György Gámán

Biliary complications after liver transplantation

Biliary complications (BCs) remain one of the most outstanding factors influencing long-term results after orthotopic liver transplantation. The authors carried out a systematic overview of 1720 papers since 2008, and focused on 45 relevant ones. Among 14,411 transplanted patients the incidence of BCs was 23%. Biliary leakage occurred in 8.5%, biliary stricture in 14.7%, mortality rate was 1–3%. Risk factors: preoperative sodium level; p = 0.037, model of end-stage liver disease score >25; p = 0.048, primary sclerosing cholangitis; p = 0.001, malignancy; p = 0.026, donor age >60, macrovesicular graft steatosis; p = 0.001, duct-to-duct anastomosis; p = 0.004, long anhepatic phase; p = 0.04, cold ischemic time >12 h; p = 0.043, use of T-tube; p = 0.032, insufficient flush of bile ducts; p = 0.001, acute rejection; p = 0.003, cytomegalovirus infection; p = 0.004 and hepatic artery thrombosis; p = 0.001. The management was surgical in case of biliary leakage, and interventional radiology or endoscopic retrograde cholangiopancreatography in case of biliary stricture. Mapping of miRNA profile is a new field of research. Nemes–Doros score is a useful tool in the estimation of hepatic artery thrombosis. Management of BCs requires a multidisciplinary expert team.

Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation

ABSTRACT Extended-criteria donors (ECDs) have an impact on early allograft dysfunction (EAD), biliary complications, relapse of hepatitis C virus (HCV), and survivals. Early allograft dysfunction was frequently seen in grafts with moderate and severe steatosis. Donors after cardiac death (DCD) have been associated with higher rates of graft failure and biliary complications compared to donors after brain death. Extended warm ischemia, reperfusion injury and endothelial activation trigger a cascade, leading to microvascular thrombosis, resulting in biliary necrosis, cholangitis, and graft failure. The risk of HCV recurrence increased by donor age, and associated with using moderately and severely steatotic grafts. With the administration of protease inhibitors sustained virological response was achieved in majority of the patients. Donor risk index and EC donor scores (DS) are reported to be useful, to assess the outcome. The 1-year survival rates were 87% and 40% respectively, for donors with a DS of 0 and 3. Graft survival was excellent up to a DS of 2, however a DS >2 should be avoided in higher-risk recipients. The 1, 3 and 5-year survival of DCD recipients was comparable to optimal donors. However ECDs had minor survival means of 85%, 78.6%, and 72.3%. The graft survival of split liver transplantation (SLT) was comparable to that of whole liver orthotopic liver transplantation. SLT was not regarded as an ECD factor in the MELD era any more. Full-right-full-left split liver transplantation has a significant advantage to extend the high quality donor pool. Hypothermic oxygenated machine perfusion can be applied clinically in DCD liver grafts. Feasibility and safety were confirmed. Reperfusion injury was also rare in machine perfused DCD livers.

Extended criteria donors in liver transplantation Part I: reviewing the impact of determining factors

ABSTRACT The definition and factors of extended criteria donors have already been set; however, details of the various opinions still differ in many respects. In this review, we summarize the impact of these factors and their clinical relevance. Elderly livers must not be allocated for hepatitis C virus (HCV) positives, or patients with acute liver failure. In cases of markedly increased serum transaminases, donor hemodynamics is an essential consideration. A prolonged hypotension of the donor does not always lead to an increase in post-transplantation graft loss if post-OLT care is proper. Hypernatremia of less than 160 mEq/L is not an absolute contraindication to accept a liver graft per se. The presence of steatosis is an independent and determinant risk factor for the outcome. The gold standard of the diagnosis is the biopsy. This is recommended in all doubtful cases. The use of HCV+ grafts for HCV+ recipients is comparable in outcome. The leading risk factor for HCV recurrence is the actual RNA positivity of the donor. The presence of a proper anti-HBs level seems to protect from de novo HBV infection. A favourable outcome can be expected if a donation after cardiac death liver is transplanted in a favourable condition, meaning, a warm ischemia time < 30 minutes, cold ischemia time < 8–10 hours, and donor age 50–60 years. The pathway of organ quality assessment is to obtain the most relevant information (e.g. biopsy), consider the co-existing donor risk factors and the reserve capacity of the recipient, and avoid further technical issues.

Can a Cutoff Value for Cystatin C in the Operative Setting Be Determined to Predict Kidney Function After Liver Transplantation

Correct assessment and follow-up of kidney function is essential in liver transplant recipients. Glomerular filtration rate (GFR) represents the functional capacity of the kidney. The GFR is generally determined on the basis of creatinine clearance using several methods. It has been suggested that cystatin C be used rather than GFR. Production of cystatin C is not dependent on the same factors as creatinine. It is filtered and completely metabolized in the glomeruli, and is not secreted by the kidney tubules. The objective of this study was to determine a preoperative cutoff value for cystatin C based on kidney function estimated after liver transplantation. At prefixed times before and after orthotopic liver transplantation (OLT), serum cystatin C and creatinine concentrations were measured, and GFR was calculated using the Cockroft-Gault equation. Patients were divided into 2 groups according to GFR on postoperative days 1 to 5. Group 1 (healthy recipients) included patients with post-OLT GFR greater than 70 mL/min; and group 2 (kidney-impaired recipients), post-OLT GFR less than 70 mL/min. Group 2 demonstrated greater risk of postoperative complications, abnormal postoperative creatinine concentrations and GFR values, and worse patient and graft survival. Based on the preoperative cystatin C concentration, postoperative kidney function can be assessed. The cutoff value for preoperative cystatin was determined using receiver operating characteristics analysis. When the preoperative cystatin C concentration exceeded 1.28 mg/L, the postoperative GFR was less than 70 mL/min in the first 5 days after OLT. These findings suggest that if the cystatin C concentration exceeds the cutoff point preoperatively, there will be deterioration of kidney function after OLT. Along with other researchers, we suggest that cystatin C is a sensitive marker of post-OLT kidney function.

Recurrence of primary sclerosing cholangitis after liver transplantation - The Hungarian experience.

INTRODUCTION Recurrence of primary sclerosing cholangitis (rPSC) after liver transplantation (OLT) significantly affects long-term graft survival. We aimed to evaluate the incidence of rPSC and clinical data of these patients in Hungary. PATIENTS AND METHODS We retrospectively analyzed data of 511 whole liver transplantations from 1995 to 2011. During the study period, 49 OLTs were performed in 43 adult patients with end-stage PSC (10%). RESULTS Out of 49 OLT, 24 cases were excluded, rPSC was diagnosed in six patients (12%). Patients with rPSC had significantly higher mortality (p = 0.009) and graft loss (p = 0.009) in comparison to patients without recurrent disease. Younger recipient age, higher donor BMI was observed in the rPSC group. One patient was diagnosed with de novo IBD, the remaining five patients had worsening IBD activity in the posttransplant period. PreOLT colectomy was performed in 21% of the control and none of the rPSC group. PostOLT colectomy was performed in two rPSC patients due to severe therapy resistant colitis. CONCLUSIONS Recurrent PSC significantly affects long-term mortality and graft loss. Younger age at OLT, higher donor BMI and severe active IBD may be associated with PSC recurrence. PreOLT total colectomy might have protective effect against rPSC.

Bakteriális infekciók májátültetés után

INTRODUCTION The authors reviewed the prevalence of postoperative infections, the results of bacterium cultures, and the incidence of multidrug resistance in their liver transplanted patients during a period between 2003 and 2012. AIM The aim of this study was to analyse risk factors and colonisations of bacterial infections. METHOD The files of 408 patients (281 bacterium cultures) were reviewed. RESULTS Of the 408 patients 70 had a postoperative infection (17%); 58 patients (14.2%) had positive and 12 patients (2.9%) negative bacterial culture results. Cholangitis was found in 7 cases (12.1%), abdominal infection in 17 cases (29.3%), and pulmonary infection in 28 cases (48.3%). Postoperative infection was more frequent in patients with initial poor graft function, acute renal insufficiency, biliary complication, and in those with intraabdominal bleeding. The 1-, 3- and 5-year cumulative survival of patients who had infection was 70%, 56% and 56%, respectively, whereas the cumulative survival data of patients without infection was 94%, 87% and 85%, respectively (p<0.001). Multidrug resistance was found in 56% of the positive cultures, however, the one-year survival was not different in patients who had multidrug resistance positive and negative bacterial infection (both 70.2%). CONCLUSIONS Infection control must target the management of multidrug resistance microbes through encouraging prevention, hygienic, and isolation rules, improving the operative, transfusion, and antimicrobial policy in a teamwork setting.Absztrakt Bevezetes: A szerzők a majatultetest kovetően kialakult mikrobas fertőzeseket, a mintavetelek eredmenyeit, a multidrug-rezisztencia incidenciajat vizsgaltak a hazai betegek koreben. Celkitűzes: Tanulmanyoztak a bakterialis fertőzes kialakulasanak kockazati tenyezőit, az infekciokhoz kapcsolodo szovődmenyek előfordulasat, lefolyasat, es reszletes korokozo-spektrumelemzest vegeztek. Modszer: 2003–2012 kozott majatultetett 408 beteg adatait (281 bakteriologiai tenyesztest) vizsgaltak. Eredmenyek: A 408 beteg kozul 70 betegnel (17%) eszleltek klinikai tunetekkel jaro fertőzest. A tenyesztesi lelet 58 betegnel (14,2%) pozitiv, 12 betegnel (2,9%) negativ volt. Het esetben (12,1%) alakult ki cholangitis, 17 esetben (29,3%) fordult elő hasűri es 28 esetben (48,3%) pulmonalis eredetű fertőzes. Posztoperativ fertőzes gyakrabban lepett fel kezdeti csokkent graftműkodes, akut veseelegtelenseg, epeuti szovődmeny es hasűri verzes mellett. Infekcio kialakulasa eseten az 1, 3 es 5 eves betegtuleles 70%, 56% es ...

Hepatitis C virus recurrence after liver transplantation in Hungary. Trends over the past 10 years

INTRODUCTION Management of hepatitis C virus recurrence is a challenge after liver transplantation. AIM The aim of the authors was to analyse the outcome of liver transplantation performed in hepatitis C virus positive patients during the past ten years and to compare recent data with a previous report of the authors. METHOD The authors retrospectively evaluated the data (donors, recipients, perioperative characteristics, patient and graft survival, serum titer of hepatitis C virus RNA, histology) of 409 patients who underwent liver transplantation between 2003 and 2012. RESULTS 156 patients were transplanted due to hepatitis C virus associated liver cirrhosis (38%). Worse outcome was observed in these patients in comparison to hepatitis C virus negative recipients. The cumulative patient survival rates at 1, 5, and 10 year were 80%, 61%, 51% in the hepatitis C virus positive group and 92%, 85%, 79% in the hepatitis C virus negative group, respectively (p<0.001). The cumulative graft survival rates at 1, 5 and 10 year were 79%, 59% and 50% in hepatitis C virus positive and 89%, 80% and 70% in hepatitis C virus negative patients (p<0.001). Hepatitis C virus recurrence was observed in the majority of the patients (132 patients, 85%), mainly within the first year (83%). The authors observed recurrence within 6 months in 71 patients (56%), and within 3 months in 26 patients (20%). The mean hepatitis C virus recurrence free survival was 243 days. Higher rate of de novo diabetes was detected in case of early recurrence. The cumulative patient survival rates at 1, 3, 5, 10 years were 98%, 89.5%, 81% and 65% when hepatitis C virus recurrence exceeded 3 months and 64%, 53%, 30.5% and 30.5% in patients with early recurrence (p<0.001). CONCLUSIONS Poor outcome of liver transplantation in hepatitis C virus positive patients is still a challenge. Hepatitis C virus recurrence is observed earlier after liver transplantation in comparison with a previous report of the authors. De novo diabetes occurs more frequently in case of early recurrence. Despite an immediate start of antiviral treatment, early recurrence has a significant negative impact on the outcome of transplantation.

Kidney function and liver transplantation

INTRODUCTION In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. AIM The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. METHOD Retrospective data analysis was performed after primary liver transplantations (n = 319). RESULTS impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). CONCLUSIONS Selection of personalized immunosuppressive medication has a positive effect on renal function.