Julio Trentadue

MELD is superior to King's college and Clichy's criteria to assess prognosis in fulminant hepatic failure

Assessment of prognosis in fulminant hepatic failure (FHF) is essential for the need and appropriate timing of orthotopic liver transplantation (OLT). In this study we investigated the prognostic efficacy of Kings College criteria, Clichys criteria, Model for End‐Stage Liver Disease (MELD), and Pediatric End‐Stage Liver Disease (PELD) in 120 consecutive patients with FHF. Survival with medical therapy (18%), death without OLT (15%), and receipt of a liver transplant were similar in adults (n = 64) and children (n = 56). MELD scores were significantly higher in patients who died compared to those who survived without OLT, both in adults (38 ± 7 vs. 26 ± 7, P = 0.0003) and children (39 ± 7 vs. 23 ± 6, P = 0.0004). Using logistic regression analysis in this cohort of patients, concordance statistics were significantly higher for MELD (0.95) and PELD (0.99) when compared to Kings College (0.74) and Clichys criteria (0.68). When data was analyzed in a Cox model including patients receiving transplants and censoring the time from admission, the concordance statistic for MELD (0.77) and PELD (0.79) remained significantly higher than that of Kings College criteria but not higher than that of Clichys criteria. In conclusion, this study is the first to show that MELD and PELD are superior to Kings College and Clichys criteria to assess prognosis in FHF. However, because data was generated from a single center and included a rather low number of patients who survived or died without OLT, further confirmation of our findings is required. Liver Transpl 13:822–828, 2007.

Long Term Outcomes after Intestinal Transplantation from a Single South-American Center, Lessons Learned

Introduction In many countries, intestinal failure patients (IF pts) had the only option of parenteral nutrition (PN) as available treatment until intestinal transplantation (ITx) evolves as part of a multidisciplinary team. We would like to report the long-term outcomes of a series of ITx performed in children and adults at a single center, 9 years after its creation. Material and Methods retrospective analysis of all consecutive ITx performed between May 2006 and Oct 2017. Diagnoses, pre ITx mean time on PN, indication for ITx, time on the waiting list (WL), type of ITx, mean total ischemia time (TIT), and warm ischemia time (WIT), time for PN discontinuation, 5-year actuarial patient survival are reported. Results 44 patients received 47 ITx. The mean time on PN for the Tx group was 1604 days*. The main indication for ITx was: lack of central venous accesses followed by PN associated liver disease, and catheter related infectious complications. The mean time on the WL was 222 days (SD: 195 days). ITx were performed in 28 children and 16 adults. Thirty-seven procedures were isolated ITx; 10 multiorgan (MTO) (4 combined, 7 multivisceral - 2 with kidney); 4 (8,5%) were re-transplants: 3 isolated, 1 multivisceral; 8 included right colon. Sixteen pts (36%) received the abdominal rectus fascia. All procedures were performed by the same team; TIT was 7:36±2:10 hs, WIT was 39.1±10.5 min. Mean length of implanted intestine: 325 ± 59.5 cm, BC ileostomy were performed in 59.5% of the cases. 18/47 Tx required early re-operations. The overall mean follow up time is 49±45.2 months; the mean time to be off PN was 68 days (* p: 0,001); the overall 5 year pt survival is 55.1%; 60.5% for Isolated ITx vs 35% for MTO (p=0,01); 60.3% for ped recipient’s vs 44.9% for adults (p=NS). Conclusions After 11 years of establishing a dedicated adult and ped IF program, we proved that ITX is a valid therapeutic alternative for pediatric and adult candidates. Long term results are comparable to a large series reported from centers of develop countries or the ITR.

Double Heterozygous Mutation Causing PFIC2 with Synchronic Hepatocellular Carcinomas before Two Years of Age

Introduction Bile salts are exclusively synthesized in the liver. The bile salt export pump (BSEP), an adenosine triphosphate (ATP)-dependent transporter, is exclusively located in the hepatic canalicular membrane, and exports the bile salts into the canaliculus against a concentration gradient. Mutations in the ABCB11 gene alter BSEP and cause progressive intrahepatic familial cholestasis (PFIC2) type 2. This disease is characterized by low GGT hepatitis and early onset of cholestasis and pruritus; these patients are at increased risk of developing hepatocellular carcinoma (HCC) or cholangiocarcinoma. Aim To communicate a case or PFIC 2 with early development of synchronic HCC, with two ABCB11 heterozygous mutations, one of them not described before. Case Report This is a female referred to this center at 3 months of age due to cholestasis and coagulopathy. Coagulation corrected after vitamin K administration; hepatocellular enzymes and bilirubin persisted elevated with normal GGT. Further workup was done, ruling out viral hepatitis, biliary atresia and cystic fibrosis. Alpha-fetoprotein and bile serum salts were markedly elevated. A percutaneous liver biopsy was remarkable for giant cell hepatitis with moderate activity, portal and periportal fibrosis with incomplete bridges. PFIC was suspected and a molecular analysis was requested. Two heterozygous mutations were identified: p.Glu297Gly already reported in association to PFIC2 and p.Arg303Met previously not identified as related with this disease. The patient remained clinically stable, with progression of cholestasis and pruritus that was managed medically. At 17 months of age she presented sustained increase of Alpha-fetoprotein. A liver ultrasound showed a 7 mm nodule that was confirmed by CT hepatic angiography. She was promptly evaluated for liver transplant; extra hepatic lesions were excluded. Three weeks later the patient was transplanted with a split liver. The transplant was uneventful and she was discharged home 10 days after the surgery. The explanted liver showed cirrhosis and 4 nodules of poorly differentiated HCC measuring less than 1 cm each. The Alpha-fetoprotein decreased to normal values three weeks after TX and it has remained normal. The patient is now 14 months post TX with a functioning graft and showing no lesions of HCC. Conclusion PFIC type 2 is one of the few entities that might present HCC at a very early age. It is important to perform an adequate follow up in order to make the appropriate diagnosis and to perform a timely adequate liver transplant. It is of great interest for the medical community that newly identified mutations are reported, in order to enrich the medical knowledge.