Adult Polycystic Liver Disease Research Articles

Liver transplantation in adult polycystic liver disease: the Ontario experience

BackgroundLiver transplantation (LT) remains the curative treatment for symptomatic Polycystic Liver Disease (PCLD) patients and is associated with excellent survival rates. The aim of the study is to review the Ontario experience in LT for PCLD.MethodsA retrospective study was performed from pre-existing LT databases from the LT Units at Toronto General Hospital and London Health Sciences Center, which are the two LT programs in Ontario, Canada. This database contains demographic, clinical parameters and follow-up of all patients transplanted for PCLD. Data was extracted for patients who underwent LT between January 2000–April 2017 and included follow up until December 31st, 2018.ResultsA total of 3560 patients underwent LT, of whom 51 (1.4%) had PCLD and met inclusion criteria. 43 (84%) of these patients were female. The median physiologic Model for End Stage Liver Disease (MELD-Na) score at time of referral was 13 (IQR = 7–22), however all patients required MELD-Na exception points to receive LT. The median age of transplant was 62 years (IQR = 59–64) for male vs. 52 (IQR = 45–56) for female patients. 33 (65%) of our cohort had PCLD while 9 (17.5%) had ADPKD and 9 (17.5%) had both diseases. 39 (76%) had LT due to symptoms of mass effect, while 8 (16%) had portal hypertensive complications. After a median follow-up of 6.3 (IQR = 2.9–12.5) years, the probability of survival was 96% (95% CI: 90%, 100%). Log-rank test, comparing survival analysis between males and females did not show a statistically significant difference (p = 0.26).ConclusionMost patients underwent LT for PCLD due to symptoms of mass effect with women being more likely than men to undergo LT. LT for PCLD had excellent long-term survival.

A novel hybrid emergency approach for bleeding gastric varices in adult polycystic liver disease: A case report

A novel hybrid emergency approach for bleeding gastric varices in adult polycystic liver disease: A case report

A Retrospective Histopathological Survey on Canine and Feline Liver Diseases at the University of Tokyo between 2006 and 2012

ABSTRACTTo determine the incidence of hepatic diseases in dogs and cats in Japan, a retrospective study was performed using data of 463 canine and 71 feline liver biopsies at the Veterinary Medical Center of the University of Tokyo. The most common canine hepatic disease was microvascular dysplasia (MVD) and occupied 29.4% of all diagnoses. This terminology might contain “real” MVD and primary portal vein hypoplasia, because these two conditions were difficult to be clearly distinguished histopathologically. Parenchymal and interstitial hepatitis and primary hepatic tumors accounted for 23.5% and 21.0% of the diagnoses, respectively. Parenchymal and interstitial hepatitis occupied 34.1% of non-proliferative canine hepatic diseases, while hepatocellular adenoma and carcinoma were 26.6% and 24.5% of proliferative hepatic diseases, respectively. Breed-specificity was seen in MVD for Yorkshire terrier, Papillon and Toy poodle, in hepatitis for Doberman pinscher and Labrador retriever, in cholangiohepatitis for American cocker spaniel, Miniature schnauzer and Pomeranian, in hepatocellular adenoma for Golden retriever and Shiba and in hepatocellular carcinoma for Shih Tzu. The most common feline liver disease was parenchymal and interstitial hepatitis (45.1% of all diagnoses). Among feline hepatitis, neutrophilic cholangiohepatitis (23.9%), lymphocytic cholangiohepatitis (14.1%) and chronic hepatitis (5.6%) were recorded. Adult polycystic liver disease was 5.6%. Among proliferative diseases in the feline liver (11.3% of the all), lymphoma (4.2%) and primary epithelial tumors (4.2%) including hepatocellular carcinoma, cholangiocellular adenoma and cholangiocellular carcinoma were observed. Hepatic degeneration was 14.1%, and MVD was 12.7%, respectively.

Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management.

Polycystic liver disease (PLD) is the result of embryonic ductal plate malformation of the intrahepatic biliary tree. The phenotype consists of numerous cysts spread throughout the liver parenchyma. Cystic bile duct malformations originating from the peripheral biliary tree are called Von Meyenburg complexes (VMC). In these patients embryonic remnants develop into small hepatic cysts and usually remain silent during life. Symptomatic PLD occurs mainly in the context of isolated polycystic liver disease (PCLD) and autosomal dominant polycystic kidney disease (ADPKD). In advanced stages, PCLD and ADPKD patients have massively enlarged livers which cause a spectrum of clinical features and complications. Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ. Renal failure due to polycystic kidneys and non-renal extra-hepatic features are common in ADPKD in contrast to VMC and PCLD. In general, liver function remains prolonged preserved in PLD. Ultrasonography is the first instrument to assess liver phenotype. Indeed, PCLD and ADPKD diagnostic criteria rely on detection of hepatorenal cystogenesis, and secondly a positive family history compatible with an autosomal dominant inheritance pattern. Ambiguous imaging or screening may be assisted by genetic counseling and molecular diagnostics. Screening mutations of the genes causing PCLD (PRKCSH and SEC63) or ADPKD (PKD1 and PKD2) confirm the clinical diagnosis. Genetic studies showed that accumulation of somatic hits in cyst epithelium determine the rate-limiting step for cyst formation. Management of adult PLD is based on liver phenotype, severity of clinical features and quality of life. Conservative treatment is recommended for the majority of PLD patients. The primary aim is to halt cyst growth to allow abdominal decompression and ameliorate symptoms. Invasive procedures are required in a selective patient group with advanced PCLD, ADPKD or liver failure. Pharmacological therapy by somatostatin analogues lead to beneficial outcome of PLD in terms of symptom relief and liver volume reduction.

Symptomatic and complicated nonhereditary developmental liver cysts: cross-sectional imaging findings

Commonly encountered in the general population, in the vast majority of cases nonhereditary developmental liver cysts are asymptomatic, not associated with altered hepatic function and confidently diagnosed on imaging studies, and do not require further workup, follow-up, or treatment. However, particularly in women, simple hepatic cysts may reach large sizes and cause symptoms and signs resulting from mass effect, vascular compression, and biliary obstruction. Furthermore, although rarely compared to the incidence observed in patients with adult polycystic kidney and liver disease, sporadic hepatic cysts sometimes undergo life-threatening complications such as intracystic hemorrhage, infection, or rupture, which require prompt imaging triage and appropriate interventional, laparoscopic, or open surgical treatment. This pictorial essay reviews with examples the cross-sectional imaging findings of symptomatic and complicated nonhereditary liver cysts, aiming to provide radiologists with an increased familiarity with these uncommon, challenging occurrences. Emphasis is placed on the role of MRI as a useful problem-solving modality to elucidate the complex imaging appearances resulting from intracystic bleeding and superinfection, and to differentiate complicated cysts from other hemorrhagic liver lesions and biliary cystic tumors.

Peri‐operative challenges and long‐term outcomes in liver transplantation for polycystic liver disease

BackgroundThe purpose of this study was to determine peri‐operative mortality and long‐term outcomes in patients undergoing liver transplantation in the US using the United Network for Organ Sharing (UNOS) database. MethodsThis study is a retrospective review of liver transplantations (LT) recorded in the UNOS database performed between 1988 and 2010. In total, 107 411 LT were performed in the US, 357 (0.3%) were for adult polycystic liver disease (PLD). A random group of 9416 adult patients transplanted for other diagnoses was created for comparison (10% of the adult non‐PLD database). ResultsTwo hundred and seventy‐one patients in the adult PLD group were females (75.9%), the mean age was 52.3 ± 8.2 [standard deviation (SD)] years. The median length of transplantation hospital stay was 11 days (interquartile range 8–21). Patients from the PLD group versus the comparison group (9416 patients) consisted of more females, lower Model for End‐Stage Liver Disease (MELD) scores (17 versus 21 points), more multi‐organ transplants (41% versus 4 %), chronic renal failure (creatinine 2.7 versus 1.5) and fewer patients with chronic hepatitis C (1.4% versus 32%). Peri‐operative mortality (≤30 days) was 9% in the PLD versus 6% in the comparison group; however, at 1 year PLD survival was similar (85% versus 85%) to other diagnoses and better at 3 (81% versus 77%) and 5 years (77% versus 71%, overall Log Rank P = 0.006). A similar PLD survival advantage was observed in isolated initial transplants (P = 0.019). ConclusionIn spite of early technical challenges and mortality, transplantation should be considered an option for selected patients with PLD as excellent long‐term outcomes can be achieved.

Feasibility of Liver Transplantation with Preservation of the Inferior Vena Cava and without Veno-Venous Bypass Use in Adult Polycystic Liver Disease

Feasibility of Liver Transplantation with Preservation of the Inferior Vena Cava and without Veno-Venous Bypass Use in Adult Polycystic Liver Disease

Cystic Lesions of the Liver

Simple cyst Benign developmental hepatic cyst von Meyenburg complex Caroli disease Adult polycystic liver disease Complex cyst Neoplasm Biliary cystadenoma or cystadenocarcinoma Cystic metastases Hepatocellular carcinoma Cavernous hemangioma Embryonal sarcoma Inflammatory or infectious Abscess Pyogenic Amebic Echinococcal cyst Postraumatic and miscellaneous Pseudocyst Hematoma Biloma Infected or hemorrhagic cysts Cystic liver lesions, or fluid-containing lesions of the liver, are commonly encountered findings on radiologic examinations that may represent a broad spectrum of entities ranging from benign developmental cysts to malignant neoplasms (Table 1). The wide range of pathologic processes that may result in cystic liver lesions can present a difficult diagnostic conundrum. The radiologist must carefully assess such imaging features as location, size, and unifocal or multifocal nature of the cyst or cysts as well as evaluate cyst complexity and associated findings. In addition, because radiologic features of various cystic liver lesions overlap, it is necessary to integrate imaging with clinical and laboratory findings to allow more definitive diagnosis. An important first step in narrowing the differential diagnosis is to determine the presence or absence of complex features in cystic liver lesions. To this end, fluid-containing liver lesions can be grouped broadly into simple or complex cysts. Vachha et al. Cystic Lesions of the Liver

Value of clinical classification of adult polycystic liver disease for selection of treatments

Objective:To study the role of clinical classification of adult polycystic liver disease(APLD)in guiding the selection of treatments for the patients.Methods:The clinical data of 43 APLD patients who were treated in our hospital from May 1995 to Oct.2007 were retrospectively analyzed.The patients were divided into 3 stages according to the clinical manifestations and imaging examination:non-symptom or slight symptom stage,obvious symptom stage,and lethal symptom stage.Seventeen patients in our group received outpatient clinical follow-up;26 were treated by partial hepatectomy combined with fenestration.Results:Among the 15 cases at non-symptom or slight symptom stage,one had primary hepatic carcinoma simultaneously and died 4 mouths after diagnosis;the rest 14 case were followed up for a mean of(42.8±37.9)months;12 of them had slow progression and 2 had rapid progression of APLD;the latter 2 cases received operation.The 24 cases at obvious symptom stage were treated by partial hepatectomy combined with fenestration.There were no perioperation deathes and the mean follow-up period was(61.4±43.0)months;2 cases died of renal failure and 3 had post-operation recurrence.Two of the 4 cases at the lethal symptom stage were treated by partial hepatectomy combined with fenestration:one had no symptom relieve after operation and one developed hepatic dysfunction and received liver transplantation 8 months after operation;the other 2 patients received percutaneous cyst aspiration at the outpatient department,one patient died of upper gastrointestinal hemorrhage 5 months later,and one had the symptom slightly relieved.Conclusion:Our classification of APLD can help to select treatments for patients:patients at non-symptom or slight symptom stage should be followed up,those at the obvious symptom stage can be treated surgically,and those at the lethal symptom stage are not suitable for routine operation and liver transplantation may be the best choice for them.

Therapeutical effect of combined hepatic resection and fenestration on patients with severe adult polycystic liver disease

To evaluate therapeutical effect of combined hepatic resection and fenestration on patients with severe adult polycystic liver disease (APLD). Preoperative clinical symptoms, postoperative complications and prognoses from 33 patients with severe adult polycystic liver disease (APLD) treated with combined hepatic resection and fenestration were recorded. According to the number and location of cysts before surgery and the remnant liver parenchyma after operation, all patients were classified into two types: class A and B. And patients in each type were further classified into three grades: Grade I, II and III. The frequency of postoperative complications of two types patients was compared. The mean follow-up time was 57 months. There were three patients with recurrence of symptoms at 81, 68 and 43 mouths after operation. Two patients died of renal failure due to polycystic kidney disease at 137 and 85 mouths after operation. And one patient with postoperative hepatic inadequacy received an orthotopic liver transplantation. The total number of patients with postoperative complications was 26 cases, including one patient with bleeding, two patients with bile leakage, fourteen patients with mild ascites, twelve patients with severe ascites and eighteen patients with pleural effusion, and the overall incidence was 78.8%. There were 22 patients with imaging data, including 6 patients within A type and sixteen patients within B type. The frequencies of postoperative complications were 4 and 31, respectively, and the difference was statistically significant (Chi-square test = 4.99, P less than 0.05). Combined hepatic resection and fenestration is a safe and acceptable procedure for the treatment of severe APLD.

Polycystic Liver Disease and Liver Transplantation: Single-Institution Experience

Adult polycystic liver disease (PLD) can cause massive hepatomegaly leading to pain, caval obstruction, and hemorrhage. Many surgical techniques including aspiration, fenestration, and resection have been used to treat PLD. In addition to substantial morbidity and mortality, conservative surgery may have limited success, and palliation may be temporary. With improved results of liver transplantation, it has become the definitive treatment for PLD. We retrospectively reviewed our experience in patients with PLD between 1998 and 2007. Thirteen patients underwent liver only or liver-kidney transplantation. All surgical procedures were performed with preservation of the recipient inferior vena cava and without venovenous bypass (piggyback technique). Our patients experienced a high rate of perioperative morbidity. However, long-term patient and graft survival were excellent.

Gender Differences in Estrogen Regulation of Intrahepatic Biliary Epithelial Cell IL‐6 Expression

Females are significantly more susceptible to primary biliary cirrhosis and debilitating consequences of adult polycystic liver disease than males. Also, biliary strictures contribute to poor outcome of female‐to‐male liver transplant compared to other donor‐recipient sex combinations. Since IL‐6 is critically important in biliary epithelial barrier function and wound repair and estrogens regulate IL‐6 expression, we tested the hypothesis that estrogens differentially regulate biliary epithelial cell (BEC) IL‐6 production in males and females. Results show that estradiol treatment either inhibited or had no effect on male mBEC IL‐6 expression but increased female IL‐6 expression. Male mBEC expressed less estrogen receptor‐alpha (ERα) protein than female mBEC but had similar levels of estrogen receptor‐beta (ER β). Female mBEC were also more dependent on estradiol for robust survival. Male mBEC, however, in an estrogen‐rich environment, upregulated ERα and then became estrogen‐responsive. In vivo studies show that biliary epithelia from female mice in estrus expressed IL‐6, but anestrus female mice did not. Experiments in two male human cholangiocarcinoma cell lines showed that signaling through ERα, and not the underlying sex, was responsible for the differential regulation of IL‐6 by estrogen. In conclusion, female BEC are estrogen responsive and dependent because of higher levels of ERα. Male BEC can adapt to an estrogen‐rich environment by upregulating ERα. Since estrogens can influence BEC barrier functions and wound healing both directly and indirectly via IL‐6 signalling, the differential regulation of BEC IL‐6 in males and females likely contribute significantly to sex differences seen in biliary diseases and cross‐sex liver transplants.

초음파 검사에서 성인의 다낭성 간질환에 대한 고찰

Adult polycystic liver disease (PLD) is a rare, benign condition association with autosomal dominant polycystic kidney disease (ADPKD). It is an autosomal dominantly inherited disorder characterized by multiple diffuse cystic lesions of the liver parenchyma. Significant symptoms or complications from liver involvement can occur cases. Surgical therapy is the mainstay of therapy including laparoscopic or open fenestration with or without hepatic resection and orthotopic liver transplantation. We report the literature addressing the presence of abdominal discomport, a case of a patient with PLD. This case showed the typical ultrasonogaphic and computer tomogaphic findings of this disease.

A case of orthodeoxia platypnoea in a patient with adult polycystic kidney and liver disease with a patent foramen ovale

We describe a case of a patient with polycystic kidney and liver disease presenting with a 4 year history of shortness of breath. This was caused by a liver cyst pressing on the inferior vena cava, right atrium and ventricle, leading to a right to left shunt across a patent foramen ovale. This is consistent with the condition Orthodeoxia Platypnoea, which occurs when desaturation and dyspnoea occur in the upright position in association with an intra atrial shunt.

Surgical management of polycystic liver disease

Adult polycystic liver disease (PCLD) is an autosomal dominant condition commonly associated with autosomal dominant polycystic kidney disease (ADPKD). However in the last decade, it has been recognized that there is a distinct form of autosomal dominant PCLD that arises without concomitant ADPKD. Early knowledge of the pathogenesis was gained from the study of hepatic cysts in patients with ADPKD. Bile duct overgrowth after embryogenesis results in cystic hepatic dilatations that are known as biliary microhamartomas or von Meyenburg complexes. Further dilatation arises from cellular proliferation and fluid secretion into these cysts. There is a variable, broad spectrum of manifestations of PCLD. Although PCLD is most often asymptomatic, massive hepatomegaly can lead to disabling symptoms of abdominal pain, early satiety, persistent nausea, dyspnea, ascites, biliary obstruction, and lower body edema. Complications of PCLD include cyst rupture and cyst infection. Also, there are associated medical problems, especially intracranial aneurysms and valvular heart disease, which clinicians need to be aware of and evaluate in patients with PCLD. In asymptomatic patients, no treatment is indicated for PCLD. In the symptomatic patient, surgical therapy is the mainstay of treatment tailored to the extent of disease for each patient. Management options include cyst aspiration and sclerosis, open or laparoscopic fenestration, liver resection with fenestration, and liver transplantation. The surgical literature discussing treatment of PCLD, including techniques, outcomes, and complication rates, are summarized in this review.

Spontaneous rupture of non-parasitic hepatic cyst

Intrahepatic cysts are generally classified as congenital, traumatic, infectious or neoplastic. Non-parasitic hepatic cysts (NPHCs) include simple cysts and adult polycystic liver disease in which the liver is diffusely occupied by cysts. NPHCs usually reach a large size before causing symptoms, unless a complication such as rupture, bleeding, infection, obstructive jaundice or neoplastic transformation occurs. We report the case of a 67-year-old man with spontaneous rupture of simple liver cyst. The clinical pictures and the unusual ultrasound features of this rare condition are discussed.

Laparoscopic fenestration in polycystic liver disease.

Sixteen laparoscopic cyst fenestrations for symptomatic adult polycystic liver disease (APLD) were performed in 13 women, including four patients who had had previous attempts at treatment (percutaneous sclerotherapy in two and fenestration via a laparotomy in two). The median number of cysts deroofed was 32 (range 18-58) during the 13 primary procedures. There was no in-hospital death. Postoperative transient ascites occurred in six patients. After operation 11 patients experienced immediate relief of symptoms but during a median follow-up of 26 (range 6-49) months, eight of these patients developed recurrent symptoms. Two patients underwent three repeat laparoscopic fenestrations, at which time perihepatic adhesions were rare and no complication occurred. Because repeat procedures may be performed, laparoscopic fenestration appears to be useful for the treatment of symptomatic APLD. However, it is less effective than fenestration at open surgery or liver resection and should be employed only in patients with predominantly large cysts.

Clinical experience with adult polycystic liver disease.

Adult polycystic liver disease is characterized by multiple diffuse cystic lesions of the liver, usually in association with polycystic kidney disease. Rarely, significant liver disease will produce enough symptoms to call for surgical attention. Symptoms range from simple compression to fatal liver failure. Treatment of seven patients (six women) with symptomatic polycystic liver disease over 18 months is reported. Rapidly progressing liver failure and sepsis from infected ascites following puncture developed in one patient and precluded surgery. Another presented with an acute abdomen and anaemia from liver cyst bleeding and was treated conservatively. Five patients with massive hepatomegaly and compression symptoms underwent fenestration and resection to debulk the cystic liver mass. No intra-abdominal drains were used after operation and there were no hospital deaths. One patient developed a bile leak which was managed by percutaneous drainage. Clinical approach, complications and treatment options in adult polycystic liver disease are reviewed.

Adult polycystic disease of the liver

Adult polycystic liver disease (APLD) is a rare disorder of liver parenchyma occasionally requiring surgical treatment. Its association with adult polycystic kidney disease has meant that as renal dialysis has become widely available there is an increased number of patients surviving with cystic liver changes. Although usually asymptomatic, patients with APLD may present with abdominal pain or swelling. Liver function is not usually compromised and computed tomography or abdominal ultrasonography are the most useful investigations. The complications of cyst rupture, infection, cholangiocarcinoma and compression of surrounding structures are discussed. Surgical treatment remains controversial, and the options of cyst puncture, fenestration with or without hepatic resection, and liver transplantation are reviewed.

New Advances in Evaluation and Management of Patients with Polycystic Liver Disease

Adult polycystic liver disease (APLD) is an autosomal dominant condition most commonly associated with polycystic kidney disease. However, over the last decade it has come to be recognized that APLD is a genetically heterogeneous disorder involving derangements on at least three different chromosomes. Mutations involving chromosomes 16 and 4 accounting for autosomal dominant polycystic kidney disease (ADPKD) type 1 and type 2 have been well described as have their gene products, polycystin-1 and polycystin-2. These have since been joined by a more recently recognized mutation in the short arm of chromosome 19 thought to be responsible for a much rarer form of autosomal dominant polycystic liver disease without any associated renal involvement. Despite the sometimes impressive physical and radiologic findings, only a minority of patients will progress to advanced liver disease or develop complications as a result of massive hepatomegaly. In these patients, medical management alone has proved ineffectual. Therefore, in the symptomatic APLD patient, surgical therapy remains the mainstay of therapy and includes cyst aspiration and sclerosis, fenestration with and without hepatic resection and orthotopic liver transplantation. The surgical literature on treatment of APLD, to include outcome measurements and complication rates are summarized. Additionally, we review other potential organ involvement and resultant complications.