Liver CT Perfusion Imaging as a Non-Invasive Method for Assessing Hemodynamics of the Hepatic Parenchyma in Patients with Fibrosis and Cirrhosis as a Result of Chronic Viral Hepatitis C

Objective: to determine whether liver computed tomography (CT) perfusion imaging can assess hemodynamics in patients with fibrosis and cirrhosis as a result of chronic viral hepatitis C (CVHC). Subjects and methods. The prospective study conducted at the Department of Radiation Diagnosis, M.F. Vladimirsky Moscow Regional Research and Clinical Institute, enrolled 61 patients with liver fibrosis and cirrhosis as a result of CVHC, of whom 26 patients had received antiviral therapy (AVT) and achieved a sustained virological response (SVR) at 24 weeks after the end of treatment. All the patients underwent liver CT perfusion imaging on a 256-slice Philips ICT computed tomography scanner (Netherlands). The parameters of arterial, portal, general perfusion and hepatic perfusion index were measured in each patient in his/her liver segments III, VII, and VIII, by calculating the slope of a curve. Results. The values of perfusion parameters in patients who had undergone AVT and attained SVR and who had received no specific treatment were compared with those in the fibrosis, compensated, subcompensated, and decompensated liver cirrhosis groups. In the liver fibrosis group, the patients who had achieved SVR after AVT had higher portal and total perfusion values than those who had received no specific treatment (p = 0.001 and p = 0.002; respectively). In the same group, the liver perfusion index was higher in the patients who had not undergone AVT than in the treated patients (p = 0.028). The values of total perfusion were statistically significantly higher in patients with compensated liver cirrhosis who had attained SVR after AVT than in the untreated patients (p = 0.008). In the decompensated liver cirrhosis group, portal perfusion after specific treatment was higher than in the non-AVT group (p = 0.012). The subcompensated liver cirrhosis group showed no statistically significant differences when comparing the values of liver perfusion parameters depending on the availability of treatment. Conclusion. Liver CT perfusion imaging cannot give an idea of how the hemodynamics of liver tissue changes in the presence of fibrosis and cirrhosis in patients with CVHC after AVT

ВЛИЯНИЕ РАЗЛИЧНЫХ ФАКТОРОВ НА ПРИНЯТИЕ РЕШЕНИЯ О ПРИГОДНОСТИ ДОНОРСКОЙ ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ К ТРАНСПЛАНТАЦИИ РЕЦИПИЕНТУ

AAim. To identify factors influencing upon decision on pancreas allograft suitability for transplant and their clinical significance. Materials and methods. We reviewed 95 multiorgan donors under the age of 45, who were considered as pancreas donor between January 2010 and December 2013. 28 pancreata were procured (Group I), 67 pancreata were refused (Group II). Demographic, clinical and laboratory data, anatomical hepatopancreatoduodenal varieties were taken into account. Results. We found that only three factors have an effect on pancreas allograft refusal probability. According to our data, non-transplantation of the liver from the same donor increases the pancreas graft refusal in 4 times. Elevated donor’s sodium and urea blood levels also increase the probability of donor pancreas denial for transplantation. For example, the probability of pancreas graft refusal from the donor with sodium level 145 mmol/l and urea level 6.0 mol/l is only 32%. As compared to the donor with sodium level 160 mmol/l and urea 12.0 mol/l where probability reaches 85%. Other factors: demographic, laboratory, clinical indicators, gepatopancreatoduodenal blood supply variations were not predictive for the procurement decision. Conclusion. Main predictors of pancreas allograft refusal to be taken into account, appropriate correction of donor metabolic disturbances and sufficient experience of the surgeon performing the procurement can increase the availability of pancreas transplantation.  Цель исследования: выявить закономерности, критерии и факторы, влияющие на решение об изъятии поджелудочной железы для трансплантации реципиенту и их клиническую значимость. Материалы и методы. Проанализированы донорские карты 95 мультиорганных доноров в возрасте до 45 лет, которые рассматривались как возможные доноры поджелудочной железы, в период с 1 января 2010 г. по 31 декабря 2013 г. Поджелудочная железа была изъята в составе других органов у 28 доноров (I группа), отказ от изъятия поджелудочной железы при изъятии других органов зафиксирован у 67 доноров (II группа). Учитывались возраст, рост, вес, половая и расовая принадлежности, клинические, лабораторные данные, анатомические  особенности  гепатопанкреатодуоденальной  зоны  доноров.  Результаты.  Установлено, что на вероятность изъятия поджелудочной железы влияют 3 фактора. Согласно полученным данным, отказ от изъятия печени увеличивает вероятность отказа от поджелудочной железы в 4 раза. Повышенные уровни натрия и мочевины в крови донора также повышают вероятность признания поджелудочной железы не пригодной для трансплантации. Например, вероятность отказа от поджелудочной железы у донора с уровнем Nа 145 ммоль/л, мочевиной 6,0 моль/л составляет лишь 32%. А у донора с уровнем Nа 160 ммоль/л, мочевиной 12,0 моль/л намного выше – 85%. Другие факторы – лабораторные, клинические показатели, вариантное кровоснабжение гепатопанкреатодуоденальной зоны – не являлись предикторами принятия решения об изъятии. Заключение. Учет при принятии решения качества донорской поджелудочной железы, своевременная коррекция метаболических нарушений у донора, достаточный опыт хирурга, выполняющего эксплантацию, могут увеличить доступность трансплантации поджелудочной железы

Результаты трансплантации печени в эпоху современной противовирусной терапии гепатита С

The emergence of direct-acting antivirals (DAAs) has become the basis for a new potential treatment for chronic hepatitis C (CHC) in patients with decompensated cirrhosis, who previously had no other alternative than liver transplantation (LT). However, optimal timing of antiviral therapy (AVT) remains an issue. Objective: to present a spectrum of clinical outcomes in LT waitlisted patients with HCV-related cirrhosis, who received and did not receive DAA therapy. Materials and methods. Enrolled for the study were 49 waitlisted patients with HCV-related end-stage liver diseases. The patients were divided into 2 groups: Group 1 included 40 patients who received DAA therapy before LT, while Group 2 consisted of 9 patients who did not receive antiviral treatment while on the LT waiting list. Results. The sample was represented in most cases by patients who had MELD/Na score <20. Only six had MELD/Na score >20, but <25. At the time of analysis, 38 patients had reached 12 weeks post AVT. Of these, 35 (92.1%) had sustained virologic response (SVR). Of these, 51.4% (n = 18) of cases showed decreased MELD/Na. There were no changes in 22.9% (n = 8). Increased MELD/Na was noted in 25.7% (n = 9). In 42.8% (n = 15) of cases, sustained elimination of HCV infection led to delisting. Among patients without SVR, increased MELD/Na was observed in all cases (n = 3). In the non-AVT group, one patient showed improved liver function (11.1%); in the rest, MELD/Na either remained stable or continued to increase - 44.5% (n = 4). A comparison of the frequency of deaths depending on AVT showed statistically significant differences (p < 0.001, V = 0.728). Among the non-AVT patients, the likelihood of waitlist death increased 66.5 times (95% CI: 7.99-554). Conclusion: DAA therapy carries significant advantages for waitlisted patients with MELD/Na score <25.Появление препаратов прямого противовирусного действия (ПППД) стало основой для формирования нового потенциала для лечения хронического гепатита С (ХГС) у больных с декомпенсированным циррозом печени, которые ранее не имели иной альтернативы, как трансплантация печени (ТП). Однако открытым остается вопрос оптимальных сроков проведения противовирусной терапии (ПВТ). Цель: представить спектр клинических исходов у пациентов с циррозом печени HCV-этиологии, получавших ПВТ ПППД и без нее, в листе ожидания ТП. Материалы и методы. Для исследования было отобрано 49 пациентов из листа ожидания с терминальной стадией заболевания печени в исходе ХГС. Данные были разделены на 2 группы: 1-я включала 40 пациентов, получавших ПВТ ПППД до ТП, 2-я - 9 пациентов без противовирусного лечения в листе ожидания ТП. Результаты. Выборка представлена в большинстве случаев пациентами с MELD-Na <20 баллов, и лишь у шести MELD-Na был больше 20 баллов, но не превышал 25 баллов. На момент анализа 38 пациентов достигли срока 12 недель после ПВТ. Из них у 35 (92,1%) зарегистрирован устойчивый вирусологический ответ (УВО). Из них в 51,4% (n = 18) случаев наблюдалось снижение MELD-Na. Изменения отсутствовали в 22,9% (n = 8), в то время как у 25,7% (n = 9) отмечено нарастание MELD-Na. В 42,8% (n = 15) случаев стойкая элиминация HCV-инфекции привела к делистингу. Среди пациентов без УВО во всех случаях (n = 3) зарегистрировано увеличение показателя MELD-Na. В группе без ПВТ у одного пациента наблюдалось улучшение функции печени (11,1%), у остальных MELD-Na либо оставался стабильным, либо продолжал расти: такие случаи составили равные доли по 44,5% (n = 4). При сравнении частоты летального исхода в зависимости от проведения ПВТ были получены статистически значимые различия (p < 0,001, V = 0,728). При отсутствии ПВТ шансы погибнуть в листе ожидания увеличивались в 66,5 раза (95% ДИ: 7 ,99-554). Заключение. Результаты нашего исследования продемонстрировали значимые преимущества проведения ПВТ ПППД для пациентов в листе ожидания с уровнем MELD-Na <25 баллов

ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ ТРАНСПЛАНТАЦИИ ТРУПНОЙ ПЕЧЕНИ

Aim of the study was to evaluate patient and graft survival after liver transplantation (LT) and to determine if primary disease diagnosis, early graft dysfunction or other factors affect it. Furthermore, we analyzed the reasonsof short-term and long-term deaths or retransplantations.Materials and methods. 192 LTs from donors with brain death were performed from December 2004 until June 2014. Recipient age varied from 5 to 71 years. Most frequent diagnosis was liver cirrhosis (mainly due to hepatitis C), then hepatocellular carcinoma (HCC), liver graft dysfunction, etc.Results and discussion. 1-year patient survival is 89.5%, graft survival is 87.7%, 3-year –87% and 84.6%, respectively, and 5-year – 83.5% and 83.0%, respectively. Early mortality (in fi rst 30 days after transplantation) was 8%, long-term mortality – 5.9%. Primary non-function graft (PNF) was the reason of 66.7% early deaths. In the long term, infections and oncology were the reasons of death with the same frequency – 36.4%. Early graft dysfunction including primary non-function signifi cantly decreases short term survival (p = 0.0002). Nevertheless, in the majority of cases graft function improves and doesn’t affect survival. Donor factors play role in outcomes: early dysfunction is higher (40.6%) in extended criteria donor group than in standard donor group (р = 0.0431). PNF has the same trend – 8.5% and 0.0%, respectively, but without signifi cance (р =0.0835). 5-year survival is remarkably lower in HCC group 40.8% (p = 0.003) than in other groups.Conclusion: survival after liver transplantation in our Center is comparable with the results of the world’s centers.Цель данного исследования – изучить выживаемость больных и трансплантатов в зависимости от диагно-за первичного заболевания, наличия ранней дисфункции трансплантата, причины летальности на разныхсроках, проанализировать результаты ретрансплантаций.Материалы и методы. С декабря 2004 года по июнь 2014 года в ФНЦТИО было выполнено 192 трансплантации печени от доноров с диагнозом «смерть мозга» 186 реципиентам в возрасте от 5 лет до 71 года. В структуре показаний к трансплантации на первом месте по частоте находился цирроз печени, чаще всего в исходе гепатита С, затем гепатоцеллюлярная карцинома, дисфункция трансплантата печени и другие заболевания.Результаты и обсуждение. Однолетняя выживаемость реципиентов составляет 89,5%, трансплантатов – 87,7%, трехлетняя – 87 и 84,6%, пятилетняя – 83,5 и 83,0% соответственно. Периоперационная летальность составила 8%, отдаленная – 5,9%. Основной причиной смерти в раннем послеоперационном периоде являлись первично не функционирующие трансплантаты (ПНФТ) – 66,7% потерь, в отдаленном – одинаково часто (36,4% потерь) злокачественные новообразования и инфекции. Ранняя дисфункция трансплантата (РДТ), включая ПНФТ, статистически значимо снижает выживаемость в раннем послеоперационном периоде (p = 0,0002). Однако у большинства больных РДТ обратима и в этом случае в дальнейшем не влияет на выживаемость. При использовании трансплантата от стандартного донора частота РДТ была статистически значимо меньше – 21,2%, чем при расширении критериев – 40,6% (р = 0,0431), а частота ПНФТ составила 0,0 и 8,5%, соответственно (р = 0,0835). Пятилетняя выживаемость при трансплантации по поводу ГЦК значимо ниже, чем при наличии других показаний – 40,8% (p = 0,003).Заключение: выживаемость реципиентов после трансплантации печени в нашем центре на сроке до 10 лет сопоставима с результатами мировых регистров

AB0-incompatible living donor kidney transplantation: the long-term outcomes

Background: AB0-incompatible kidney transplantation is one of the ways to effectively expand the pool of living donors. In Russia, this technology has been used for more than 10 years, but until now there have been no reports on its long-term results. Aim: To evaluate the short- and long-term outcomes of the living-related AB0-incompatible kidney transplantations. Materials and methods: We analyzed the results of 49 consecutive AB0-incompatible kidney transplantations, performed from 2011 to 2017. Preoperative management of recipients included administration of rituximab and intravenous immunoglobulin, plasmapheresis and/or selective immunoadsorption, and combination of tacrolimus, mycophenolates and steroids. The target of anti-A/B antibody levels were is 1:8. All patients received standard immunosuppression after transplantation. Results: At baseline, median anti-A/B titer was 1:16 (1:2 to 1:1024) for IgM and 1:4 (0 to 1:512) for IgG. Median rituximab dose was 286 mg/m2 (range, from 94 to 396). To achieve target antibody levels, up to 10 plasmapheresis and/or immunoadsorption sessions (median, 2) were required. There were no deaths during the follow-up. Five grafts were lost, one of them due to hyperacute rejection. The incidence of biopsy-proven rejection was 6%. One-, three and six-year graft survival was 94%, 90% and 80%, respectively. Conclusion: Kidney transplantation across the AB0-incompatibility barrier is a  safe, successful and reasonable option to reduce the organ shortage

Preservation and perfusion rehabilitation of donor organs: achievements of the last decade

At present, it is widely recognized that machine perfusion allows for a decreased rate of delayed function of the renal graft and of the risk of liver graft early dysfunction. The aim of the review is to present the actual changes of the donor pool related to prevailing numbers of donors by expanded criteria, to determine the prospects of expanding of the available donor pool based on their selection, as well as development of functional rehabilitation and modification at tissue, cell and molecular levels with the help of perfusion technologies. The article presents the state-of-the art view on the mechanisms of ischemic-reperfusion injury of donor organs, delineates the trends in the maintenance of their viability, and gives the literature data on the role and outlook of perfusion methods in organ transplantation. The authors provide the rationale for a comprehensive systemic approach to the assessment of the functional status of a donor organ with any baseline parameters and discuss a number of theoretical provisions on the implementation of a personalized perfusion approach to ensure the availability of transplantation care

Early liver allograft dysfunction: risk factors, clinical course and outcomes

Early liver allograft dysfunction (EAD) is associated with a high incidence of graft loss and patient mortality in the first 6 weeks after orthotopic liver transplantation (OLT).The aim of this retrospective single-center study is to identify the risk factors of EAD and to compare the short- and long-term results in EAD and non-EAD groups.Materials and methods. The results of 213 consecutive deceased donor liver transplantations performed between December 2004 and February 2015 were included in the analysis. Indications for OLT were non-viral liver cirrhosis in 52% of cases, viral hepatitis C or B in 34 %, hepatocellular carcinoma in 8 %; retransplantations were performed in 6% of cases due to previous liver graft dysfunction. EAD was defined by Olthoff criteria (Olthoff et al., 2010).Results. Overall incidence of EAD was 41.3%, including 5.6% of primary non-function grafts (PNF), i.e. irreversible EAD. No significant differences between EAD and non-EAD groups were seen either among donors in their age, gender, cause of death, bilirubin, plasma sodium level, aminotransferases aktivity, or among the recipients in their age, gender, body mass index, MELD. Retransplantation, donor time on mechanical ventilation in the intensive care unit for more than 2 days, highrisk donor category, transplant surgery duration more than 9.5 hours, and cold ischemia time (CIT) > 8 hours were independent significant risk factors of EAD in a multivariate model. A 42-day mortality rates were 18.2% in EAD group (mostly due to PNF without urgent retransplantanion in 9.1%), and 0% in non-EAD group. Long-term results in EAD group were also significantly poorer: 1-, 5-, and 10-year graft survival rates were 74%, 68%, and 64%, respectively, versus 96%, 90%, and 83% in non-EAD group, Log-rank p = 0.0001.Conclusion. EAD significantly (≈ 20%) decreases the short-term graft and patient survival rates. Meanwhile, a reversible EAD has no impact on long-term results. Despite the increased risk of EAD, the liver grafts from high-risk donors are suitable for transplantation. The most important and modifiable risk factor is CIT (optimal timeframe 6 - 8 h), especially when HTK solution is used. The risk of EAD / PNF dramatically increases in case of combined donor and recipient risk factors