A Review of Humoral and Cellular Immune Responses to SARS-CoV-2 Vaccination Following Solid Organ Transplantation.

The introduction of vaccines preventing a severe course of COVID-19 disease is particularly important in immunocompromised patients, among whom organ recipients and patients awaiting transplantation constitute a large group. The article is a critical review of 68 recent publications on the impact of the SARS-CoV-2 pandemic on transplantology worldwide. The study discusses research results concerning various aspects of SARS-CoV-2 vaccination in transplant patients; it also lists important factors influencing vaccination effectiveness. A suboptimal immune response to 2 doses of vaccine in this group of patients is a major challenge prompting further research. Therefore, this review aims to provide an update on the humoral and cellular immune responses to SARS-CoV-2 vaccination following solid organ transplantation.

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models.

Liver transplantation (LTx) is the best treatment for patients with early-stage hepatocellular carcinoma (HCC). The Milan criteria positively influenced results of liver transplantation and were adopted by the majority of cancer centers, becoming the criterion standard treatment for early-stage HCC. Despite the use of restrictive criteria, recurrence is still high, affecting between 8% and 20% of cases, and is a significant predictor of survival after LTx. The diagnosis of both micro-and macro-invasion of vessels, which are significant factors in determining the frequency of recurrence and overall survival, significantly decreases the success of transplantation, causing an increase in mortality of 50% in comparison to recipients with no vascular invasion. The risk of recurrence depends on several factors, which are discussed in this review. The authors also discuss the clinical presentation and treatment methods of recurrence and its prognosis. In addition, the role of different models developed to identify groups of patients with high versus low risk of recurrence is discussed, enabling the planning of recommendations and screening protocols after transplantation to help early diagnosis and guide effective treatment. In the era of an increasing numbers of liver transplants due to HCC, the need to create robust screening tools is urgent.

Effects of the COVID-19 Pandemic on Solid Organ Transplantation During 2020 in Poland Compared with Countries in Western Europe, Asia, and North America: A Review.

The coronavirus disease 2019 (COVID-19) pandemic, due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began in March 2020, affected organ donor acceptance and rates of heart, lung, kidney, and liver transplants worldwide. According to data reported to POLTRANSPLANT, the number of solid organ transplants decreased by over 35% and the number of patients enlisted de novo for organ transplantation was reduced to 70% of its pre-COVID-19 volume in Poland. Most transplant centers in Western Europe and the USA have also drastically reduced their activity when compared to the pre-pandemic era. Areas of high SARS-CoV-2 infection incidence, like Italy, Spain, and France, were most affected. Significant decreases in organ donation and number of transplant procedures and increase in waitlist deaths have been noted due to overload of the healthcare system as well as uncertainty of donor SARS-CoV-2 status. Intensive care unit bed shortages and less intensive care resources available for donor management are major factors limiting access to organ procurement. The impact of the COVID-19 outbreak on transplant activities was not so adverse in Asia, as a result of a strategy based on experience gained during a previous SARS pandemic. This review aims to compare the effects of the COVID-19 pandemic on solid organ transplantation during 2020 in Poland with countries in Western Europe, North America, and Asia.

Overall Survival in Patients with Hepatocellular Carcinoma Treated with Sorafenib: A Polish Experience.

BACKGROUND The mortality caused by hepatocellular carcinoma is expected to rise in the upcoming decade. Sorafenib has become the preferred systemic treatment option in patients with unresectable HCC. This study aimed to present the median overall survival (OS) in a group of patients with advanced HCC, treated with sorafenib in Poland between 2011 and 2019. MATERIAL AND METHODS The analyzed group of patients was qualified for treatment with sorafenib, financed by the National Health Fund, based on the guidelines of the Polish Drug Program. Kaplan-Meier method was used to plot the OS curves, and the log-rank test was used for testing. Multivariate assessment of factors (sex and age) related to the time to death of the patient was done using Cox regression. RESULTS Of the 2072 treated patients, 75% were men (1556) and 25% were women (516). The minimum age of patients in the trial group was 18 years and the maximum age was 90 years. Among the 1556 analyzed cases in males, 27.44% (427) did not end with death (by the date of completing the analysis). The percentage of one-year survival for this population was 58.16%, and the 2-, 3-, and 5-year survival rates were 34.45%, 21.81%, and 9.72%, respectively. The percentage of censored cases in the 516 females was 25.78% (133). The 1-2-, 3-, and 5-year survival for this population was 59.30%, 36.27%, 22.47%, and 11.34%, respectively. Statistical tests did not reveal a significant difference in the curve profiles by sex. There were no associations between OS and age. CONCLUSIONS Systemic treatment with sorafenib in accordance with the presented criteria allows for very good results, comparable to the results of selected groups of patients presented by other authors.

First Report of Echinococcus ortleppi in Human Cases of Cystic Echinococcosis in Poland.

Cystic echinococcosis is considered as an emerging zoonosis that can develop asymptomatically for years, clinically nonpathognomic. The disease is of public health importance due to often late, difficult diagnostics, uncertain results of treatment, the need to remove hydatid cysts surgically in advanced cases, and poor prognosis in untreated patients. Six Polish female patients with diagnosed cystic echinococcosis (CE) were examined. DNA extracted from the liver and lung samples served for amplification of mitochondrial nad1 gene fragment. Sequence alignments of 5 isolates showed identity with the pig strain, Echinococcus canadensis G7. One case was in 100% identical with Echinococcus ortleppi G5, the cattle strain. These data demonstrate first report of E. ortleppi, regarded as extinct species, causing human cystic echinococcosis in Poland, where the most frequent causative agent of human CE is E. canadensis.

The epidemiology of hepatocellular cancer in Poland.

INTRODUCTION: This article summarize the available data on hepatocellular carcinoma (HCC) epidemiology in Poland. Data regarding the HCC incidence rate are divergent. Statistical data presented by NFZ appear more credible in that matter than data published by the Polish Oncology Center (POC). MATERIAL AND METHODS: The analysis included data from the Polish Bibliography Database (GBL), the Polish National Health Fund Institution (NFZ), the scientific paper "Malignant neoplasms in Poland" issued by POC and the central liver transplant registry maintained by the Polish transplant coordinating center "Poltransplant" (2010-2015). RESULTS: Data regarding the HCC incidence rate are divergent. Statistical data presented by NFZ appear more credible in that matter than data published by POC. CONCLUSIONS: The occurrence of HCC in Poland is at the average European level and is similarly rising. The incidence rate is underestimated. It is due to faulty epidemiology data collection techniques. The highest risk group comprises men over the age of 50 with concomitant liver cirrhosis. The most common HCC etiology is HCV infection.

Accelerated hepatocellular carcinoma recurrence rate after postoperative direct-acting antivirals treatment - preliminary report.

AIM OF THE STUDY: New interferon-free direct-acting antiviral (DAA) therapy has led to major progress in hepatitis C virus (HCV) treatment. Current outcomes are promising, especially in compensated cirrhosis. However, there are reports of accelerated hepatocellular carcinoma (HCC) recurrence after surgery in patients treated with DAAs. The influence of DAA therapy on the timing and frequency of recurrence after surgical treatment needs further observation. MATERIAL AND METHODS: Fifty-one HCV infected patients with advanced liver cirrhosis and history of surgical treatment for HCC in 2012-2016 were analyzed in a case-control study. Nineteen patients received DAA therapy (DAA group) after tumor remission achieved by surgery and 32 patients were not treated with DAA (NDAA group). Follow-up included multiphase computed tomography scan or magnetic resonance imaging of the liver and alpha-fetoprotein level in 3-6-month intervals. RESULTS: An sustained virological response was achieved in 18 (95%) DAA treated patients. Hepatocellular carcinoma recurrence was observed in 8 (42.1%) patients from the DAA group and in 21 (65.6%) from the NDAA group (p = 0.058). Relapse occurred within 265 days after surgery in the DAA group vs. 532 days in the NDAA group (p = 0.033). The one-year recurrence-free survival (RFS) rate was 47.3% vs. 75% in the DAA and NDAA group respectively (p = 0.45). CONCLUSIONS: Use of DAA therapy in patients with a history of HCC may result in significantly accelerated relapse of the disease. The number of analyzed patients in this study is too small to state unquestionable conclusions. Further observation with a longer follow-up and larger patient group is needed. The study confirms that contemporary HCV treatment is highly effective.

The first Polish liver transplantation after Roux-en-Y gastric bypass surgery for morbid obesity: a case report and literature review.

BACKGROUND: Morbid obesity is associated with liver pathology, most commonly non-alcoholic steatohepatitis (NASH) leading to cirrhosis. However, the morbid obesity impedes qualification for organ transplantation. CASE REPORT: We present a case report of a 56-year-old woman who underwent bariatric procedure followed by liver transplantation (LTx). Her initial weight was 130.2 kg (BMI 50.9 kg/m2). The patient had a history of arterial hypertension, diabetes, gonarthrosis, and obstructive sleep apnea syndrome and no history of alcohol abuse. She underwent Roux-en-Y gastric bypass (RYGB) procedure. The routine intraoperative liver biopsy revealed fibrosis (III°), steatosis (II°), and intra-acinar inflammation. The operation led to a substantial loss of weight. Two years after the surgery the patient was referred to the Transplantation Clinic of Department of General Surgery and Transplantology with suspicion of liver failure due to advanced cirrhosis, which could be a result of previously diagnosed NASH and, probably, excessive alcohol use after bariatric surgery. The patient was qualified for elective LTx, which was performed 3 years after the RYGB. Immediately before LTx, the patient's weight was 65 kg (BMI 25.4 kg/m²). The postoperative period was complicated by bleeding into the peritoneal cavity, which required reoperation. She also had renal failure, requiring renal replacement therapy. One year after LTx, she showed stable liver function with normal transaminases activity and bilirubin concentration, remission of diabetes, and good renal function. CONCLUSIONS: Steatohepatitis in morbidly obese patients may lead to cirrhosis. Bariatric procedure can be a bridge to liver transplantation for morbidly obese patients with advanced liver fibrosis.

Bariatric surgery as a bridge for kidney transplantation in obese subjects. Case report.

BACKGROUND: The epidemiological studies indicate that the problem of obesity and associated metabolic syndrome affects the steadily increasing population. The obesity also applies to the patients with the end-stage renal failure requiring renal replacement therapy. Morbid obesity is a contraindication to renal transplantation procedure. A significant excess weight greatly increases the waiting time for transplantation, increases the risk of surgical complications, including complications due to cardiovascular and metabolic disorders. The combination of these risk factors with the immunosuppressive therapy may worsen the symptoms associated with the renal failure, contribute to the deterioration of graft function, shorten the survival, and increase the risk of patient death. CASE REPORT: In this paper we described the first Polish case of kidney transplantation, in a patient after bariatric surgery. The patient was disqualified from kidney transplantation because of obesity and referred to our department for metabolic surgery and weight reduction before potential kidney transplantation. 10 months post the bariatric surgery patient was selected as a kidney transplant recipient from a deceased donor. Both procedures have been performed in this same center. CONCLUSIONS: Bariatric surgery procedures are safe and effective in patients with end-stage renal disease. Bariatric procedures may be considered as a procedural bridge for a group of morbidly obese patients with renal failure, allowing them to be qualified for transplantation.

Liver transplantation for HCV cirrhosis; cautious optimism after 10 years of experience.

BACKGROUND: Currently, HCV (hepatitis C virus) cirrhosis is one of the most common indications for liver transplantation (LTx) in Europe and North America among adults. Very early after LTx, histological examinations of liver biopsies in a group of HCV-positive recipients show important differences compared to other indications for transplantation. MATERIAL/METHODS: We described results of 121 primary LTx for HCV cirrhosis. HCV-RNA PCR was positive in 94% of primary graft recipients prior to LTx. Co-existing HCC was diagnosed in 20.66% of recipients. RESULTS: One-year, 5-year, and 10-year survivals in the HCV-positive recipient group were 87.6%, 85.9%, and 84.3%, respectively. Symptomatic recurrent hepatitis was diagnosed in 58/121 (47.54%) recipients, and 41.3% presented with recurrence within the first 6 months. None of the PCR-negative recipients developed recurrent hepatitis prior to LTx. The rescue therapy for recurrent HCV hepatitis consist of Interferon and Ribavirin; the sustained virologic response (SVR) was obtained in 50% and 41% of recipients at 24 and 48 weeks, respectively, after treatment cessation. CONCLUSIONS: Despite almost universal recurrence of HCV after LTx, results of transplantation are relatively good. Modification of immunosuppression, younger organ selection, and avoiding steroid pulses for rejection improve the results. Inclusion of combination therapy with interferon and Ribavirin allows for more than 40% SVR.

Invasive fungal infections following liver transplantation - risk factors, incidence and outcome.

BACKGROUND: The incidence of invasive fungal infections (IFIs), particularly candidiasis and aspergillosis, following solid organ transplantation vary from 1.4% to 42%. IFIs most commonly occur after orthotropic liver transplantation (OLT), lung/heart and pancreas transplantation. Mortality related to IFIs depends on the type of transplant and vary from 3% to 100% of cases. The results largely depend on early initiation of specific treatment for IFIs. Therefore, the diagnosis has to be prompt and based on known risk factors - time of surgical procedure, type of biliary anastomosis, blood loss, rate of rejection and re-transplantation. MATERIAL/METHODS: We evaluated the incidence of fungal infections in patients after liver transplantation in our center. The retrospective analysis of 175 consecutive OLT patients was undertaken to estimate incidence, risk factors and clinical courses of IFIs in the last 6 years at our center. RESULTS: Infections involving Aspergillus (6 cases), Candida (24 cases) and Cryptococcus (1 case) were observed in 17.7% of our recipients. Except for 1 case (Cryptococcus encephalitis), all of the episodes developed during the first month post-transplantation. All cases of lung aspergillosis developed in patients with autoimmune cholestasis prior to transplantation. In 1 case after transplantation, in a patient with bile duct necrosis requiring reoperation, pneumonia developed. In 3 cases, pulses of steroids were used to treat acute rejection. Apart from that, none of the potential risk factors of IFIs described by other authors were noted. Five out of 6 cases of aspergillosis survived on combined antifungal therapy. The recipient diagnosed with cryptococcal encephalitis died. All cases with urinary tract (n=18; 8.6%) or respiratory (n=6; 3.4%) candidiasis survived. CONCLUSIONS: Early diagnosis and prompt treatment is fundamental for patient survival.

The use of thromboelastometry in the assessment of hemostasis during orthotopic liver transplantation reduces the demand for blood products.

BACKGROUND: Bleeding due to fibrinolysis is a serious intraoperative complication during orthotopic liver transplantation (OLT). For a number of years aprotinin was used to minimize risk of this complication. This drug was however banned in 2007 and substituted with other antifibrinolytics. The aim of the study was to assess the potential of intraoperative thromboelastometry to evaluate hemostasis and channelize antifibrinolytic therapy. MATERIAL/METHODS: Since ban on aprotinin, 39 patients underwent OLT in our center with no monitoring of fibrinolysis (NMF). Severe disturbances of hemostasis assessed clinically only as a need for blood and blood products transfusion and were treated with transfusion of fresh frozen plasma only. In 2008 we started to use thromboelastometry (ROTEM group, n=39), which allowed for targeted treatment of hyperfibrinolysis with tranexamic acid. RESULTS: The need for blood transfusion in ROTEM group was insignificantly a lower than in NMF group (4.1±4.76 vs 5.53±4.89 units, p=0.2). Patients from ROTEM group required also less plasma transfusions (10.01±7.47 vs 13.15±6.62, p=0.06). Severe fibrinolysis was found in 3 patients from ROTEM group (7.7%) and was treated with tranexamic acid. CONCLUSIONS: Thromboelastometry provides an immediate diagnosis of fibrinolysis, justifies implementation of targeted treatment and confirms effectiveness of the therapy. In a larger study group it can also result in significant minimization of blood products transfusion during OLT.

Thoracic epidural analgesia in anaesthesia for liver transplantation: the 10-year experience of a single centre.

BACKGROUND: Improvements in operating techniques, methods of anaesthesia and postoperative care in liver transplantation (LT) contribute to better outcomes. In order to restrict postoperative mechanical ventilation, a thoracic epidural analgesia (TEA) has been performed in our centre since 2000. In this report we present our 10-year experience of using TEA as a component of LT anaesthesia. MATERIAL/METHODS: TEA was performed, by anaesthetists experienced in this method, on patients qualified for LT, who consented and met inclusion criteria: INR<1.5, APTT<45s and platelets >70 G/L. Since 2008 the decision to insert an epidural catheter has been additionally supported by thromboelastometry. We assessed extubation time, frequency of complications of TEA and undesired accidents. RESULTS: From 279 patients undergoing LT, TEA was performed on 67 (24%), and from these 56 (84%) were extubated in the operating theatre. There were 5 cases of unsatisfactory thoracic epidural analgesia. Only 1 epidural catheter was removed accidentally, on the 2nd postoperative day. None of the complications of TEA were observed in the TEA group. CONCLUSIONS: Based on our observations, it can be assumed that TEA done by experienced an anaesthetist is a safe component of anaesthesia in selected groups of patients undergoing LT, and allows for early extubation.

Bacterial infections in the early period after liver transplantation: etiological agents and their susceptibility.

BACKGROUND: The study comprises an analysis of bacterial infections in the early period after liver transplantation (LT) in adults. MATERIAL/METHODS: Eighty-three patients were followed for four weeks after LT. Samples comprised mainly blood, urine, surgical-site specimens, sputum, and stool. Culture and identification of the isolated microorganisms was done in accordance with standard microbiological procedures. Susceptibility testing was carried out using CLSI guidelines. Statistical analysis was done with Medi-Stat. RESULTS: In total, 913 samples from LT recipients were cultured. Of the 469 isolated strains, 331 (70.6%) were Gram-positive bacteria, 133 (28.4%) were Gram-negative bacteria, and 5 (1.0%) were yeast-like fungal strains. Of the 284 surgical-site isolates, 222 (78%) were Gram-positive and 61 (21.5%) were Gram-negative bacteria. Of the 99 blood culture isolates, 75 (75.8%) were Gram-positive and 22 (22.2%) of Gram-negative bacterial strains. Of the 73 urine samples, 46 (63.0%) were strains of Gram-negative, 25 (34.0%) of Gram-positive bacteria, and 2 (3.0%) fungal strains. In the 13 respiratory tract samples were 9 (69.0%) Gram-positive and 4 (31.0%) Gram-negative strains. In the 54 stool samples, 63.0% and 16.7% were C. difficile toxin- and culture-positive, respectively. In total, 138 strains of MRCNS, 10 of MRSA, 80 of HLAR, and 19 ESBL(+) were detected. CONCLUSIONS: The isolation of MDR bacterial strains such as MRSA (52.6%), MRCNS (81.7%), HLAR (86.0%), and ESBL(+) Gram-negative rods (12.5%) from patients after LT indicates the need for strict adherence to infection control procedures.

Quality of life after liver transplantation--preliminary report.

BACKGROUND: Liver transplantation (OLTx) is an optimal method of treatment of end-stage liver failure. It gives a chance to get back to an active life. 80-90% of patients survive over 1 year after liver transplantation with a perspective of a long life.Recently more attention is being paid to health related quality of life (QoL). It is considered as a combination of physical and mental condition, social and economical state and somatic experience. The aim of the study was to analyze patient's QoL after OLTx compared to the condition before OLTx. MATERIAL/METHODS: 123 patients 1-12 years after transplantation were included in the study. The study was conducted in Outpatients Clinic of Immunology, Transplantology and Internal Medicine Department and Transplantation Medicine and Nephrology Department of Warsaw Medical University between October 2007 and January 2008. Original questionnaire was used, consisting of 8 general questions and 44 detailed questions concerning pre- and posttransplant period. Information about physical condition (health, mobility, basic functions, drug side effects), mental condition (anxiety, happiness, cognition disorders), social function (family, friends, work) and economic status were gathered. "Never, sometimes, often, very often" score was used. RESULTS: Majority of subjects de fi ned their quality of life and physical condition before transplantation as poor, and post transplantation - as good. The respondent's mental condition didn't differ much before and after transplantation. Level of satisfaction was higher after transplantation. Health condition in some cases affected patients' family life, however it often devastated their social life before OLTx. Most patients were on disability pension and after transplantation they indicated the influence of health on their financial condition. CONCLUSIONS: The quality of life after liver transplantation gets better and it's de fi ned as good or very good. During the analysis of QoL a difference between conditions before and after LTX wasn't observed.

Long-term survival after kidney transplantation from homozygotic twin--a case report.

Grafts from genetically related living donors have better survival rates than ones from deceased donors. Immunological match is one of the beneficial factors involved. The aim of this paper is to discuss a case of a 55-year old patient living for 33 years with transplanted kidney, weaned off immunosuppressive therapy for 20 years. Perfect match between donor and recipient, homozygotic siblings, was vital for such long-term graft survival.

Assessment of cadaveric livers discarded from transplantation. A correlation between clinical and histological parameters.

BACKGROUND: We designed a study with the following aims: to assess tissue quality of 100 cadaveric livers discarded from transplantation, to identify discarded organs which could have been used either for transplantation or for isolation of hepatocytes, to assess donor clinical factors which may impact the histology. MATERIAL/METHODS: Liver wedge biopsies were performed during kidney procurement, sent for processing and data interpretation. RESULTS: In 46% of the evaluated tissues severe changes were found; these organs according to pathologists were "not suitable for transplantation". In 19% less pronounced changes classified organs as "probably not suitable for transplantation". In 35% biopsies only minimal changes were found; these organs were classified as "probably suitable for transplantation" and could have been harvested as marginal organs or at least used for hepatocytes isolation. CONCLUSIONS: Results of biopsies suggested that approximately in one third of livers discarded from transplantation due to clinical donor parameters could have been harvested from histological point of view. Several donor clinical risk factors (alcohol addiction, hyperbilirubinemia, increased transaminase activity) correlate with severe histological changes rending the liver "not suitable for transplantation".

The objective of psychological evaluation in the process of qualifying candidates for bariatric surgery.

Psychosocial and behavioral variables play an important role in both the development and treatment of obesity. Therefore, in the process of qualifying the patient for bariatric surgery, it is necessary to professionally evaluate his/her psychological state. Such evaluation is very helpful in the identification of factors potentially disturbing the effectiveness of the treatment. Clinical interviews with a group of 80 patients were conducted by a psychologist in the pre- and post-surgical period. The qualitative analysis of the interviews led to the identification of the major elements which should become the object of psychological evaluation in the process of qualifying patients for bariatric surgery. Conducting a clinical interview comprising these elements allows one to evaluate their potential influence on the process of surgical treatment of obesity and to provide optimal psychological support for the patient before and after the surgery.

[Hepatocellular carcinoma--epidemiology and treatment]. / Rak watrobowokomórkowy-- epidemiologia i leczenie.

Hepatocellular carcinoma (HCC) is one of the most commonly occurring solid tumors worldwide and is the most frequent cause of cancer death in some parts of the world such as China and sub-Saharan Africa. HCC appears to be rising dramatically in incidence in developed western countries too. The most frequent underlying factors causing HCC are chronic viral hepatitis and cirrhosis. Early detection of HCC is a key factor in improving outcomes of therapies. There is growing evidence that HCC may be prevented with strategies aimed at preventing or treating viral hepatitis. Surgery, including liver transplantation, remains the most efficient treatment but only for 15-30% of patients. Recent developments suggest that other therapeutic modalities such as loco-regional (ablative) methods are also potentially curative.