Publications by authors named "Krzysztof Zieniewicz"

90 Publications

Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: results of the ELITA/EF-CLIF collaborative study (ECLIS).

J Hepatol 2021 Apr 24. Epub 2021 Apr 24.

Department of hepatogastroenterology, Hepatology and Liver Transplantation Unit, HCL Hopital de la Croix-Rousse, Lyon, France.

Background And Aims: Liver transplantation (LT) has been proposed to be an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to address the current clinical practice and outcomes of ACLF patients wait listed (WL) for LT in Europe.

Methods: Retrospective study including 308 consecutive ACLF patients, listed in 20 centres across 8 European countries, from January 2018 to June 2019.

Results: 2677 patients received a LT, 1216 (45.4%) for decompensated cirrhosis (DC). Of these, 234 (19.2%) had ACLF at LT: ACLF-1, 58 (4.8%); ACLF-2, 78 (6.4%); and ACLF-3, 98 (8.1%). Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and Netherlands had medium rates (9-15%); and United Kingdom and Spain had low rates (3-5%) (p <.0001). One-year probability of survival after LT for patients with ACLF was 81% (95% CI 74-87). Pre-LT arterial lactate levels >4 mmol/L (HR 3.14, 95% CI 1.37-7.19), recent infection from multi-drug resistant organisms (HR 3.67, 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74, 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the WL. In an intention-to-treat analysis, one-year survival of ACLF patients on the LT WL was 73% for ACLF-1 or -2 and 50% for ACLF-3.

Conclusion: The results reveal wide variations in listing patients with ACLF in Europe despite favorable post-LT survival. Risk factors for mortality were identified, allowing a more precise prognostic assessment of ACLF patients for potential LT.

Lay Summary: Acute on chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonized to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified for selecting patients with favorable outcomes.
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http://dx.doi.org/10.1016/j.jhep.2021.03.030DOI Listing
April 2021

Cardiac Morphology, Function, and Hemodynamics in Patients With Morbid Obesity and Nonalcoholic Steatohepatitis.

J Am Heart Assoc 2021 Apr 13;10(8):e017371. Epub 2021 Apr 13.

Department of Internal Medicine, Hypertension and Angiology Medical University of Warsaw Poland.

Background The patients with nonalcoholic fatty liver disease demonstrate an increased cardiovascular risk. The adverse influence of liver abnormalities on cardiac function are among many postulated mechanisms behind this association. The aim of the study was to evaluate cardiac morphology and function in patients with morbid obesity referred for bariatric surgery with liver biopsy. Methods and Results We evaluated with echocardiography 171 consecutive patients without known cardiac disease (median age 42 [interquartile range, 37-48] years, median body mass index 43.7 [interquartile range, 41.0-47.5], 67% female patients. Based on the liver biopsy results, there were 44 patients with nonalcoholic steatohepatitis (NASH), 69 patients with isolated steatosis, and 58 patients without steatosis. Patients with NASH demonstrated signs of left ventricular concentric remodeling and hyperdynamic circulation, including indexed left ventricular end-diastolic diameter [cm/m]: NASH 1.87 [0.22]; isolated steatosis 2.03 [0.33]; without steatosis 2.01 [0.19], =0.001; relative wall thickness: NASH 0.49±0.05, isolated steatosis 0.47±0.06, without steatosis 0.46±0.06, =0.011; cardiac index [L/m]: NASH 3.05±0.54, isolated steatosis 2.80±0.44, without steatosis 2.79±0.50, =0.013. After adjustment for sex, age, blood pressure, and heart rate, most of the measures of the left ventricular systolic and diastolic function, left atrial size, right ventricular function, and right ventricular size did not differ between groups. Conclusions In a group of patients with extreme obesity, NASH was associated with left ventricular concentric remodeling and hyperdynamic circulation. Increased cardiac output in NASH may represent an additional risk factor for incident cardiovascular events in this population.
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http://dx.doi.org/10.1161/JAHA.120.017371DOI Listing
April 2021

Performance of initial LI-RADS 2018 treatment response in predicting survival of patients with hepatocellular carcinoma following TACE: a retrospective, single-center cohort study.

J Cancer Res Clin Oncol 2021 Mar 28. Epub 2021 Mar 28.

Second Department of Radiology, Medical University of Warsaw, Ul. Banacha 1a, 02-097, Warsaw, Poland.

Purpose: Treatment response following transarterial chemoembolization (TACE) is frequently evaluated with Liver Imaging Reporting and Data System Treatment Response (LR-TR) algorithm, but its association with patients' outcomes is not supported in the literature. The purpose of this study was to provide such data.

Methods: A retrospective analysis of 99 TACE patients with stage A/B hepatocellular carcinoma according to Barcelona-Clinic Liver Cancer staging system was performed. Two radiologists assessed LR-TR, while a third radiologist re-assessed divergent results. Overall survival (OS) and time to disease progression (TTP) were the primary endpoints of the study, while the Cox proportional hazard model was used for outcome analyses.

Results: Interobserver agreement was substantial between the two readers with κ = 0.69 (95% CI 0.58-0.81). The median OS in viable, equivocal, and non-viable groups were 27, 27, and 73 months, respectively (p < 0.001). However, after adjustment for confounding factors, there was no significant association between initial viable response and OS (HR 0.98 [95% CI 0.37-2.63], p = 0.97), while equivocal response remained statistically significant (HR 3.52. [95% CI 1.27-9.71], p = 0.015). No significant association was noted when viable and equivocal groups were analyzed in aggregate (HR 1.03 [95% CI 0.4-2.4], p = 0.96). The median TTP did not differ between non-viable and viable groups (23 vs 18 months, respectively; p = 0.98). None of the analyzed predictors was associated with TTP.

Conclusion: Initial LR-TR response was not an independent predictor for OS nor TTP. The preliminary results suggest the necessity for more aggressive management of equivocal patients.
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http://dx.doi.org/10.1007/s00432-021-03603-9DOI Listing
March 2021

Kidney Function After Liver Transplantation in a Single Center.

Ann Transplant 2021 Feb 23;26:e926928. Epub 2021 Feb 23.

Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

BACKGROUND Renal dysfunction in the peri-transplant period appears to complicate both short- and long-term outcome of liver transplantation (LT). The aim of this study was to analyze the impact of selected clinical features in the peri-liver transplant period, as well calcineurin inhibitor, particularly tacrolimus given after LT, on kidney function in a single liver transplant center's experience. MATERIAL AND METHODS A total 125 consecutive liver-grafted individuals (82 M, 43 F), mean age 50±13 y (with alcohol-related liver disease in 48 (38%) patients) were included into the study. Their clinical data were collected in the database until 46 months of follow-up, and the Python packages Pandas (version 0.22.0) and scikit-learn (version 0.21.3) were used for data analysis. RESULTS More advanced liver disease as judged by Child-Pugh class and MELD score differed significantly patients with preserved (serum creatinine SCr <1.5 mg/dL) and impaired (SCr ≥1.5 mg/dL) kidney function before LT. Older age and higher SCr pre-LT were associated with higher levels of SCr after LT in 2 time-points. SCr before LT was correlated with delta SCr for the highest and last recorded value (P<0.0001). Higher amounts of transfused colloids during surgery were associated with increased delta SCr for the highest value (P=0.019) after grafting in logistic regression analysis. There were no associations between SCr after LT and duration of anhepatic phase, urine output ≤100 mL/h, or post-reperfusion syndrome during transplantation (all P>0.05). There were no associations between SCr after LT and tacrolimus trough levels in analyses of correlations and linear regression analyses (all P>0.05). CONCLUSIONS We found that pretransplant serum creatinine was the only factor affecting kidney function after LT in our liver transplant center. The restricted fluid policy was safe and effective in terms of long-term renal function. The role of kidney-saving immunosuppressive protocols in preserving renal function long-term after LT was also confirmed.
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http://dx.doi.org/10.12659/AOT.926928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911851PMC
February 2021

Response to: Comment on "Shadows Behind Using Simple Risk Models in Selection of HCC patients for LT".

Ann Surg 2020 Nov 17. Epub 2020 Nov 17.

Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Poland.

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http://dx.doi.org/10.1097/SLA.0000000000004509DOI Listing
November 2020

Characteristics, trends and Outcomes of Liver Transplantation for Primary sclerosing cholangitis in female vs male patients: An analysis from the European Liver Transplant Registry.

Transplantation 2020 Nov 13. Epub 2020 Nov 13.

Background: The influence of sex on primary sclerosing cholangitis (PSC), pre and post-liver transplantation (LT) is unclear.

Aims: to assess whether there have been changes in incidence, profile and outcome in LT- PSC patients in Europe with specific emphasis on sex.

Methods: Analysis of the ELTR database (PSC patients registered before 2018), including baseline demographics, donor, biochemical and clinical data at LT, immunosuppression (IS) and outcome.

Results: ELTR analysis (n=6463, 32% female) demonstrated an increasing number by cohort (1980-89, n=159; 1990-99, n=1282; 2000-09, n=2316; 2010-17, n=2549) representing on average 4% of all transplant indications. This increase was more pronounced in women (from 1.8% in the first cohort to 4.3% in the last cohort). Graft survival rate at 1, 5, 10, 15, 20 and 30 years was 83.6%, 70.8%, 57.7%, 44.9%, 30.8% and 11.6%, respectively. Variables independently associated with worse survival were male sex, donor and recipient age, cholangiocarcinoma (CC) at LT, non-DBD donor and reduced size of the graft. These findings were confirmed using a more recent LT population closer to the current standard of care (LT after the year 2000).

Conclusion: an increasing number of PSC patients, particularly women, are being transplanted in European countries with better graft outcome in female recipients. Other variables impacting outcome include donor and recipient age, CC, non-DBD donor and reduced graft size.
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http://dx.doi.org/10.1097/TP.0000000000003542DOI Listing
November 2020

Importance of Intraoperative Transfusions of Packed Red Blood Cells and Fresh Frozen Plasma in Liver Transplantation for Hepatocellular Cancer.

Ann Transplant 2020 Oct 9;25:e923665. Epub 2020 Oct 9.

Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

BACKGROUND The impact of packed red blood cells (PRBCs) and fresh frozen plasma (FFP) transfusions in patients with hepatocellular cancer (HCC) undergoing liver transplantation has rarely been evaluated. The aim of the current study was to assess the impact of intraoperative transfusions on posttransplant outcomes. MATERIAL AND METHODS This retrospective cohort study was based on 229 HCC transplant recipients. The primary outcome measure was 5-year recurrence-free survival. Secondary outcome measures comprised overall and long-term survival at 5 years and 90-day mortality. Cox proportional hazard models and logistic regression were used to assess risk factors. RESULTS After adjustment for potential confounders, no association was found with respect to tumor recurrence for PRBCs (P=0.368) or FFP (P=0.081) transfusions. Similarly, PRBC transfusion (P=0.623) and FFP transfusion (P=0.460) had no impact on survival between 90 days and 5 years. PRBC transfusion increased the risk of 90-day mortality (P=0.005), while FFP transfusion was associated with a lower risk (P=0.036). CONCLUSIONS Intraoperative transfusions of blood products does not impair recurrence-free and long-term survival of patients with HCC undergoing liver transplantation. Intraoperative PRBC transfusion increases the risk of early mortality, whereas adequate supplementation of FFP plays a protective role.
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http://dx.doi.org/10.12659/AOT.923665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552880PMC
October 2020

[ Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma.

Eur J Nucl Med Mol Imaging 2021 Mar 3;48(3):883-892. Epub 2020 Sep 3.

Nuclear Medicine Department, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland.

Purpose: Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [Ga]Ga-PSMA-11 in HCC and its impact on patient management.

Methods: Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, single-institution study. All patients underwent contrast-enhanced MRI/CT, [Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions.

Results: No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUV) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC.

Conclusion: [Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.
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http://dx.doi.org/10.1007/s00259-020-05017-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036201PMC
March 2021

Pregnancy Weight Gain as a Predictor of Fetal Wellbeing in Liver Transplant Recipients.

Ann Transplant 2020 Aug 28;25:e923804. Epub 2020 Aug 28.

1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland.

BACKGROUND Gestational weight gain (GWG) is an important index influencing perinatal outcomes. Inappropriate weight gain during pregnancy is strongly associated with multiple pregnancy complications. In pregnant liver transplant recipients whose risk of adverse pregnancy outcomes is already high, this aspect may be even more significant. The present study analyzed the gestational weight gain in female liver transplant recipients and its effect on neonatal complications. MATERIAL AND METHODS A cohort study of retrospective data was performed in the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw. There were 23 patients who fulfilled all inclusion criteria. The gestational weight gain was analyzed in the context of pre-pregnancy BMI, immunosuppression, and perinatal outcomes. RESULTS The preterm delivery rate was 39.13% and GWG increased according to the duration of pregnancy. The model adjusted to week of delivery revealed no association between weight gain and the length of pregnancy (p=0.82). GWG in liver transplant recipients did not affect hypotrophy incidence, adverse perinatal outcomes, or caesarian delivery rate. A positive correlation between GWG and neonatal birth weight was observed (p=0.06). One patient, with coexisting PIH, had a stillbirth at 23 weeks. In all other cases, the 5-min Apgar score was 10 points. CONCLUSIONS Current obstetrical recommendations do not consider patients with chronic diseases undergoing immunosuppressive treatment. Proper counselling and preparing liver transplant recipients for pregnancy, especially optimizing maternal pre-pregnancy BMI, may be an important element in improving perinatal outcomes by lowering the risk of maternal complications. GWG itself is not relevant as a predictor of term gestation, but it might be important in achieving eutrophic fetus growth.
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http://dx.doi.org/10.12659/AOT.923804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480087PMC
August 2020

Synergistic effects of extracellular vesicle phenotyping and AFP in hepatobiliary cancer differentiation.

Liver Int 2020 12 14;40(12):3103-3116. Epub 2020 Jul 14.

Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.

Background: Biliary cancer, comprising cholangio- and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary cancer screening and hepatobiliary cancer differentiation.

Methods: Serum EVs of biliary cancer, hepatocellular carcinoma, colorectal cancer and non-small cell lung cancer patients, as well as from healthy individuals, were isolated by sequential two-step centrifugation and presence of indicated EVs was evaluated by fluorescence activated cell sorting (FACS) analysis.

Results: Two directly tumour-related antigen combinations (AnnV CD44v6 and AnnV CD44v6 CD133 ) and two combinations related to progenitor cells from the tumour microenvironment (AnnV CD133 gp38 and AnnV EpCAM CD133 gp38 ) were associated with good diagnostic performances that could potentially be used for clinical assessment of biliary cancer and differentiation from other cancer entities. With 91% sensitivity and 69% specificity AnnV CD44v6 EVs showed the most promising results for differentiating biliary cancers from HCC. Moreover using a combined approach of EV levels of the four populations with serum AFP values, we obtained a perfect separation of biliary cancer and HCC with sensitivity, specificity, positive and negative predictive value all reaching 100% respectively.

Conclusions: EV phenotyping, especially if combined with serum AFP, represents a minimally invasive, accurate liquid biopsy tool that could improve cancer screening and differential diagnosis of hepatobiliary malignancies.
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http://dx.doi.org/10.1111/liv.14585DOI Listing
December 2020

Impact of COVID-19 on liver transplantation in Europe: alert from an early survey of European Liver and Intestine Transplantation Association and European Liver Transplant Registry.

Transpl Int 2020 10 13;33(10):1244-1252. Epub 2020 Aug 13.

Medical Liver Transplant Unit and Liver Department, Henri Mondor Hospital AP-HP, Paris Est University, Créteil, France.

There are scarce data on the impact of COVID-19 pandemic on liver transplantation (LT) in Europe. The aim of this study was to obtain a preliminary data on incidence, management, and outcome of COVID-19 in liver transplant recipients and candidates in Europe. An Internet-based survey was sent to the centers affiliated with European Liver Transplant Registry (ELTR). One hundred nine out of 149 (73%) of ELTR centers located in 28 European countries (93%) responded. Ninety-four (86%) of the centers tested all donors, and 75 (69%) centers tested all LT recipients for SARS-CoV-2. Seventy-three (67%) centers selected recipients for LT in the COVID-19 pandemic, whereas 33% did not. Eighty-eight centers reported COVID-19 infection in 57 LT candidates and in 272 LT recipients. Overall crude incidence of COVID-19 among LT candidates and recipients was estimated 1.05% (range 0.5-20%) and 0.34% (range 0.1-4.8%), respectively, and it was significantly higher among candidates (P < 0.001). Crude rate of death was 18% (10/57) among candidates and 15% (36/244) among recipients. This first large-scale European snapshot study clearly shows that both LT candidates and recipients are at a high risk for COVID-19. These results plead for an early and pro-active screening of COVID-19 symptoms in these populations.
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http://dx.doi.org/10.1111/tri.13680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361228PMC
October 2020

Intraoperative Dialysis During Liver Transplantation.

Transplant Proc 2020 Oct 21;52(8):2454-2458. Epub 2020 May 21.

Department of Nephrology, Dialysis, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.

Background: Orthotopic liver transplantation (LT) is a technically complex surgical procedure associated with a major risk of hemodynamic instability and metabolic derangement, especially in patients with coexisting renal dysfunction. Some centers have applied intraoperative renal replacement therapy (ioRRT) to support patients with preoperative renal failure and prevent critical complications. Although there is a strong theoretical rationale for this treatment, there remains a paucity of definite data demonstrating its benefits.

Methods: This was a retrospective observational study of all adult patients undergoing intraoperative dialysis in our center from January 2010 till December 2016.

Results: The study group consisted of 88 patients with a mean MELD score of 31.4. Six patients underwent simultaneous liver and kidney transplantation. Forty-four (50%) recipients were admitted to the intensive care unit before transplantation, and 19 (21.6%) needed mechanical ventilation. Twenty-eight (31.8%) of the procedures were retransplantations, and 40 (45.4%) patients had been undergoing renal replacement therapy before LT. The mean preoperative serum creatinine was 2.82 ± 1.13 mg/dL. The majority of patients (54.5%) was operated on using the veno-venous bypass technique. The mean arterial blood pH and potassium levels after reperfusion were 7.2 ± 0.12 and 4.04 ± 0.95 mmol/L, respectively. Postreperfusion syndrome (PRS) occurred in 11 (13.9%) patients in whom dialysis started at least 15 minutes before reperfusion. Dialysis circuit clotting occurred in 9.1% of cases. There were no other adverse events of ioRRT.

Conclusion: Our data suggests that intraoperative dialysis in severely ill patients with a high MELD score is safe and effective. Lower than expected PRS occurrence needs to be confirmed in a study with a control group.
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http://dx.doi.org/10.1016/j.transproceed.2020.01.129DOI Listing
October 2020

Acute-On-Chronic Liver Failure: The Role of Prognostic Scores in a Single-Center Experience.

Med Sci Monit 2020 May 16;26:e922121. Epub 2020 May 16.

Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

BACKGROUND Acute-on-chronic liver failure (ACLF) is associated with multi-organ failure and high short-term mortality. We evaluated the role of currently available prognostic scores for prediction of 90-day mortality in ACLF patients. MATERIAL AND METHODS Fifty-five (M/F=40/15, mean age 60.0±11.1years) consecutive cirrhotic patients with severe liver insufficiency (mean MELD 28.4±9.0, Child-Pugh score - C-12) were enrolled into the study. MELD variants and SOFA, CLIF-SOFA, and CLIF-C scores were calculated, mortality predicting factors were identified, and clinical comparisons between ACLF and AD patients were performed. RESULTS In total, 30 (55%) patients were transplanted (22 ACLF and 8 AD), and 20 (30%) died (19 ACLF and 1 AD). Five (9%) patients survived without liver transplantation (LT) (3 ACLF and 2 AD), and 3 transplant recipients died within 1 month. SOFA, CLIF-SOFA, CLIF-C OF, and INR were significantly associated with the incidence of 90-day mortality in competing risk regression analysis (all p<0.001). The model based on SOFA had the lowest BIC, with the optimal cut-off for 90-day mortality prediction ≥12, with the area under the receiver operating characteristic (AUROC) of 0.901 (95% CI 0.779-1.000; p<0.001), and corresponding incidence of transplantation rates of 85.5% and 11.8%, respectively (p<0.001). Of note, the important role of 24-h urine output is emphasized. CONCLUSIONS In this series of ACLF patients, SOFA score outperformed the CLIF-C scores in predicting 90-day mortality. Multi-organ failure scores performed better in predicting patient mortality than conventional liver function assessment. LT is possible and remains effective in selected ACLF patients.
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http://dx.doi.org/10.12659/MSM.922121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249742PMC
May 2020

Unsatisfactory Long-term Results of Liver Transplant in Patients With Intrahepatic Cholangiocarcinoma.

Transplant Proc 2020 Oct 21;52(8):2463-2467. Epub 2020 Apr 21.

Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

Background: Cholangiocarcinoma is the primary liver tumor forming from the biliary epithelium. Two major subtypes of this disease are distinguished because of the initial location: the extra- and intrahepatic form. The latter disease is currently a controversial indication for liver transplant (LT). The aim of this study was to evaluate the outcomes of LT of patients with intrahepatic cholangiocarcinoma.

Methods: Based on postoperative histopathologic examination of the explanted liver, 8 patients with intrahepatic cholangiocarcinoma were identified from all LT recipients in the period between 1994 and 2019 and included in this retrospective cohort study. Four of the patients received transplants with a preoperative diagnosis of hepatocellular carcinoma; the remaining tumors were incidental findings. Patient survival was the primary outcome measure.

Results: Six recipients had solitary lesion with a maximum tumor diameter of 6 cm. The median carbohydrate antigen 19-9 concentration prior to LT was 52.3 U/mL. The overall survival was 75.0%, 37.5%, and 25% after the first, third, and fifth year, respectively, with a median survival of 18 months. Age (P = .758), carbohydrate antigen 19-9 (P = .282), largest tumor size (P = .862), and the sum of the number of lesions and diameter of the largest tumor (P = .530) were not significantly associated with overall survival. Recurrence-free survival was 71.4% after 1 year and 28.6% after 3 and 5 years. Correspondingly, no significant predictors of worse recurrence-free survival were found.

Conclusions: Intrahepatic cholangiocarcinoma remains associated with a very high risk of recurrence and dismal survival after LT irrespective of macroscopic disease burden.
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http://dx.doi.org/10.1016/j.transproceed.2020.02.095DOI Listing
October 2020

Analysis of Patients With Incidental Perihilar Cholangiocarcinoma: An Old and a Persistent Burden for Liver Transplantation.

Transplant Proc 2020 Oct 17;52(8):2507-2511. Epub 2020 Apr 17.

Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

Background: Selected patients with unresectable perihilar cholangiocarcinoma (p-CCA) are now considered as candidates for liver transplant, provided they fulfill a strict perioperative treatment and staging protocol. The aim of this study was to examine the outcomes of patients after liver transplant with incidental p-CCA found in the liver explants.

Methods: A cohort of 10 patients with incidental p-CCA after liver transplant in the period between 1994 and 2019 was included in this retrospective analysis. All patients with this diagnosis were scheduled for transplant because of primary sclerosing cholangitis. The primary and secondary endpoints comprised patient's death and tumor recurrence, respectively, assessed over a 5-year postoperative period.

Results: Patient median age was 35 years (range, 32-42 years). Median size of the tumor was 3.0 cm (range, 2.5-4.0 cm). Five patients (50%) had metastases to local lymph nodes. Overall survival was 100%, 37.5%, and 18.8% after the first, third, and fifth postoperative year, respectively, with median survival of 21 months. Patient age (P = .827), R1 resection status (P = .144), tumor diameter (P = .432), and presence of lymph node metastases (P = .663) were not significantly associated with overall survival. Recurrence-free survival was 60.0% after the first postoperative year and 22.5% after the third and fifth postoperative years, with median recurrence-free survival of 13.6 months. No significant predictors of tumor recurrence were found.

Conclusions: Incidental p-CCA in patients with primary sclerosing cholangitis undergoing liver transplant is associated with universally very high risk of postoperative tumor recurrence and short expected survival.
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http://dx.doi.org/10.1016/j.transproceed.2020.02.094DOI Listing
October 2020

Hepatic Epithelioid Hemangioendothelioma: A Rare Disease With Favorable Outcomes After Liver Transplantation.

Transplant Proc 2020 Oct 23;52(8):2447-2449. Epub 2020 Mar 23.

Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

Background: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor with indolent behavior in terms of malignancy. The treatment of choice is either resection in the case of resectable lesions or liver transplantation (LT) for the disseminated intrahepatic form. The aim of this study was to investigate the outcomes of patients with HEHE treated by LT.

Material And Methods: There were 18 patients with HEHE who underwent LT between 2002 and 2018 included in this retrospective study. The study group was comprised of young recipients (median age of 39 years) and mainly women (15 of 18; 83.3%). Two recipients had concomitant tumors of epithelioid hemangioendothelioma in the liver and lungs prior to LT. The survival probability was calculated using the Kaplan-Meier estimator.

Results: According to histopathological data, none of the patients had a macrovascular invasion. In 4 patients (22.2%), the disease had spread to the hilar lymph nodes. The maximum diameter of the tumor in the studied group was 18 cm. The survival probability after 1, 5, and 15 years was 94.0%, 82.6%, and 41.3%, respectively. No disease recurrence was observed during a median follow-up of 65.9 months.

Conclusion: Liver transplantation provides favorable outcomes for selected patients with a hepatic form of epithelioid hemangioendothelioma.
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http://dx.doi.org/10.1016/j.transproceed.2020.02.101DOI Listing
October 2020

Applicability of common inflammatory markers in diagnosing infections in early period after liver transplantation in intensive care setting.

Sci Rep 2020 03 3;10(1):3918. Epub 2020 Mar 3.

Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

Infections remain an important cause of morbidity and mortality early after liver transplantation. The aim of this prospective longitudinal study was to evaluate clinical utility of c-reactive protein (CRP), procalcitonin, and neutrophil-to-lymphocyte ratio (NLR) in surveillance of infections early after liver transplantation in intensive care setting. A total of 60 liver transplant recipients were included. CRP, procalcitonin, and NLR assessed at 12-hour intervals were primary variables of interest. Infections and severe complications during postoperative intensive care unit stay were the primary and secondary end-points, respectively. Infections and severe complications were diagnosed in 9 and 17 patients, respectively. Only peak CRP beyond first 48 hours was associated with infections (p = 0.038) with AUC, positive and negative predictive value of 0.728, 42.9% and 92.2%, respectively (cut-off: 142.7 mg/L). Peak procalcitonin over first 60 hours was the earliest predictor (p = 0.050) of severe complications with AUC, positive and negative predictive value of 0.640, 53.3% and 80.0%, respectively (cut-off: 42.8 ng/mL). In conclusion, while CRP, procalcitonin, and NLR cannot be used for accurate diagnosis of infections immediately after liver transplantation, peak CRP beyond 48 hours and peak procalcitonin over first 60 hours may be used for initial exclusion of infections and prediction of severe complications, respectively.
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http://dx.doi.org/10.1038/s41598-020-60936-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054413PMC
March 2020

Serum bilirubin concentration as a marker of severity of acute appendicitis.

Wideochir Inne Tech Maloinwazyjne 2020 Mar 22;15(1):117-122. Epub 2019 Aug 22.

Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

Introduction: Acute appendicitis (AA) is one of the most common causes of urgent admission to the hospital. Clinically applicable classification distinguishes simple and complex inflammation. Among commonly used inflammation markers of AA, bilirubin concentration is not well studied and thus is rarely applied.

Aim: To examine the association between increased serum total bilirubin concentration and the severity of AA.

Material And Methods: This retrospective study included 169 patients with a presumptive diagnosis of AA who were operated upon between 2015 and 2017. The determined study endpoints were simple complex inflammation and a different diagnosis after surgery. The Mann-Whitney U, Kruskal-Wallis, Fisher's exact, Spearman correlation coefficient and logistic regression tests and receiver-operating characteristics (ROC) were used in analyses. The area under the curve (AUC) was presented with 95% confidence intervals (95% CIs). Statistical significance was set at 0.05.

Results: In total, 84 (49.7%) patients underwent laparotomy and 85 (50.3%) laparoscopy. After surgery, 45 (26.6%) patients had a diagnosis other than AA. Furthermore, 83 (49.1%) and 41 (24.3%) patients had simple and complex AA, respectively. The median bilirubin concentration was 0.56, 0.69, and 1.08 mg/dl in patients without AA, with simple, and complex AA, respectively (p < 0.01). The optimal cut-off for serum bilirubin concentration to predict AA severity was ≥ 0.94 mg/dl (AUC = 0.652; 95% CI: 0.543-0.761) with a 44.9% positive and 83.9% negative predictive value (p = 0.006).

Conclusions: The serum bilirubin concentration should be considered as one of the possible markers of AA. Moreover, it can be used to predict the severity of AA.
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http://dx.doi.org/10.5114/wiitm.2019.87140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020712PMC
March 2020

Longterm Survival After Liver Transplantation for Autoimmune Hepatitis: Results From the European Liver Transplant Registry.

Liver Transpl 2020 07 1;26(7):866-877. Epub 2020 May 1.

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The aim of this study was to analyze longterm patient and graft survival after liver transplantation for autoimmune hepatitis (AIH-LT) from the prospective multicenter European Liver Transplant Registry. Patient and liver graft survival between 1998 and 2017 were analyzed. Patients after AIH-LT (n = 2515) were compared with patients receiving LT for primary biliary cholangitis (PBC-LT; n = 3733), primary sclerosing cholangitis (PSC-LT; n = 5155), and alcohol-related cirrhosis (AC-LT; n = 19,567). After AIH-LT, patient survival was 79.4%, 70.8%, and 60.3% and graft survival was 73.2%, 63.4%, and 50.9% after 5, 10, and 15 years of follow-up. Overall patient survival was similar to patients after AC-LT (P = 0.44), but worse than after PBC-LT (hazard ratio [HR], 1.48; P < 0.001) and PSC-LT (HR, 1.19; P = 0.002). AIH-LT patients were at increased risk for death (HR, 1.37-1.84; P < 0.001) and graft loss (HR, 1.35-1.80; P < 0.001) from infections compared with all other groups and had a particularly increased risk for lethal fungal infections (HR, 3.38-4.20; P ≤ 0.004). Excluding patients who died within 90 days after LT, risk of death after AIH-LT was superior compared with AC-LT (HR, 0.84; P = 0.004), worse compared with PBC-LT (HR, 1.38; P < 0.001) and similar compared with PSC-LT (P = 0.93). Autoimmune hepatitis (AIH) patients with living donor liver transplantation (LDLT) showed reduced survival compared with patients receiving donation after brain death (HR, 1.96; P < 0.001). In AIH-LT patients, overall survival is inferior to PBC-LT and PSC-LT. The high risk of death after AIH-LT is caused mainly by early fatal infections, including fungal infections. Patients with LDLT for AIH show reduced survival.
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http://dx.doi.org/10.1002/lt.25739DOI Listing
July 2020

A Comparison of Intrathecal and Intravenous Morphine for Analgesia After Hepatectomy: A Randomized Controlled Trial.

World J Surg 2020 07;44(7):2340-2349

Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 1A Banacha Street, 02-097, Warsaw, Poland.

Background: Effective analgesia is essential for patient recovery after liver resection. This study aimed to evaluate the effects of the addition of preoperative intrathecal morphine to multimodal intravenous analgesia in patients undergoing liver resection.

Methods: In this single-blind randomized controlled trial, patients undergoing liver resection were randomly assigned to the patient-controlled analgesia with (ITM-IV) or without (IV) preoperative intrathecal morphine groups. All patients received acetaminophen and dexketoprofen. The primary outcome was pain severity at rest over three postoperative days, assessed using the numerical rating scale (NRS).

Results: The study included 36 patients (18 in each group). The mean maximum daily NRS scores over the first three postoperative days in the ITM-IV and IV groups were 1.3, 1.1, and 0.3 and 1.6, 1.1, and 0.7, respectively (p = 0.580). No differences were observed in pain severity while coughing, with corresponding scores of 2.8, 2.1, and 1.1, respectively, in the ITM-IV group and 2.3, 2.2, and 1.5, respectively, in the IV group (p = 0.963). Proportions of patients reporting clinically significant pain at rest and while coughing were 11.1% and 44.4%, respectively, in the ITM-IV group, and 16.7% and 44.4%, respectively, in the IV group (both p > 0.999). Cumulative morphine doses in the ITM-IV and IV groups were 26 mg and 17 mg, respectively (p = 0.257). Both groups also showed similar time to mobilization (p = 0.791) and solid food intake (p = 0.743), sedation grade (p = 0.584), and morbidity (p = 0.402).

Conclusions: Preoperative intrathecal morphine administration provides no benefits to multimodal analgesia in patients undergoing liver resection.

Trial Registration Number: Clinicaltrial.gov Identifier: NCT03620916.
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http://dx.doi.org/10.1007/s00268-020-05437-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266793PMC
July 2020

The molecular diagnosis of rejection in liver transplant biopsies: First results of the INTERLIVER study.

Am J Transplant 2020 08 9;20(8):2156-2172. Epub 2020 Apr 9.

Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada.

Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. We measured gene expression by microarrays in 235 liver transplant biopsies from 10 centers. Unsupervised archetypal analysis based on expression of previously annotated rejection-related transcripts identified 4 groups: normal "R1 " (N = 129), T cell-mediated rejection (TCMR) "R2 " (N = 37), early injury "R3 " (N = 61), and fibrosis "R4 " (N = 8). Groups differed in median time posttransplant, for example, R3 99 days vs R4 3117 days. R2 biopsies expressed typical TCMR-related transcripts, for example, intense IFNG-induced effects. R3 displayed increased expression of parenchymal injury transcripts (eg, hypoxia-inducible factor EGLN1). R4 biopsies showed immunoglobulin transcripts and injury-related transcripts. R2 correlated with histologic rejection although with many discrepancies, and R4 with fibrosis. R2 , R3 , and R4 correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2 scores. No confirmed cases of clinical antibody-mediated rejection (ABMR) were present in the population, and strategies that previously revealed ABMR in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, molecular analysis of liver transplant biopsies detects rejection, has the potential to resolve ambiguities, and could assist with immunosuppressive management.
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http://dx.doi.org/10.1111/ajt.15828DOI Listing
August 2020

Liver transplantation for hepatocellular carcinoma after successful treatment of macrovascular invasion - a multi-center retrospective cohort study.

Transpl Int 2020 05 20;33(5):567-575. Epub 2020 Feb 20.

Division of Transplantation, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.

Macrovascular invasion is considered a contraindication to liver transplantation for hepatocellular carcinoma (HCC) due to a high risk of recurrence. The aim of the present multicenter study was to explore the outcome of HCC patients transplanted after a complete radiological regression of the vascular invasion by locoregional therapies and define sub-groups with better outcomes. Medical records of 45 patients were retrospectively reviewed, and imaging was centrally assessed by an expert liver radiologist. In the 30 patients with validated diagnosis of macrovascular invasion, overall survival was 60% at 5 years. Pretransplant alpha-fetoprotein (AFP) value was significantly different between patients with and without recurrence (P = 0.019), and the optimal AFP cutoff was 10ng/ml (area under curve = 0.78). Recurrence rate was 11% in patients with pretransplant AFP < 10ng/ml. The number of viable nodules (P = 0.008), the presence of residual HCC (P = 0.036), and satellite nodules (P = 0.001) on the explant were also significantly different between patients with and without recurrence. Selected HCC patients with radiological signs of vascular invasion could be considered for transplantation, provided that they previously underwent successful treatment of the macrovascular invasion resulting in a pretransplant AFP < 10 ng/ml. Their expected risk of post-transplant HCC recurrence is 11%, and further prospective validation is needed.
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http://dx.doi.org/10.1111/tri.13586DOI Listing
May 2020

Dissecting visceral fibromuscular dysplasia reveals a new vascular phenotype of the disease: a report from the ARCADIA-POL study.

J Hypertens 2020 04;38(4):737-744

Department of Hypertension, Institute of Cardiology, Warsaw.

Objective: Visceral artery fibromuscular dysplasia (VA FMD) manifestations range from asymptomatic to life-threatening. The aim of the study is to evaluate the prevalence and clinical characteristics of VA FMD.

Methods: A total of 232 FMD patients enrolled into ongoing ARCADIA-POL study were included in this analysis. All patients underwent detailed clinical evaluation including ambulatory blood pressure monitoring, biobanking, duplex Doppler of carotid and abdominal arteries and whole body angio-computed tomography. Three control groups (patients with renal FMD without visceral involvement, healthy normotensive patients and resistant hypertensive patients) matched for age and sex were included.

Results: VA FMD was present in 32 patients (13.8%). Among these patients (women: 84.4%), FMD lesions were more frequent in celiac trunk (83.1%), 62.5% of patients showed at least one visceral aneurysm, and five patients presented with severe complications related to VA FMD. No demographic differences were found between patients with VA FMD and individuals from the three control groups, with the exception of lower weight (P < 0.001) and BMI (P < 0.001) in VA FMD patients. Patients with FMD (with or without visceral artery involvement) showed significantly smaller visceral arterial diameters compared with controls without FMD.

Conclusion: Patients with FMD showed smaller visceral arterial diameters when compared with patients without FMD. This may reflect a new phenotype of FMD, as a generalized arteriopathy, what needs further investigation. Lower BMI in patients with VA FMD might be explained by chronic mesenteric ischemia resulting from FMD lesions. FMD visceral involvement and visceral arterial aneurysms in patients with renal FMD are far to be rare. This strengthens the need for a systematic evaluation of all vascular beds, including visceral arteries, regardless of initial FMD involvement.
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http://dx.doi.org/10.1097/HJH.0000000000002327DOI Listing
April 2020

Fat and Sugar-A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease.

Nutrients 2019 Nov 24;11(12). Epub 2019 Nov 24.

Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland.

Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver damage in patients are not fully understood. A deeper investigation of NAFLD pathogenesis is possible due to the many different animal models developed recently. In this review, we present a comparative overview of the most common dietary NAFLD rodent models with respect to their metabolic phenotype and morphological manifestation. Moreover, we describe similarities and controversies concerning the effect of NAFLD-inducing diets on mitochondria as well as mitochondria-derived oxidative stress in the progression of NAFLD.
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http://dx.doi.org/10.3390/nu11122871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950566PMC
November 2019

Impact of Body Composition on the Risk of Hepatocellular Carcinoma Recurrence After Liver Transplantation.

J Clin Med 2019 Oct 13;8(10). Epub 2019 Oct 13.

Second Department of Clinical Radiology, Medical University of Warsaw, 02-097 Warsaw, Poland.

Background: Body composition parameters are reported to influence the risk of hepatocellular carcinoma (HCC) recurrence after liver resection, yet data on patients undergoing liver transplantation are scarce. The aim of this study was to evaluate the impact of the amount of abdominal adipose tissue and skeletal muscles on the risk of HCC recurrence after liver transplantation.

Methods: This was a retrospective observational study performed on 77 HCC patients after liver transplantation. Subcutaneous fat area (SFA), visceral fat area, psoas muscle area and total skeletal muscle area were assessed on computed tomography on the level of L3 vertebra and divided by square meters of patient height. The primary outcome measure was five-year recurrence-free survival.

Results: Recurrence-free survival in the entire cohort was 95.7%, 90.8%, and 86.5% after one, three, and five years post-transplantation, respectively. SFA was significantly associated with the risk of HCC recurrence ( = 0.013), whereas no significant effects were found for visceral fat and skeletal muscle indices. The optimal cut-off for SFA for prediction of recurrence was 71.5 cm/m. Patients with SFA < 71.5 cm/m and ≥71.5 cm/m exhibited five-year recurrence-free survival of 96.0% and 55.4%, respectively ( = 0.001).

Conclusions: Excessive amount of subcutaneous adipose tissue is a risk factor for HCC recurrence after liver transplantation and may be considered in patient selection process.
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http://dx.doi.org/10.3390/jcm8101672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832484PMC
October 2019

Viruses in transplantology.

Pol Arch Intern Med 2019 10 8;129(Spec Issue 3):1-36. Epub 2019 Oct 8.

The 3 leading causes of death in patients after solid organ transplantation (SOT) include cardiovascular diseases, malignancies, and infections. According to our current understanding, the latter play the key role in the pathogenesis of atherosclerosis. Similarly, infections (mainly viral) are implicated in the pathogenesis of at least 20% of known neoplasms. In other words, the implications of acute and chronic infectious diseases in modern medicine, not only transplantology, are significant and ever‑increasing. Immunosuppressive treatment impairs the immune function, which renders the patient more susceptible to infections. Furthermore, treatment of infections in immunocompromised patients poses a challenge and SOT. The current publication provides a brief summary of the key information provided in 20 lectures on viral infections in patients after SOT delivered during the 9th Practical Transplantology Course in Warsaw, Poland on September 15-16, 2017.
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http://dx.doi.org/10.20452/pamw.15012DOI Listing
October 2019

Prognostic Relevance of a Complete Pathologic Response in Liver Transplantation for Hepatocellular Carcinoma.

Ann Surg Oncol 2019 Dec 13;26(13):4556-4565. Epub 2019 Sep 13.

Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

Background: A complete pathologic response (CPR) after neoadjuvant treatment is reported to be associated with an exceptionally low risk of recurrence after liver transplantation for hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic role of CPR in liver transplantation for HCC.

Methods: This retrospective cohort study was based on 222 HCC transplant recipients. Incidence of recurrence and survival at 5 years were the primary and secondary outcome measures, respectively. Competing risk analyses were applied to evaluate recurrence incidence and its predictors. Propensity score matching was performed to compare the outcomes for patients after neoadjuvant treatment with and without CPR.

Results: Neoadjuvant treatment was performed for 127 patients, 32 of whom achieved CPR (25.2%). Comparison of baseline characteristics showed that the patients with CPR were at lowest baseline recurrence risk, followed by treatment-naïve patients and patients without CPR. Adjusted for potential confounders, CPR did not have any significant effects on tumor recurrence. No significant net reclassification improvement was noted after addition of CPR to existing criteria. Neoadjuvant treatment without CPR was associated with increased risk of recurrence in subgroups within the Milan criteria (p = 0.016), with alpha-fetoprotein concentration (AFP) model not exceeding 2 points (p = 0.021) and within the Warsaw criteria (p = 0.007) compared with treatment-naïve patients who were at risk similar to those with CPR. The 5-year incidences of recurrence in propensity score-matched patients with and without CPR were respectively 14.0% and 15.9% (p = 0.661), with corresponding survival rates of 73.2% and 67.4%, respectively (p = 0.329).

Conclusions: The findings showed that CPR is not independently associated with long-term outcomes after liver transplantation for HCC.
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http://dx.doi.org/10.1245/s10434-019-07811-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863942PMC
December 2019

Reply to: "Hepatic fibrosis - and not steatosis - is the main determinant of arterial stiffness in non-alcoholic fatty liver disease".

Atherosclerosis 2019 11 31;290:224-225. Epub 2019 Aug 31.

Department of Internal Medicine, Hypertension and Angiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland. Electronic address:

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http://dx.doi.org/10.1016/j.atherosclerosis.2019.08.022DOI Listing
November 2019

Immunosuppressive treatment with everolimus in patients after liver transplant: 4 years of single-center experience.

Pol Arch Intern Med 2019 10 10;129(10):686-691. Epub 2019 Sep 10.

Department of Hepatology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland

Introduction: Everolimus after liver transplant (LT) has been used to minimize the use of calcineurin inhibitors (CNIs), optimize renal function, and prevent recurre nce of hepatocellular carcinoma (HCC).

Objectives: We aimed to analyze a single‑center experience with switching from CNIs to everolimus in immunossupressive treatment of LT recipients.

Patients And Methods: A total of 108 LT recipients (men, 65.7%; mean [SD] age, 53.2 [11.1] years) were prospectively enrolled into the study. In all patients, everolimus and CNIs were introduced (target trough levels of 3 to 6 ng/ml and 3 to 5 ng/ml, respectively). After 3 months, CNIs were discontinued in patients who tolerated everolimus well, while everolimus dosage was increased (blood trough levels, 6-12 ng/ml).

Results: Everolimus monotherapy was introduced in 32 patients (29.6%), while a combination therapy with everolimus and CNIs was continued in 76 patients (70.4%). However, during a mean follow‑up of 27 months (range, 4-50 months), everolimus was withdrawn in 25 patients (33%) due to side effects. In the everolimus‑monotherapy group, all patients continued the therapy (P <0.005), but dyslipidemia was more frequent than in patients receiving everolimus and CNIs (40.6% vs 14.5%; P <0.03). Creatinine levels improved significantly in both groups: combination therapy, from 1.58 mg/dl to 1.24 mg/dl after 3 months, and everolimus monotherapy, from 1.19 mg/dl to more than 1 mg/dl. Renal function in the everolimus group was better than in the combination-therapy group (P <0.04). Recurrence of HCC was observed in both groups: combination therapy (9/46 [19.6%]) and everolimus monotherapy (1/17 [5.9%]; P <0.01).

Conclusions: This study showed that switching from CNIs to everolimus after LT allowed a safe weaning of CNIs and an improvement in creatinine levels. In patients on everolimus monotherapy, we observed dyslipidemia as a dose‑dependent side effect of the drug as well as a lower risk of HCC recurrence.
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http://dx.doi.org/10.20452/pamw.14968DOI Listing
October 2019

Resection of liver metastases from differentiated thyroid cancer: who might benefit? A report of 2 cases with review of literature.

Pol Przegl Chir 2018 Nov;91(4):52-56

Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

Background: Liver metastases of differentiated thyroid cancers (DTC) are uncommon. Surgery has proven to be effective in patients with 131I-negative hepatic lesions. Here, we present two patients who underwent liver resection for metastatic DTC.

Case Presentation: The first patient is a 36-year-old woman who reported with 70-mm hepatic metastases of papillary thyroid cancer. After primary treatment of cancer, she was disease-free for 8 years when the elevation of TSH levels resulted for the need to search for metastasis. Notably, the 131I SPECT did not show any lesions. The CT scan revealed an 80mm diameter mass in the liver. Histology confirmed metastasis of thyroid cancer. Lack of iodine uptake and the size of lesion excluded treatment with radioactive iodine. Radical resection of the metastasis was performed with good short- and long-term postoperative result. The second patient is a 65-year-old man previously treated for follicular thyroid cancer. When a iodine-negative 70mm diameter metastasis was detected within the liver, he was referred for surgery. Extended right hepatectomy was performed. In a 12-months follow-up, he remained stable, with no signs of recurrence.

Conclusions: These two cases show that resection of hepatic metastases of DTC is an option even in the case of large lesions. Given the effectiveness and safety of liver surgery, we reckon that it should be the treatment of choice when possible. The decision to perform surgical treatment should be based on analysis of the ability to perform radical and safe resection.
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http://dx.doi.org/10.5604/01.3001.0012.7391DOI Listing
November 2018