Management of liver failure in general intensive care unit.

OBJECTIVE: To produce French guidelines on Management of Liver failure in general Intensive Care Unit (ICU). DESIGN: A consensus committee of 23 experts from the French Society of Anesthesiology and Critical Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Association for the Study of the Liver (Association française pour l'étude du foie, AFEF) was convened. A formal conflict-of-interest (COI) policy was developed at the start of the process and enforced throughout. The entire guideline process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of the quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Some recommendations were ungraded. METHODS: Two fields were defined: acute liver failure (ALF) and cirrhotic patients in general ICU. The panel focused on three questions with respect to ALF: (1) Which etiological examinations should be performed to reduce morbidity and mortality? (2) Which specific treatments should be initiated rapidly to reduce morbidity and mortality? (3) Which symptomatic treatment should be initiated rapidly to reduce morbidity and mortality? Seven questions concerning cirrhotic patients were addressed: (1) Which criteria should be used to guide ICU admission of cirrhotic patients in order to improve their prognosis? (2) Which specific management of kidney injury should be implemented to reduce morbidity and mortality in cirrhotic ICU patients? (3) Which specific measures to manage sepsis in order to reduce morbidity and mortality in cirrhotic ICU patients? (4) In which circumstances, human serum albumin should be administered to reduce morbidity and mortality in cirrhotic ICU patients? (5) How should digestive haemorrhage be treated in order to reduce morbidity and mortality in cirrhotic ICU patients? (6) How should haemostasis be managed in order to reduce morbidity and mortality in cirrhotic ICU patients? And (7) When should advice be obtained from an expert centre in order to reduce morbidity and mortality in cirrhotic ICU patients? Population, intervention, comparison and outcome (PICO) issues were reviewed and updated as required, and evidence profiles were generated. An analysis of the literature and recommendations was then performed in accordance with the GRADE® methodology. RESULTS: The SFAR/AFEF Guidelines panel produced 18 statements on liver failure in general ICU. After two rounds of debate and various amendments, a strong agreement was reached on 100% of the recommendations: six had a high level of evidence (Grade 1 ±), seven had a low level of evidence (Grade 2 ±) and six were expert judgments. Finally, no recommendation was provided with respect to one question. CONCLUSIONS: Substantial agreement exists among experts regarding numerous strong recommendations on the optimum care of patients with liver failure in general ICU.

Ad Integrum Functional and Volumetric Recovery in Right Lobe Living Donors: Is It Really Complete 1 Year After Donor Hepatectomy?

The partial liver's ability to regenerate both as a graft and remnant justifies right lobe (RL) living donor liver transplantation. We studied (using biochemical and radiological parameters) the rate, extent of, and predictors of functional and volumetric recovery of the remnant left liver (RLL) during the first year in 91 consecutive RL donors. Recovery of normal liver function (prothrombin time [PT] ≥70% of normal and total bilirubin [TB] ≤20 µmol/L), liver volumetric recovery, and percentage RLL growth were analyzed. Normal liver function was regained by postoperative day's 7, 30, and 365 in 52%, 86%, and 96% donors, respectively. Similarly, mean liver volumetric recovery was 64%, 71%, and 85%; whereas the percentage liver growth was 85%, 105%, and 146%, respectively. Preoperative PT value (p = 0.01), RLL/total liver volume (TLV) ratio (p = 0.03), middle hepatic vein harvesting (p = 0.02), and postoperative peak TB (p < 0.01) were predictors of early functional recovery, whereas donor age (p = 0.03), RLL/TLV ratio (p = 0.004), and TLV/ body weight ratio (p = 0.02) predicted early volumetric recuperation. One-year post-RL donor hepatectomy, though functional recovery occurs in almost all (96%), donors had incomplete restoration (85%) of preoperative total liver volume. Modifiable predictors of regeneration could help in better and safer donor selection, while continuing to ensure successful recipient outcomes.

Infectious complications after liver transplantation in human immunodeficiency virus-infected recipients.

BACKGROUND: Few studies have investigated infections in human immunodeficiency virus (HIV)-infected liver transplant patients. The aim of this study was to describe the prevalence, time of onset, mortality of infectious complications, other than hepatitis C virus (HCV), and to identify risk factors for their development in a large single-center cohort of HIV-infected liver transplant patients. METHODS: We studied 109 consecutive HIV-infected patients who underwent liver transplantation (LT) between 1999 and 2010 and followed until December 2012. RESULTS: The median age was 44 years (interquartile range [IQR] 41-49), 82.6% were male, and the median follow-up was 45.7 months (IQR 14-65). The major indications for LT were HCV cirrhosis (61%) and hepatocellular carcinoma (19%). Forty patients (37%) developed at least 1 infection during the first year after LT. Twenty-eight (26%) patients had an episode of bacteremia. Five (4.6%) patients developed a cytomegalovirus infection. Fungal infections occurred in 5 (4.5%) patients. Four (3.6%) patients developed an HIV-related opportunistic infection. A total of 43 (39.4%) patients died during follow-up. Mortality related to infection occurred in 9 (7%) cases, and 20 (42.5%) patients died because of HCV recurrence. No patients died from opportunistic infections. Model for end-stage liver disease (MELD) score >17 was associated with a 2-fold higher risk (hazard ratio 1.96; 95% confidence interval 1.01-3.80) of developing infectious complications. CONCLUSIONS: Infections are not a major cause of mortality after LT in HIV patients and opportunistic infections of acquired immunodeficiency syndrome are infrequent. A MELD score >17 increased the risk of developing post-LT infectious complications. Recurrence of HCV infection remains a major cause of mortality.

Real-time PCR on the first galactomannan-positive serum sample for diagnosing invasive aspergillosis in liver transplant recipients.

Invasive aspergillosis (IA) is a life-threatening complication of liver transplantation. Detection of circulating galactomannan (GM) in serum samples is a method to improve the microbiological diagnosis in patients at risk for IA. However, the assay is hampered by false-positive results. The search for circulating Aspergillus DNA in the first GM-positive sample could improve the specificity of the test. Among 484 liver transplant recipients followed in a single center over 4 years, 25 patients had at least 1 GM-positive serum sample. The threshold of GM positivity was a ratio >or=1. These 25 patients were classified by the clinicians as probable IA (n=11), possible IA (n=2), and no IA (n=12) using the EORTC/MSG criteria with blinding to the polymerase chain reaction (PCR) results. After 1 mL aliquots of the first GM-positive serum sample were thawed, 2 independent DNA extractions were performed using the MagNA Pure Compact apparatus. Real-time amplification targeted at Aspergillus fumigatus mitochondrial DNA was performed on 10 microL of the final eluate in duplicate in the 2 independent DNA extractions using a LightCycler instrument. A sample was considered positive when the crossing point was

Disseminated toxoplasmosis, resulting from infection of allograft, after orthotopic liver transplantation: usefulness of quantitative PCR.

Disseminated toxoplasmosis is a life-threatening disease in liver transplant recipients that can result from an organ-transmitted infection. We report here a case of fatal disseminated toxoplasmosis after orthotopic liver transplantation from a seropositive donor (immunoglobulin G [IgG](+) and IgM(-)) in a patient who was nonimmune for toxoplasmosis prior to transplantation. Quantitative PCR analyses of various clinical specimens, including serum samples, appeared retrospectively to be a valuable diagnostic tool that might guide therapeutic attitudes.

Auxiliary partial orthotopic versus standard orthotopic whole liver transplantation for acute liver failure: a reappraisal from a single center by a case-control study.

OBJECTIVE: To reappraise the results of auxiliary partial orthotopic liver transplantation (APOLT) compared with those of standard whole-liver transplantation (OLT) in terms of postoperative death and complications, including neurologic sequelae. SUMMARY BACKGROUND DATA: Compared with OLT, APOLT preserves the possibility for the native liver to recover, and to stop immunosuppression. METHODS: In a consecutive series of 49 patients transplanted for fulminant or subfulminant hepatitis, 37 received OLT and 12 received APOLT. APOLT was done when logistics allowed simultaneous performance of graft preparation and the native liver partial hepatectomy to revascularize the graft as soon as possible. Each patient undergoing APOLT (12 patients) was matched to two patients undergoing OLT (24 patients) according to age, grade of coma, etiology, and fulminant or subfulminant type of hepatitis. All grafts in the study population were retrieved from optimal donors. RESULTS: Before surgery, both groups were comparable in all aspects. In-hospital death occurred in 4 of 12 patients undergoing APOLT compared with 6 of 24 patients undergoing OLT. Patients receiving APOLT had 1 +/- 1.3 technical complications compared with 0.3 +/- 0.5 for OLT patients. Bacteriemia was significantly more frequent after APOLT than after OLT. The need for retransplantation was significantly higher in the APOLT patients (3/12 vs. 0/24). Brain death from brain edema or neurologic sequelae was significantly more frequent after APOLT (4/12 vs. 2/24). One-year patient survival was comparable in both groups (66% vs. 66%), and there was a trend toward lower 1-year retransplantation-free survival rates in the APOLT group (39% vs. 66%). Only 2 of 12 (17%) patients had full success with APOLT (i.e., patient survival, liver regeneration, withdrawal of immunosuppression, and graft removal). One of these two patients had neurologic sequelae. CONCLUSIONS: Using optimal grafts, APOLT and OLT have similar patient survival rates. However, the complication rate is higher with APOLT. On an intent-to-treat basis, the efficacy of the APOLT procedure is low. This analysis suggests that the indications for an APOLT procedure should be reconsidered in the light of the risks of technical complications and neurologic sequelae.

Salvage transjugular intrahepatic portosystemic shunt for uncontrolled variceal bleeding in patients with decompensated cirrhosis.

BACKGROUND/AIMS: The place of transjugular intrahepatic porto-systemic shunt (TIPS) for variceal haemorrhage uncontrolled by sclerotherapy and medical treatment is still undefined. To investigate the outcome of early salvage TIPS for active uncontrolled variceal haemorrhage, and to identify the factors associated with mortality. METHODS: Salvage TIPS was performed in 58 patients as soon as possible after the diagnosis of variceal bleeding refractory to the combination of sclerotherapy and of pharmacological therapy. Twenty-three variables were assessed prospectively to identify predictors of mortality within 60 days of the procedure. RESULTS: The haemorrhage was controlled in 52 of 58 patients (90%). Bleeding persisted in six of 58 patients (10%), and recurred in four patients (7%). Overall, 17 (29%) and 20 (35%) patients died within respectively 30 days and 60 days of TIPS: five patients died of persistent bleeding, two patients died of recurrent bleeding, and 13 patients died of terminal liver failure. The actuarial survival following salvage TIPS was 51.7% at 1 year. On multivariate analysis, independent predictors of early mortality were: the presence of sepsis (P=0.001), the use of catecholamines for systemic hemodynamic impairment (P=0.009), and the use of balloon tamponade (P=0.04). Neither a single factor, nor a combination of factors before TIPS allowed to predict mortality confidently in a given patient. CONCLUSIONS: Early salvage TIPS is an effective treatment to stop active variceal bleeding refractory to sclerotherapy and pharmacological treatment. Pre-treatment prognostic determinants that correlate to mortality can not be used to predict the outcome in individual cases.

[Adult to adult living-related liver transplantation. The Paul-Brousse Hospital preliminary experience]. / Transplantation hépatique de l'adulte à partir de donneur vivant.

AIM: Liver-graft shortages justify the development of adult living-related liver transplantation. The preliminary experience with this technique at Paul-Brousse Hospital is reported. PATIENTS ET METHODES: From January to July 2000, 7 adult to adult living-related liver transplantations were performed. Donors were 5 females and 2 males aged 20 to 53 years old (median: 41). A right liver graft was harvested in all cases. Recipients were 5 males and 2 females aged from 17 to 58 years old (median: 50) transplanted for viral cirrhosis (4 cases including 2 with hepatocellular carcinoma), subfulminant hepatitis (1 case), hepatocellular carcinoma on a healthy liver (1 case), and epithelioid hemangioendothelioma (1 case). Follow-up ranged from 41 to 157 days (median: 117 days). RESULTS: One donor had a biliary fistula that healed spontaneously. One donor had asterixis for 24 hours. The 7 donors are alive at home without any late complications. One recipient was retransplanted for hepatic artery thrombosis and 2 recipients had a biliary fistula that healed spontaneously. The 7 recipients are alive at home with normal liver function. CONCLUSION: Our experience and other reports suggest that adult to adult living-related liver transplantation is feasible with rare mortality and low morbidity in donors. Results in recipients are comparable to those obtained with cadaveric grafts. For a given patient the possibility of living related donation might extend the indications for transplantation without penalizing patients waiting for a cadaveric graft.

Neoadjuvant transjugular intrahepatic portosystemic shunt: a solution for extrahepatic abdominal operation in cirrhotic patients with severe portal hypertension.

BACKGROUND: Major abdominal surgery, although technically feasible per se, can be contraindicated in some cirrhotic patients because of severe portal hypertension. The present study reports our experience of seven such patients who were prepared for major abdominal surgery by transjugular intrahepatic portosystemic shunt (TIPS). STUDY DESIGN: There were seven cirrhotic patients (six men and one woman aged 47 to 69 years) with portal hypertension. Portal hypertension was considered severe because of the presence of at least one of the following: history of variceal bleeding (five of seven patients), varices at risk of bleeding (red signs or cardial location of varices; four of seven patients), or intractable ascites (three of seven patients). The planned operations included colon, gastroesophageal, kidney, and aortic procedures in three, two, one, and one patient, respectively. Because portal hypertension was the leading cause of surgical contraindication, the following "two-step strategy" was applied to the seven patients: first, TIPS to control portal hypertension, followed, after a delay of at least 1 month, by abdominal surgery. RESULTS: The TIPS procedure was successfully performed in all patients without complications. The hepatic venous pressure gradient decreased from 18+/-5 to 9+/-5 mm Hg (p<0.01). All patients were operated on with a delay ranging from 1 month to 5 months after TIPS (2.9+/-1.3 months; median 3 months). The planned operation was performed in six of the seven patients. One patient with cancer of the cardia did not have resection because of extensive abdominal spreading of the tumor. Intraoperative transfusion was necessary in only two patients. Operative mortality occurred in one patient, 36 days after resection of a left colon cancer. CONCLUSIONS: The minimally invasive nature of TIPS allows us to propose the following two-step management of cirrhotic patients with severe portal hypertension needing abdominal surgery: decompression of the portal system by TIPS followed by elective surgery.

The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation.

Familial amyloid polyneuropathy (FAP) associated with mutations of the transthyretin (TTR) gene is the most common type of FAP, a devastating disease causing death within 10 years after the first symptoms. Because most of the amyloidogenic mutated TTR is secreted by the liver, transplantation is widely used to treat these patients, but long-term quantitative evaluation of the effects of liver transplantation on the progression of the neuropathy are not available. We have treated 45 patients with symptomatic TTR-FAP, including 43 with the Met30 TTR gene mutation, and report on the results of periodic evaluation of markers of neuropathy in 25 of them, who have been followed for more than 2 years after liver transplantation (mean follow-up 4 years). The overall survival rates at 1 and 5 years were 82 and 60%, respectively. Urinary incontinence and a low Norris score at liver transplantation were associated with poorer outcome. The motor score stabilized in seven of 11 patients (64%) with mild sensorimotor neuropathy (walking unaided) and in two of the eight patients (25%) with severe sensorimotor deficit (walking with aid) at liver transplantation. In five other patients, deterioration of motor deficit occurred only within the first year after liver transplantation, but was progressive after this interval in two patients. None of the six patients with pure sensory neuropathy developed motor loss and superficial sensory loss remained unchanged. Two years after liver transplantation, the rate of myelinated axon loss in nerve biopsy specimens was markedly lower in seven transplanted patients (0.9/mm(2) of endoneurial area/month) than in non-transplanted patients (70/mm(2) of endoneurial area/month). Symptoms of dysautonomia and quantitated cardiocirculatory autonomic tests remained unchanged. In all patients, serum mutated TTR decreased to 2.5% of pre-liver transplantation values and remained at this level during follow-up. We presently recommend liver transplantation in FAP patients at onset of first symptoms and exclusion of those with a Norris score below 55 and/or with urinary incontinence.

Paul Brousse Liver Transplantation: the first 1,500 cases.

During the past 16 years, more than 1,500 liver transplants were performed at Paul Brousse Hospital. The overall patient survival rates were 83% at one year and 65% at 10 years. Our group has pioneered a variety of new approaches to liver transplantation, including: 1. Anti-HBs (HBIG) prophylaxis for the prevention of HBV recurrence. To date more than 270 patients have received long-term treatment and the overall 10-year recurrence rate was 27%. 2. Transplantation for hepatocellular carcinoma of the cirrhotic liver in patients with uni- or binodular HCC (< 3 cm). Survival for transplanted patients was 83% compared with 18% if the liver was resected. 3. Transplantation for familial amyloidotic polyneuropathy (FAP). More than 60 patients had 5- and 10-year survival rates of 85% and 83%, respectively. Ten livers obtained after hepatectomy from these FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with satisfactory short-term results. 4. Reduced-size liver grafts have been used successfully to reduce pretransplant mortality and posttransplant morbidity and mortality by shortening the wait for our pediatric patients. 5. Split-liver transplantation has increased the number of transplantable livers by 28%. 6. Split-liver transplantation for 2 adults. Using optimal livers we have transplanted 34 adults with grafts prepared by ex-vivo or in-situ splitting with good survival rates. 7. Adult-to-adult living-related donor liver transplantation. In 2000, 7 adult-to-adult living donor transplants were performed with no complications from the donor surgeries. One recipient was retransplanted for arterial thrombosis, but all 7 recipients are alive at home. The Paul Brousse Hospital is committed to exploring new technologies to improve the outcome of and expand the indications for liver transplantation. We have taken a surgical approach to the organ shortage, finding new ways to serve the most patients with the limited number of livers available.

[Labor complications of the HELLP syndrome without any predictive factors]. / Accouchement compliqué de HELLP syndrome sans facteur prédictif de survenue. Deux observations.

Liver disease is a rare complication of pregnancy which can be serious for both the mother and the infant. In particular, HELLP syndrome (hemolysis, elevated liver enzymes and a low platelet count) is a life threatening complication of severe preeclampsia. Pregnancies complicated by the HELLP syndrome are usually associated with increased maternal and perinatal morbidity and mortality including disseminated intravascular coagulopathy, pulmonary and cerebral oedema, acute renal failure, rupture of the liver hematoma and a variety of hemorrhagic complications. The HELLP syndrome occurs in 4 to 12% of patients with severe preeclampsia and prompt delivery is the only treatment. We report two cases of HELLP syndrome which developed in women during delivery and without any predictive factors during pregnancy.

Long-term follow-up after liver transplantation for autoimmune hepatitis: evidence of recurrence of primary disease.

BACKGROUND/AIMS: After liver transplantation for autoimmune hepatitis, the long-term results and the incidence of recurrence of primary disease are unknown. METHODS: In this retrospective study we reviewed the clinical course of 25 patients transplanted for autoimmune hepatitis and followed for a mean of 5.3 years (2-8.5 years). RESULTS: The actuarial 5-year patient and graft survival rates were 91% (+/-6%) and 83% (+/-8%). The actuarial 1-year rate of acute rejection was 50% (+/-10.2%), which was comparable to that of patients transplanted for primary biliary cirrhosis and primary sclerosing cholangitis. Autoantibodies persisted in 77% of patients, at a lower titer than before liver transplantation. Ten patients were excluded from the study of autoimmune hepatitis recurrence, one because of an early postoperative death and nine because of hepatitis C virus infection acquired before or after liver transplantation. In the remaining 15 patients, who were free of hepatitis C virus infection, 5-year patient and graft survivals were 100% and 87%, respectively. Despite triple immunosuppressive therapy, three patients (20%) developed chronic hepatitis with histological and serological features of autoimmune hepatitis in the absence of any other identifiable cause. The disease was severe in two patients, leading to graft failure and asymptomatic in another, despite marked histological abnormalities. In one of these three patients, autoimmune hepatitis recurred on the second liver graft as well. CONCLUSIONS: Patients undergoing liver transplantation for autoimmune hepatitis have an excellent survival rate although severe primary disease may recur, suggesting the need for stronger post-operative immunosuppressive therapy.

The first clinical isolate of Legionella parisiensis, from a liver transplant patient with pneumonia.

A bluish white autofluorescent strain of Legionella was isolated from the tracheal aspirate of a female liver transplant patient who developed hospital-acquired pneumonia. This strain had biochemical characteristics compatible with those of L. cherrii, L. anisa, and L. parisiensis and could not be differentiated from L. bozemanii and L. parisiensis by the direct fluorescent-antibody assay. Phylogenetic analysis of partial 16S rRNA gene sequences of this strain (ATCC 700174) revealed the closest homology to the species L. parisiensis (99.5%). An L. parisiensis species-specific profile was also identified by a random amplified polymorphic DNA technique. This is the first report of L. parisiensis isolation from humans.

[Intrahepatic portasystemic shunt as a salvage treatment of uncontrolled hemorrhage caused by rupture of esophageal varices in patients with liver cirrhosis]. / Shunt intrahépatique porto-sushépatique de sauvetage pour hémorragie par rupture de varices oesophagiennes non contrôlée chez le cirrhotique.

OBJECTIVES: Patients who continue to bleed despite standard treatment including sclerotherapy have a poor prognosis with a mortality up to 90%. TIPS has been used as salvage therapy for ruptured oesophageal varices refractory to all conventional treatments. METHODS: During a period of 3 years, 65 cases of variceal rupture in cirrhotic patients were treated at our center and a salvage TIPS was performed in 15 patients (23%) for active uncontrolled hemorrhage despite standard medical and endoscopic treatment (Child A, 2; B, 1; C, 12). The procedure was technically successful in all cases and hemorrhage was controlled in 11/15 cases (73%). RESULTS: Three patients died of persistent bleeding and liver failure; one case of moderate and persistant hemorrhage was controlled by transfusions until bleeding ceased. This patient was transplanted 3 months after TIPS and is alive 3.5 years later. Two patients had early recurrence of hemorrhage due to TIPS thrombosis. These 2 cases of thrombosis were deobstructed but both patients died of liver failure despite bleeding control. Overall, 7 patients died within 60 days of TIPS by hemorrhage and/or liver failure. One patient died of liver failure 7 months after TIPS following surgery for aortic aneurysm. None of the 8 survivors after 60 days had bleeding recurrence or encephalopathy. Actuarial survival was 42.7 +/- 14% at 1 and 2 years. CONCLUSION: TIPS is currently the alternative of choice for persistant bleeding refractory to standard management. However despite control of hemorrhage, operative mortality remains high due to the underlying severe cirrhosis.