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.
Epithelioid haemangioendothelioma (EHE) is a rare vascular soft tissue malignant tumour with unknown etiology; the estimated prevalence of EHE is less than one in 1 million. A 56-year-old man was ...admitted in our department due to pain in the right side of the abdomen lasting for two years and weight loss up to 10 kg. Since 2012, the patient underwent lung and abdominal CT scanning as well as biopsy, however the diagnosis was challenging. In 2015, repeated abdominal CT scanning and a liver core biopsy was performed. The epithelioid haemangioendothelioma was diagnosed based by histopathological examination with subsequent radiological and clinical correlation. Therefore, accurate histopathological examination with radiological and clinical correlation is essential in the diagnosis of epithelioid haemangioendothelioma.
Background
Symptoms in polycystic liver disease (PLD) are thought to be caused by compression of organs and structures by the enlarged liver.
Aim
The aim of this article is to assess the impact of ...liver volume on symptoms and quality of life (QoL) in PLD.
Methods
We included PLD patients from two prospective studies that used the PLD-questionnaire (PLD-Q) for symptom assessment. QoL was assessed through SF-36, summarized in a physical (PCS) and mental (MCS) component score. Liver volume was correlated with PLD-Q total scores. Patients were classified based on height-corrected liver volume in mild (<1600 ml), moderate (1600–3200 ml), and severe (>3200 ml) disease. PLD-Q and QoL (PCS and MCS) scores were compared across disease stages.
Results
We included 82 of 131 patients from the original studies (disease stages; mild n = 26, moderate n = 33, and severe n = 23). Patients with larger liver volume reported higher symptom burden (r = 0.516, p < 0.001). Symptom scores increased with disease progression, except for abdominal pain (p = 0.088). PCS decreased with advancing disease (p < 0.001), in contrast to MCS (p = 0.055). Moderate (p = 0.007) and severe (p < 0.001) PLD patients had lower PCS scores than the general population.
Conclusion
PLD with larger liver volume is more likely to be symptomatic and is associated with lower QoL.
Clinical management of polycystic liver disease van Aerts, René M.M.; van de Laarschot, Liyanne F.M.; Banales, Jesus M. ...
Journal of hepatology,
April 2018, 2018-04-00, 20180401, Volume:
68, Issue:
4
Journal Article
Peer reviewed
Open access
A 41-year old female underwent a computed tomography (CT) scan in 2010 because of symptoms suggestive of appendicitis. Incidentally, multiple liver lesions characterised as cysts were detected. The ...presence of small to medium sized liver cysts (diameter between <1 cm and 4 cm) in all liver segments (>100 cysts) and absence of kidney cysts in the context of normal renal function led to the clinical diagnosis of autosomal dominant polycystic liver disease (ADPLD). Five years later she was referred to the outpatient clinic with increased abdominal girth, pain in the right upper abdomen and right flank, and early satiety. She had difficulties bending over and could neither cut her toenails nor tie her shoe laces. In her early twenties she had used oral contraception for five years. She has been pregnant twice. Clinical examination showed an enlarged liver reaching into the right pelvic region and crossing the midline of the abdomen. Laboratory testing demonstrated increased gamma-glutamyl transferase (80 IU/L, normal <40 IU/L) and alkaline phosphatase (148 IU/L, normal <100 IU/L) levels. Bilirubin, albumin and coagulation times were within the normal range. A new CT scan in 2015 was compatible with an increased number and size of liver cysts. The diameter of cysts varied between <1 cm and 6 cm (anatomic distribution shown Fig. 2B). There were no signs of hepatic venous outflow obstruction, portal hypertension or compression on the biliary tract. Height-adjusted total liver volume (htTLV) increased from 2,667 ml/m in 2012 to 4,047 ml/m in 2015 (height 172 cm).
The case we present here is not uncommon, and prompts several relevant questions:I.What causes the development of liver cysts?II.Is genetic testing and genetic counselling recommended?III.What is the natural course of polycystic liver disease and what can patients do to stop growth of liver cysts?IV.Which complications may occur during the course of polycystic liver disease?V.What treatment options are currently available?VI.What other potential new and effective therapies will be available in the near future?
Chronic pancreatitis (CP) may be caused by oxidative stress. An important source of reactive oxygen species (ROS) is the methylglyoxal-derived formation of advanced glycation endproducts (AGE). ...Methylglyoxal is detoxified by Glyoxalase I (GLO1). A reduction in GLO1 activity results in increased ROS. Single nucleotide polymorphisms (SNPs) of GLO1 have been linked to various inflammatory diseases. Here, we analyzed whether common GLO1 variants are associated with alcoholic (ACP) and non-alcoholic CP (NACP).
Using melting curve analysis, we genotyped a screening cohort of 223 ACP, 218 NACP patients, and 328 controls for 11 tagging SNPs defined by the SNPinfo LD TAG SNP Selection tool and the functionally relevant variant rs4746. For selected variants the cohorts were extended to up to 1,441 patient samples.
In the ACP cohort, comparison of genotypes for rs1937780 between patients and controls displayed an ambiguous result in the screening cohort (p = 0.08). However, in the extended cohort of 1,441 patients no statistically significant association was found for the comparison of genotypes (p = 0.11), nor in logistic regression analysis (p = 0.214, OR 1.072, 95% CI 0.961-1.196). In the NACP screening cohort SNPs rs937662, rs1699012, and rs4746 displayed an ambiguous result when patients were compared to controls in the recessive or dominant model (p = 0.08, 0.08, and 0.07, respectively). Again, these associations were not confirmed in the extended cohorts (rs937662, dominant model: p = 0.07, logistic regression: p = 0.07, OR 1.207, 95% CI 0.985-1.480) or in the replication cohorts for rs4746 (Germany, p = 0.42, OR 1.080, 95% CI 0.673-1.124; France, p = 0.19, OR 0.90, 95% CI 0.76-1.06; China, p = 0.24, OR 1.18, 95% CI 0.90-1.54) and rs1699012 (Germany, Munich; p = 0.279, OR 0.903, 95% CI 0.750-1.087).
Common GLO1 variants do not increase chronic pancreatitis risk.
Liver cysts are common,affecting 5%-10% of the population.Most are asymptomatic,however 5% of patients develop symptoms,sometimes due to complications and will require intervention.There is no ...consensus on their management because complications are so uncommon.The aim of this study was to perform a collected review of how a series of complications were managed at our institutions.Six different patients presenting with rare complications of liver cysts were obtained from Hepatobiliary Units in the United Kingdom and The Netherlands.History and radiological imaging were obtained from case notes and computerised radiology.As a result,1 patient admitted with inferior vena cava obstruction was managed by cyst aspiration and lanreotide;1 patient with common bile duct obstruction was first managed by endoscopic retrograde cholangiopancreatography and stenting,followed by open fenestration;1 patient with ruptured cysts and significant medical co-morbidities was managed by percutaneous drainage;1 patient with portal vein occlusion and varices was managed by open liver resection;1 patient with infected cysts was treated with intravenous antibiotics and is awaiting liver transplantation.The final patient with a simple liver cyst mimicking a hydatid was managed by open liver resection.In conclusion,complications of cystic liver disease are rare,and we have demonstrated in this series that both operative and non-operative strategies have defined roles in management.The mainstays of treatment are either aspiration/sclerotherapy or,alternatively laparoscopic fenestration.Medical management with somatostatin analogues is a potentially new and exciting treatment option but requires further study.
BackgroundThe Netherlands has a low hepatitis C virus (HCV) prevalence, estimated at 0.16%. Previous studies have shown that up to 30% of the diagnosed HCV population in the Netherlands has been lost ...to follow-up (LTFU). Retrieval of these patients could halt progression of liver disease in infected patients, reduce the number of infected individuals and limit HCV transmission. Several regional Dutch retrieval projects have already been executed, which demonstrated that retrieval is feasible. Therefore, we initiated a nationwide retrieval project, aiming to achieve microelimination in previously diagnosed but LTFU patients with chronic HCV through retrieval.MethodsLaboratory records will be used to identify possible patients with chronic hepatitis C, defined as either a positive most recent HCV RNA or positive HCV antibodies without known RNA result. Reviewing patient records and obtaining current contact information from municipality databases will identify LTFU patients who are eligible for retrieval. These patients will be invited for outpatient clinic care. The primary outcome of the study is the total number of LTFU patients who have been successfully linked to care.DiscussionHepatitis C ELimination In the NEtherlands (CELINE) is within the remit of WHO elimination targets and the Dutch National Hepatitis Plan. The methodology of CELINE is based on previously conducted regional retrieval projects and is designed to overcome some of their limitations. After ethical approval was obtained in 2018, the first centre initiated retrieval in 2018 and the project is expected to finish in 2021.Trial registration numberNCT04208035.
Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are ...associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 × 10−8). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.
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