Time of Dropout From the Liver Transplant List in Patients With Hepatocellular Carcinoma: Clinical Behavior According to Tumor Characteristics and Severity of Liver Disease.

BACKGROUND: Prolonged time on the waiting list affects post-transplant survival of patients with hepatocellular carcinoma (HCC). However, it is not yet known which patients will be at higher risk for early dropout from the list. We investigate specific risk factors for early waiting list dropout in patients with HCC. METHODS: This was a single-center, intention-to-treat analysis of adults with HCC, within the Milan criteria, from July 2006 through September 2013. Patients were divided into groups according to waiting list time. The main end point was dropout from the list. RESULTS: The dropout rates of the study cohort at 3, 6, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Patients who dropped out from the list tended to be older, with blood types A and O, and with higher Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. They also had larger nodules, responded poorly to trans-arterial chemo-embolization (TACE), and had a higher alpha-fetoprotein. Those with blood types B and AB appeared to be protected for dropout (odds ratio [OR] = 0.21, P = .02). Patients who responded to TACE were also protected (OR = 0.22, P < .001). When we looked into time to dropout, the only baseline characteristic that stood out was a higher MELD score (13 for those dropping out up to 90 days vs 10 for those dropping out after 180 days, P = .0025). CONCLUSIONS: We conclude that patients who drop out early from the list are primarily driven by the severity of liver disease. Patients who had progressive HCC had a high tumor load and poor response to loco-regional therapies, dropping out from the list after 180 days of inclusion.

Impact of cumulative risk factors for expanded criteria donors on early survival after liver transplantation.

There are various options to help overcome the organ shortage, including performing transplants using grafts from marginal donors with characteristics previously described as unacceptable because of the high risk of graft failure. Nowadays, expanded criteria donors for liver transplantation (OLT) is a strategy used routinely by many teams. Some donor features have been suggested to jeopardize initial function or survival; when these features are aggregated, they may impact prognosis. The aim of this study was to evaluate the impact of donor risk factors on early patient survival and retransplantation. Donor risk factors were considered to be older than 60 years, body mass index > 30, serum sodium level > 155 mEq/L, cold ischemia time > 12 hours, and intensive care unit stay > 4 days. We prospectively recorded data from 139 patients who underwent 152 OLT from March 2003 to May 2007. Patients were classified into four groups: I, no risk factors; II, one risk factor; III, two risk factors; IV, three or more risk factors. Retransplantation or OLT due to acute liver failure was considered to be an exclusion criterion. Early overall survival rate was 83.76%; 12 retransplantations were required (10.25%). Comparing the four groups, patient survivals (P = .41) and retransplantation rates (P = .518) were similar. In conclusion, cumulative risk factors showed no impact on early (30-day) recipient survival and or on the necessity of retransplantation after OLT.

Impact of renal failure on liver transplantation survival.

Renal failure after orthotopic liver transplantation (OLT) is a common complication (ranging from 12% to 70%) associated with worse outcomes, particularly when it requires renal replacement therapy (RRT). Renal dysfunction is a common scenario among waiting list patients. It can lead to a worse prognosis after OLT, due to an increased incidence of postoperative renal failure. The aim of this study was to analyze the incidence of renal failure after OLT, its relationship to pretransplant renal dysfunction, and its impact on outcomes. We analyzed data collected prospectively from 152 consecutive OLTs in 139 patients performed by the same team from March 2003 to November 2007. Exclusion criteria for 34 cases included transplantation due to acute liver failure, combined liver-kidney transplantation, retransplantation, and patients who died up to 2 days posttransplantation. Based on creatinine clearance (CCr) calculated at the time of OLT, the 118 patients were classified in two groups: group I, normal pre-OLT renal function (CCr > or = 70 mL/min) versus group II, pre-OLT renal failure (CCr < 70 mL/min). Each group was analyzed according to the development of post-OLT renal failure, being classified as subgroup A (normal renal function post-OLT), subgroup B (mild renal impairment post-OLT-serum creatinine level between 2.0 and 3.0 mg/dL or doubled basal value up to 3.0 mg/dL) versus subgroup C (severe renal impairment post-OLT-serum creatinine level > or = 3.0 mg/dL or utilization of RRT). The overall incidence of post-OLT renal impairment was 41.52% with RRT in 22 patients (18.64%). Group II patients showed a greater incidence of post-OLT renal failure when compared with other patients (P < .05), but without a statistical difference when compared according to RRT requirement. Comparison of average hospital stay was similar between groups I and II, and also among its subgroups (A, B, and C, respectively). There was no statistical difference in early (30-day) and 1-year survival rates between groups I and II. Comparing all subgroups for early and 1-year survival, we observed that patients who developed severe renal failure post-OLT (subgroups I-C and II-C) showed worse outcomes compared with other patients (subgroups I-A, I-B, II-A, and II-B), respectively 95.29% versus 69.69% and 86.95% versus 41.66% for early and 1-year survivals (P < .001). In conclusion, our findings suggested that patients who developed severe renal failure post-OLT, independent of pretransplant renal function, showed worse outcomes.

Analysis of Model for End-Stage Liver Disease (MELD) score in a liver transplantation waiting list.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) was introduced in 1999 to quantify the 3-month prognosis of cirrhotic patients after a transjugular intrahepatic portosystemic shunt (TIPS). Because of the imbalance between organ donors and patients on the waiting list, the MELD was adopted by the United States in 2002 to allocate liver grafts for transplantation. Preliminary results have indicated a reduction in waiting list deaths and an increase in transplantation rates for candidates. Seeking to find a new model to predict death on the waiting list and after liver transplantation, retrospective studies have examined MELD scores in waiting list patients. The aim of this study was to analyze the MELD scores of patients on the liver waiting list for comparisons between transplanted patients. PATIENTS AND METHODS: A retrospective study was performed analyzing 131 registrations of 127 orthotopic liver transplant (OLT) patients (4 underwent retransplantation) grafted between November 2000 and January 2006, excluding 24 patients: 2 had urgent retransplantations due to hepatic artery thrombosis and 22 had incomplete data. These patients were divided into 3 groups: group I (transplanted patients)-53 patients underwent 55 OLT; group II-29 patients who died on the waiting list; group III-patients on the waiting list including 23 patients still waiting as of the date of the study. RESULTS: The main indication for OLT was hepatitis C virus cirrhosis (50.50%), followed by alcoholic liver cirrhosis (23.30%), cryptogenic cirrhosis (12.60%), autoimmune hepatitis (5.80%), hepatitis B virus cirrhosis (4.85%), and primary biliary cirrhosis (2.91%). Group I: MELD score 15.62 (range, 6-39) on admission to the list, and 18.87 (range, 7-39) at transplantation. The mean waiting time for OLT was 478.39 days (range, 2-1270 days). The 38 patients who survived underwent 39 OLT (1 retransplantation). The MELD score at entrance to the list was 14.62 (range, 7-30) and at transplantation, 17.70 (range, 7-39). The mean time between admission to the list and transplantation was 505.37 days (range, 6-1270 days). The 15 patients who died had received 16 OLT (1 retransplantation). Their MELD scores were 17.80 (range, 6-39) and 21.81 (range, 9-39) at admission to the list and at transplantation, respectively, with a mean time on the waiting list of 417.93 days (range, 2-872 days). Group II: 29 patients died before OLT, at a mean age of 52.60 years (range, 22-67 years). Their MELD score was 19.24 (range, 7-45), and the interval between admission to the waiting list and death was 249.55 days (range, 3-1247 days). Group III: 23 patients still active on the OLT waiting list at the time of study displayed a mean MELD score of 13.65 (range, 6-28) and 354.30 days (range, 2-905 days) waiting until the moment. In conclusion, MELD score at the time of admission to the waiting list was higher among those patients who died either awaiting a liver graft (19.24) or after OLT (17.80) compared with those who survived after OLT (14.60) or are still awaiting OLT (13.65).

Correlation between graft arterial anatomy and biliary complications after liver transplantation.

Knowledge of the arterial vascular anatomy of the liver is important for orthotopic liver transplantation (OLT) because the lack of an adequate arterial blood supply results in biliary and parenchymal complications or graft loss. A number of reports have shown a relationship between aberrations of graft arteries and an increased incidence of early or late complications. Recent studies suggest no differences unless multiple anastomoses are required. The aim of this study was to report the incidence of aberrant hepatic arterial anatomy and its impact on vascular and biliary complications. We retrospectively reviewed data of 90 OLT performed on 82 patients, including 4 who underwent retransplantation from March 2003 to March 2006. The means recipient age was 52.47 years and 49 were men. The main caval vein reconstruction technique was piggyback (n = 55; 61.2%). The biliary reconstruction was performed by an end-to-end choledocho-choledocho anastomosis in 83 cases (92.3%) with choledocho-jejunal anastomosis (Roux-in-Y) in 7 cases (7.7%). Aberrant arterial anatomy was noted in 20 liver grafts (22.2%), namely, accessory right hepatic artery (n = 6; 6.6%), accessory left (n = 10; 11%), both accessory right and left (n = 3; 3.3%), and hepatic common artery from mesenteric artery (n = 1; 1.1%). Among the transplantations of grafts with aberrant arterial anatomy, 2 cases (10%) developed hepatic artery thrombosis (HAT) and 4 (20%) biliary complications. The rate of HAT and biliary complications among grafts with normal arterial anatomy was 3 and 8 cases (4.2% and 11.42%), respectively. Despite a greater number of complications among OLT with aberrant arterial anatomy, the Fisher test showed no significant relationship between HAT or biliary complications and aberrant arterial anatomy.

Donor liver dysfunction: application of a new scoring system to identify the marginal donor.

Livers from marginal donors are increasingly used for transplantation due to the shortage of donor organs. The definition of a marginal donor remains unclear; prediction of organ function is a challenge. In the literature the use of steatotic livers has been associated with poor liver function or even primary dysfunction of the allograft. Tekin et al created a scoring system that classifies a donor as marginal or nonmarginal, using a mathematical model based on donor age and steatosis degree. The aims of this study were to apply the Tekin method to identify marginal and nonmarginal donors and evaluate the influence of the cold ischemia time (CIT) on allograft evolution. We retrospectively reviewed deceased donor liver transplantations performed from October 1995 to March 2006, namely, 177 adult liver transplantations in 163 patients. Fifty-five were excluded due to retransplantation (14) or insufficient data (41). Donor age and macrovesicular steatosis were evaluated according to the mathematical formula proposed by Tekin et al, classifying the donors as marginal versus nonmarginal. The authors also analyzed the CIT, 3-month mortality, and development of primary nonfunction or primary dysfunction. The median donor age was 38.9 years (range, 6-71). The postreperfusion biopsy specimen showed moderate to intense steatosis (>30%) in 14.75% of specimens, with no steatosis or mild steatosis in 85.25%. Sixty-one grafts (50%) developed primary graft dysfunction (PGD): 10 grafts, with primary nonfunction (PNF); and 51 with initial poor function (IPF). Using the criteria provided by Tekin et al, we obtained 41 marginal and 81 nonmarginal allografts. The marginal group showed 61.9% PGD, compared with 59.2% of PGD by the nonmarginal group. The CIT was greater than 12 hours in 5 marginal group transplants and 4 PGD cases (80%). Of the nonmarginal allografts, the CIT was greater than 12 hours in 29.6%, with 75% PGD. The 3-month graft survival rate was 80% in the marginal group with ischemia time more than 12 hours: 86.1% of the same group when CIT was less than 12 hours, and 82.7% in the nonmarginal group. In contrast, when we analyzed the occurrence of allograft dysfunction, the 3-month mortality rate was 34% among, grafts with dysfunction, whereas, in those without initial dysfunction, it was 4.1%. In conclusion, the score suggested by Tekin et al that classifies the donors as ideal (nonmarginal) or marginal was not able to predict initial primary dysfunction.

Results of urgent liver retransplantation in the state of São Paulo, Brazil.

The treatment of end-stage liver disease includes transplantation as a life-saving procedure although it has serious complications of hepatic artery thrombosis, liver dysfunction, or primary nonfunction, which frequently lead to the need for retransplantation. According to various reports, the incidence of retransplantation is around 10%. Given the critical organ shortage, the chance for a second transplant remains a controversial discussion in medical, ethical, and economic grounds because patient and graft survival rates after retransplantation are lower than those for primary transplantations. We retrospectively reviewed all of the urgent liver retransplants from October 2001 to February 2005 (52 months) by analyzing the number of retransplants, blood group, time between first and second liver transplantation, age, sex, and mortality. Data were obtained from the Transplantation System, State of Sao Paulo Health Secretariat. Among 1252 liver transplants performed during this period, 98 (7.82%) were urgent retransplantations. The primary procedure employed 955 (76.28%) deceased donors and 297 (23.72%) living donors. All 98 retransplants were performed using an organ from the pool of deceased donors. The retransplant rate was acceptable according to the literature, although we observed high rates of early mortality (<60 days), leading to a discussion of which patients had a better chance of survival and the best time to perform the second transplantation to use this scarce and precious resource in the best possible way.

Apolipoprotein and lipid abnormalities in chronic liver failure

Total serum lipids, as well as apolipoproteins A-I (apo A-I) and B (apo B), were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36 percent, 24 percent and 46 percent, respectively (P<0.001). Apolipoproteins A-I and B were also reduced by 26 percent and 25 percent, respectively (P<0.001). However, the reduction of HDL cholesterol (HDLc) was more pronounced than that of apo A-I and HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05). We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver.

Apolipoprotein and lipid abnormalities in chronic liver failure.

Total serum lipids, as well as apolipoproteins A-I (apo A-I) and B (apo B), were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P < 0.001). Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P < 0.001). However, the reduction of HDL cholesterol (HDLc) was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P < 0.05). We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver.

[Bacterial endocarditis in patients over 60 years of age]. / Endocarditis bacteriana en pacientes mayores de 60 años.

Bacterial endocarditis (BE) is a disease difficult to diagnose and with poor prognosis in older people. A total of 76 episodes of this disease occurring in 73 patients were studied with particular attention to clinical manifestation, underlying heart disease, etiological germs, hospitalary mortality and prognosis within 6 months from diagnosis. All patients were 60 years old or older. Mean age was 72 +/- 7 years and male/female relation 1.7/1 Fever and heart murmur were present in 93% and 89% of patients, respectively; 33% of patients complained of vertebral or paravertebral pain which can be an early symptom of this disease. BE was suspected in 47% of patients at admission. Hospitalary mortality was 33% and increased to 47% within 6 months. The mean age of survivors was 71.7 +/- 7 years, versus 73.9 +/- 6 in the deceased (p = 0.08). Lack of suspicion of BE at admission was related with increased mortality (p = 0.04). The germ more frequently isolated was Streptococcus (73%). 53% of patients had some underlying heart disease. Aortic valve was involved in 50% and mitral valve in 21% of the cases. Of all the patients that in retrospect would have had indication of surgery (n = 25) 9 patients were operated, 6 during the first admission with a mortality of 17%. In those patients who were not operated, the mortality was 100% (16/16), making this difference statistically significant, p less than 0.001.

Endocarditis bacteriana en pacientes mayores de 60 años / Bacterial endocarditis in patients older than 60 years

La endocarditis bacteriana es una enfermedad de dificil diagnóstico y mal prognóstico en el paciente anciano. Con el objeto de establecer las características clínicas más salientes, valvulopatía subyacente y gérmenes causales, se estudiaron 76 episodios de endocarditis bacteriana en 73 pacientes mayores de 60 años. La edad promedio fue 72 ñ 7 años y la relación hombre-mujer de 1,7/1. La fiebre y el soplo cardiaco estuvieron presentes en el 93% y respectivamente. Un 33% de los pacientes presentaron dolor vertebral o paravertebral, que puede ser un síntoma precoz de la enfermedad. La sospecha diagnóstica al ingreso fue de 47%. La mortalidad hospitalaria fue de 33% y llegó, dentro de los seismeses, al 47%. La edad promedio de los vivos fue 71,1 ñ 7 años versus 73,9 ñ 6 en los muertos (p=0,08). La falta de sospecha diagnóstica la ingreso estuvo asociada estadísticamente a una mayor mortalidad (p = 0,04). El gérmen más frecuente fue el estreptococo (73%). El 53% de los pacientes presentaban valvulopatía previa. El compromiso valvular aórtico se manifestó en el 50% y mitral en 21%. De los pacientes que retrospectivamente hubieron tenido indicación quirúrgica (n = 25), 9 fueron operados (6 durante hospitalización con una mortalidad 1/6 (17%)) y en aquellos que no se sometieron a la cirugía la mortalidad fue del 100% (16/16). Esta diferencia resultó ser significativa (p < 0,001)

Endocarditis bacteriana en pacientes mayores de 60 años / Bacterial endocarditis in patients older than 60 years

La endocarditis bacteriana es una enfermedad de dificil diagnóstico y mal prognóstico en el paciente anciano. Con el objeto de establecer las características clínicas más salientes, valvulopatía subyacente y gérmenes causales, se estudiaron 76 episodios de endocarditis bacteriana en 73 pacientes mayores de 60 años. La edad promedio fue 72 ñ 7 años y la relación hombre-mujer de 1,7/1. La fiebre y el soplo cardiaco estuvieron presentes en el 93% y respectivamente. Un 33% de los pacientes presentaron dolor vertebral o paravertebral, que puede ser un síntoma precoz de la enfermedad. La sospecha diagnóstica al ingreso fue de 47%. La mortalidad hospitalaria fue de 33% y llegó, dentro de los seismeses, al 47%. La edad promedio de los vivos fue 71,1 ñ 7 años versus 73,9 ñ 6 en los muertos (p=0,08). La falta de sospecha diagnóstica la ingreso estuvo asociada estadísticamente a una mayor mortalidad (p = 0,04). El gérmen más frecuente fue el estreptococo (73%). El 53% de los pacientes presentaban valvulopatía previa. El compromiso valvular aórtico se manifestó en el 50% y mitral en 21%. De los pacientes que retrospectivamente hubieron tenido indicación quirúrgica (n = 25), 9 fueron operados (6 durante hospitalización con una mortalidad 1/6 (17%)) y en aquellos que no se sometieron a la cirugía la mortalidad fue del 100% (16/16). Esta diferencia resultó ser significativa (p < 0,001) (AU)

Endocarditis bacteriana en pacientes mayores de 60 años. / [Bacterial endocarditis in patients over 60 years of age]

Bacterial endocarditis (BE) is a disease difficult to diagnose and with poor prognosis in older people. A total of 76 episodes of this disease occurring in 73 patients were studied with particular attention to clinical manifestation, underlying heart disease, etiological germs, hospitalary mortality and prognosis within 6 months from diagnosis. All patients were 60 years old or older. Mean age was 72 +/- 7 years and male/female relation 1.7/1 Fever and heart murmur were present in 93

and 89

of patients, respectively; 33

of patients complained of vertebral or paravertebral pain which can be an early symptom of this disease. BE was suspected in 47

of patients at admission. Hospitalary mortality was 33

and increased to 47

within 6 months. The mean age of survivors was 71.7 +/- 7 years, versus 73.9 +/- 6 in the deceased (p = 0.08). Lack of suspicion of BE at admission was related with increased mortality (p = 0.04). The germ more frequently isolated was Streptococcus (73

). 53

of patients had some underlying heart disease. Aortic valve was involved in 50

and mitral valve in 21

of the cases. Of all the patients that in retrospect would have had indication of surgery (n = 25) 9 patients were operated, 6 during the first admission with a mortality of 17

. In those patients who were not operated, the mortality was 100

(16/16), making this difference statistically significant, p less than 0.001.