Management of cystic liver disease

Author(s):  
René M. M. van Aerts ◽  
Tom J. G. Gevers ◽  
Joost P. H. Drenth

In a subset of autosomal dominant polycystic kidney disease patients, hepatic cysts dominate the clinical picture. These patients may develop polycystic liver disease, and enlargement of the liver leads to compression of adjacent abdominal and thoracic organs. The main risk factors for growth of liver cysts are female sex, exogenous oestrogen use, multiple pregnancies, and severity of renal disease. Treatment is only indicated in those with symptoms, and choice of treatment depends on total liver volume, size, and location of the liver cysts. Current radiological and surgical therapies include aspiration-sclerotherapy, fenestration, segmental hepatic resection, and liver transplantation. They all are palliative in nature and are partially effective and have non-negligible morbidity and mortality. Somatostatin analogues are still in development for polycystic liver disease.

2018 ◽  
Vol 11 ◽  
pp. 175628481880478 ◽  
Author(s):  
René M. M. van Aerts ◽  
Marieke Kolkman ◽  
Wietske Kievit ◽  
Tom J. G. Gevers ◽  
Frederik Nevens ◽  
...  

Background: Somatostatin analogues (SAs) reduce liver volume and relief symptoms in polycystic liver disease (PLD). Its effect wears off after continuing therapy suggesting development of SA tolerance in patients on chronic therapy. We postulate that a drug holiday resensitizes the liver to its acute pharmacological effects. Therefore, this study examines the liver volume-reducing effect of SAs after a drug holiday. Methods: Patients were identified from the International PLD Registry and included in our analysis when (1) treated with SAs during two cycles separated by a drug holiday and (2) height-adjusted total liver volume (hTLV) was available at start and end of each cycle. For our primary outcome we compared the effect of SAs (in % per 6 months) on hTLV between the first and second treatment cycle. Results: In 34 patients, initial liver volume-reducing effect was similar to that after rechallenge [−2.6% per 6 months (interquartile range, −3.8–0.8) versus −1.6% per 6 months (interquartile range, −3.1–1.1), p = 0.510]. Cessation of treatment led to a rebound effect, but liver volume remained stable compared with the baseline with intermittent therapy in responders to SA [−0.6% (interquartile range, −7.4–5.7) after 46.5 months]. Conclusions: PLD patients treated with SAs benefit from retreatment after a drug holiday. The significant increase of liver volume after cessation of treatment complicates widespread use of a drug holiday as new treatment strategy. Our results contribute to a better understanding of the pharmacological effect of SAs and help to identify patients who might benefit.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carlo Garofalo ◽  
Ivana Capuano ◽  
Luigi Pennino ◽  
Ilaria De Gregorio ◽  
Eleonora Riccio ◽  
...  

AbstractA clear evidence on the benefits of somatostatin analogues (SA) on liver outcome in patients affected by polycystic liver disease is still lacking. We performed a meta-analysis of RCTs and a trial sequential analysis (TSA) evaluating the effects of SA in adult patients with polycystic liver disease on change in liver volume. As secondary outcome, we evaluated the effects on quality of life as measured by SF36-questionnaire. Six RCTs were selected with an overall sample size of 332 adult patients with polycystic liver disease (mean age: 46 years). Mean liver volume at baseline was 3289 ml in SA group and 3089 ml in placebo group. Overall, unstandardized mean difference in liver volume was − 176 ml (95%CI, − 406, 54; p < 0.133). Heterogeneity was low (I2:0%, p < 0.992). However, we performed a moderator analysis and we found that a higher eGFR significantly correlates to a more pronounced effect of SA on liver volume reduction (p = 0.036). Cumulative Z-curve in TSA did not reach either significance and futility boundaries or required information size. Three RCTs have evaluated Quality of life parameters measured by SF36-QOL questionnaire for a total of 124 patients; no significant difference was found on the effect of SA on QOL parameters when compared with placebo. The present meta-analysis revealed a potential effect of SA on reduction of liver volume and quality of life parameters, but results did not reach a statistical significance. These data could be explained by the need of further studies, as demonstrated through TSA, to reach an adequate sample size to confirm the beneficial outcomes of SAs treatment.


2016 ◽  
Vol 98 (1) ◽  
pp. 18-23 ◽  
Author(s):  
S Khan ◽  
A Dennison ◽  
G Garcea

Introduction Somatostatin analogues and rapamycin inhibitors are two classes of drugs available for the management of polycystic liver disease but their overall impact is not clearly established. This article systematically reviews the literature on the medical management of polycystic liver disease. The outcomes assessed include reduction in liver volume and the impact on quality of life. Methods The English language literature published between 1966 and August 2014 was reviewed from a MEDLINE®, PubMed, Embase™ and Cochrane Library search. Search terms included ‘polycystic’, ‘liver’, ‘sirolimus’, ‘everolimus’, ‘PCLD’, ‘somatostatin’, ‘octreotide’, ‘lanreotide’ and ‘rapamycin’. Both randomised trials and controlled studies were included. References of the articles retrieved were also searched to identify any further eligible publications. The studies included were appraised using the Jadad score. Results Seven studies were included in the final review. Five studies, of which three were randomised trials, investigated the role of somatostatin analogues and the results showed a mean reduction in liver volume ranging from 2.9% at six months to 4.95 ±6.77% at one year. Only one randomised study examined the influence of rapamycin inhibitors. This trial compared dual therapy with everolimus and octreotide versus octreotide monotherapy. Liver volume reduced by 3.5% and 3.8% in the control and intervention groups respectively but no statistical difference was found between the two groups (p=0.73). Two randomised trials investigating somatostatin analogues assessed quality of life using SF-36®. Only one subdomain score improved in one of the trials while two subdomain scores improved in the other with somatostatin analogue therapy. Conclusions Somatostatin analogues significantly reduce liver volumes after six months of therapy but have only a modest improvement on quality of life. Rapamycin inhibitors do not confer any additional advantage.


2020 ◽  
Vol 15 (9) ◽  
pp. 1267-1278
Author(s):  
Marie C. Hogan ◽  
Julie A. Chamberlin ◽  
Lisa E. Vaughan ◽  
Angela L. Waits ◽  
Carly Banks ◽  
...  

Background and objectivesWe assessed safety and efficacy of another somatostatin receptor analog, pasireotide long-acting release, in severe polycystic liver disease and autosomal dominant polycystic kidney disease. Pasireotide long-acting release, with its broader binding profile and higher affinity to known somatostatin receptors, has potential for greater efficacy.Design, setting, participants, & measurementsIndividuals with severe polycystic liver disease were assigned in a 2:1 ratio in a 1-year, double-blind, randomized trial to receive pasireotide long-acting release or placebo. Primary outcome was change in total liver volume; secondary outcomes were change in total kidney volume, eGFR, and quality of life.ResultsOf 48 subjects randomized, 41 completed total liver volume measurements (n=29 pasireotide long-acting release and n=12 placebo). From baseline, there were −99±189 ml/m absolute and −3%±7% change in annualized change in height-adjusted total liver volume (from 2582±1381 to 2479±1317 ml/m) in the pasireotide long-acting release group compared with 136±117 ml/m absolute and 6%±7% increase (from 2387±759 to 2533±770 ml/m) in placebo (P<0.001 for both). Total kidney volumes decreased by −12±34 ml/m and −1%±4% in pasireotide long-acting release compared with 21±21 ml/m and 4%±5% increase in the placebo group (P=0.05 for both). Changes in eGFR were similar between groups. Among the n=48 randomized, adverse events included hyperglycemia (26 of 33 [79%] in pasireotide long-acting release versus four of 15 [27%] in the placebo group; P<0.001), and among the 47 without diabetes at baseline, 19 of 32 (59%) in the pasireotide long-acting release group versus one of 15 (7%) in the placebo group developed diabetes (P=0.001).ConclusionsAnother somatostatin analog, pasireotide long-acting release, slowed progressive increase in both total liver volume/total kidney volume growth rates without affecting GFR decline. Participants experienced higher frequency of adverse events (hyperglycemia and diabetes).Clinical Trial registry name and registration numberPasireotide LAR in Severe Polycystic Liver Disease, NCT01670110PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_28_CJN13661119.mp3


Gut ◽  
2008 ◽  
Vol 57 (9) ◽  
pp. 1338-1339 ◽  
Author(s):  
L van Keimpema ◽  
R A de Man ◽  
J P H Drenth

2016 ◽  
Vol 101 (11-12) ◽  
pp. 535-541
Author(s):  
Kazuya Yamaguchi ◽  
Daisuke Morioka ◽  
Atsuo Kobayashi ◽  
Nobutoshi Horii ◽  
Kentaro Miyake ◽  
...  

Ascites necessitating persistent drainage or paracentesis after drain removal has been found among early postoperative complications after combined hepatectomy and cyst fenestration (CHCF) for polycystic liver disease (PLD). It has been reportedly observed in 20% to 70% of cases and seemed to easily cause recurrent symptoms unless properly treated. We utilized distilled water lavage for treating localized fluid collection after combined hepatectomy and cyst fenestration for PLD. A 63-year-old female patient underwent CHCF for PLD, which caused severe abdominal fullness. Early postoperative course was uneventful until 10 days after surgery when the patient suffered sudden abdominal fullness and resultant severe anorexia because of right subphrenic massive localized monolocular fluid collection diagnosed by abdominal computed tomography—although total liver volume was reduced to less than half of that before surgery. Percutaneous drainage relieved symptoms immediately, but the drainage tube could not be removed because of massive outflow. Then we utilized distilled water lavage for treating this condition. After that, drain outflow dramatically reduced and the drainage tube was successfully removed. Total liver volume of the patient continued to reduce up to 1 year after surgery and retained less than one-third of preoperative total liver volume thereafter. Sustained reduction of total liver volume in the present case suggested a sclerosant effect of hypotonic cytocidal property of distilled water for cyst endothelium and/or retrieved effectiveness of fenestration. Hence, we consider this approach to be useful for patients with PLD receiving CHCF and thus present it here.


2021 ◽  
Vol 49 ◽  
Author(s):  
Isabela Das Neves Piana ◽  
Alexandre Coltro Gazzone ◽  
Luciana Lopes Simplício ◽  
Mariana Isa Poci Palumbo ◽  
Verônica Jorge Babo-Terra

Background: Hepatic cysts are rarely described in association with infections by Platynosomum sp. Infected animals are most often asymptomatic, and the severity of symptoms is associated with the number of biliary tract parasites, which may lead to cholangitis and cholangiohepatitis. Although platinosomiasis is often associated with cholangitis and cholangiohepatitis, it rarely is with polycystic disease. For the parasite’s life cycle to occur, the infected cat must eliminate the eggs in the feces and three intermediate hosts are needed: snails, terrestrial isopods and vertebrates like the frog or the gecko. The eggs are ingested by the snails, then the miracids are released and matured into the mother sporocyst form, which originates child sporocysts containing the cercariae, that leave the mollusks for the soil and are ingested by the terrestrial isopod in which the cercariae matures until metacercariae. Vertebrates ingest terrestrial isopods and are ingested by felines. The present study aimed to report an unusual case of platinosomiasis with the development of multiple hepatic cysts.Case: A mixed breed male kitten was admitted with a history of apathy, hyporexia, increased abdominal volume and jaundice. In the ultrasound examination, we could see hepatomegaly and several hypoecogenic rounded structures, similar to cysts. There was an increase of serum concentration of the hepatic enzymes alanine transaminase and gamma glutamyl transferase enzyme. The parasite’s eggs were investigated in the patient’s feces using the simple sedimentation method, with a negative result. The animal was submitted to celiotomy and it was possible to observe several cystic structures in the liver. The cysts content was sent to cytology and culture. Cytology result was compatible with liver cyst and there was no bacterial growth in the culture. Bile fluid was collected and sent for Platynosomum sp. research using the centrifugal sedimentation test in formalin-ether solution, which allowed the parasite’s eggs to be observed. The cat was treated with praziquantel,silymarin, S-Adenosyl methionine, and ursodeoxycholic acid. The patient gradually improved from jaundice and there was a reduction in abdominal volume. Discussion: This report describes a case of platinossomiasis associated with polycystic liver disease in a domestic cat, which seems to be an uncommon presentation. Most infected cats are asymptomatic, but some animals may exhibit anorexia, apathy, increased abdominal volume due to hepatomegaly and/or ascitis and jaundice. Although infestation in domestic cats is relatively common, its association with liver cysts is rare or poorly reported in the literature, representing a diagnostic challenge, which makes mandatory the inclusion of this differential diagnosis in polycystic liver diseases in cats. The diagnosis of this parasitosis can be made based on the association among clinical signs, laboratory tests and ultrasound examination, but the definitive diagnosis is usually made by visualizing the parasite’s eggs. In the case described, it was not possible to observe parasite’s eggs in the patient’s feces, but in the bile. Platynosomum sp. infection should always be considered as a differential diagnosis in cases of polycystic liver disease in cats, especially in countries with tropical or subtropical climate. Early diagnosis and appropriate treatment were fundamental for the improvement of the patient’s clinical condition.Keywords: feline, liver, platinosomiasis, polycystic disease, jaundice, cystic lesions.


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