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Abstract Polycystic liver disease (PLD) is a rare condition observed in three genetic diseases, including autosomal dominant polycystic liver disease (ADPLD), autosomal dominant polycystic kidney disease (ADPKD), and autosomal recessive polycystic kidney disease (ARPKD). PLD usually does not impair liver function, and advanced PLD becomes symptomatic when the enlarged liver compresses adjacent organs or increases intra-abdominal pressure. Currently, the diagnosis of PLD is mainly based on imaging, and genetic testing is not required except for complex cases. Besides, genetic testing may help predict patients’ prognosis, classify patients for genetic intervention, and conduct early treatment. Although the underlying genetic causes and mechanisms are not fully understood, previous studies refer to primary ciliopathy or impaired ciliogenesis as the main culprit. Primarily, PLD occurs due to defective ciliogenesis and ineffective endoplasmic reticulum quality control. Specifically, loss of function mutations of genes that are directly involved in ciliogenesis, such as Pkd1 , Pkd2, Pkhd1, and Dzip1l, can lead to both hepatic and renal cystogenesis in ADPKD and ARPKD. In addition, loss of function mutations of genes that are involved in endoplasmic reticulum quality control and protein folding, trafficking, and maturation, such as PRKCSH, Sec63, ALG8, ALG9, GANAB, and SEC61B, can impair the production and function of polycystin1 (PC1) and polycystin 2 (PC2) or facilitate their degradation and indirectly promote isolated hepatic cystogenesis or concurrent hepatic and renal cystogenesis. Recently, it was shown that mutations of LRP5, which impairs canonical Wnt signaling, can lead to hepatic cystogenesis. PLD is currently treated by somatostatin analogs, percutaneous intervention, surgical fenestration, resection, and liver transplantation. In addition, based on the underlying molecular mechanisms and signaling pathways, several investigational treatments have been used in preclinical studies, some of which have shown promising results. This review discusses the clinical manifestation, complications, prevalence, genetic basis, and treatment of PLD and explains the investigational methods of treatment and future research direction, which can be beneficial for researchers and clinicians interested in PLD.

Polycystic liver disease (PLD) is a rare condition observed in three genetic diseases, including autosomal dominant polycystic liver disease (ADPLD), autosomal dominant polycystic kidney disease (ADPKD), and autosomal recessive polycystic kidney disease (ARPKD). PLD usually does not impair liver function, and advanced PLD becomes symptomatic when the enlarged liver compresses adjacent organs or increases intra-abdominal pressure. Currently, the diagnosis of PLD is mainly based on imaging, and genetic testing is not required except for complex cases. Besides, genetic testing may help predict patients' prognosis, classify patients for genetic intervention, and conduct early treatment. Although the underlying genetic causes and mechanisms are not fully understood, previous studies refer to primary ciliopathy or impaired ciliogenesis as the main culprit. Primarily, PLD occurs due to defective ciliogenesis and ineffective endoplasmic reticulum quality control. Specifically, loss of function mutations of genes that are directly involved in ciliogenesis, such as Pkd1, Pkd2, Pkhd1, and Dzip1l, can lead to both hepatic and renal cystogenesis in ADPKD and ARPKD. In addition, loss of function mutations of genes that are involved in endoplasmic reticulum quality control and protein folding, trafficking, and maturation, such as PRKCSH, Sec63, ALG8, ALG9, GANAB, and SEC61B, can impair the production and function of polycystin1 (PC1) and polycystin 2 (PC2) or facilitate their degradation and indirectly promote isolated hepatic cystogenesis or concurrent hepatic and renal cystogenesis. Recently, it was shown that mutations of LRP5, which impairs canonical Wnt signaling, can lead to hepatic cystogenesis. PLD is currently treated by somatostatin analogs, percutaneous intervention, surgical fenestration, resection, and liver transplantation. In addition, based on the underlying molecular mechanisms and signaling pathways, several investigational treatments have been used in preclinical studies, some of which have shown promising results. This review discusses the clinical manifestation, complications, prevalence, genetic basis, and treatment of PLD and explains the investigational methods of treatment and future research direction, which can be beneficial for researchers and clinicians interested in PLD. [ABSTRACT FROM AUTHOR]

Abstract Background Enterococcus casseliflavus is a rare pathogenic bacterium that is characterized by vancomycin resistance and can lead to multiple infections in the human body. This report describes a rare case of polycystic intrahepatic infection with E. casseliflavus which necessitated antibiotic treatment and surgical intervention involving cystic drainage. Case Presentation A 59-year-old woman, a long-term hemodialysis patient, was hospitalized due to a 5-day history of fever, abdominal pain, and diarrhea, which were possibly caused by the ingestion of contaminated food. Her blood culture yielded a positive result for E. casseliflavus, and she was initially treated with piperacillin/tazobactam and linezolid. Later, the antibiotic regimen was adjusted to include meropenem and linezolid. Despite treatment, her body temperature remained elevated. However, subsequent blood cultures were negative for E.casseliflavus.Conventional CT scans and ultrasound examinations did not identify the source of infection. However, a PET-CT examination indicated an intrahepatic cyst infection. Following MRI and ultrasound localization, percutaneous intrahepatic puncture and drainage were performed on the 20th day. Fluoroquinolones were administered for 48 days. On the 32nd day, MRI revealed a separation within the infected cyst, leading to a repeat percutaneous drainage at a different site. Subsequently, the patient’s temperature returned to normal. The infection was considered resolved, and she was discharged on the 62nd day. Follow-up results have been favorable thus far. Conclusions Based on the findings from this case, it is recommended to promptly conduct PET-CT examination to exclude the possibility of intracystic infection in cases of polycystic liver infection that are challenging to control. Furthermore, timely consideration should be given to puncture drainage in difficult cases.

A 20‐week‐old, unneutered, female Great Dane was evaluated for failure to thrive and anorexia after 4 weeks of adequate caloric provision. Initial bloodwork results indicated elevated liver enzymes, azotaemia, hyperphosphataemia and non‐regenerative anaemia. Abdominal radiographs following a 24‐hour fast revealed hepatomegaly. Additional bloodwork was submitted to screen for possible infectious and immune‐mediated causes, of which none were discovered. The patient was referred to an American Veterinary College board‐certified internal medicine specialist for abdominal ultrasound, whose diagnostic findings were consistent with polycystic liver disease and bilateral renal dysplasia. Due to the grim prognosis provided by the ultrasonographic findings, the owners elected to euthanase the patient. To the authors' knowledge, this is not only the first reported case of polycystic liver disease in a Great Dane, but its concurrence with bilateral renal dysplasia has also never been reported in any species. [ABSTRACT FROM AUTHOR]

Key Clinical Message Timely recognition, accurate diagnosis, and proper management are vital for preventing complications and improving outcomes in polycystic liver disease. Abstract Polycystic liver disease is an uncommon genetic condition characterized by the presence of over 20 liver cysts. It is symptomatic in only 5% of cases. Surgical intervention remains the primary treatment approach for managing symptoms in affected patients. Herein, we report a case of PLD revealed by severe abdominal pain.

Key Clinical Message: Timely recognition, accurate diagnosis, and proper management are vital for preventing complications and improving outcomes in polycystic liver disease. Polycystic liver disease is an uncommon genetic condition characterized by the presence of over 20 liver cysts. It is symptomatic in only 5% of cases. Surgical intervention remains the primary treatment approach for managing symptoms in affected patients. Herein, we report a case of PLD revealed by severe abdominal pain. [ABSTRACT FROM AUTHOR]

Introduction: Persistent symptoms of pain, early satiety, dyspnea, and gastrointestinal reflux due to significant liver enlargement are indications for surgical debulking in patients with polycystic liver disease (PCLD) due to the lack of effective medical therapies; however, few data exist on outcomes of surgical intervention for PCLD. Methods: We conducted a retrospective analysis of consecutive patients who underwent operative intervention due to persistent symptoms secondary to PCLD. Preoperative patient characteristics, 30-day postoperative outcomes, and long-term postoperative outcomes, including complications and symptom resolution, were analyzed. Results: We identified 50 patients who underwent hepatic resection for symptomatic PCLD. Nine patients (19%) had concomitant polycystic kidney disease, and 14 (28%) had previously undergone interventions for PCLD management. The overall complication rate was 30%, with 8 patients (16%) experiencing Clavien-Dindo Grade III-V complications and no mortalities. The median relative reduction in liver volume was 41%. At a median follow-up of 2 years, 94% has sustained symptom resolution. Conclusions: This is among the largest case series exploring PCLD operative outcomes, revealing that surgical intervention for debulking for advanced PCLD is safe and effective for symptom management. Furthermore, patients with PCLD undergoing hepatectomy tolerate significant liver volume loss without evidence of impaired hepatic function. [ABSTRACT FROM AUTHOR]

The role of miRNA in the development of cho­langiopathies is considered in the scientific review. This article discusses the role of miRNA in biliary atresia, polycystic liver disease, and cholangiocarcinoma. To write the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library databases. The results of experimental studies indicate that the influence of miRNA causes the development of biliary atresia. It is found that, according to the results of ­miRNA expression profiling of extrahepatic bile ducts and gallbladder, miR-133a/b, ­miR-30b/c, miR-200a, miR-195, miR-365 and miR-320 are involved in the pathogenesis of biliary atresia. The article states that the scientists demonstrated a high level of ADD3 mRNA expression in the liver tissue of patients with biliary atresia. ADD3 overexpression promotes the adhesion and accumulation of epithelial cells in the bile ducts, which can lead to obstruction of the bile ducts and cholestasis. In turn, an excess of bile acids stimulates the proliferation of cholangiocytes and causes the development of liver fibrosis. Given that hyperproli­feration of epithelial cells of the bile ducts due to an impaired cell cycle is a key feature of cystogenesis in polycystic liver disease, researchers hypothesized that miRNAs, changing the cell cycle, may contribute to hepatic cystogenesis. The authors showed that polycystic liver disease is accompanied by a decrease in the expression of miR-15a, whose target is the mRNA of the cell division cycle 25A regulator. Numerous miRNAs are involved in the development of cholangiocarcinoma, changes in the expression and content of which in blood serum were noted in patients with this form of neoplasms. Thus, after a comprehensive review using the latest information search databases, it was found that in the modern scientific literature, the authors determine the association of micro-RNA generation activity and the development of cholangiopathies, namely: biliary atresia, polycystic liver disease, cholangiocarcinoma.

Abstract Background Hemodynamic management during anesthesia in liver transplantation for patients with polycystic liver disease (PLD) can be more challenging because of the bleeding and hemodynamic alterations due to the markedly enlarged liver. We hereby report a case of PLD wherein transesophageal echocardiography (TEE) was employed for optimal hemodynamic monitoring during liver transplantation. Case presentation A 61-year-old man was scheduled to undergo liver transplantation for massive PLD. Hemodynamic instability was associated with mechanical displacement of the giant cystic liver. TEE results revealed the collapse of the inferior vena cava due to liver displacement. TEE also detected intrathoracic hemorrhage triggered by detachment from the markedly enlarged liver. Conclusion TEE is a valuable monitoring tool for sharing information with surgeons and diagnostic modality for finding the source of bleeding in liver transplantation for PLD and may contribute majorly to the quality of perioperative management.

Polycystic liver disease (PLD) is a hereditary disease characterized by the presence of 20 or more liver cysts. It is classified into three types: isolated autosomal dominant PLD, PLD with autosomal dominant polycystic kidney disease, and PLD with autosomal recessive polycystic kidney disease. Genetic alterations, ciliary dysfunction of the biliary epithelial cells, and aberrant cell signaling pathways are the main factors contributing to the pathophysiology of PLD; however, other complicated mechanisms are also involved. The Gigot and Schnelldorfer classifications are widely used in clinical practice. Most patients with PLD are asymptomatic; however, a few patients with advanced-stage disease may develop symptoms and complications that impair their quality of life and require treatment. The known treatment options for PLD are somatostatin analogues, aspiration with sclerotherapy, fenestration, hepatic resection, and liver transplantation. Although liver transplantation remains the only curative treatment for PLD, medical therapies are gradually being developed with the increasing knowledge of the disease’s pathophysiology. This review focuses on the clinical manifestations and diagnosis of PLD, as well as treatment strategies, to support clinicians regarding the clinical management of the disease.

Background: Hemodynamic management during anesthesia in liver transplantation for patients with polycystic liver disease (PLD) can be more challenging because of the bleeding and hemodynamic alterations due to the markedly enlarged liver. We hereby report a case of PLD wherein transesophageal echocardiography (TEE) was employed for optimal hemodynamic monitoring during liver transplantation. Case presentation: A 61-year-old man was scheduled to undergo liver transplantation for massive PLD. Hemodynamic instability was associated with mechanical displacement of the giant cystic liver. TEE results revealed the collapse of the inferior vena cava due to liver displacement. TEE also detected intrathoracic hemorrhage triggered by detachment from the markedly enlarged liver. Conclusion: TEE is a valuable monitoring tool for sharing information with surgeons and diagnostic modality for finding the source of bleeding in liver transplantation for PLD and may contribute majorly to the quality of perioperative management. [ABSTRACT FROM AUTHOR]

Protein-truncating variants in α-1,3-glucosyltransferase (ALG8) are a risk factor for a mild cystic kidney disease phenotype. The association between these variants and liver cysts is limited. We aim to identify pathogenic ALG8 variants in our cohort of autosomal dominant polycystic liver disease (ADPLD) individuals. In order to fine-map the phenotypical spectrum of pathogenic ALG8 variant carriers, we performed targeted ALG8 screening in 478 ADPLD singletons, and exome sequencing in 48 singletons and 4 patients from two large ADPLD families. Eight novel and one previously reported pathogenic variant in ALG8 were discovered in sixteen patients. The ALG8 clinical phenotype ranges from mild to severe polycystic liver disease, and from innumerable small to multiple large hepatic cysts. The presence of <5 renal cysts that do not affect renal function is common in this population. Three-dimensional homology modeling demonstrated that six variants cause a truncated ALG8 protein with abnormal functioning, and one variant is predicted to destabilize ALG8. For the seventh variant, immunostaining of the liver tissue showed a complete loss of ALG8 in the cystic cells. ALG8-associated ADPLD has a broad clinical spectrum, including the possibility of developing a small number of renal cysts. This broadens the ADPLD genotype–phenotype spectrum and narrows the gap between liver-specific ADPLD and kidney-specific ADPKD. [ABSTRACT FROM AUTHOR]

Solid organ transplantation has become an integral part of the management of patients with end-stage diseases of the kidney, liver, heart and lungs. Most procedures occur in isolation, but multi-organ transplantation of the liver with either the kidney or heart has become an option. As more patients with congenital heart disease and cardiac cirrhosis survive into adulthood, particularly after the Fontan procedure, liver transplant teams are expected to face questions regarding multi-organ (heart-liver) transplantation. Similarly, patients with polycystic kidneys and livers may be managed by multi-organ transplantation. Herein, we review the indications and outcomes of simultaneous liver-kidney transplantation for polycystic liver-kidney disease, and discuss the indications, timing and procedural aspects of combined heart-liver transplantation. We also summarise the evidence for, and potential mechanisms underlying, the immunoprotective impact of liver allografts on the simultaneously transplanted organs. [ABSTRACT FROM AUTHOR]

Benign liver lesions are common and can pose a diagnostic challenge due to difficulty in differentiating them from malignant hepatic lesions. Most benign liver lesions are asymptomatic and are frequently detected incidentally during investigations for other conditions. Liver function tests are usually normal or only mildly deranged. Diagnosis is principally established by abdominal ultrasound, contrast-enhanced computed tomography, and magnetic resonance imaging together with hepatobiliary contrast agents and magnetic resonance cholangiography. Biopsy, if required in diagnosis of benign liver tumours, should be done sparingly due to the potential risk of bleeding or tumour seeding from malignant lesions. Some benign liver lesions are precursors to malignant lesions, while others have no risk of malignancy. Management strategies may vary from simple reassurance, lifestyle advice and surveillance imaging, through to complex hepatic resections or even liver transplantation in rare cases. Awareness of the natural history, clinical presentation and management strategies will ensure appropriate initial diagnostic work-up and prompt referral to a specialist hepatobiliary unit. [ABSTRACT FROM AUTHOR]

Objectives: Polycystic liver disease (PLD) is characterized by growth of hepatic cysts, causing hepatomegaly. Disease severity is determined using total liver volume (TLV), which can be measured from computed tomography (CT). The gold standard is manual segmentation which is time-consuming and requires expert knowledge of the anatomy. This study aims to validate the commercially available semi-automatic MMWP (Multimodality Workplace) Volume tool for CT scans of PLD patients. Methods: We included adult patients with one (n = 60) or two (n = 46) abdominal CT scans. Semi-automatic contouring was compared with manual segmentation, using comparison of observed volumes (cross-sectional) and growth (longitudinal), correlation coefficients (CC), and Bland-Altman analyses with bias and precision, defined as the mean difference and SD from this difference. Inter- and intra-reader variability were assessed using coefficients of variation (CV) and we assessed the time to perform both procedures. Results: Median TLV was 5292.2 mL (IQR 3141.4–7862.2 mL) at baseline. Cross-sectional analysis showed high correlation and low bias and precision between both methods (CC 0.998, bias 1.62%, precision 2.75%). Absolute volumes were slightly higher for semi-automatic segmentation (manual 5292.2 (3141.4–7862.2) versus semi-automatic 5432.8 (3071.9–7960.2) mL, difference 2.7%, p < 0.001). Longitudinal analysis demonstrated that semi-automatic segmentation accurately measures liver growth (CC 0.908, bias 0.23%, precision 4.04%). Inter- and intra-reader variability were small (2.19% and 0.66%) and comparable to manual segmentation (1.21% and 0.63%) (p = 0.26 and p = 0.37). Semi-automatic segmentation was faster than manual tracing (19 min versus 50 min, p = 0.009). Conclusions: Semi-automatic liver segmentation is a fast and accurate method to determine TLV and liver growth in PLD patients. Key Points: • Semi-automatic liver segmentation using the commercially available MMWP volume tool accurately determines total liver volume as well as liver growth over time in polycystic liver disease patients. • This method is considerably faster than manual segmentation through the use of Hounsfield unit settings. • We used a real-life CT set for the validation and showed that the semi-automatic tool measures accurately regardless of contrast used for the CT scan or not, presence of polycystic kidneys, liver volume, and previous invasive treatment for polycystic liver disease. [ABSTRACT FROM AUTHOR]

Cholangiocytes transit from quiescence to hyperproliferation during cystogenesis in polycystic liver disease (PLD), the severity of which displays prominent sex differences. Epigenetic regulation plays important roles in cell state transition. We aimed to investigate the sex-specific epigenetic basis of hepatic cystogenesis and to develop therapeutic strategies targeting epigenetic modifications for PLD treatment. Normal and cystic primary cholangiocytes were isolated from wild-type and PLD mice of both sexes. Chromatin states were characterized by analyzing chromatin accessibility (ATAC sequencing) and multiple histone modifications (chromatin immunoprecipitation sequencing). Differential gene expression was determined by transcriptomic analysis (RNA sequencing). Pharmacologic inhibition of epigenetic modifying enzymes was undertaken in PLD model mice. Through genome-wide profiling of chromatin dynamics, we revealed a profound increase of global chromatin accessibility during cystogenesis in both male and female PLD cholangiocytes. We identified a switch from H3K9me3 to H3K9ac on cis -regulatory DNA elements of cyst-associated genes and showed that inhibition of H3K9ac acetyltransferase or H3K9me3 demethylase slowed cyst growth in male, but not female, PLD mice. In contrast, we found that H3K27ac was specifically increased in female PLD mice and that genes associated with H3K27ac-gained regions were enriched for cyst-related pathways. In an integrated epigenomic and transcriptomic analysis, we identified an estrogen receptor alpha-centered transcription factor network associated with the H3K27ac-regulated cystogenic gene expression program in female PLD mice. Our findings highlight the multi-layered sex-specific epigenetic dynamics underlying cholangiocyte state transition and reveal a potential epigenetic therapeutic strategy for male PLD patients. In the present study, we elucidate a sex-specific epigenetic mechanism underlying the cholangiocyte state transition during hepatic cystogenesis and identify epigenetic drugs that effectively slow cyst growth in male PLD mice. These findings underscore the importance of sex difference in the pathogenesis of PLD and may guide researchers and physicians to develop sex-specific personalized approaches for PLD treatment. [Display omitted] • Chromatin accessibility is increased in both male and female PLD cholangiocytes. • A switch from H3K9me3 to H3K9ac activates cyst-associated genes in male PLD cholangiocytes. • Reducing H3K9ac or increasing H3K9me3 slows cyst growth in male, but not female, PLD mice. • Gain of H3K27ac specifically correlates with cyst-associated gene expression in female PLD cholangiocytes. • An ERα-centered TF network is enriched in H3K27ac-gained regions in female PLD cholangiocytes. [ABSTRACT FROM AUTHOR]

Luiz Fernando Norcia,1 Erika Mayumi Watanabe,2 Pedro Tadao Hamamoto Filho,3 Claudia Nishida Hasimoto,1 Leonardo Pelafsky,1 Walmar Kerche de Oliveira,1 Ligia Yukie Sassaki4 1Department of Surgery, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil; 2Department of Radiology, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil; 3Department of Neurology, Psychology and Psychiatry, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil; 4Department of Internal Medicine, São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, BrazilCorrespondence: Luiz Fernando Norcia, Department of Surgery, São Paulo State University (UNESP), Medical School, 783 Pedro Delmanto Street, Botucatu, São Paulo, 18610-303, Brazil, Tel +55 19982840542, Email lf.norcia@unesp.brAbstract: Polycystic liver disease (PLD) is a clinical condition characterized by the presence of more than 10 cysts in the liver. It is a rare disease Of genetic etiology that presents as an isolated disease or assoc\iated with polycystic kidney disease. Ductal plate malformation, ciliary dysfunction, and changes in cell signaling are the main factors involved in its pathogenesis. Most patients with PLD are asymptomatic, but in 2– 5% of cases the disease has disabling symptoms and a significant reduction in quality of life. The diagnosis is based on family history of hepatic and/or renal polycystic disease, clinical manifestations, patient age, and polycystic liver phenotype shown on imaging examinations. PLD treatment has evolved considerably in the last decades. Somatostatin analogues hold promise in controlling disease progression, but liver transplantation remains a unique curative treatment modality.Keywords: liver, polycystic liver disease, hepatomegaly, liver cysts, therapeutics

Objective: Rare disease Background: The polycystic kidney and hepatic disease 1 (PKHD1) gene codes for fibrocystin-polyductin, a protein that takes part in cell-signaling for cell differentiation, especially in kidney tubules and bile ducts. A homozygous or compound heterozygous defect in this gene can cause autosomal recessive polycystic kidney disease (ARPKD). Polycystic liver disease (PCLD) can also be caused by single heterozygous variants in the PKHD1 gene. ARPKD presents with renal insufficiency and cystic dilatation of bile ducts, although disease is not expected with a single heterozygous mutation. PCLD presents with multiple cysts in the liver and dilated bile ducts as well, but with less of an impact on the kidneys than with ARPKD. Our purpose in publishing this report is to introduce an as-yet unknown variant to the body of genetic defects associated with ARPKD and PCLD, as well as to argue for the likely pathogenicity of the variant according to the prevailing criteria used for classifying gene variants. Case Report: We present a patient with a de novo PKHD1 variant currently classified as a variant of unknown significance manifesting with bilaterally enlarged cystic kidneys and echogenic cystic structures in the hepatic portal system, indicative of cystic disease. Conclusions: Given this patient's liver and kidney presentation that does not fully align with either ARPKD or PCLD, the au- thors believe that the single heterozygous variant in this patient's PKHD1 gene is worthy of reporting. This new single heterozygous variant in PKHD1 gene causing cystic kidney and cystic hepatic disease in the patient should be considered 'likely pathogenic' according to the criteria set by the American College of Medical Genetics. [ABSTRACT FROM AUTHOR]

A 57-year-old man complained about abdominal distension and pain, constant feeling of early satiety. He was diagnosed with polycystic kidneys at the age of 24 and liver cysts discovered at the age of 38. The CT scan revealed 33 x 21 x 27 cm polycystic liver with cysts up to 7 cm in diameter. In 2009–2019 the patient was repeatedly punctured for liver cysts. Considering the continued enlargement of the liver and the worsening of complaints, the patient was put on the waiting list for a liver transplant in the spring of 2019. The patient went through liver transplantation on 11th of July 2022, the liver measures were 53 x 37 x 39 x 16 cm and weight 14,75 kg. The postoperative course was uneventful. Liver transplantation can be very effective treatment method that significantly improves the quality of life in PLD patients. [ABSTRACT FROM AUTHOR]

Management of splenomegaly is important in the treatment of portal hypertension. We report 2 cases who were treated by an emergency hybrid procedure combining endoscopic treatment and partial splenic embolization (PSE) based on a new concept ''splanchnic caput Medusae''. Case 1 with refractory esophageal variceal bleeding due to alcoholic liver cirrhosis was treated by endoscopic injection sclerotherapy (EIS) with ligation and PSE at the same time. Case 2 with gastric variceal bleeding due to polycystic liver disease was treated by EIS using n-butyl-2-cyanoacrylate and PSE at the same time. Six days after the hybrid procedure, transjugular retrograde obliteration was added. In both cases, post-treatment 3D-CT reconstruction images revealed that the spleen-portal system reversed to almost normal form. We conclude that an emergency hybrid procedure combining endoscopic treatment and PSE is effective for patients with bleeding esophagogastric varices.

IntroductionPolycystic kidney disease (PKD) is a common autosomal dominant or recessive genetic disease, often accompanied by polycystic liver disease (PLD). Many cases of PKD in animals have been reported. However, little is known about the genes that cause PKD in animals.MethodsIn this study, we evaluated the clinical phenotypes of PKD in two spontaneously aged cynomolgus monkeys and explored the genetic etiology using whole-genome sequencing (WGS). Ultrasonic and histological consequences were further investigated in PKD- and PLD-affected monkeys.ResultsThe results indicated that the kidneys of the two monkeys had varying degrees of cystic changes, and the renal cortex was thinned and accompanied by fluid accumulation. As for hepatopathy, inflammatory cell infiltration, cystic effusion, steatosis of hepatocytes, and pseudo-lobular were found. Based on WGS results, the variants of PKD1:(XM_015442355: c.1144G>C p. E382Q) and GANAB: (NM_001285075.1: c.2708T>C/p. V903A) are predicted to be likely pathogenic heterozygous mutations in PKD- and PLD-affected monkeys.DiscussionOur study suggests that the cynomolgus monkey PKD and PLD phenotypes are very similar to those in humans, and are probably caused by pathogenic genes homologous to humans. The results indicate that cynomolgus monkeys can be used as the most appropriate animal model for human PKD pathogenesis research and therapeutic drug screening.

Benign liver lesions are increasingly diagnosed in daily clinical practice due to the growing use of imaging techniques for the study of the abdomen in patients who have non-specific symptoms and do not have an increased risk of hepatic malignancy. They include simple or parasitic cysts and solid benign tumors which differ widely in terms of prevalence, clinical relevance, symptoms and natural history and often lead to significant clinical problems relating to diagnosis and clinical management. Following the need to have updated guidelines on the management of benign focal liver lesions, the Scientific Societies mainly involved in their management have promoted the drafting of a new dedicated document. This document was drawn up according to the present Italian rules and methodologies necessary to produce clinical, diagnostic, and therapeutic guidelines based on evidence. Here we present the first part of the guideline, concerning the characterization of focal hepatic lesions detected by ultrasound, and the diagnosis and clinical management of simple and parasitic hepatic cysts, and of polycystic liver disease. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the long-term safety and efficacy of hepatic transarterial embolization (TAE) in patients with symptomatic polycystic liver disease (PLD). Materials and Methods: A total of 26 patients were included, mean age of 52.3 years (range: 33–78 years), undergoing 32 TAE procedures between January 2012 and December 2019 were included in this retrospective study. Distal embolization of the segmental hepatic artery was performed with 300–500 µm embolic microspheres associated with proximal embolization using microcoils. The primary endpoint was clinical efficacy, defined by an improvement in health-related quality of life using a modified Short Form-36 Health Survey and improvement in symptoms (digestive or respiratory symptoms and chronic abdominal pain), without invasive therapy during the follow-up period. Secondary endpoints were a decrease in total liver volume and treated liver volume and complications. Results: Hepatic embolization was performed successfully in 30 of 32 procedures with no major adverse events. Clinical efficacy was 73% (19/26). The mean reduction in hepatic volume was −12.6% at 3 months and −27.8% at the last follow-up 51 ± 15.2 months after TAE (range: 30–81 months; both ps < 0.01). The mean visual analog scale pain score was 5.4 ± 2.8 before TAE and decreased to 2.7 ± 1.9 after treatment. Three patients had minor adverse events, and one patient had an adverse event of moderate severity. Conclusion: Hepatic embolization using microspheres and microcoils is a safe and effective treatment for PLD that improves symptoms and reduces the volume of hepatic cysts. [ABSTRACT FROM AUTHOR]

The most common hereditary kidney illness, disease of autosomal dominant polycystic kidney disease (ADPKD), is associated with numerous cysts that induce kidney size enlargement. The most common extrarenal symptom of ADPKD is liver cysts. A condition in which patients have >20 cysts in the liver is defined as polycystic liver disease (PLD). The goal of this study was to find out how often PLD was in ADPKD patients and whether there was an association between the incidence of PLD and age, sex, and clinical manifestations using magnetic resonance imaging (MRI) results. In this study, the abdominal MRI results of 32 patients with ADPKD who underwent abdominal MRI at Hospital X between January 01, 2020 and September 30, 2021 were retrospectively evaluated by 2 radiologists. Twenty-nine (90.6%) patients had a minimum 1 cyst in the liver, whereas 12 (37.5%) patients had PLD. The women had a greater rate in of PLD than males, and a statistical difference had been observed (p = 0.033). PLD incidence was found to increase with age. The mean ages of patients with and those without PLD were 46.3 and 35.9 years, respectively, and between the foregoing mean age values, a significant difference was detected (p = 0.003). Furthermore, there was no difference between the patients with and those without PLD in terms of the clinical indicators of ADPKD, including total kidney volume and mean rate of glomerular filtration. In conclusion, the incidence of PLD in ADPKD patients was found to be high in our study, and the presence of PLD was not associated with the clinical findings of ADPKD. For this reason, we think that it may be beneficial to perform liver imaging at the time of diagnosis of ADPKD and in their routine follow-up. [Med-Science 2022; 11(1.000): 239-42]

Autosomal dominant polycystic liver disease (ADPLD) is a rare disease with variable clinical presentations, characterized by cystic enlargement of the liver. The diagnosis is made based on family history, patient’s age, and liver phenotype and is confirmed by imaging tests. The treatment aims to reduce symptoms caused by the increased liver volume and can be performed by aspiration with sclerotherapy, fenestration, and liver resection. Although ADPLD is a rare disease, it is an important differential diagnosis of cystic diseases such as polycystic kidney disease; therefore, the aim of this article was to present the diagnostic and therapeutic approach of a case of ADPLD and conducting a literature review. This is the case of a 32-year-old male patient, who was hospitalized due to abdominal pain, hepatomegaly, lack of appetite, and weight loss. Imaging propaedeutics showed a significant increase in the liver volume due to hepatic cysts. After a multidisciplinary evaluation, given the clinical changes and the location of the hepatic cysts, fenestration was performed by laparotomy. The postoperative period was uneventful. The treatment was efficient in promoting symptomatic relief and improving the quality of life in this patient. Case reports on this disease are quite limited in the currently available literature, and there are gaps in knowledge with regard to the diagnosis and management of ADPLD. The importance of this article is that it will highlight the limitations in treatment options and allow physicians to make a more informed decision when diagnosing and treating a patient with ADPLD in the future.

Abstract Background In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume decreases after menopause. Female sex hormones could therefore be a target for therapy. The AGAINST-PLD study will examine the efficacy of the GnRH agonist leuprorelin, which blocks the production of estrogen and other sex hormones, to reduce liver growth in PLD. Methods The AGAINST-PLD study is an investigator-driven, multicenter, randomized controlled trial. Institutional review board (IRB) approval was received at the University Medical Center of Groningen and will be collected in other sites before opening these sites. Thirty-six female, pre-menopausal patients, with a very large liver volume for age (upper 10% of the PLD population) and ongoing liver growth despite current treatment options will be randomized to direct start of leuprorelin or to 18 months standard of care and delayed start of leuprorelin. Leuprorelin is given as 3.75 mg subcutaneously (s.c.) monthly for the first 3 months followed by 3-monthly depots of 11.25 mg s.c. The trial duration is 36 months. MRI scans to measure liver volume will be performed at screening, 6 months, 18 months, 24 months and 36 months. In addition, blood will be drawn, DEXA-scans will be performed and questionnaires will be collected. This design enables comparison between patients on study treatment and standard of care (first 18 months) and within patients before and during treatment (whole trial). Main outcome is annualized liver growth rate compared between standard of care and study treatment. Secondary outcomes are PLD disease severity, change in liver growth within individuals and (serious) adverse events. The study is designed as a prospective open-label study with blinded endpoint assessment (PROBE). Discussion In this trial, we combined the expertise of hepatologist, nephrologists and gynecologists to study the effect of leuprorelin on liver growth in PLD. In this way, we hope to stop liver growth, reduce symptoms and reduce the need for liver transplantation in severe PLD. Trial registration Eudra CT number 2020-005949-16, registered at 15 Dec 2020. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-005949-16 .

Protein-truncating variants in α-1,3-glucosyltransferase (ALG8) are a risk factor for a mild cystic kidney disease phenotype. The association between these variants and liver cysts is limited. We aim to identify pathogenic ALG8 variants in our cohort of autosomal dominant polycystic liver disease (ADPLD) individuals. In order to fine-map the phenotypical spectrum of pathogenic ALG8 variant carriers, we performed targeted ALG8 screening in 478 ADPLD singletons, and exome sequencing in 48 singletons and 4 patients from two large ADPLD families. Eight novel and one previously reported pathogenic variant in ALG8 were discovered in sixteen patients. The ALG8 clinical phenotype ranges from mild to severe polycystic liver disease, and from innumerable small to multiple large hepatic cysts. The presence of ALG8-associated ADPLD has a broad clinical spectrum, including the possibility of developing a small number of renal cysts. This broadens the ADPLD genotype–phenotype spectrum and narrows the gap between liver-specific ADPLD and kidney-specific ADPKD.

Cystic lesions of the liver are a heterogeneous group of disorders with varied etiology, prevalence, and clinical manifestations. Fibropolycystic liver disease encompasses a spectrum of related liver and biliary tract lesions caused by abnormal embryologic development of the ductal plates. These disorders include congenital hepatic fibrosis, biliary hamartomas, polycystic liver disease (PCLD), choledochal cysts, and Carolis disease. PCLD is arbitrarily defined as a liver that contains >20 cysts. Most liver cysts are incidentally found on imaging studies, and the majority of the patients with liver cysts are asymptomatic. Rarely, complications such as compression, infection, and bleeding within the cyst can occur. Under the effect of the increased pressure, the epithelial lining of the cyst undergoes necrosis and sloughing, causing injury of the fragile blood vessels, leading to intracystic bleeding. The bleeding within or from the cyst can be precipitated by anticoagulation. We present a patient with PCLD who developed intracystic bleeding after he was started on apixaban for the prevention of thromboembolism.

Background: In this study, our objective was to determine gender differences in the outcomes of patients with PLD undergoing liver (LT) or liver/kidney transplantation (SLK).Methods: We analyzed the UNOS datasets of all adults who had transplanted for PLD between 1988 and 2018.Results: During the study period, 663 LT/SLK (51% LT only and 49% SLK) were done for PLD patients and of these 500 (75%) were in women. Women were younger (52.8 vs. 56.7 years, p < 0.001), had lower MELD at transplant (16.6 vs. 19.4, p < 0.001), had higher serum albumin (3.7 vs. 3.5, p < 0.001), and had a lower CTP class (p < 0.008). During the follow-up, 18% (n = 89) women and 29% (n = 47) men died (p = 0.002). Kaplan-Meier (KM) survival estimates showed similar survival rate for patients who had LT and SLK (p = 0.459), but survival rate was significantly higher for women compared to men (p < 0.001). Multivariable analysis showed that female gender (aHR 0.54, 95% CI 0.33-0.90) was associated with a lower mortality. Moreover, Karnofsky Performance Status was excellent for 70% of women and 55% of men (p = 0.03) after LT. Women had better survival whether they received liver or SLK. The era of transplant, whether they were transplanted with MELD exception points or whether they were on dialysis at the time of transplant, did not have an effect on the gender differences in outcomes.Conclusions: Women had 46% lower risk of mortality after adjusting for other covariates compared to men after LT/SLK for PLD. [ABSTRACT FROM AUTHOR]

Glycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident N-glycans participate with the Glc3Man9GlcNAc2 highly conserved sequence, in protein folding process, where the physiological balance between glycosylation/deglycosylation on the innermost glucose residue takes place, according GANAB/UGGT concentration ratio. However, under abnormal conditions, the cell adapts to the glucose availability by adopting an aerobic or anaerobic regimen of glycolysis, or to external stimuli through internal or external recognition patterns, so it responds to pathogenic noxa with unfolded protein response (UPR). UPR can affect Multiple Sclerosis (MS) and several neurological and metabolic diseases via the BiP stress sensor, resulting in ATF6, PERK and IRE1 activation. Furthermore, the abnormal GANAB expression has been observed in MS, systemic lupus erythematous, male germinal epithelium and predisposed highly replicating cells of the kidney tubules and bile ducts. The latter is the case of Polycystic Liver Disease (PCLD) and Polycystic Kidney Disease (PCKD), where genetically induced GANAB loss affects polycystin-1 (PC1) and polycystin-2 (PC2), resulting in altered protein quality control and cyst formation phenomenon. Our topics resume the role of glycans in cell physiology, highlighting the N-glycans one, as a substrate of GANAB, which is an emerging key molecule in MS and other human pathologies. [ABSTRACT FROM AUTHOR]

Right superior resection (segments 7 and 8) is an uncommon resection for liver malignancies, with most of the literature limited to case reports and small series. Resection of segments 4, 7, and 8 has been reported in only a few cases. When the right hepatic vein is resected, venous reconstruction or identification of one or more right inferior hepatic veins is considered mandatory, to maintain segmentary function of segments 5 and 6. We present a case of liver resection of segments 4, 7, and 8 including the right and middle hepatic veins for symptomatic benign liver disease with no right hepatic vein reconstruction, nor a prominent right inferior hepatic vein(s). After the resection, there was no change in liver function tests, and the patient made an unremarkable recovery. Three months after the operation, partial atrophy of segments 5 and 6 with hypertrophy of the left lateral section was observed, while two and one half years after resection, the patient is asymptomatic. When right hepatic vein reconstruction would add unnecessary operative time, and there is low likelihood of the need for repeated resection, particularly when the hepatic vein is difficult to dissect, this approach can be safe and useful, while providing an adequate postoperative liver mass in the short-term to recover uneventfully from major liver resection.

Polycystic liver disease is characterized by multiple cystic lesions on the liver. Liver cysts are typically incidental findings, with occasional complications including cyst hemorrhage, infection and rupture. Polycystic liver disease may be part of autosomal dominant polycystic liver disease (ADPLD). Autosomal dominant polycystic liver disease is considered rare autosomal dominant disease, with prevalence of 1/100,000-1,000,000. Without family history of polycystic liver disease, ADPLD is defined as the presence of more than 20 liver cysts with no renal cysts, however up to third of ADPLD may have small number of renal cysts without kidney function impairment. This case of a 73-year-old woman with symptomatic polycystic liver disease, and we performed cyst fenestration-deroofing via laparoscopic.

Abstract Background Polycystic liver disease is a clinical feature of autosomal dominant polycystic kidney disease, and it can sometimes cause health damage more serious than polycystic kidney. Dialysis therapy can be used for renal failure, but liver transplantation is the only method available for liver failure. Thus, giant and multiple hepatic cysts may affect mortality. However, liver transplantation is not indicated in many cases because of the preserved liver function. Case presentation A 54-year-old Japanese woman with polycystic liver disease was transferred back to our hospital for abdominal pain caused by liver cyst infection with abdominal wall herniation. She had been diagnosed with polycystic liver disease associated with sporadic autosomal dominant polycystic kidney disease 25 years earlier. Although she had several surgical interventions to reduce her liver volume, including right hepatic lobectomy and fenestration for liver cysts in another hospital, she needed further repair of the recurrent incisional herniation with patch graft surgery using fascia lata to cover the herniation site. However, new herniation sites reemerged in the fragile abdominal wall area around the patch, and therefore, she reduced the recurrent abdominal wall herniation by herself. Recurrent intestinal obstructions were luckily released by fasting with decompression treatment via nasogastric tube insertion, but multiple skin ulcers around the enlarged hernia sac gradually developed, and ascites was extremely difficult to control with any medication. At final admission, her abdominal wall was even more prominent, causing shortness of breath, and it spontaneously ruptured many times, which was accompanied by discharge of around 5 liters of ascites each time. She died from sepsis caused by drug-resistant Enterococcus. Conclusions We report a case of autosomal dominant polycystic kidney disease with ruptured abdominal wall resulting from a hepatic cyst enlargement despite multiple laparotomy operations. Throughout the entire disease course, her liver volume increased rapidly, and her quality of life was severely impaired, but she could not undergo liver transplantation after readmission to our hospital. We will discuss the therapeutic strategy for this patient, including the timing and indication for liver transplantation.

Horseshoe kidney is a renal fusion anomaly during embryogenesis and adult polycystic kidney disease is a hereditary disorder which is transmitted in autosomal dominant pattern. Polycystic and horseshoe kidney are two separate disease entities, only about 20 cases of polycystic kidney disease in horseshoe kidney disease have been described in the literature, with an incidence ranging from 1 in 134 000 to 1 in 8 000 000 live births. We are presenting ultrasound findings of a patient who was incidentally diagnosed with polycystic horseshoe kidney on routine screening. [ABSTRACT FROM AUTHOR]

Polycystic liver disease (PLD) is a rare autosomal dominant disorder including two genetically and clinically distinct forms: autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease (PCLD). The main manifestation of ADPKD is kidney cysts, while PCLD has predominantly liver presentations with mild or absent kidney cysts. Over the past decade, PRKCSH , SEC63 , ALG8 , and LRP5 have been candidate genes of PCLD. Recently, more candidate genes such as GANAB , SEC61B , and ALR9 were also reported in PCLD patients. This review focused on all candidate genes of PCLD, including the newly established novel candidate genes. In addition, we also discussed some other genes which might also contribute to the disease. [ABSTRACT FROM AUTHOR]