Criteria For Orthotopic Liver Transplantation Research Articles

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria

Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N=214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein <400ng/mL before orthotopic liver transplantation, through locoregional therapies. Recurrence of hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for transplantation.

A 5-Year Overview of MELD X Liver Transplantation in a University Hospital in Brazil

Introduction: The MELD (Model for End-Stage Liver Disease) score was adopted as a new criteria for orthotopic liver transplantation (OLT) in 2006 in Brazil. We aimed to analyze the value of MELD as a predictor of survival after OLT. Methods: We analyzed the data from 329 liver transplants performed in the “Hospital das Clínicas” of the University of São Paulo School of Medicine from August 2006 to June 2010. In this period, we had 11 living donors liver transplants (LDLT), 6 split-liver transplants (SLT), 24 retransplants and 288 OLT. Patients were classified in two groups: Group I (MELD ≤ 25) and Group II (MELD > 25). Patients submitted to LDLT, SLT and re-transplant were not included. We analyzed the following data: age, MELD, cold ischemia time (CIT) and warm ischemia time (WIT), and mortality rate(MR). Results: Group I: 89 patients and Group II: 199 patients. Patients in Group II had a higher mortality rate (31,66%, 63/199) than patients in Group I (24,72%, 22/89). However, patients in Group I had a higher re-transplantation rate (7,86%, 7/89) than patients in Group II (5,52%, 11/199). CIT, WIT and patient age were similar in both groups. Conclusions: Although Group I had the highest retransplantation rate, patients in Group II had a higher mortality rate after the procedure. Therefore patients with MELD above 25 or higher have fewer chance of long-term survival after OLT. MELD score can be used as a predictor factor of good results.

Predictive Index for Tumor Recurrence after Liver Transplantation for Locally Advanced Intrahepatic and Hilar Cholangiocarcinoma

Current criteria for orthotopic liver transplantation (OLT) for cholangiocarcinoma (CCA) remain restricted to early stage and small hilar tumors, excluding patients with locally advanced intrahepatic and hilar CCA for potential cure. The present study was undertaken to define a prognostic scoring system for risk stratification of patients with intrahepatic and hilar CCA who might benefit from OLT and to allow expansion of current OLT criteria. We conducted a retrospective review of 40 patients who underwent OLT for locally advanced intrahepatic and hilar CCA at our center between February 1985 and June 2010. Median follow-up was 3 years. Independent risk factors for tumor recurrence after OLT were identified using the Cox model and were assigned risk score points. Points were summed and assigned to predictive index categories: 0 to 3 for low risk, 4 to 7 for intermediate risk, and 8 to 15 for high risk. Seven multivariate factors predictive for tumor recurrence included multifocal tumor, perineural invasion, infiltrative growth pattern, lack of neoadjuvant and adjuvant therapy, history of primary sclerosing cholangitis, hilar tumors, and lymphovascular invasion. The 5-year tumor recurrence-free patient survival was significantly higher in low-risk (78%) compared with intermediate- (19%) and high-risk (0%) groups (p < 0.001); survival benefit was also seen in intermediate- compared with high-risk groups. This model was highly predictive of long-term outcomes after OLT for locally advanced intrahepatic and hilar CCA and can be applied clinically for risk stratification of patients considered for OLT. Long-term disease recurrence-free survival was excellent in low-risk and acceptable in intermediate-risk groups, justifying the expansion of liver transplant criteria for treatment of this challenging malignancy.

Liver Resection Associated With Mini Porto-Caval Shunt as Salvage Treatment in Patients With Progression of Hepatocellular Carcinoma Before Liver Transplantation: A Case Report

Tumor progression before orthotopic liver transplantation (OLT) is the main cause of dropouts from waiting lists among patients with hepatocellular carcinoma (HCC). Performing a porto-caval shunt (PCS) before parenchymal liver transection has the potential to allow an extended hepatectomy in patients with decompensated liver cirrhosis, reducing portal hyperflow and therefore the sinusoidal shear-stress on the remnant liver. We report the case of a 59-year-old man affected by hepatitis C virus (HCV)-related decompensated liver cirrhosis (Child Pugh score presentation, C-10; Model for End Stage Liver Disease score, 18) and HCC (2 lesions of 2 and 2.8 cm). The patient began the evaluation to join the OLT waiting list, but, in the 3 months required to complete the evaluation, he developed tumor progression: 3 HCC lesions, the largest 1 with a diameter of about 4.4 cm. These findings excluded transplantation criteria and the patient was referred to our center. After appropriate preoperative studies, the patient underwent a major liver resection (trisegmentectomy) after side-to-side PCS by interposition of an iliac vein graft from a cadaveric donor. The patient overcame the worsened severity of cirrhosis. After 6 months of follow-up, he developed 2 other HCC nodules. He was then included on the waiting list at our center, undergoing OLT from a cadaveric donor at 8 months after salvage treatment. At 36 months after OLT, he is alive and free from HCC recurrence. Associating a partial side-to-side PCS with hepatic resection may represent a potential salvage therapy for patients with decompensated cirrhosis and HCC progression beyond listing criteria for OLT.

Clinical implications of hepatitis A virus ribonucleic acid detection and genotyping in acute liver failure in children in Argentina

To investigate the detection of hepatitis A virus ribonucleic acid in patients with acute liver failure and to assess if the results have any clinical implications for the evolution of acute liver failure in children. Hepatitis A infection, a vaccine-preventable disease, is an important cause of acute liver failure in children in Argentina. Universal vaccination in 1-yr-old children was implemented in June 2005. Observational study in which patients were divided into Group 1 consisting of positive hepatitis A virus ribonucleic acid and Group 2 consisting of negative hepatitis A virus ribonucleic acid. Pediatric intensive care unit in National Pediatric Hospital "Dr. J. P. Garrahan," Buenos Aires, Argentina. Thirty-three patients with the diagnosis of acute liver failure secondary to hepatitis A virus infection and admitted to the Garrahan Pediatric Hospital between September 2003 and September 2005 were enrolled in the study. Twenty of these children were admitted to the pediatric intensive care unit. None. Samples for total ribonucleic acid detection and genotyping were obtained from serum and/or stools on admission. We found positive hepatitis A virus ribonucleic acid in 13 patients and negative hepatitis A virus ribonucleic acid in 20 patients. The following clinical variables were evaluated: time of evolution, hospital stay, admission to the pediatric intensive care unit, pediatric intensive care unit stay, time on mechanical ventilation, criteria for orthotopic liver transplantation, and mortality. Characterization of the isolates did not reveal differences related to genotype; all cases were IA. No statistical significance was found as to the variables. However, positive hepatitis A virus ribonucleic acid showed lower percentages of pediatric intensive care unit admissions, criteria for orthotopic liver transplantation, number of orthotopic liver transplantation, and mortality than the group of patients with negative hepatitis A virus ribonucleic acid. Hepatitis A virus genotyping studies did not show any particularities, all cases were IA and, thus, apparent associations between genotype and the clinical presentation of acute liver failure could not be found.

Beyond the milan criteria: Is it the right time?

Beyond the milan criteria: Is it the right time?

Expanded criteria for liver transplantation in patients with hepatocellular carcinoma

Following the seminal publication by the group from Milan, Italy using a restrictive set of criteria for orthotopic liver transplantation in patients with hepatocellular carcinoma to limit the risk for tumor recurrence, excellent 5-year patient survival of greater than 70% after liver transplantation has been reported from many centers using criteria similar to or slightly exceeding the Milan criteria (single lesion of </=5 cm, or 2-3 lesions of </=3 cm). The growing experience and success of orthotopic liver transplantation for HCC have also fueled controversies related to expansion of conventional criteria for cadaveric or living-donor liver transplantation based on tumor size and number. The limitations of imaging studies, exemplified by tumor under-staging in up to 25% of patients,have been a major concern for liberalizing the current criteria for liver transplantation. The University of California, San Francisco criteria (single lesion of </=6.5 cm, or 2-3 lesions of </=4.5 cm with a total tumor diameter </=8 cm) have been independently tested in several studies, and undergone prospective evaluation based on preoperative imaging. This article provides an in-depth review of published data on expansion of current criteria for liver transplantation.

Response to trans-arterial chemoembolization prior to orthotopic liver transplantation or hepatic resection in patients with hepatocellular carcinoma

15114 Background: Trans-arterial chemoembolization (TACE) is often used as pre-operative therapy for patients with hepatocellular carcinoma (HCC) prior to orthotopic liver transplantation (OLT) or hepatic resection (HR). However, the benefit of response to TACE on overall survival (OS) and progression free survival (PFS) remains unclear. Methods: Complete data was available for 24 patients with HCC who underwent TACE prior to either OLT or HR from 1998–2006. Known prognostic factors including tumor size, histology, number of nodules, Child-Pugh class, Okuda stage, MELD score, CLIP score were recorded. Clinical features before and after TACE were identified and tested by univariate analysis. Results: The mean patient age was age 51 years (range 31–65). Underlying diagnoses included: HBV (17%), HCV (54%), alcohol abuse (63%), cryptogenic (8%), nonalcoholic steotohepatitis (4%). The mean maximum tumor diameter was 6.2 cm (range 1.6–16.1 cm), with 13 tumors (54%) measuring &gt;5 cm. The median number of lesions were 2 (range 1 - 7). The Milan criteria was met in 15 patients (63%). Eighteen subjects underwent OLT, while 6 had HR. Median PFS was 35 months (m) (95% C.I. 17–58 m). One- and three-year OS were 95.8% and 73%, respectively. TACE was performed within a mean time of 2.5 months from diagnosis (range 0.5–9 m). Post-TACE, eleven subjects demonstrated a biologic response, defined as decrease in serum alfa-fetoprotein (AFP) by &gt;50%, or reduction in AFP level to &lt;10 ng/mL. However, biologic response did not predict for improved PFS (p =0.41). Additionally, nine patients had a radiographic response to TACE as measured by RECIST criteria, but this also did not predict for improved PFS (p = 0.79). Only tumor size &gt;5 cm (p = 0.04) and CLIP score (p = 0.01) were found to be independent predictors of improved PFS. Conclusions: Neither radiographic nor biologic responses to TACE appear to serve as selection criteria for OLT or HR. Those patients who fail to demonstrate response to TACE should not necessarily be denied surgical therapy. Larger, prospective trials are needed to better evaluate which patients will benefit most from TACE prior to OLT or HR. No significant financial relationships to disclose.

Results of liver transplantation: With or without milan criteria?

Results of liver transplantation: With or without milan criteria?

A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation

In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco-regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and < or =8 cm, 2 or 3 lesions at least 1 >3 cm but < or =5 cm with total tumor diameter of < or =8 cm, or 4 or 5 nodules all < or =3 cm with total tumor diameter < or =8 cm. Patients were eligible for living-donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria.13 A minimum follow-up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow-up of 16 months after OLT. The Kaplan-Meier intention-to-treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow-up is needed to further access the risk of HCC recurrence after OLT.

Radiochemotherapy and Transplantation Allow Long‐Term Survival For Nonresectable Hilar Cholangiocarcinoma

Results of liver transplantation in the treatment of cholangiocarcinoma have been poor as a result of the high incidence of locoregional dissemination and tumor recurrence. This study evaluates the effect of neoadjuvant chemoradiation therapy combined with orthotopic liver transplantation in a carefully selected group of patients with hilar cholangiocarcinoma. Seventeen patients were included in the study. The neoadjuvant protocol included 6,000 cgy biliary brachy-therapy delivered through percutaneous transhepatic catheters and intravenous infusion of 5-fluorouracil (300mg/m2/day) until transplantation. Five of the 17 patients demonstrated tumor progression precluding transplantation. One patient died of sepsis on the waiting list. Eleven patients underwent liver transplantation, a median of 3.4 months (range = 1-26 months) after diagnosis. Five of the 11 (45%) are alive without evidence of tumor recurrence with a median follow up of 7.5 years (range = 2.8-14.5 years). Six deaths occurred in the transplanted patients. Tumor recurrence was responsible for two deaths at 10 and 18months, respectively, after transplantation. Three mortalities resulted from bacterial or fungal peritonitis and sepsis. One patient underwent re-transplantation for chronic rejection and died from graft failure resulting from hepatic artery thrombosis 16 months after diagnosis without evidence of tumor recurrence. Complications of transhepatic catheter placement included bile duct perforation (n = 4) and biliary-portal vein fistula (n = 1). All these patients died of tumor recurrence or sepsis. Cholangiocarcinoma should not be considered an absolute exclusion criteria for orthotopic liver transplantation. Long-term, tumor-free survival was achieved in 45% of the transplanted patients. Complications of biliary catheter placement for brachytherapy were associated with poor outcome.