often combined with polycystic kidneys, which usually have clinical manifestations such as hypertension, abdominal pain, hematuria, elevated blood creatinine, and elevated blood urea nitrogen.
Complications
Polycystic liver can cause complications such as hemorrhagic shock, jaundice, and infection.
Hemorrhagic shock
When the cysts of polycystic liver patients are too big and rupture or internal bleeding, it can cause hemorrhagic shock.
The main manifestations are panic, pallor, cold sweat, drop in blood pressure, fainting and so on.
Jaundice
Jaundice can be caused by the compression of bile ducts by more or larger cysts in patients with polycystic liver.
The main manifestations are yellow staining of sclera, skin and mucous membrane, itching of skin, etc.
Infection
Polycystic liver may develop intracystic infection.
The main manifestations are chills, fever, increased white blood cell count, etc.
Consultation
Department of Medicine
Hepatobiliary Surgery
When the patient has symptoms such as right upper abdominal pain, abdominal distension, nausea, vomiting, etc., or the physical examination suggests polycystic liver, it is recommended to consult the Department of Hepatobiliary Surgery or the Department of General Surgery in time.
Preparation
Consultation: Registration, Preparation of Information, Frequently Asked Questions
Tips for medical treatment
It is recommended to wear clothes that are easy to put on and take off before the doctor’s visit, so that the doctor can conduct a physical examination.
Preparation Checklist
症状清单
Time of onset of symptoms, special symptoms, etc.
Are there any symptoms such as pain in the upper right abdomen, abdominal distension, nausea, vomiting, etc.?
Are there symptoms such as decreased appetite, fatigue, anorexia, dyspnea, etc.?
When did these discomforts start and were there any aggravating or relieving factors?
病史清单
Does an immediate family member have polycystic liver?
Has the female patient ever given birth? What is the number of pregnancies?
检查清单
Test results in the last six months to bring to the doctor’s office
Laboratory tests: liver function tests, kidney function tests, CA19-9.
Imaging tests: abdominal ultrasound, CT examination.
Diagnosis
Diagnosis is based on
Medical history
The patient may have a family history of polycystic liver.
Clinical manifestations
症状
Patients may present with symptoms such as abdominal distension, abdominal pain, nausea, vomiting, decreased appetite, and yellowish skin.
体征
In some patients with polycystic liver, scattered cystic nodules without obvious tenderness can be palpated in the liver area, and when the cysts are large, a mass can be palpated in the right upper abdomen, usually without obvious pressure pain.
Laboratory tests
肝功能检查
In most patients with PLD, liver function tests are usually normal because the liver parenchyma is not completely destroyed.
However, in some severe patients, there are elevations of gamma-glutamyltransferase (γ-GT), alkaline phosphatase (AKP), aspartate aminotransferase (AST) and total bilirubin (TBIL).
肾功能检查
Patients with polycystic liver combined with polycystic kidney may have elevated blood creatinine and blood urea nitrogen.
糖类抗原199（CA19-9）
Some patients exhibit elevated CA19-9, and the degree of elevation is positively correlated with polycystic liver volume.
Patients with significantly elevated CA19-9 should be considered for cystic co-infection.
Imaging
腹部B超检查
Abdominal ultrasound is a reliable and easy way to diagnose polycystic liver, which can understand the location, size, and adjacent tissues.
Ultrasound examination of patients with polycystic liver reveals hepatomegaly, multiple echogenic foci with clear borders, connected to each other in pieces, and the slender and smooth cystic wall separating them into multilocular cystic cavities of varying sizes.
腹部CT检查
It can visualize the size, number and anatomical location of the cysts and assist in the diagnosis of polycystic liver.
CT examination of patients with polycystic liver shows diffuse intrahepatic variable-sized, watery low-density shadows with smooth and clear edges.
Differential diagnosis
Polycystic liver should be differentiated from hepatic cysticercosis, primary hepatocellular carcinoma, hepatic cavernous hemangioma and other diseases:
Hepatic cysticercosis
Similarities: both may present with symptoms of bloating, abdominal pain, nausea, vomiting, and decreased appetite.
Differences:
多囊肝患者可有多囊肝家族遗传史，一般早期无临床症状，肝功能检查一般无异常，腹部B超、CT等影像学检查即可鉴别。
肝包虫病多见于牧区，患者一般有牛、羊接触史，血常规检查可发现嗜酸性粒细胞增多、转氨酶升高，包虫皮内试验和包虫补体结合试验阳性。B超检查出现弧形钙化、双层壁囊肿结构的典型特征，一般可以通过病理检查明确诊断。
Primary liver cancer
Similarities: both may present with abdominal pain, weakness, and decreased appetite.
Points of difference:
多囊肝患者可有多囊肝家族遗传史，CT检查显示肝内弥漫大小不一、水样低密度阴影、边界清楚，CT增强下无变化。
原发性肝癌患者一般有肝炎、肝硬化病史，肝功能检查可发现甲胎蛋白明显升高，CT增强下可出现肝脏占位明显强化。
Treatment
Aim of treatment: improve patients’ symptoms, treat complications, protect liver function, and try to delay disease progression.
Treatment principle: Polycystic liver without clinical symptoms generally does not need treatment; some patients need surgery and drug treatment when organ failure occurs due to increased liver size or when complications such as rupture of cysts, infection and bleeding occur.
Surgical treatment
Cyst aspiration and sclerotherapy
Suitable for patients with Gigot type I or patients with polycystic liver whose single cyst diameter is >5 cm.
The cystic cavity is injected with a sclerosing agent such as ethanol, which destroys the epithelial cells of the cyst wall and inhibits the production of cystic fluid, thus closing the cystic cavity.
Cystotomy
It is suitable for patients with Gigot type I or II, or patients with polycystic liver who have failed sclerotherapy by cyst aspiration.
The cystic fluid is drained into the abdominal cavity by creating a channel between the cysts.
Patients may experience postoperative complications such as ascites, pleural effusion, bleeding, and bile leakage.
Transcatheter arterial embolization
For patients with polycystic liver who cannot tolerate surgery.
An embolic agent is used to selectively embolize the arterial branches that supply blood to the cysts, thereby destroying the cyst wall cells, cutting off the source of cystic fluid, and controlling the progression of the disease.
Hepatic resection
It is suitable for patients with Gigot type II or III polycystic liver who have good liver function and at least part of the liver without obvious lesions.
It is often combined with open decortication to deal with unresectable cysts.
Liver transplantation
It is indicated for patients with Schnelldorfer type D or polycystic liver with severe symptoms and complications such as portal hypertension and malnutrition.
Liver transplantation is currently the only cure for polycystic liver.
Medication
Growth inhibitor analogs
Growth inhibitor analogs can inhibit the secretion of cystic fluid and the proliferation of bile duct cells, thus inhibiting the growth of liver cysts.
Commonly used drugs include Octreotide, Lanreotide, Paritide.
Precautions: The use of these drugs is contraindicated in pregnant women, lactating women, and children.
Target protein (mTOR) inhibitors
As immunosuppressants, mTOR inhibitors can inhibit the growth of liver cysts and slow down the progression of the disease.
Commonly used drugs: sirolimus and everolimus.
The evidence for recommending treatment with mTOR inhibitors is not yet comprehensive and more research evidence is needed to support this.
Frontline therapy
Gene editing is the transporter of DNA for the purpose of amplifying endogenous gene expression by stimulating endogenous cellular repair mechanisms after causing a break in the double strand of the target DNA. With the discovery of the disease-causing gene GANAB, it provides the basis for gene therapy for PLD. However, the technology is still immature, and it is still time for gene therapy to enter the clinic [1].
Ursodeoxycholic acid was confirmed to have the effect of delaying the growth of liver cysts in PLD animal model experiments.
Prognosis
Cure
The vast majority of patients are asymptomatic and do not require surgical intervention, while only a small percentage of patients develop symptoms and require treatment.
In these asymptomatic or minimally symptomatic patients, i.e., Schnelldorfer type A patients, observation or growth inhibitor analog therapy is sufficient.
In patients with Schnelldorfer B, who have large cysts but a small number of cysts, a decortication procedure is performed to reduce the size of the cysts and alleviate symptoms.
Patients with Schnelldorfer D polycystic liver have a poorer prognosis and are prone to portal or hepatic vein occlusion.
Daily
Daily management
Dietary management
Reasonable dietary arrangement, pay attention to eat more nutritious and easy-to-digest food, such as lean meat, eggs and fish.
Intake of vitamin-rich fresh fruits and vegetables can supplement the vitamins needed by the body to promote recovery.
Need to quit smoking and alcohol, avoid greasy and spicy food.
Patients with combined kidney damage should have a low protein diet and eat more food such as corn, spinach, beans and tomatoes.
Life management
Avoid exertion, regular work and rest, and ensure sufficient sleep.
Appropriate exercise is needed in daily life to improve physical fitness and avoid low immunity.
Pay attention to protect yourself, especially the right upper abdomen to avoid external impact.
Prevention
People with a family history of polycystic liver should have genetic counseling and prenatal diagnosis before pregnancy and delivery.
People with a family genetic history of polycystic liver should have regular medical checkups in order to detect the disease in time and intervene early if treatment is needed.
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