ABSTRACT Background Fulminant hepatic failure (FHF) is associated with high mortality; few patients survive without liver transplantation. It is important to have a sensitive, specific early predictor of outcome to distinguish potential survivors (S) from nonsurvivors (NS). Objective Because we had previously shown that glycine conjugation of para‐aminobenzoic acid (PABA) quantitatively reflects liver function in children with chronic liver disease, in this pilot study we wanted to determine whether the measurement of the glycine conjugates of PABA could distinguish S from NS in FHF in comparison with standard prognostic indices. Methods Twenty‐four patients were studied: acute severe hepatitis (n = 7), subfulminant hepatic failure (n = 7), and FHF (n = 10). Assessment of King's College criteria, measurement of factor V and VII levels, PABA testing, and transjugular liver biopsies were performed in almost all patients within 48 hours of admission. Serum PABA and its glycine conjugates (para‐aminohippurate (PAHA) and para‐acetamidohippurate (PAAHA)) were measured thirty minutes after oral administration by high‐pressure liquid chromatography. Poor prognostic categories as previously established in the literature were defined as factor V < 0.20U/ml, factor VII < 0.08 U/ml, % necrosis >70%, hippurate ratio = 0%, and PAHA = 0M. Results The measurement of PAHA was the best predictor of a poor outcome in patients with acute liver failure with a sensitivity of 92%, and negative predictive value (NPV) of 92% compared with a sensitivity of 54% and a NPV of 63% with King's College criteria. Conclusion Measurement of serum PAHA is the best early prognostic marker of death in children who suffer from FHF.
Abstract We describe the novel use of radiofrequency ablation (RFA) in combination with surgical resection for treatment of multifocal hepatic adenoma. We show three cases without recurrent lesions detected in follow‐up examination. Two of the patients have subsequently gone on to carry pregnancies successfully to term.
Background and Aims The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down‐staged (DS) with locoregional therapy (LRT). We evaluated post‐LT outcomes, predictors of down‐staging, and the impact of LRT in patients with beyond‐MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002‐2013). Approach and Results Clinicopathologic characteristics, overall survival (OS), recurrence‐free survival (RFS), and HCC recurrence (HCC‐R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down‐staged (DS, n = 465), treated with LRT and not down‐staged (LRT‐NoDS, n = 242), or untreated (NoLRT‐NoDS, n = 82). Five‐year post‐LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5‐year HCC‐R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5‐year HCC‐R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down‐staging included alpha‐fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT‐NoDS had greater HCC‐R compared with NoLRT‐NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment‐weighted propensity matching (HR = 1.82, P < 0.001). Conclusions In LT recipients with HCC presenting beyond MC, successful down‐staging is predicted by wait time, alpha‐fetoprotein response to LRT, and tumor burden and results in excellent post‐LT outcomes, justifying expansion of LT criteria. In LRT‐NoDS patients, higher HCC‐R compared with NoLRT‐NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.
A 10-week-old girl was admitted for evaluation and management of acute fulminant hepatic failure. She had been healthy until she presented with acholic stool and jaundice at the age of 9 weeks. A work up showed ALT 787 U/L, total bilirubin 14.9 mg/dL, and severe coagulopathy with an INR of 3.4. Metabolic disorders and autoimmune liver disease were ruled out. Though viral etiology was strongly suspected, serologies were negative for Hepatitis A, B, and C viruses, Ebstein-Barr virus, cytomegalovirus, etc. She underwent plasma exchange to control coagulopathy. Her condition continued to worsen with the onset of encephalopathy, progressive ascites, and seizure activity. Due to the deteriorating condition, she was approved for liver transplant. The patient underwent liver transplantation using full-sized graft without complications on hospital admission day 10. Pathology on the native liver showed massive hepatic necrosis. No viral cytopathic changes were identified. Initial postoperative course was uneventful until postoperative day (POD) 14 when AST and ALT began to elevate. Over the next several days, her mental status and transaminase worsened significantly. Biopsy showed severe acute hepatitis suspicious for viral origin. She developed acute renal failure due to foscarnet and cidofovir, and was placed on central venovenous hemodialysis (CVVHD) on POD 26. She developed pulmonary hemorrhage and respiratory failure on POD 27. Various ventilatory maneuvers including high frequency oscillatory ventilation and use of nitric oxide failed. A 15 Fr. cannula was inserted to her right internal jugular vein and venovenous extracorporeal membrane oxygenation (ECMO) was installed with a flow of 0.2–0.8 l/min. She was relisted for liver transplantation. On POD 28, she underwent second liver transplantation while on ECMO. Transplantation was performed uneventfully and ECMO was weaned and successfully discontinued. Total length of ECMO use was 4 days. Although she needed the third and fourth liver transplantation due to portal vein thrombosis and intrahepatic arteriovenous fistula respectively, she is currently doing fine 15 months after the last transplantation. Indication of ECMO has been applied for patients with acute, potentially reversible, life-threatening respiratory failure which is unresponsive to conventional therapies. ECMO is currently used as a bridging device to lung and heart transplantation (1). One report showed that ECMO support after heart, lung, heart-lung, and liver transplants has yielded a 57% survival to discharge (2). ECMO has been used after liver transplant for critical pulmonary embolism which occurred during transplantation (3,4). To the best of our knowledge, however, this is the first case report that liver transplantation was performed successfully while the patient was on ECMO. Due to acute renal failure and pulmonary hemorrhage, the present patient was on CVVHD and ECMO during the second liver transplantation. Experience of device usage and satisfactory support system are essential in successful application of ECMO to such patients with critical conditions. Our case shows the extended efficacy and indication of ECMO as a bridge to pediatric orthotopic liver transplantation. Shiro Fujita Alan W. Hemming Takahisa Fujikawa Alan I. Reed Richard J. Howard Max R. Langham Jr. Department of Surgery University of Florida College of Medicine Gainesville, FL David W. Kays Department of Pediatrics University of Florida College of Medicine Gainesville, FL Michael A. Froelich Department of Anesthesiology University of Florida College of Medicine Gainesville, FL Fumiki Kushihata Jota Watanabe Department of Pathology, Immunology and Laboratory Medicine University of Florida College of Medicine Gainesville, FL
Objective To examine the authors’ experience with preoperative ipsilateral portal vein embolization (PVE) and assess its role in extended hepatectomy. Summary Background Data Extended hepatectomy (five or more liver segments) has been associated with higher complication rates and increased postoperative liver dysfunction than have standard hepatic resections involving lesser volumes. Recently, PVE has been used in patients who have a predicted (postresection) future liver remnant (FLR) volume less than 25% of total liver volume in an attempt to increase the FLR and reduce complications. Methods Sixty patients from 1996 to 2002 were reviewed. Thirty-nine patients had PVE preoperatively. Eight patients who had PVE were not resected either due to the discovery of additional unresectable disease after embolization but before surgery (n = 5) or due to unresectable disease at surgery (n = 3). Therefore, 31 patients who had PVE subsequently underwent extended hepatic lobectomy. A comparable cohort of 21 patients who had an extended hepatectomy without PVE were selected on the basis of demographic, tumor, and liver volume characteristics. Patients had colorectal liver metastases (n = 30), hepatocellular carcinoma (n = 15), Klatskin tumors (n = 9), peripheral cholangiocarcinoma (n = 3), and other tumors (n = 3). The 52 resections performed included 42 extended right hepatectomies, 6 extended left hepatectomies, and 4 right hepatectomies extended to include the middle hepatic vein and the caudate lobe but preserving the majority of segment 4. Concomitant vascular reconstruction of either the inferior vena cava or hepatic veins was performed in five patients. Results There were no differences between PVE and non-PVE groups in terms of tumor number, tumor size, tumor type, surgical margin status, complexity of operation, or perioperative red cell transfusion requirements. The predicted FLR was similar between PVE and non-PVE groups at presentation. After PVE the FLR was higher than in the non-PVE group. No complications were observed after PVE before resection. There was no difference in postoperative mortality, with one death from liver failure in the non-PVE group and no operative mortality in the PVE group. Postoperative peak bilirubin was higher in the non-PVE than the PVE group, as were postoperative fresh-frozen plasma requirements. Liver failure (defined as the development of encephalopathy, ascites requiring sustained diuretics or paracentesis, or coagulopathy unresponsive to vitamin K requiring fresh-frozen plasma after the first 24 hours postresection) was higher in the non-PVE patients than the PVE patients. The hospital stay was longer in the non-PVE than the PVE group. Conclusions Preoperative PVE is a safe and effective method of increasing the remnant liver volume before extended hepatectomy. Increasing the remnant liver volume in patients with estimated postresection volumes of less than 25% appears to reduce postoperative liver dysfunction.
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