[Analysis of the organ allocation system for liver transplantation in Chile]. / Análisis del sistema de alistamiento y priorización para trasplante hepático de adultos en Chile.

BACKGROUND: In Chile, organ allocation for liver transplantation (LT) in adults is prioritized according to the MELD-Na score. Exceptions such as Hepatocellular Carcinoma (HCC) and other non-HCC exceptions receive a score called Operational MELD score. AIM: To evaluate the effectiveness of the MELD-Na score and the operational MELD score as a prioritization system for LT in Chile. MATERIAL AND METHODS: Retrospective analysis of the waiting list (WL) of adult candidates (≥ 15 years) for elective LT in Chile from 2011 to 2017. The probability of leaving the WL, defined by death or contraindication for LT was compared in three groups: 1) Cirrhotic patients prioritized according to their real MELD-Na score (CPM), 2) HCC and 3) other non-HCC exceptions. RESULTS: We analyzed 730 candidates for LT, with a median age of 57 years, 431 (56%) were men. In the study period, 352 LT were performed (48%). The annual exit rate was significantly higher in the CPM group (45.5%) compared to HCC (33.1%) and non-HCC (29.3%), (p < 0.001). Post LT survival was 86% at 1 year and 85% at 5 years, without significant differences between groups. In the CPM group, post-transplant survival was significantly lower (p < 0.05) in patients with MELD-Na ≥ 30 at transplant (81% per year) compared to patients with patients with MELD-Na < 30 (91% per year). CONCLUSIONS: MELD-Na score can discriminate very well patients who have a higher risk of death in the short and medium term. However, the assignment of operational scores for situations of exception produces inequities in the allocation of organs for LT and must therefore be carefully adjusted.

Prioritization for liver transplantation using the MELD score in Chile: Inequities generated by MELD exceptions.: A collaboration between the Chilean Liver Transplant Programs, the Public Health Institute and the National Transplant Coordinator.

INTRODUCTION AND AIM: The MELD score has been established as an efficient and rigorous prioritization system for liver transplant (LT). Our study aimed to evaluate the effectiveness of the MELD score as a system for prioritization for LT, in terms of decreasing the dropout rate in the waiting list and maintaining an adequate survival post-LT in Chile. MATERIALS AND METHODS: We analyzed the Chilean Public Health Institute liver transplant registry of candidates listed from October 15th 2011 to December 31st 2014. We included adult candidates (>15 years old) listed for elective cadaveric LT with a MELD score of 15 or higher. Statistical analysis included survival curves (Kaplan-Meier), log-rank statistics and multivariate logistic regression. RESULTS: 420 candidates were analyzed. Mean age was 53.6±11.8 years, and 244 were men (58%). Causes of LT included: Liver cirrhosis without exceptions (HC) 177 (66.4%); hepatocellular carcinoma (HCC) 111 (26.4%); cirrhosis with non-HCC exceptions 102 (24.3%) and non-cirrhotic candidates 30 (7.2%). LT rate was 43.2%. The dropout rate was 37.6% at 1-year. Even though the LT rate was higher, the annual dropout rate was significantly higher in cirrhotic candidates (without exceptions) compared with cirrhotics with HCC, and non-HCC exceptions plus non-cirrhotic candidates (47.9%; 37.2% and 24.2%, respectively, with p=0.004). Post-LT survival was 84% per year, with no significant differences between the three groups (p=0.95). CONCLUSION: Prioritization for LT using the MELD score system has not decreased the dropout rate in Chile (persistent low donor's rate). Exceptions generate inequities in dropout rate, disadvantaging patients without exceptions.

[Liver transplantation in a patient with human immunodeficiency virus (HIV). Case report]. / Trasplante hepático exitoso en un paciente portador del Virus de la Inmunodeficiencia Humana (VIH).

Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.

Validation of the Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Chilean-Hispanic Patients.

INTRODUCTION AND AIM: In 2008 the International autoimmune hepatitis (AIH) Group proposed the simplified diagnostic criteria for this disease. The original cohort study was performed in 11 international centers, but validation studies are scarce in Latin-America. The aim of this study is validate these criteria in Hispanic patients. MATERIAL AND METHODS: A retrospective cohort of patients undergoing percutaneous liver biopsy and follow-up of at least 12 months was recruited from a Chilean University hospital. Patients with previous immunosuppressive therapy and liver transplant recipients were excluded. The diagnostic accuracy was analyzed using as gold standard the clinical course during long-term follow-up. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and area under the ROC curve (AUROC) were calculated. RESULTS: Four hundred eighty one patients were evaluated, 294 were included. 218 (74.15%) were female, mean age 48.5 (± 12.3) years, mean follow-up 34 (± 18) months. 66 patients had AIH or overlap syndrome (22.45%), 96 (32.65%) non-alcoholic steatohepatitis, 40 (13.61%) primary biliary cholangitis, 31 (10.54%) hepatitis C, 8 (2.72%) hepatitis B, 53 (18.02%) other etiologies. The AUROC for AIH simplified criteria was 0.976. Using a cutoff ≥ 6 and ≥ 7 points, the sensitivity was 86.4% and 54.6%; specificity, 98.7% and 99.6%; PPV, 95% and 97.3%; and NPV, 96.2% and 88.6%, respectively. CONCLUSION: Simplified criteria for the diagnosis of AIH have a high accuracy in our Chilean-Hispanic cohort. The female gender is strongly associated to AIH and could help in difficult cases. Further studies with a prospective design are necessary to confirm these observations.

Conversion to mycophenolate mofetil monotherapy in liver recipients: Calcineurin inhibitor levels are key.

 The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

Portal hypertension and acute liver failure as uncommon manifestations of primary amyloidosis.

Hepatic involvement in primary amyloidosis is an infrequent challenge to the hepatologist. Although usually asymptomatic, amyloidosis may have unusual manifestations. Liver biopsy is an important diagnostic tool for this condition. Herein, we report three cases of portal hypertension related to primary hepatic amyloidosis, one of them in the form of acute liver failure.

Should we undertake surveillance for HCC in patients with MAFLD?

Over the last decade, metabolic-associated fatty liver disease (MAFLD) has become an important public health issue worldwide. In many countries, MAFLD has become the most common cause of chronic liver disease. On the contrary, hepatocellular carcinoma (HCC) mortality is rising. Liver tumors have become the third cause of cancer mortality worldwide. HCC is the most frequent liver tumor. While the burden of HCC related to viral hepatitis is declining, the prevalence of MAFLD-related HCC is rising rapidly. Classical screening criteria for HCC consider cirrhotic, advanced fibrosis, and viral hepatitis patients. Metabolic syndrome with liver involvement or MAFLD is associated with a higher risk of HCC development, even in the absence of cirrhosis. The question about the cost effectiveness of surveillance for HCC in MAFLD is yet not fully answered. There are no guidelines that address the question of when to start or how to define the population who can benefit of surveillance for HCC in MAFLD patients. This review aims to revise the evidence of HCC development in MAFLD. It hopes to be a step closer to defining screening criteria for HCC in MAFLD.

Transjugular intrahepatic portosystemic shunt in patients with hepatocellular carcinoma: A systematic review.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension (PH)-related complications without worsening liver function, and increase overall survival. Data on the efficacy and safety of TIPS to treat PH complications in HCC patients, as well as the HCC treatment response, were evaluated. METHODS: Studies reporting efficacy in controlling bleeding/ascites or response to HCC therapy, safety, and survival in patients with HCC and TIPS were searched systematically on PubMed and Embase. An extraction of articles using predefined data fields and quality indicators was used. RESULTS: We selected 19 studies and found 937 patients treated for ascites/bleeding and 177 evaluating HCC treatment response. Over half were under 5 cm and solitary lesions, and most studies included tumours with portal vein thrombosis. Regarding PH studies, TIPS resolved bleeding/ascites in >60% of patients, more effective for bleeding. There were no lethal complications reported and procedural bleeding occurred in <5%. Hepatic encephalopathy occurred in 15%-30% within three months. In the HCC treatment-response studies, major complication rates were low with no mortality. In the studies that evaluated the response to transarterial chemoembolization, complete response rate of patients with TIPS varied from 16% to 75%. Liver transplantation rate varied from 8% to 80%, with >40% rate in half of the studies. CONCLUSIONS: In the published studies, TIPS is effective in treating PH complications in patients with HCC. Prospective studies on TIPS placement in patients with HCC are urgently needed to evaluate the efficacy and safety of TIPS in this setting.

Análisis del sistema de alistamiento y priorización para trasplante hepático de adultos en Chile

Background: In Chile, organ allocation for liver transplantation (LT) in adults is prioritized according to the MELD-Na score. Exceptions such as Hepatocellular Carcinoma (HCC) and other non-HCC exceptions receive a score called Operational MELD score. Aim: To evaluate the effectiveness of the MELD-Na score and the operational MELD score as a prioritization system for LT in Chile. Material and Methods: Retrospective analysis of the waiting list (WL) of adult candidates (≥ 15 years) for elective LT in Chile from 2011 to 2017. The probability of leaving the WL, defined by death or contraindication for LT was compared in three groups: 1) Cirrhotic patients prioritized according to their real MELD-Na score (CPM), 2) HCC and 3) other non-HCC exceptions. Results: We analyzed 730 candidates for LT, with a median age of 57 years, 431 (56%) were men. In the study period, 352 LT were performed (48%). The annual exit rate was significantly higher in the CPM group (45.5%) compared to HCC (33.1%) and non-HCC (29.3%), (p < 0.001). Post LT survival was 86% at 1 year and 85% at 5 years, without significant differences between groups. In the CPM group, post-transplant survival was significantly lower (p < 0.05) in patients with MELD-Na ≥ 30 at transplant (81% per year) compared to patients with patients with MELD-Na < 30 (91% per year). Conclusions: MELD-Na score can discriminate very well patients who have a higher risk of death in the short and medium term. However, the assignment of operational scores for situations of exception produces inequities in the allocation of organs for LT and must therefore be carefully adjusted.

Trasplante hepático exitoso en un paciente portador del Virus de la Inmunodeficiencia Humana (VIH) / Liver transplantation in a patient with human immunodeficiency virus (HIV): case report

Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.

Conversion to Mycophenolate Mofetil Monotherapy in Liver Recipients: Calcineurin Inhibitor Levels are Key

Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

[Outcome of surgical treatment of liver metastasis from colorectal cancer]. / Resultados del tratamiento quirúrgico de las metástasis hepáticas por cáncer colorrectal.

BACKGROUND: Surgical resection is the only treatment associated with long-term cure in patients with liver metastasis from colorectal cancer, achieving a 30% to 40% five years survival. AIM: To evaluate the results of liver resection for metastatic colorectal cancer in our centre. PATIENTS AND METHODS: Retrospective study. Epidemiological, perioperative and follow up data of patients undergoing liver resection for metastatic colorectal cancer between January 1990 and July 2007 were assessed. We compared the results between two periods; period 1 (1990-1997) and period 2 (1998-2007). RESULTS: Sixty six patients aged 61+/- 12 years (46 males) underwent 75 resections. An anatomical excision was performed in 54 (72%) cases, a right hepatectomy in 18, an extended right hepatectomy in 11, a left hepatectomy in 1, and a segmentectomy in 24. In 24 (32%) patients the liver resection was simultaneous with the colorectal cancer resection. Operative time was 221+/-86 min. Hospital stay was 11+/-5 days. Postoperative morbidity was 35% and surgical mortality was 0%. Resection margin was free of tumor in 53 (80%) patients. Five years overall and hepatic disease-free survival was 38% and 23%, respectively. In period 2, more anatomical resections than in period 1 were performed (77% and 55%, respectively, p =0.04), without an increase in complications (35% and 34%, respectively; p =ns), but with a better five years survival (45% and 21 %, respectively, p =0.04). CONCLUSIONS: Five years survival for excision of liver metastatic colorectal cancer in our center is similar to that reported abroad. During the second period there has been a trend toward more extensive resections which was associated with a better survival, without an increase in complications or mortality .

[Accuracy of magnetic resonance cholangiopancreatography for the diagnosis of common bile duct stones]. / Rendimiento de la colangiografía por resonancia magnética en el diagnóstico de coledocolitiasis.

BACKGROUND: Magnetic resonance cholangiopancreatography MRCP) is a non-invasive diagnostic method for choledocholithiasis. AIM: To evaluate the results of MRCP in the diagnosis of choledocholithiasis. PATIENTS AND METHODS: Retrospective review of MRCP reports performed between October 2001 and December 2004. We included patients with suspected choledocholithiasis who were studied with MRCP and some other confirmatory test such as endoscopic retrograde cholangiopancreatography ERCP), surgical common bile duct exploration or transcystic colangiography TC). RESULTS: One hundred and twenty five patients aged 58+/-20 years 70 females) were included. In 54 patients 43%) we compared the results of MRCP with the findings of surgical common bile duct exploration or TC and in 71 57%) we did so with ERCP. MRCP suggested choledocholithiasis in 93 patients and in 32 it was negative. Eighty six 67%) patients had choledocholithiasis according to TC or ERCP, including 3 patients who had a negative MRCP. Therefore the sensibility was 97%, specificity 74% positive predictive value 89%, negative predictive value 90% and accuracy of MRCP was 90% for the diagnosis of choledocholithiasis. CONCLUSIONS: MRCP has a high accuracy for the diagnosis of choledocholithiasis.

Resultados del tratamiento quirúrgico de las metástasis hepáticas por cáncer colorrectal / Outcome of surgical treatment of liver metastasis from colorectal cancer

Background: Surgical resection is the only treatment associated with long-term cure in patients with liver metastasis from colorectal cancer, achieving a 30% to 40% five years survival. Aim: To evaluate the results of liver resection for metastatic colorectalcancer in our centre. Patients and methods: Retrospective study. Epidemiological, perioperative and follow up data of patients undergoing liver resection for metastatic colorectalcancer between January 1990 and July 2007 were assessed. We compared the results between two periods; period 1 (1990-1997) and period 2 (1998-2007). Results: Sixty six patients aged61±12 years (46 males) underwent 75 resections. An anatomical excision was performed in 54 (72%) cases, a right hepatectomy in 18, an extended right hepatectomy in 11, a left hepatectomy in 1, and a segmentectomy in 24. In 24 (32%) patients the liver resection wassimultaneous with the colorectal cancer resection. Operative time was 221±86 min. Hospital stay was 11±5 days. Postoperative morbidity was 35% and surgical mortality was 0%. Resectionmargin was free of tumor in 53 (80%) patients. Five years overall and hepatic disease-free survival was 38% and 23%, respectively. In period 2, more anatomical resections than in period1 were performed (77% and 55%, respectively, p =0.04), without an increase in complications (35% and 34%, respectively; p =ns), but with a better five years survival (45% and 21%, respectively, p =0.04). Conclusions: Five years survival for excision of liver metastatic colorectal cancer in our center is similar to that reported abroad. During the second period there has been a trend toward more extensive resections which was associated with a better survival, without an increase in complications or mortality.

Rendimiento de la colangiografía por resonancia magnética en el diagnóstico de coledocolitiasis / Accuracy of magnetic resonance cholangiopancreatography for the diagnosis of common bile duct stones

Magnetic resonance cholangiopancreatography MRCP) is a non-invasive diagnostic method for choledocholithiasis. Aim: To evaluate the results of MRCP in the diagnosis of choledocholithiasis. Patients and methods: Retrospective review of MRCP reports performed between October 2001 and December 2004. We included patients with suspected choledocholithiasis who were studied with MRCP and some other confirmatory test such as endoscopic retrograde cholangiopancreatography ERCP), surgical common bile duct exploration or transcystic colangiography TC). Results: One hundred and twenty five patients aged 58±20 years 70 females) were included. In 54 patients 43 percent) we compared the results of MRCP with the findings of surgical common bile duct exploration or TC and in 71 57 percent) we did so with ERCP. MRCP suggested choledocholithiasis in 93 patients and in 32 it was negative. Eighty six 67 percent) patients had choledocholithiasis according to TC or ERCP, including 3 patients who had a negative MRCP. Therefore the sensibility was 97 percent, specificity 74 percent positive predictive value 89 percent, negative predictive value 90 percent and accuracy of MRCP was 90 percent for the diagnosis of choledocholithiasis. Conclusions: MRCP has a high accuracy for the diagnosis of choledocholithiasis.

Subdiagnóstico de depresión en atención primaria, en pacientes del área sur-oriente de Santiago, 2006 / Depression underdiagnosis in the primary healthcare: a study of patient of south-western area of Santiago, during 2006

La depresión es altamente prevalente en Chile, sin embargo, muchos pacientes no son pesquisados por los médicos de atención primaria (MAP). El objetivo de esta estudio es analizarla concordancia entre el diagnóstico de depresión hecho por MAP, respecto a una entrevista clínica estructurada basada en criterios DSM-IV (Manual Diagnóstico y Estadístico de los Trastornos Mentales) para depresión, realizada en un centro de atención secundaria (CAS). Se estudiaron 174 pacientes (edad 57.6 15.1 años, 131 mujeres), derivados por diversas patologías distintas a la depresión, a un CAS, atendidos durante el último mes por MAP. Todos los pacientes fueron evaluados con la escala de ansiedad y depresión de Goldberg (E.A.D.G) y a los probables casos según el instrumento (puntaje 3, subescala depresión) se les realizó una entrevista clínica estructurada basada en criterios DSM-IV para depresión. Treinta y tres pacientes tenían diagnóstico de depresión hecho por MAP. Sin embargo, 103 pacientes (59.2 por ciento) tuvieron puntajes 3 en la E.A.D.G y 59 (33.9 por ciento) cumplieron criterios DSM-IV para depresión. La concordancia entre el diagnóstico de depresión hecho por MAP, respecto al diagnóstico según criterios DSM-IV, mediante el índice Kappa, fue 0.39 (acuerdo débil), existiendo coincidencia positiva sólo en 25 casos. Se observó baja concordancia entre el diagnóstico de depresión hecho por MAP y el realizado a través de una entrevista clínica estructurada, con importante subdiagnóstico, cercano al 60 por ciento. En forma adicional, la aplicación de un test de tamizaje, fue de utilidad para detectar casos previamente no diagnosticados.