Background Laparoscopic fenestration is one of the treatment options for symptomatic hepatic cysts, either solitary or in context of polycystic liver disease (PLD), but indications, efficacy and surgical techniques are under debate. Methods A systematic literature search (1950–2017) of PubMed, Embase, Web of Science and the Cochrane Library was performed (CRD42017071305). Studies assessing symptomatic relief or symptomatic recurrence after laparoscopic fenestration in patients with symptomatic, non-parasitic, hepatic cysts were included. Complications were scored according to Clavien–Dindo. Methodological quality was assessed by Newcastle–Ottawa scale (NOS) for cohort studies. Pooled estimates were calculated using a random effects model for meta-analysis. Results Out of 5277 citations, 62 studies with a total of 1314 patients were included. Median NOS-score was 6 out of 9. Median follow-up duration was 30 months. Symptomatic relief after laparoscopic fenestration was 90.2% (95% CI 84.3–94.9). Symptomatic recurrence was 9.6% (95% CI 6.9–12.8) and reintervention rate was 7.1% (95% CI 5.0–9.4). Post-operative complications occurred in 10.8% (95% CI 8.1–13.9) and major complications in 3.3% (95% CI 2.1–4.7) of patients. Procedure-related mortality was 1.0% (95% CI 0.5–1.6). In a subgroup analysis of PLD patients (n = 146), symptomatic recurrence and reintervention rates were significantly higher with respective rates of 33.7% (95% CI 18.7–50.4) and 26.4% (95% CI 12.6–43.0). Complications were more frequent in PLD patients, with a rate of 29.3% (95% CI 16.0–44.5). Conclusions Laparoscopic fenestration is an effective procedure for treatment of symptomatic hepatic cysts with a low symptomatic recurrence rate. The symptomatic recurrence rate and risk of complications are significantly higher in PLD patients.

Genome-wide association studies revealed that loss-of-function mutations in protein tyrosine phosphatase non-receptor type 2 (PTPN2) increase the risk of developing chronic immune diseases, such as inflammatory bowel disease (IBD) and celiac disease. These conditions are associated with increased intestinal permeability as an early etiological event. The aim of this study was to examine the consequences of deficient activity of the PTPN2 gene product, T cell protein tyrosine phosphatase (TCPTP), on intestinal barrier function and tight junction organization in vivo and in vitro. Here, we demonstrate that TCPTP protected against intestinal barrier dysfunction induced by the inflammatory cytokine IFN-γ by 2 mechanisms: it maintained localization of zonula occludens 1 and occludin at apical tight junctions and restricted both expression and insertion of the cation pore-forming transmembrane protein, claudin-2, at tight junctions through upregulation of the inhibitory cysteine protease, matriptase. We also confirmed that the loss-of-function PTPN2 rs1893217 SNP was associated with increased intestinal claudin-2 expression in patients with IBD. Moreover, elevated claudin-2 levels and paracellular electrolyte flux in TCPTP-deficient intestinal epithelial cells were normalized by recombinant matriptase. Our findings uncover distinct and critical roles for epithelial TCPTP in preserving intestinal barrier integrity, thereby proposing a mechanism by which PTPN2 mutations contribute to IBD.

The association between estrogen‐containing oral contraceptives and history of pregnancies with disease severity in women with polycystic liver disease (PLD) is unclear. We performed a cross‐sectional cohort study to assess this association by selecting female patients with PLD of which imaging was available prior to any liver volume‐reducing therapy. Patients received a questionnaire to collect detailed information on estrogen use and pregnancies. Preplanned subgroup analyses were performed on premenopausal and postmenopausal patients. The questionnaire was returned by 287 of 360 selected patients (80%). There was no significant association between estrogen‐containing oral contraceptives and height‐adjusted total liver volume (hTLV) in the total group (P = 0.06) and postmenopausal subgroup (P = 0.7). By contrast, each year of exposure corresponds with a 1.45% higher hTLV (P = 0.02) in the premenopausal subgroup, equivalent to a 15.5% higher hTLV for every 10 years of use. Pregnancy duration was not associated with hTLV. In conclusion, patients with PLD should avoid exogenous estrogens.

Patients suffering from polycystic liver disease can develop large liver volumes, leading to physical and psychological complaints, reducing quality of life. There is an unmet need for new therapies in these patients. Estrogen seems to be a promising target for new therapies. Female sex is the most important risk factor for the presence and severity of disease, estrogen supplementation enhances liver growth and after menopause, liver growth decreases. Experimental studies show the presence of the estrogen receptors alfa and beta on cystic cholangiocytes, and increased in vitro growth after administration of estrogen. In this review, we summarize the available experimental and epidemiological evidence to unravel the role of estrogens and other female hormones in polycystic liver disease. Based on the available evidence, female polycystic liver disease patients should be discouraged from taking estrogen-containing contraceptives or hormone replacement therapy. Since liver growth rates decline after menopause, treatment decisions should be based on measured liver growth in postmenopausal women. Finally, blockage of estrogen receptors or estrogen production is a promising target for new therapies.

The European Reference Network for rare liver diseases (ERN RARE-LIVER) is a Europe-wide network of paediatric and adult hepatologists from expert centres in close collaboration with patient advocates from the various disease-areas covered in our ERN. The ERN is focused on providing more equitable care across Europe and creates a network of both medical specialists and patient experts in rare liver disease. This position paper summarizes the achievements of the first year and plots the route for the near future for ERN RARE-LIVER, as discussed during a strategy meeting that took place 27 and 28 February 2018 in Nijmegen, the Netherlands. ERN RARE-LIVER has established itself as a group with experts, hospitals and patients. One of the tools to improve communication is the clinical patient management system (CPMS) that allows access to expert consultation by European physicians confronted with a patient with rare liver disease. ERN RARE-LIVER will function as the platform to improve healthcare by initiating registries, foster research efforts and coordinate development of clinical guidelines in Europe.

Patients suffering from polycystic liver disease may develop Hepatic Venous Outflow Obstruction, Portal Vein Obstruction and/or Inferior Caval Vein Syndrome because of cystic mass effect. This can cause portal hypertension, leading to ascites, variceal haemorrhage or splenomegaly. For this review, we evaluate the evidence to provide clinical guidance for physicians faced with this complication. Diagnosis is made with imaging such as ultrasound, computed tomography or magnetic resonance imaging. Therapy includes conventional therapy with diuretics and paracentesis, and medical therapy using somatostatin analogues. Based on disease phenotype various (non‐)surgical liver‐volume reducing therapies, hepatic or portal venous stenting, transjugular intrahepatic portosystemic shunts and liver transplantation may be considered. Because of complicated anatomy, use of high‐risk interventions and lack of empirical evidence, patients should be treated in expert centres.