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Hepatocellular carcinoma (HCC) is the leading primary liver tumor and a main indication for transplant. Transplant criteria are based on clinicopathologic features, meanwhile adequate downstaging and molecular mechanisms are getting more attention in evolving therapeutic algorithm of HCC. The aim of our study was to overview the results of the Hungarian Liver Transplant Program in the field of HCC and introduce new aspects of personalized treatment options.We performed retrospective analysis of survival and tumor recurrence of HCC-associated liver transplant recipients between October 2013 and December 2020. Patients were categorized in Milan criteria (MC), beyond MC but within University of California, San Francisco (UCSF), and beyond UCSF criteria groups after pathologic examination of the explanted liver. Demographic data and preoperative locoregional treatments were assessed.A total of 529 primer liver transplants were performed, 88 because of HCC. A total of 87 patients had underlying cirrhosis because of hepatitis C (54%), alcohol-related liver disease (33.7%), hepatitis B (4.5%), or unknown etiology. A total of 55.6% of the patients had at least one locoregional treatment. A total of 67.4% of the patients were within MC, 5.6% were within UCSF criteria, and 27% were beyond UCSF criteria. The 1-, 3-, and 5-year survival rates were 80%, 79%, and 75%. The outcome was better in early-stage tumors, but the difference was not significant (P = .745) CONCLUSIONS: The favorable survival in our department legitimates the strict transplant criteria of HCC. Adequate locoregional therapy as downstaging can expand recipient pool. Molecular tumor profiling may lead to personalized treatment of HCC.

Absztrakt: Az új koronavírus okozta COVID–19-járvány kihívást jelent a szervátültetett betegek ellátását illetően is, ezért lényegesnek tartjuk az ezzel kapcsolatos friss ismeretek megosztását a hazai ellátásban dolgozók számára. Nagyobb esetszámmal májátültetettekről még nincsenek adatok az irodalomban, vesetranszplantáltak esetén azonban a spanyol és a francia adatbázisok 18,6%-os és 13%-os halálozásról számoltak be, ami kissé magasabb az ottani átlagpopulációénál. Tünetmentes esetekben SARS-CoV-2-pozitív PCR-eredmény birtokában nem szükséges a transzplantáltak immunszuppresszív terápiáján változtatni, azonban láz, gastrointestinalis vagy légúti tünetek kialakulását követően a mikofenolsav és mTOR-gátló készítmények elhagyása javasolt, és a kalcineurininhibitorok vérszintjét a legalacsonyabb effektív szintre kell csökkenteni. Tüdőkárosodás észlelését követően vesetranszplantáltak esetében a kalcineurininhibitorokat is le kell állítani, míg a májtranszplantáltak esetében a dózis csökkentése szükséges a fenntartó kortikoszteroid mellett. Ez utóbbi dózisának emelése szükséges hyperinflammatiós szindróma (HIS) kialakulásakor. A HIS terápiás befolyásolására transzplantáltakban is sikerrel lehet alkalmazni az IL1- és IL6-gátló monoklonális antitesteket. Célzott vírusellenes készítmény nem áll rendelkezésre, a legszerencsésebb, ha a beteg bevonható a remdesivir vagy a favipiravir klinikai vizsgálatába. A hidroxiklorokin transzplantáltaknak is adható, bár hatékonysága és biztonságossága kérdésessé vált. A lopinavir/ritonavir kombináció a kalcineurininhibitorokkal fennálló súlyos gyógyszerkölcsönhatás miatt nem adható. A SARS-CoV-2 cytopathiás hatása endotheldiszfunkciót okoz, amely prokoaguláns állapot kialakulásához vezet, emellett megváltozik a renin-angiotenzin-aldoszteron rendszer egyensúlya is. Fontos ezért a betegek kezelése során a thrombosisprofilaxis korai elkezdése alacsony molekulasúlyú heparinnal és alacsony dózisú acetilszalicilsavval. Az angiotenzinkonvertálóenzim-gátló (ACEI) és az angiotenzin-II-receptor-antagonista (ARB) terápiára beállított betegek kezelését a COVID–19 miatt nem szabad abbahagyni. Orv Hetil. 2020; 161(32): 1310–1321.

Due to the COVID-19 pandemic caused by infection with the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transplant medicine also had to face a new, hitherto unknown challenge. To be prepared for any possibility, we consider it important to summarize the current knowledge regarding COVID-19 of liver and kidney transplant patients. Very early reports from Spanish and French registry recorded fatality rates of 18.6% and 13%, respectively, in renal patients which suggests a moderately worse outcome compared to the general population. In patients with positive PCR test but not showing clinical signs, the reduction of immunosuppression is not advised. In the case of gastrointestinal or respiratory signs with fever, the discontinuation of mycophenolate or mTOR inhibitors is recommended with decrease of the trough levels of calcineurin inhibitors to the lowest effective limit. Stop (kidney transplanted patients) or decrease (liver transplanted patients) immunosuppression and maintain corticosteroids when pulmonal injury develops and consider anti-IL1 and anti-IL6 monoclonal antibody use when hyperinflammatory syndrome is evolving. No proven effective treatment for SARS-CoV-2 exists currently. The use of lopinavir/ritonavir should be avoided because of the severe drug interaction with calcineurin inhibitors. The efficacy and tolerability of hidroxychloroquin remains to be also questionable; enroll patients into clinical trial with remdesivir or favipiravir if available. COVID-19 is characterized by virus-induced endothelial dysfunction, procoagulant state and renin-angiotensin-aldosteron system imbalance. Early thromboprofilaxis combination with low-molecular-weight heparin and low-dose aspirin is strongly recommended with the maintenance of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II-receptor blocker (ARB) therapy when they were prescribed earlier. Orv Hetil. 2020; 161(32): 1310-1321.

Unresectable liver metastases of gastroenteropancreatic neuroendocrine tumors are an accepted indication for liver transplant. Patients undergoing liver transplant because of neuroendocrine tumor liver metastases have similar long-term survival compared with hepatocellular carcinoma; however, recurrence rates are reported to be higher. Methods We performed a retrospective analysis of medical records of patients who received transplants for neuroendocrine tumor liver metastases in the Department of Transplantation and Surgery of Semmelweis University between January 1995 and August 2018. The median follow-up period was 33 months. Results Ten liver transplants have been performed because of neuroendocrine tumor liver metastases during the observed period. Recurrence occurred in 5 cases, and 3 patients died. Estimated 1- and 5-year patient survival rates after transplant were 89% and 71%, respectively. Estimated 1- and 5-year recurrence-free rates were 80% and 43%, respectively. Every patient whose primary tumor was of pancreatic origin or those recipients who had Ki67 index values in the explanted liver higher than 5% had disease recurrence. Conclusion Patient survival and recurrence rates after liver transplant were comparable with the results reported by other centers. In line with previous findings, primary pancreatic neuroendocrine tumors and higher Ki67 index values in the explanted livers were both associated with higher recurrence rates. We believe that an international registry would be helpful to better understand factors leading to tumor recurrence in these cases.

Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE.A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment.All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline.In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.