Effects of antiportal hypertensive therapy, such as nonselective beta-blockers or transjugular PLX4032 intrahepatic portosystemic shunt (TIPS) implantation, on vWF-Ag levels will provide further mechanistic insights in the mechanism regulating vWF-Ag levels in patients with cirrhosis and PH. vWF-Ag levels can be easily determined in standard laboratories at a cost of less than 6 US$€ per patient sample. To increase the probability of a proper testing, it is advisable that

the measurement should be done at a facility with immediate on-site processing in their own specialized coagulation laboratory,24 which is not always found in small hospitals. However, certain known limitations to the application of vWF-Ag levels in patients with cirrhosis have to be considerd (e.g., infections, malignancies, physical training or IFN therapy),14,

15 which have been shown to elevate vWF-Ag levels. Hereditary vWF-Ag deficiency or acute bleeding may diminish vWF-Ag levels and the degree of PH might be underestimated. On the other hand, measurement of HVPG is invasive, expensive, not widely available and technically not successful in up to 4% of patients.25 TE, investigated as another promising noninvasive tool for the assessment of patients with liver disease, may not be successful in up to 25% of cases, not to mention the cost of the system and maintenance, and is therefore inferior when standard probes are used. selleck compound Clinical consequences of cirrhosis are foremost related to CSPH more than to any other cause,26 which prompted the proposal of a new staging system for patients with cirrhosis.5 The invasiveness and lack of general availability of HVPG measurement prevents the broad use of pressure-guided diagnostic and therapeutic algorithms

in patients with cirrhosis. In our large cohort, we could show an impressive correlation between portal pressure and vWF-Ag levels, which is independent of CPS.8 Thus, vWF-Ag can be used for the selection of high-risk patients within respective Child Metalloexopeptidase Pugh stages. This is of particular importance in patients with CPS A and B, who might not be considered for liver transplantation. We additionally could show that the reported increase of vWF-Ag with higher CPS stages9 is probably more related to PH, because patients with cirrhosis without PH had only slightly elevated vWF-Ag levels. Furthermore, we demonstrated a correlation of vWF-Ag with clinical outcome parameters and a high predictive value of disease-related mortality. In line with our results, La Mura et al.12 investigated the effect of vWF-Ag levels on clinical outcome in 42 patients with cirrhosis and PH. The investigators reported a vWF-Ag cut-off value of 216 U/dL to disclose between patients with cirrhosis with a highly different probability of survival free of PH-related events and transplantation. This cut-off level is similar to our 241%, which represents the optimal cutoff to discriminate between the presence or absence of CSPH in patients with cirrhosis.

Key Word(s): 1. SirT1; 2. iTRAQ; 3. fatty liver; 4. lipid metabolism; Presenting Author: AJAY DUSEJA Additional Authors: learn more SHWETA KAPIL, PALLAB RAY, ASHIM DAS, ANURADHA

CHAKRABORTI, RADHAK DHIMAN, YOGESH CHAWLA Corresponding Author: AJAY DUSEJA Affiliations: PGIMER Objective: Background: Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease. Genetic polymorphisms of Toll like receptors (TLRs) and its co-receptor CD14 (Cluster of differentiation 14) may be involved in the pathogenesis of NAFLD. Aim: To study the role of genetic variants of CD14 gene [C (-550) T and C (-159) T] in the pathogenesis of NAFLD. Methods: Methods: In a prospective study, 130 patients with NAFLD (Cases) (M:F =78:52, mean age 38.47 ± 10.6 years) and 50 healthy volunteers (Controls) (M:F = 38:12, Mean age 36.56 ± 4.2 years) were included. Genotyping of C(-550)T and C(-159)T polymorphisms in the promoter region of CD14 gene was done using polymerase chain reaction and restriction fragment length polymorphism. Results were confirmed by DNA sequencing and data analyzed

using multiplicative, Cochran armitage test for trend (CATT), Panobinostat dominant and recessive models for the association of these polymorphisms with NAFLD. Results: Results: Among C(-550)T polymorphism, frequency of different genotypes among cases and controls were CC [77/130 (59.2%) vs.34/50 (68%)], CT [45(34.6%) Vs 14(28%), OR = 1.41(0.68-2.92) p =0.34] and TT [(8(6.1%) Vs 2(4%), OR = 1.76 (0.35-8.75) p =0.48]. There was no difference in the T allele frequency between cases and controls [(23.46% Vs 18%) p =0.262] and no association of C(-550)T polymorphism with NAFLD on multiplicative, CATT, dominant and recessive models of analysis. Among C(-159)T polymorphism frequency of different genotypes among cases and controls were CC [20(15.8%) Vs. 10(20%)], CT [51(39.2%) Vs. 30(60%), OR = 0.85(0.35-2.0) p =0.71] and TT [59/130(45.38%) vs.10/50(20%),

OR = 2.9(1.07-8.12) p =0.03]. T allele frequency (65% Vs 50%, p = 0.009) was higher among cases than controls with significant association of C(-159)T polymorphism with NAFLD on recessive model (p = 0.0001). Conclusion: Conclusion: Amino acid C(-159)T polymorphism of TLR co-receptor CD14 is associated with NAFLD. Key Word(s): 1. NAFLD; 2. NASH; 3. Toll like receptor; 4. Gene polymorphism; Presenting Author: ELENAVITALYEVNA PELLO Additional Authors: SOFIAKONSTANTINOVNA MALYUTINA, GALINAILYNICHNA SIMONOVA, YURIPETROVICH NIKITIN Corresponding Author: ELENAVITALYEVNA PELLO, SOFIAKONSTANTINOVNA MALYUTINA, GALINAILYNICHNA SIMONOVA, YURIPETROVICH NIKITIN Affiliations: Institute of Internal Medicine, Siberian Branch of the Russian Academy of Medical Sciences Objective: Background and aims: In the world the rapidly growing prevalence of fatty liver disease (FLD) evokes anxiety.

All laboratory tests were performed for each patient just before initiation of IFN therapy. Blood cell counts, serum alanine transaminase, gamma-glutamyl transpeptidase, hemoglobin A1c, total bilirubin, albumin, prothrombin time, and alpha-fetoprotein (AFP) were measured using commercially available assays. The HCV genotype was determined using polymerase chain reaction with the HCV Genotype Primer Kit (Institute of Immunology Co., Ltd., Tokyo, Japan) and classified as genotype 1, genotype 2, or other, according to Simmonds’ classification system. Serum HCV viral load

was determined using quantitative reverse transcription polymerase chain reaction using the COBAS TaqMan HCV Test (Roche Diagnostics, Branchburg, NJ, USA). The treatment protocol for CHC patients consisted of 1.5 μg/kg of pegylated Angiogenesis inhibitor IFN-α-2b or 180 μg of pegylated IFN-α-2a once a week, combined with ribavirin at an oral dose of 600–1000 mg/day. Duration of the treatment was 48–72 weeks for those with HCV genotype 1 buy Roxadustat and a serum HCV viral load > 5 log IU/mL. For all other patients, treatment lasted for 24 weeks. SVR was defined as undetectable serum HCV-RNA at 24 weeks after the end of treatment. Measurement of liver stiffness by transient elastography was performed using FibroScan (Echosens, Paris, France) within a week before treatment initiation. Technical

details of the examination and procedure have been reported previously.[17] Ten validated measurements were made on each patient, and results were expressed in kilopascals (kPa). Only procedures with 10 validated measurements and a success rate of at least 60% were considered reliable, and the median value was considered representative of the liver

elastic modulus. Serum AFP was measured every month, and ultrasonography or computed tomography were performed at least every 3–6 months for HCC surveillance during and after treatment, with a minimum follow-up duration of 6 months after the initiation of IFN therapy. HCC was diagnosed by histological examination and/or triphasic computerized tomography, in check details which hyperattenuation in the arterial phase with washout in the late phase is pathognomonic for HCC.[20] The status of patients enrolled in this study was confirmed as of March 2012. All analyses were conducted using IBM SPSS version 19 (IBM SPSS, Chicago, IL, USA), and P values less than 0.05 were considered statistically significant. Continuous variables and categorical variables were summarized as median (range) and percentage, respectively. Mann–Whitney U and chi-square tests were used when appropriate. The strength of the association between LSM and the histological fibrosis stage was estimated using the Spearman’s rank correlation coefficient.

Similar elevation of Gr1high and F4/80+ cells was

also observed in STAT3Hep−/− mice. In addition, the total number of infiltrating Gr1high and F4/80+ cells was much higher in the livers of STAT3Mye−/− and STAT3Mye−/−Hep−/− mice as compared to wild-type and STAT3Hep−/− mice, both before surgery, as well as post-sham and PHx. This suggests that PHx-induced activation of STAT3 in myeloid find more cells inhibits their infiltration into the liver. Figure 3B summarizes the serum levels of proinflammatory cytokines such as TNF-α, IL-6, and IFN-γ. In general, after sham operation, serum levels of IL-6 but not other cytokines were elevated in wild-type mice, whereas both STAT3Mye−/− and STAT3Mye−/−Hep−/− mice had higher serum levels of IL-6 as well as TNF-α and IFN-γ. After PHx, serum levels of IL-6 were markedly elevated in wild-type and STAT3Hep−/− mice, such elevation was prolonged

in STAT3Mye−/− and STAT3Mye−/−Hep−/− mice. Serum levels TNF-α and IFN-γ were slightly elevated in wild-type and STAT3Hep−/− mice but were dramatically higher in STAT3Mye−/− and STAT3Mye−/−Hep−/− mice. In addition, serum TNF-α levels were higher in STAT3Mye−/−Hep−/− mice than STAT3Mye−/− mice 6 and 9 hours post-PHx Next, learn more we investigated the mechanisms underlying liver failure and impaired liver regeneration in STAT3Mye−/−Hep−/− mice by analyzing the activation of the STAT3 pathway, which promotes hepatocyte survival and liver regeneration,12, 16 as well as STAT1 activation, which induces hepatocyte apoptosis and inhibits liver regeneration.21 STAT3 was activated by PHx in wild-type mice, as reflected Clomifene by elevated levels of pSTAT3 that peaked 3-6 hour after surgery (Fig. 4 A). Compared to wild-type mice, in STAT3Mye−/− mice, the STAT3 pathway was constitutively active, with both the STAT3 protein levels and pSTAT3 being elevated (PHx 0 hour), and increased slightly further following PHx. In contrast, hepatic STAT3 and pSTAT3 were both very low in STAT3Hep−/− and STAT3Mye−/−Hep−/− mice, as expected. STAT1 activation (pSTAT1) was

not detected in the liver of wild-type and STAT3Mye−/− mice after PHx. However, in both STAT3Hep−/− and STAT3Mye−/−Hep−/− mice hepatic levels of pSTAT1 were greatly increased following PHx, with peaks occurring 3-6 hours post-PHx. A delayed increase in the expression of the STAT1 protein was observed 24 to 40 hours post-PHx in STAT3Hep−/− mice, whereas in STAT3Mye−/−Hep−/− mice, STAT1 protein levels were constitutively elevated compared to wild-type and STAT3Hep−/− mice. Weak pSTAT3 activation was also detected in the liver after sham operation in wild-type and STAT3Mye−/− mice but not in STAT3Hep−/− and STAT3Mye−/−Hep−/− mice (Supporting Fig. 4a). Interestingly, in the spleen STAT3 was activated similarly after PHx in all four lines of mice, whereas pSTAT1 activation was not detected in any of them (Supporting Fig. 4b).

All results were measured by densitometry and displayed as relation of phosphorylated/nonphosphorylated protein and fold induction to untreated controls. A total of 168 carcinomas of the liver were retrieved from the surgical pathology files of the Department of Pathology, University Hospital Zürich, Switzerland, and the Institute of Pathology, University of Regensburg, Germany. Tumors were classified according to the World Health Organization (WHO) Classification of the Digestive System

(2000). The study was approved by the local ethics committees of Zurich (Kantonale Ethikkommission Zurich, StV 26–2005). Formalin-fixed paraffin-embedded tumor tissues were used to construct tissue microarrays (TMA) with cores of 168 HCC and 20 normal liver tissues. The TMAs were constructed as described.15 http://www.selleckchem.com/products/FK-506-(Tacrolimus).html Two tissue cores per tumor with a diameter of 0.6 mm were punched out of the donor block and transferred to the recipient block. Three-micron-thick sections of TMA blocks and formalin-fixed, paraffin-embedded tissues were mounted on glass slides (SuperFrost Plus;

Menzel), deparaffinized, rehydrated, and stained with hematoxylin-eosin using standard histological techniques. For immunohistochemical staining the Ventana Benchmark automated staining system (Ventana Medical Systems) and GW-572016 mw Ventana reagents were used. After deparaffinization in xylene, slides were rehydrated in decreasing concentrations of ethanol. Endogenous peroxidase was blocked using the Ventana endogenous peroxidase blocking kit after a rinse with distilled water. For antigen retrieval slides were heated with cell conditioning solution (CC1, Ventana) according to the manufacturers instructions. The same primary antibodies as for western blotting were used against and adjusted to the Ventana Benchmark system after performing titrations. iVIEW-DAB was used as chromogen. Ki-67 proliferation index was defined as percentage mafosfamide of positive nuclei per 100 tumor cells and was determined on TMA tumor tissue cores. All animal experiments

were in accordance with Swiss federal animal regulations and approved by the cantonal veterinary office of Zurich. Athymic female NU/NU mice ages 6 to 8 weeks were kept on a 12-hour day/night cycle with free access to food and water. Huh7 cells were trypsinized (Invitrogen), washed in PBS, and resuspended in serum-free DMEM. Three × 106 Huh7 cells in 200 μL DMEM were injected subcutaneously in the lower back. After 3 weeks 33% of the mice bore visible tumors. When tumors reached a mean volume of 150 mm3 mice were randomized into two groups (six animals per group): Animals were treated with 0.16% DMSO in 500 μL H20 subcutaneously or 10 mg/kg BW SB204741 in 500 μL H20 twice a day.

However, because of the high rate of mortality without transplantation and the extremely limited availability of DDLT, allocating patients with ALF to a no-LT or DDLT control group would be unethical or impossible. In conclusion, we have shown here that emergency adult LDLT can be performed expeditiously and safely for patients with ALF, and that the procedure greatly improves patient survival rate. Adult LDLT should therefore be

considered one of the first-line treatment options for patients with ALF, especially Rapamycin in vitro in areas where most cases of ALF are caused by etiologies associated with poor outcome and the supply of organs from deceased donors is severely limited. The authors thank Drs. Ki-Hun Kim, Chul-Soo Ahn, Duk-Bog Moon, Tae-Yong Ha, Gi-Won Song, Dong-Hwan Jung, Kang Mo Kim, Young-Hwa Chung, and Yung Sang Lee for their help in data collection and critical review of the article. “
“Chronic ethanol consumption is associated with persistent hepatitis C viral (HCV) infection. This study explores the role of the host cellular immune response to HCV core protein in a murine model and how chronic ethanol consumption alters T-cell regulatory (Treg) populations. BALB/c mice were fed an isocaloric control or ethanol liquid diet. Dendritic cells (DC) were isolated after expansion Selleck HDAC inhibitor with a hFl3tL-expression plasmid and subsequently transfected with HCV core protein. Core-containing

DC (1 × 106) were s.c. injected (×3) in mice every 2 weeks. Splenocytes from immunized mice were isolated and stimulated with HCV core protein to measure generation of viral antigen-specific

Treg, as well as secretion of interleukin (IL)-2, tumor necrosis factor (TNF)-α and IL-4. Cytotoxicity was measured by lactate dehydrogenase release from HCV core-expressing syngeneic SP2/19 myeloma cells. Splenocytes from mice immunized with ethanol-derived and HCV core-loaded DC exhibited significantly lower in vitro cytotoxicity triclocarban compared to mice immunized with HCV core-loaded DC derived from isocaloric pair-fed controls. Stimulation with HCV core protein triggered higher IL-2, TNF-α and IL-4 release in splenocytes following immunization with core-loaded DC derived from controls as compared to chronic ethanol-fed mice. Splenocytes derived from mice immunized with core-loaded DC isolated from ethanol-fed mice exhibited a significantly higher CD25+FOXP3+ and CD4+FOXP3+Treg population. These results suggest that immunization with HCV core-containing DC from ethanol-fed mice induces an increase in the CD25+FOXP3+ and CD4+FOXP3+Treg population and may suppress HCV core-specific CD4+ and CD8+ T-cell immune responses. “
“Iron is implicated in the pathogenesis of liver injury and insulin resistance and thus phlebotomy has been proposed as a treatment for non-alcoholic fatty liver disease (NAFLD).

72,73 Because HNF4α has no therapeutic ligand and therefore is still of limited clinical relevance, it is not further discussed here (review74). HDL-cholesterol creates a net flux of cholesterol from the periphery back to the liver, where it is excreted either as free cholesterol or bile acids into bile, a process termed “reverse cholesterol transport.” Expression of both

apoAI and apoAII (the structural apolipoproteins of HDL particles) is under the control of HNF4α.75 PPARα activation by fibrates increases levels of apoAI and apoAII, and thus HDL in humans.75 In contrast, mouse and rat apoAI is paradoxically repressed by fibrates,75 which needs http://www.selleckchem.com/products/Lapatinib-Ditosylate.html to be taken into account when interpreting experimental studies in rodents. LXRα was also found to repress apoAI synthesis, further adding to concerns on the potential utility of LXR agonists in the treatment of dyslipidemia.76 Finally, PPARα/γ and RXR77 as well as LXR14,77 up-regulate ATP binding cassette 1 (ABCA1) expression

in macrophages and thus promote cholesterol efflux to HDL. Bile acid-binding sequestrants/resins such as cholestyramine increase HDL-cholesterol.78 Conversely, accumulation of intrahepatic bile acids in cholestatic PFIC patients lowers,77 whereas biliary diversion again increases HDL-cholesterol levels.79 These findings can be explained by bile acid-mediated activation of FXR resulting in repression of apoAI by way of a negative FXR response element.77 In line with this, FXR-deficient mice are hypercholesterolemic due to an increase of HDL-cholesterol levels.80 These findings may need to be considered Selleckchem Erlotinib when applying FXR ligands for treatment of dyslipidemia. Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum ranging from simple fatty liver to nonalcoholic streatohepatitis (NASH) cirrhosis and hepatocellular carcinoma (HCC).81 Apart from the inherent mafosfamide risk for progression of liver disease, NAFLD has recently been identified as an independent risk factor for endothelial dysfunction

and cardiovascular death.81 NRs control fatty acid flux from peripheral white adipose tissue to the liver and regulate several critical metabolic steps involved in the pathogenesis of NAFLD, including fat storage, lipolysis, export, uptake, and oxidation. Surprisingly, little information is available about hepatic and WAT NR alterations in NAFLD patients and their role in progression from bland fatty liver to more aggressive NASH. As gatekeepers of fatty acid flux from adipose tissue to the liver and key regulators of hepatic metabolism, inflammation, and fibrosis, NRs could play a central role in this progression. PPARγ is expressed at very low levels in normal liver (mainly in Kupffer cells), but is increased in animal models with insulin resistance and fatty liver.82,83 WAT expandability may be a critical determinant of preventing fatty acid overflux to ectopic storage sites such as liver.

212 This model, available on the internet (www.lillemodel.com) may allow identification of patients who remain at high risk to be treated with other interventions. A wealth of evidence suggests that dysregulated Tyrosine Kinase Inhibitor Library clinical trial cytokines, including tumor necrosis factor alpha (TNFα) and a host of downstream cytokines play a pivotal role in the pathophysiology of AH. Thus, several agents have been studied that impact

the immunologic milieu, targeting specific cytokines, and TNFα in particular. Among the first agents to be studied was pentoxifylline, an oral phosphodiesterase inhibitor which also inhibits the production of TNFα, among other cytokines. A randomized placebo controlled clinical trial tested pentoxifylline in 101 patients with clinical evidence of severe AH.213 The in-hospital mortality in the treated ABT-263 patients was 40% lower than in the

placebo arm, with the bulk of the reduction related to a substantially lower likelihood of developing hepatorenal syndrome (HRS). HRS was responsible for 50% of the 12 deaths in the treatment arm, compared to 91.7% of the 24 deaths in the placebo group. Other specific inhibitors of TNF that have been studied include infliximab, a monoclonal chimeric anti-TNF antibody, and etanercept, a fusion protein containing the ligand-binding portion of the human TNF receptor fused to the Fc portion of human immunoglobulin G1.214 In the

first clinical trial of infliximab, 20 patients with biopsy proven alcoholic hepatitis and an MDF score between 32 and 55 (based on the original Maddrey score, which demonstrated an increased mortality at a Idelalisib score > 93) were randomized to either 5 mg/kg of infliximab plus 40 mg/day of prednisone (n = 11) or to prednisone alone.215 No substantial difference in overall mortality was found, but substantial decreases in other prognostic markers, including cytokine levels and MDF scores were seen in patients treated with combination therapy. Another trial, performed at 19 centers in France, randomized 36 patients with biopsy proven alcoholic hepatitis and an MDF ≥ 32 to prednisolone (40 mg/day for 4 weeks), versus prednisolone along with infliximab (10 mg/kg, given at study entry, and again at 2 weeks and 4 weeks after entry).216 The trial was stopped prematurely after seven deaths had occurred in the infliximab group, compared with three in the prednisolone arm. Four of the seven deaths in the infliximab arm were related to infectious etiologies, compared to one in the prednisolone group. The design, and in particular, the dose of infliximab chosen in the study, has been criticized as predisposing to these infections.

Figure 3 highlights the differentially regulated proteins associated with the significant biological pathways and functions noted above. These include immune response

proteins indicative of an early and sustained up-regulation of proinflammatory, type 1 acute phase protein production (pre-angiotensinogen, serum amyloid A1). We further observed an increase Palbociclib in the abundance of proteins associated with various aspects of immune cell recruitment, adhesion, and/or activation, including candidates functioning in phagocytosis, ubiquitin-mediated proteolysis and class 1 and 2 antigen presentation (leukotriene A4 hydrolase, CD44 antigen, bone marrow stromal cell antigen 2, proteasome beta subunit type 4, major histocompatibility class 1 antigen C (HLA-C), major histocompatibility class 2 antigen DR beta 1, cytochrome b-245 beta). Together, the data show a pattern of increased immune and inflammatory Protein Tyrosine Kinase inhibitor protein abundances observed prior to histologic evidence of significant fibrosis. Patients

with rapidly progressive fibrosis exhibited a decreased abundance of proteins functioning in hepatoprotective responses associated with superoxide, cysteine, glutathione, and xenobiotic metabolism (superoxide dismutase 1, cystathionine beta synthase [CBS], various glutathione S-transferases [GSTs], FK506 binding

protein 14, carboxymethylenebutenolidase homolog) (Fig. 3). These findings suggest that patients with rapidly progressive fibrosis are likely to experience increased oxidative stress. Consistent with this idea, we further observed an increase in the abundance of proteins that function to counteract damaging protein Methisazone and DNA modifications caused by reactive oxidants (aryl sulfotransferase 1A3, thioredoxin reductase 1, alpha thalassemia/mental retardation syndrome X-linked, 5′-3′ exoribonuclease 1) (Fig. 3). Early progression to fibrosis was further associated with the coordinated up- and down-regulation of proteins previously linked to epithelial-to-mesencyhmal transition (family with sequence similarity 3, member C [FAM3C], nexilin, CD44, epithelial cell adhesion molecule), a process recognized as a potential contributor to liver fibrogenesis.24-26 A concomitant up-regulation of cytokines (galectin 3 [LGALS3], insulin-like growth factor binding protein 7 [IGFBP7], angiotensinogen) and cytoskeletal/membrane proteins (tropomyosin 1 [TPM1]; myosin, heavy chain 11 [MYH11]; N-acylsphingosine amidohydrolase 2B) that have been previously associated with the proliferative and contractile phenotype of activated hepatic stellate cells (HSC) was also observed.

The distortion of the intrahepatic vasculature and biliary system

by cysts is a potential source of complications and accurate definition of these structures preoperatively remains difficult, even with current imaging modalities. Moreover, with the unusual large size of the polycystic liver, the liver is rigid and limits its mobility. Although the hilar vessels are easily accessed, the hepatic veins are particularly difficult to access. These factors increase the risk of a venous bleed or bile leakage. Another drawback of Roxadustat supplier hepatic resection is the risk of subsequent adhesions, which may complicate future liver transplantation. We found 26 articles on 337 PLD patients. Morbidity occurred in 51% of patients and included ascites, pleural effusion, biliary leakage, and hemorrhage. Morbidity was higher in patients who underwent previous surgery or who were on immunosuppressive drugs. Mortality was 3%,

and causes of death were intracerebral hemorrhage, septic shock, and Budd-Chiari syndrome. Mean hospital stay was about 10-15 days. Reoperation was performed because of persistent bleeding, thrombosis, or biliary leakage. The complication rate depended on experience and was lower in high-volume centers. Symptom relief was achieved in 86%. Cyst recurrence was seen in 34% of all patients (Supporting Information Table 3). However, the immediate improvement in patients after the postoperative period was significant. Liver transplantation beta-catenin inhibitor is the only curative therapeutic option in patients with severe polycystic liver.3 next Transplantation is indicated in those patients with extremely disabling symptoms that lead to a seriously decreased quality of life. In addition, untreatable complications, such as portal hypertension and nutritional compromise, are indications for liver transplantation. Liver transplantation

as a therapeutic option should be weighed carefully in view of the shortage of liver donors, the fact that PLD is not associated with excess liver-related mortality, and that liver synthetic function remains normal even in advanced cases. There were 29 articles on 206 PLD patients. The main indications for transplantation were abdominal pain, distension, fullness, dyspnea, extreme fatigue, and malnutrition. Overall, quality of life was severely impaired and patients were physically and socially disabled by these symptoms. A significant proportion of procedures (42%) were a combined liver and kidney transplant. Morbidity was seen in 83 of all patients (41%), whereas 30-day mortality was 5% and overall mortality 17% (Supporting Information Table 4).