Hepatocellular transporter levels were quantified using quantitative reverse transcription polymerase chain reaction and liquid chromatography-tandem mass spectrometry methods. Liver function deterioration (Child-Pugh class C) produced significant protein abundance (mean values) increase (to healthy livers) in P-gp (to 260% (CV (coefficient of variation) 82%)) and MRP4 (CV 230%) (not detected in healthy livers), decrease in MRP2 (to 30% (CV 126%)), NTCP (to 34% (CV 112%)), OCT1 (to 35% (CV 153%)), OATP1B1 (to 46% (CV 73%)), and OATP2B1 (to 27% (CV 230%)), whereas BSEP (CV 99%), MRP3 (CV 106%), OAT2 (CV 97%), OCT3 (CV 113%), and OATP1B3 (CV 144%) remained unchanged. Alcoholic liver disease produced significant protein downregulation of MRP2 (to 30% (CV 134%)), NTCP (to 76% (CV 78%)), OAT2 (to 26% (CV 117%)), OATP1B1 (to 61% (CV 76%)), OATP1B3 (to 79% (CV 160%)), and OATP2B1 (to 73% (CV 90%)) of healthy tissue values. Hepatitis C produced BSEP (to 47% (CV 99%)) and OATP2B1 (to 74% (CV 91%)) protein reduction. Primary biliary cholangitis and primary sclerosing cholangitis demonstrated P-gp and MRP4 protein upregulation (to 350% (CV 47%) and 287% (CV 38%), respectively). Autoimmune hepatitis revealed P-gp (to 410% (CV 49%)) and MRP4 (CV 96%) increase, and MRP2 (to 18% (CV 259%)) protein decrease. Drug transporters' protein abundance depends on liver pathology type and its functional state.Drug transporters have a major impact on the overall drug disposition, efficacy, toxicity, and drug-drug interactions. While transporters present at the basolateral membrane mediate the uptake of substrates from blood into hepatocytes and/or efflux of substrates in the opposite direction, transporters at the canalicular membrane mediate the excretion of substrates into bile. Transporters present in intracellular membranes sequester substrates in subcellular compartments within hepatocytes. The expression and function of transporters are subjected to complex regulatory mechanisms and may be affected by liver disease states and liver dysfunction.

BackgroundAlcoholic cirrhosis is an indication for 40% of liver transplantations (LT) in Europe. In most centers, 6 months of abstinence is required before listing. However, alcohol recidivism is quite high after LT, and approximately 20–25% of recipients with ALD resume harmful drinking, resulting in liver insufficiency, which casts doubt on the 6-months rule as a reliable marker of abstinence maintenance after LT.Material/MethodsWe analyzed data on patients who underwent orthotopic LT in Marie Curie Hospital, Szczecin, Poland, from 2000 to 2015 due to alcoholic or cryptogenic cirrhosis. Every ALD patient met the 6-month abstinence requirement. Alcohol recidivism has been studied based on a history of alcohol abuse taken from the patients or from their relatives, and in case of denial, on laboratory tests for alcohol abuse. Five patterns of recidivism were distinguished: death, constant heavy drinking, heavy drinking with abstinence attempts, occasional laps, and a single episode of alcohol intake. The analysis of survival was performed according to the Kaplan-Meier method. Patient survival rates in ALD recipients vs. non-ALD recipients were compared using the log-rank test.ResultsAlcohol recidivism was finally evaluated in 109 patients: 81 males and 28 females, with a median age of 53.3 years (range 30–66). Harmful drinking was discovered in 16 patients (14.7%), including seven deaths due to alcoholic hepatitis. Sporadic or episodic drinking was found in 29 patients (27%). In heavy drinkers, the abstinence period after transplantation was significantly shorter and patients were younger than the average (median age 43.8 years). Women break abstinence faster than men and are at greater risk of liver insufficiency. Five, 10 and 15-year survival in the ALD group was superior in comparison with non-ALD group, but differences did not reach statistical significance (p=0.066, p=0.063, p=0.075, respectively).ConclusionsThe prognostic value of a 6-month abstinence period before transplantation is rather low as it does not predict sobriety after transplantation. However, only a minority of such patients drink harmfully. Survival in ALD recipients tends to be better in comparison with survival in the other etiologies. Younger women dependent on alcohol shortly before LT are at greatest risk of recidivism.

BakgroundStandard methods for endoscopic retrograde cholangiopancreatography (ERCP) management of anastomotic strictures (AS) after OLT includes repeated balloon dilation of the stricture with subsequent insertion of a plastic biliary stent (PBS). In post-OLT patients not responding to standard endoscopic treatment, the placement of fully covered self-expanding metal stents (FCSEMS) is a valid alternative to surgical treatment. The aim of this study was to compare the results of new FCSEMS implantation with the standard ERCP stricture management protocol and with conventional FCSEMS insertion.Material/MethodsThis retrospective study involved 39 post-OLT patients with confirmed diagnosis of biliary AS. Enrolled subjects were divided into 2 groups: the FCSEMS group (study group) and the PBS group (control group). The study group was divided into 2 subgroups: the conventional FCSEMS group and the new-type FCSEMS group.ResultsStricture recurrence after PBS placement was observed in 36.36% of controls and in only 9.52% of study group members (P=0.170). Recurrence rates in patients after conventional FCSEMS and new type FCSEMS implantation was similar (10% vs. 9.09%; P=0.501). The applied treatment was successful in 82.61% of study group members and only 43.75% of controls (P=0.029). Success rates of conventional FCSEMS and new-type SEMS insertion did not differ significantly (81.82% vs. 83.33%, P=0.649). There was no statistically significant difference in complication rates between groups (P=0.879).ConclusionsImplantation of FCSEMS is more effective than repeated balloon dilatation of AS with subsequent PBS placement and is they have similar complication rates. Application of new-type FCSEMS gives results comparable to conventional FCSEMS.

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