F. Durand

Microbial epidemiology and outcome of bloodstream infections in liver transplant recipients: An analysis of 259 episodes

Bloodstream infections (BSIs) are a major cause of mortality in liver transplant recipients. The incidence, microbiology, and outcome of BSIs in the first year after liver transplantation were analyzed in 704 patients who underwent transplantation at a single center between 1997 and 2007. BSIs occurred in 205 (29.1%) of the 704 patients. Overall, 259 episodes were documented, and they resulted in an incidence rate of 36.8%. Of these episodes, 39.4%, 27.8%, 17%, and 15.8% occurred in the very early period (≤10 days after liver transplantation), the early period (days 11‐30), the intermediate period (days 31‐90), and the late period (days 91‐365), respectively. The most frequent pathogens were Enterobacteriaceae members (41%), Staphylococcus aureus (19.8%), enterococci (13.1%), Pseudomonas aeruginosa (8.8%), and yeasts (7.1%). The median time of onset ranged from 7 days for methicillin‐resistant S. aureus to 25 days for Enterobacteriaceae. Mortality at 15 days after BSIs was 16.2%. Kaplan‐Meier survival curves showed that patients with BSIs had a significantly higher 1‐year mortality rate than those without BSIs (28.3% versus 16.6%, P < 0.001 with the log‐rank test). When the time of BSI onset was considered, 1‐year mortality was significantly associated with very early and early episodes (P < 0.001) but not with intermediate and late episodes (P = 0.47). In conclusion, BSIs are frequent and early complications after liver transplantation and are mostly caused by gram‐negative bacilli. A BSI in the first posttransplant month is a significant predictor of 1‐year survival. Liver Transpl 16:393–401, 2010.

Model for end-stage liver disease exceptions in the context of the french model for end-stage liver disease score–based liver allocation system†

Model for End‐Stage Liver Disease (MELD) score–based allocation systems have been adopted by most countries in Europe and North America. Indeed, the MELD score is a robust marker of early mortality for patients with cirrhosis. Except for extreme values, high pretransplant MELD scores do not significantly affect posttransplant survival. The MELD score can be used to optimize the allocation of allografts according to a sickest first policy. Most often, patients with small hepatocellular carcinomas (HCCs) and low MELD scores receive extra points, which allow them appropriate access to transplantation comparable to the access of patients with advanced cirrhosis and high MELD scores. In addition to patients with advanced cirrhosis and HCC, patients with a number of relatively uncommon conditions have low MELD scores and a poor prognosis in the short term without transplantation but derive excellent benefits from transplantation. These conditions, which correspond to the so‐called MELD score exceptions, justify the allocation of a specific score for appropriate access to transplantation. Here we report the conclusions of the French consensus meeting. The goals of this meeting were (1) to identify which conditions merit MELD score exceptions, (2) to list the criteria needed for defining each of these conditions, and (3) to define a reasonable time interval for organ allocation for each MELD exception in the general context of organ shortages. MELD exceptions were discussed in an attempt to reconcile the concepts of transparency, equity, justice, and utility. Liver Transpl 17:1137–1151, 2011.

Risk factors for Enterobacteriaceae bacteremia after liver transplantation

Enterobacteriaceae are now the predominant pathogens isolated in bloodstream infections complicating orthotopic liver transplantation (OLT). We conducted a retrospective cohort study of patients who underwent OLT in a University hospital between 01/01/1997 and 31/03/2003 to investigate the risk factors of Enterobacteriaceae bacteremia (EB) after OLT. EB was defined as the isolation of an Enterobacteriaceae species from at least one blood culture within 3u2003months following OLT. Pre‐, per‐ and postoperative variables were collected from the medical records and analyzed in relation to EB. Forty (12.5%) of the 320 patients developed EB. The origin of EB was abdominal in 32% of the patients, urinary in 18%, pulmonary in 10%, and primary in the remaining 40% of the patients. Two‐thirds of EB occurred within 1u2003month following OLT. The main pathogens were Escherichia coli (42%), Enterobacter cloacae (17%) and Klebsiella pneumoniae (17%). Susceptibility rates varied from 82.5% for ciprofloxacin to 95% for amikacin. Fourteen patients (35%) with EB died. Variables significantly associated with EB after multivariate analysis were a MELD score >20 (OR: 2.79 [1.24–6.30], Pu2003=u20030.013), transplantation for posthepatitic B (OR: 4.47 [1.67–11.98], Pu2003=u20030.03) or posthepatitic C (OR: 3.79 [1.59–9.01], Pu2003=u20030.03) cirrhosis, a positive bile culture (OR: 3.47 [1.19–10.13], Pu2003=u20030.023) and return to surgery (including retransplantation) (OR: 2.72 [1.32–5.58], Pu2003=u20030.006). EB is a frequent and severe complication following OLT. Patients grafted for a posthepatitic cirrhosis, with a severe pretransplantation status, with a positive bile culture and those undergoing reoperation have a high risk of developing EB.

Is tumor biopsy necessary

Abbreviations: AASLD, American Association for the Study of Liver Diseases; CDR, clinical decision rule; CEUS, contrastenhanced ultrasound; CI, confidence interval; CT, computed tomography; EASL, European Association for the Study of the Liver; HCC, hepatocellular carcinoma; LHR, likelihood ratio; MELD, Model for End-Stage Liver Disease; MRI, magnetic resonance imaging; NR, not reported; US, ultrasound.

Long-term survival after portal vein arterialization for portal vein thrombosis in orthotopic liver transplantation

Portal vein thrombosis is a relatively common finding during liver transplantation. The management of portal vein thrombosis during liver transplantation is technically demanding and ensures adequate portal flow to the liver graft. Eversion thromboendovenectomy and bypass using a patent splanchnic vein and cavoportal hemitransposition are the most often used procedures to treat portal vein thrombosis. There have been anecdotal reports of portal vein arterialization. We report a case of portal vein arterialization during orthotopic liver transplantation for decompensated cirrhosis. When thromboendovenectomy failed to restore sufficient portal flow and completion of arterial anastomosis between the recipient hepatic artery and the donor celiac trunk, a calibrated end-to-side anastomosis between the donor splenic artery and the donor portal vein was performed. With a 6-year follow-up, there are no symptoms related to portal hypertension, liver function is normal. However, an aneurismal dilatation of the portal branches has progressively developed. Calibrated portal vein arterialization is a possible option for portal vein thrombosis in liver transplantation, allowing long-term patient and graft survival.

Criteria for liver transplantation for hepatocellular carcinoma: what is an acceptable outcome?

The incidence of hepato cellular carcinoma (HCC) and the shortage of grafts restrict liver transplantation (LT) in HCC patients with a low risk of recurrence. The risk of recurrence is mainly related to the presence of vascular invasion which increases in parallel with tumour size and number of nodules. A favourable post‐transplant outcome has been observed in patients who meet the empirically defined Milan criteria, namely, a single nodule < 5 cm or two or three nodules each < 3 cm in the absence of macroscopic vascular invasion, based on pre‐transplant imaging. These criteria were felt to be too restrictive, leading several centers to propose expanded criteria for LT. However, increasing both the size and number of nodules resulted in an increased risk of recurrence. It has not been demonstrated that loco‐regional treatment in HCC patients listed for LT (bridging therapies) improve post‐transplant survival. More precise predictors of negative prognostic factors including elevated α‐feto protein level, poor differentiation and molecular techniques should be considered in order to optimize the use of grafts and achieve zero recurrence.

Preoperative tumour biopsy does not affect the oncologic course of patients with transplantable HCC

BACKGROUND & AIMSnPreoperative fine-needle aspiration biopsy (PFNAB) allows obtaining reliable hepatocellular carcinoma (HCC) diagnosis before liver transplantation (LT) in doubtful situations, but may result in higher recurrence rates following LT. This study aimed to evaluate whether PFNAB actually jeopardized the outcome of patients with transplantable HCC.nnnMETHODSnFrom 2002 to 2012, among 309 HCC patients listed for LT, 80 (26%) underwent PFNAB (PFNAB+). Their characteristics, modalities of recurrence, and survivals were retrospectively compared to those of the 229 (74%) patients without PFNAB (PFNAB-).nnnRESULTSnThe two groups (PFNAB+ vs. PFNAB-) were similar in terms of demography, rates of lesions within the Milan criteria (81% vs. 79%, p=0.676), and duration on the waiting list (7.0 vs. 6.9 months, p=0.891). Dropout following tumour progression was similar between both groups (6% vs. 11%, p=0.424). Among the 278 (90%) transplanted patients, pathological analysis revealed that 11 (4%) patients had non-HCC lesions including 10 in PFNAB- patients. Median follow-up was 34 months (12-135) and recurrence after LT was observed in 25 (9%) patients with no difference between both groups (9.3% vs. 8.9%, p=0.904). Parietal recurrence was observed in one PFNAB+ patient and in 2 PFNAB- patients after radiofrequency ablation (p=0.797). On an intention to treat basis, 1-, 3-, and 5-year overall survivals (89%, 69%, and 60% vs. 85%, 67%, and 61%, p=0.601) were not significantly different between PFNAB+ and PFNAB- patients.nnnCONCLUSIONSnThis study supports that preoperative tumour biopsy does not negatively influence the oncologic course of HCC patients eligible for LT. Hence, there is no argument to restrict biopsy in doubtful situations.

Intestinal failure after bariatric surgery.

A 47-year-old woman came to our hospital with malnutrition and liver failure in August, 2011. 28 months earlier, when she had been assessed for a bari atric gastric band, medical history included morbid obesity (height 159 cm, weight 127 kg, BMI 45 kg/m2), arterial hypertension, and moderate restrictive respiratory insuffi ciency; oral food intake was high. The patient had laparoscopic adjustable gastric banding. She was subsequently lost to follow-up. 16 months after banding, she had acute vomiting, abdominal pain, dehydration, and acute renal failure, and was non-responsive to band loosening. On laparotomy, gastric necrosis necessitated subtotal gastrectomy and Roux-en-Y gastric bypass. She recovered with no surgical complications. At follow-up, low oral intake (900 kcal per day), chronic diarrhoea, weight loss, and vitamin defi ciencies were noted. Medications were proton pump inhibitors, oral vitamins, and dietary supplements. 12 months after gastric band removal, the patient had lost 80 kg since before banding (weight 47 kg, BMI 18·6 kg/m2) and came to our clinic with cachexia, liver encephalopathy, hypoglycaemia, sarco penia, oedema, ascites, and diarrhoea. There was no evidence of sepsis, bleeding, chronic hepatocellular insuffi ciency, or portal hypertension, and there were no risk factors for acute or chronic liver disease, except for previous obesity. Laboratory testing showed raised amino transferases, a prothrombin rate of 16% (indicating acute liver failure), hypoalbuminaemia, micronutrient defi ciency, and central pancytopenia (appendix). Ultra sound and CT scans showed a non-dysmorphic steatosic liver and ascites. All biological and morphological tests for infections, intoxi cations, or antitrypsin defi ciency, and gastro intestinal, cardiac, auto-immune, nephrological, haemo lytic, haemato logical, or overload diseases were negative. Trans jugular liver biopsy suggested normal hepatic venous pressure gradient and diff use acute fatty liver with pure microvesicular steatosis aff ecting all hepato cytes, without fi brosis or necrosis (fi gure). Specifi c digestive functions were assessed after parenteral nutri tion refeeding, under stable conditions and with high oral intake (2500 kcal per day) (appendix). Intestinal failure results from obstruction, dysmotility, surgical resection, congenital defect, or disease-associated loss of absorption, and is characterised by the inability to maintain protein-energy, fl uid, electrolyte, or micronutrient balance. Because the patient did not need any nutritional support before surgery, we thought that gastrojejunal bypass had profoundly altered absorptive function. This situation is similar to that seen in short bowel syndrome and is worsened by chronic bacterial overgrowth and pancreatic insuffi ciency (appendix). Intestinal failure contributed to severe malnutrition, microvesicular steatosis, and acute fatty liver failure. A multimodal intestinal failure programme was provided through a central venous line. Oral antidiarrhoeal treatment consisted of pancreatic enzymes, loperamide, and digestive decontamination. After 3 months of digestive and nutritional support, oral intake, nutritional status, liver function, and histology recovered (fi gure), although after 20 months the patient still needed parenteral nutrition. Post-bariatric intestinal failure is an emerging indication for parenteral nutrition or intestinal transplantation encountered in expert centres. Either early or delayed postsurgical chronic diarrhoea, especially combined with low oral intake, should be recognised as a strong indicator of intestinal failure. After optimising digestive functions and nutritional support (including enteral nutrition), some patients still need permanent parenteral nutrition, surgical re hab ilitation, and occasion ally intestinal transplantation.

The recipient celiac trunk as an alternative to the native hepatic artery for arterial reconstruction in adult liver transplantation

During liver transplantation (LT), the recipient hepatic artery (RHA) cannot always be used, and alternatives include aortohepatic conduits and the splenic artery (SA). We report our experience with arterial reconstruction on the recipient celiac trunk (RCT), which has rarely been described. Since January 2013, we have been using the RCT when the RHA could not be used. All cases were discussed in a multidisciplinary LT meeting, and arterial patency or anomalies were systemically viewed with computed tomography (CT) scan. The RCT was used after section‐ligation of all celiac trunk collaterals. Until May 2014, the RHA could not be used in 11/139 (8%) patients who underwent LT. Postoperative arterial patency was assessed by serial Doppler ultrasound and CT scan. The advantages and disadvantages of the different arterial conduits were evaluated. The RCT was used in 7/11 (64%) patients. Mean follow‐up was 10 (6‐15) months. The patency rate was 100%, and 1 patient with associated portal shunting died at day 20 from septic complications. No related gastric or splenic complications were encountered. The RCT could not be used in 4 patients with reconstruction on the SA (n = 2), infrarenal (n = 1), and supraceliac aorta (n = 1). The patency rate was 75%. One patient with SA conduit and portal shunting developed pancreatitis/anastomotic pseudoaneurysm with secondary rupture. An emergency infrarenal conduit was created, which was later embolized because of infected pseudoaneurysms. Although the literature reports a higher risk of thrombosis with aortohepatic conduits, no long‐term results are available for the SA conduits, and only 1 report is available for the RCT. In conclusion, this study shows that the RCT is a good alternative to the RHA and can be used in two‐thirds of patients with inadequate RHA flow. Liver Transpl 21:1133‐1141, 2015.

Assessment of adrenal function in patients with acute hepatitis using serum free and total cortisol

BACKGROUNDnAdrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol.nnnAIMSnBecause 90% of serum cortisol is bound to proteins that are altered during stress, we investigated the effect of decreased cortisol-binding proteins on serum total and free cortisol in severe acute hepatitis.nnnMETHODSn43 severe and 31 non-severe acute hepatitis and 29 healthy controls were enrolled consecutively and studied prospectively. Baseline (T0) and cosyntropin-stimulated (T60) serum total and free cortisol concentrations were measured.nnnRESULTSnT0 and T60 serum total cortisol did not differ significantly between severe, non-severe hepatitis and healthy controls. Conversely, serum free cortisol (T0p=0.012; T60p<0.001) concentrations increased from healthy controls to severe hepatitis, accompanied by a decrease in corticosteroid-binding globulin and albumin (all p<0.001). In acute hepatitis (n=74), patients with low corticosteroid-binding globulin (<28mg/L) had higher T0 serum free cortisol than others (103.1 [61.2-157] vs. 56.6 [43.6-81.9]nmol/L, p=0.0024). Analysis of covariance showed that at equal concentration of total cortisol, the free cortisol concentration was significantly higher in severe than in non-severe hepatitis (p<0.001) or healthy controls (p<0.001).nnnCONCLUSIONSnIn severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol.