P. Ruiz

Management of Hepatocellular Carcinoma Recurrence After Liver Transplantation

UNLABELLED Management of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT) is not well established. We conducted a retrospective analysis of our results in the treatment of HCC recurrence after OLT Patients. The 23 HCC recurrences developed after 182 OLT performed for HCC within Milan criteria, had an average follow-up of 60 months. RESULTS The median time to recurrence was 23.4 months. Surgical resection of the recurrence was possible in 11 patients, but an R-0 resection was obtained in 8 patients. Four of these 8 patients developed another recurrence, with 3 succumbing due to tumor recurrence and 1 alive at 12 months with recurrence. The other 4 patients without recurrences, include 3 who are alive at 19, 31, and 86 months and 1 who died at 32.6 months due to hepatitis C recurrence. The 3 patients with palliative resections developed recurrences. Twelve patients were rejected for surgery: 8 were treated symptomatically, 2 with systemic chemotherapy, and 2 with everolimus and sorafenib. This last treatment was also prescribed for 2 patients after R-0 surgery who are alive at 19 and 31 months and for 1 patient after R-1 surgery who is alive at 19 months. Of 15 patients who died, 13 succumbed to HCC recurrence. The average survival from transplantation was 61.7 +/- 37.5 and 48 +/- 34.3 months for patients without and with recurrence, respectively (P < .001). The survival from the recurrence was significantly higher among patients with R-0 surgery: 32.3 +/- 21.5 versus 11.9 +/- 6.9 months (P = .006). CONCLUSIONS HCC recurrence after OLT of patients within Milan criteria was low but had a great impact on survival. Few cases are amenable to R-0 resection, but when possible it was associated with a significantly increased survival, although with an high incidence of a new recurrence. There is a rationale for the use of sorafenib and mammalian target of rapamycin based immunosuppression, which warrants randomized studies.

Survival and Hepatitis C Virus Recurrence After Liver Transplantation in HIV- and Hepatitis C Virus–Coinfected Patients: Experience in a Single Center

INTRODUCTION Posttransplant hepatitis C virus (HCV) recurrence has been shown to negatively impact graft and patient survivals. It has been suggested that HCV recurrence among HIV- and HCV-coinfected transplant recipients is even more aggressive. OBJECTIVE To compare the histological severity and survival of posttransplant HCV recurrence between HIV- and HCV-coinfected and HCV-monoinfected patients. PATIENTS AND METHODS Among 72 adult patients who underwent primary liver transplantation at our institution for HCV-related cirrhosis between October 2001 and April 2007. We excluded one coinfected patient who died on postoperative day 5 leaving 12 HIV- and HCV-coinfected patients for comparison with 59 monoinfected patients. When listed, all coinfected patients fulfilled the criteria of the Spanish Consensus Document for transplantation in HIV patients. Immunosuppression did not differ between the two groups: all were treated with tacrolimus + steroids (slow tapering). Aggressive HCV recurrence was defined as cholestatic hepatitis and/or a fibrosis grade > or =2 during the first posttransplant year. RESULTS Coinfected patients were younger than monoinfected patients: 45 +/- 6 years vs 55 +/- 9 years (P = .0008). There were no differences in Child score, Model for End-stage Liver Disease score, donor age, graft steatosis, ischemia time, HCV pretransplant viral load or genotype between the groups. Significant rejection episodes were also equally distributed (25% vs 14%; P = .38). Seven coinfected patients and 29 monoinfected patients developed aggressive HCV recurrences (58% vs 49%; P = .75). Median follow-up was 924 days. Global survival at 3 years was 80%. Survivals at 1, 2, and 3 years were 83%, 75%, 62% in the coinfected vs 98%, 89%, 84% in the monoinfected patients, respectively (log-rank test = 0.09). CONCLUSIONS The severity of histological recurrence was similar among HIV- and HCV-coinfected and monoinfected HCV liver recipients in the first posttransplant year. Mortality attributed to recurrent HCV was similar in the groups. There were no short-term (3-year) differences in survival between the two groups of patients.

Reducing the incidence of incisional hernia after liver transplantation

Two important issues must be considered when deciding the abdominal incision for a liver transplant (LT): a good access to both liver lobes and a reduced rate of woundrelated morbidity. Historically, two incisions have been recommended for a LT: the classic Mercedes incision [1] and the subcostal bilateral incision [2]. Nevertheless, in recent years, the right subcostal incision with medial extension to xyphoid process (J-shaped incision) has arisen as a good option for liver surgery [3]. The reported frequencies of incisional hernia after LT range from 4.9% to 17.2% and several factors such as older age, acute rejection with steroids treatment, ascites or wound infection seem to be associated [4–7]. In a recent article from UCLA, an incidence of 4.6% of incisional hernia was reported after LT through a Mercedes incision [4]. The authors found that reoperation, pulmonary complications and the male gender were associated risk factors for incisional hernia. Comparing the outcome using the J-shaped incision and the classic Mercedes incision for LT, Heisterkamp et al. [8] found a significantly lower incidence of incisional hernia after the J-shaped incision (7% vs. 24% P = 0.002) with a relaparotomy rate that was not significantly different between the two groups (31% and 45% respectively P = 0.487). From January 1998 to December 2007, we performed 626 consecutive orthotopic liver transplantations. All patients were transplanted using a bilateral subcostal incision that was closed with two layers of running sutures of absorbable monofilament (Maxon 1; Synature, Covidien, Mansfield, USA). Child-Pugh score was A in 141 patients (22.5%), B in 242 (38.7%), and C in 243 (38.8%). Immunosuppression was based on tacrolimus, and steroids from the first post-transplant day (20 mg/day of prednisone). A 3-day course of methylprednisolone was used in 83 patients (13.2%) to treat a moderate or severe acute cellular rejection. Post-transplant relaparotomy was needed in 29 patients (4.6%). No patient was lost to follow-up. An incisional hernia was diagnosed, and subsequently treated in 11 patients, which means an incidence of 1.7%. The Chi-squared test was used to compare our results with the two reports already mentioned [4,8]. Our incidence of incisional hernia was significantly lower with a P value ranging from 0.03 to 0.003 depending on the type of incision, J-shaped or Mercedes. In our opinion, this significantly low incidence of incisional hernia may be explained by several circumstances: (i) the avoidance of Mercedes incision and its relative ischemic area at the trifurcation point, (ii) the low accumulated steroid dose in our patients because of our immunosuppressive protocol and the low rate of steroids-treated acute cellular rejection, and (iii) the significant low incidence of posttransplant relaparotomy (P < 0.001 when compared with the reports previously mentioned [4,8]). According to our results, subcostal bilateral incision may be considered for liver transplantation provided other risk factors for incisional hernia are prevented. Incisions with upward midline extension may be reserved for liver transplants with difficult suprahepatic vein reconstruction, as they allow a vertical access to the suprahepatic vena cava rather than from a caudal view [9].

Incidence and Clinical Relevance of Bacterial Contamination in Preservation Solution for Liver Transplantation

OBJECTIVE Postoperative infection is considered one of the most important causes of morbidity and mortality after liver transplantation. We prospectively studied the incidence and significance of infections in preservation solutions for liver transplantation. MATERIALS AND METHODS From March 2007 to March 2008, we cultured the University of Wisconsin preservation solution for 60 consecutive liver transplantations. Fluid samples were obtained at the beginning and at the end of the back table procedure. Our posttransplant infection prophylactic protocol consisted of ampicillin and cefotaxime for 48 hours. RESULTS Cultures were positive in 59 patients (98.4%). Seventy-five percent of the isolates were superficial saprophytic flora (SSF; Staphylococcus coagulase negative, Streptococcus viridans, and Corynebacterium), nevertheless in 15 cases (25.1%) we isolated high virulence pathogens (Staphylococcus aureus, Klebsiella, Escherichia coli, Enterobacter, and Pseudomonas aeruginosa). There were neither anaerobic nor fungal isolates. Sixteen patients (36%) from the group with SSF developed postoperative fever, including 12 with negative posttransplant cultures, while 4 patients showed positive cultures for various microorganisms distinct from those isolated from the preservation solution. Five patients (30%) with high virulence pathogens in the preservation solution developed posttransplant fever, although no pathogen was isolated. CONCLUSIONS Positive cultures of preservation fluids were observed in 98% of patients, although most of them (75%) were SSF. Microorganisms isolated from posttransplant cultures did not match the ones obtained from the preservation solution. Our results did not support routine culturing of the preservation solution provided that one administrator an adequate posttransplant antibiotic prophylactic regimen.

Advagraf De Novo in Liver Transplantation: A Single-Center Experience

UNLABELLED Advagraf, a prolonged release formulation of tacrolimus, is administered once daily in the morning. The aim of this study was to show the results obtained in our center, analyzing the safety, efficacy, blood trough levels, and drug doses. METHODS We analyzed 50 consecutive recipients of a first liver transplantation with 6 months follow-up. Efficacy and safety variables were collected as the incidence of acute rejection episodes, patient and graft survivals, kidney function as well as incidences of diabetes mellitus and arterial hypertension de novo. RESULTS The incidence of biopsy proven acute rejection episodes was 10% (n = 5), none 7 of which were steroid resistant and all resolved favorably. The rate of diabetes mellitus de novo was 22% (n = 11), 7 of whom required insulin. Hypertension developed in 9 patients (18%), all of whom were treated with a single drug. The mean serum creatinine level was 1.08 ± 0.25 mg/dL, with 3 patients (6%) displaying a value ≥ 1.5 mg/dL. Patient and graft survivals were 100%. CONCLUSION Advagraf is an effective immunosuppressant in liver transplantation with a low incidence of biopsy-confirmed acute rejection episodes. The good results for patient and graft survival with few side effects make it a useful drug for de novo liver transplantation.

Bacteriemia por Campylobacter jejuni asociada a pancreatitis aguda

Dentro de las causas de pancreatitis aguda infecciosa se encuentran sobre todo los virus, pero también bacterias, hongos y parásitos. Entre las infecciones bacterianas asociadas a pancreatitis aguda figuran sobre todo la tuberculosis, la leptospirosis y la brucelosis, aunque se han descrito otras. A continuación describimos un caso de pancreatitis aguda asociada a bacteriemia por Campylobacter jejuni.

Favorable longterm outcomes of liver transplant recipients treated de novo with once-daily tacrolimus: Results of a single-center cohort.

The once‐daily prolonged‐release formulation of tacrolimus has been recently related with significant graft and patient mid‐term survival advantages; however, practical information on the de novo administration after liver transplantation and longterm outcomes is currently lacking. This study is a 5‐year retrospective analysis of a single‐center cohort of liver transplant recipients treated de novo with once‐daily tacrolimus (April 2008/August 2011). The study cohort consisted of 160 patients, including 23 with pretransplant renal dysfunction, with a median follow‐up of 57.6 months (interquartile range, 46.6‐69.0). Tacrolimus target trough levels were 5‐10 ng/mL during the first 3 months after transplant, reducing progressively to <7 ng/mL after the first posttransplant year. Once‐daily tacrolimus was withdrawn in 35 (21.8%) patients during follow‐up, mostly due to renal dysfunction and/or metabolic syndrome. The biopsy‐proven acute rejection rate was 12.5% with no cases of steroid‐resistant rejection. The cumulative incidence of de novo diabetes, hypertension, and dyslipidemia were 16.9%, 31.2%, and 6.5%, respectively. Hepatocellular carcinoma recurrence rate was 2.8%. Renal function remained stable after the sixth month after transplant with a mean estimated glomerular filtration rate of 77.7 ± 19.6 mL/minute/1.73 m2 at 5 years. None of our patients developed chronic kidney disease stage 4 or 5. Patient survival at 1, 3, and 5 years was 96.3%, 91.9%, and 88.3%, respectively. Overall survival of patients with Model for End‐Stage Liver Disease (MELD) score > 25 points was not significantly different. In conclusion, our study suggests that immunosuppression based on de novo once‐daily tacrolimus is feasible in routine clinical practice, showing favorable outcomes and outstanding longterm survival even in patients with high MELD scores. Liver Transplantation 22 1391–1400 2016 AASLD.

Venous outflow obstruction after orthotopic liver transplantation: use of a breast implant to maintain graft position.

Gastaca M, Valdivieso A, Ruiz P, Gonzalez J, Ventoso A, Ortiz de Urbina J. Venous outflow obstruction after orthotopic liver transplantation: use of a breast implant to maintain graft position.
Clin Transplant 2011: 25: E320–E326.

Favorable outcomes of liver transplantation with octogenarian donors: A question of selection or surgical technique?

We read with great interest the recent article by Ghinolfi et al. describing their experience with octogenarian donors in liver transplantation (LT) and the interesting international debate that the article has generated. Through multivariate analysis, the authors found donor hemodynamic instability, donor diabetes mellitus, and donor–Model for End-Stage Liver Disease (D-MELD) score to be risk factors for ischemic-type biliary lesions (ITBL). From December 2003 to February 2016, we performed 777 LTs, 33 (4.2%) of them with octogenarian donors. Vasopressors were used in 87.5% of the cases during the intensive care unit stay, but only 12.1% suffered hemodynamic instability. Only 3 (9.1%) donors had a history of diabetes mellitus. The recipients’ mean Model for End-Stage Liver Disease (MELD) score was 14.76 5.6, and median DMELD was 1134 (range, 560-2464). Mean cold ischemia time was 3026 61 minutes. At our center, LT is routinely performed with inferior vena cava preservation and classical reconstruction without temporary portocaval shunt (TPCS). No graft developed primary nonfunction, although 7 patients developed early graft dysfunction. After a median follow-up of 18.5 months (range, 7.5-47.5), only 1 recipient developed ITBL, although it was related to hepatic artery thrombosis. Graft survival at 1 and 3 years was 92.6% and 86.4%, respectively. Unlike Rayar et al., we believe that outcomes of LT with octogenarian donors do not depend on the surgical technique but rather on good donor-recipient selection. In fact, outstanding midterm graft survival has been described with different techniques including ours. Because an interruption of portal flow for up to 90 minutes seems to be the threshold in animal models for the development of injury resulting from splanchnic congestion, we do not think that TPCS should be performed, provided a short time of hepatic inflow interruption is ensured. Moreover, this threshold for splanchnic injury could be even longer in patients with cirrhosis with portal hypertension and portosystemic circulation. Notably, all of our patients had a hepatic inflow interruption of less than 60 minutes. We agree with Ghinolfi et al. that results may improve if clinical factors are wisely combined with graft allocation. Therefore, we do not limit the use of octogenarian donors to stable patients, but we use them in sicker recipients because excellent outcomes can be achieved through strict donor selection.

Risk Factors for Biliary Complications After Orthotopic Liver Transplantation With T-Tube: A Single-Center Cohort of 743 Transplants

BACKGROUND Despite recent advances in organ preservation, surgical procedures, and immunosuppression, biliary reconstruction after orthotopic liver transplantation (OLT) remains as a major source of morbidity. The purpose of this study was to identify risk factors for the development of biliary complications (BCs) after end-to-end choledochocholedochostomy (EE-CC) with a T-tube as the standard technique for biliary reconstruction after OLT. METHODS A total of 833 consecutive liver transplantations that took place from February 1996 to April 2010 were retrospectively reviewed. Patients with concomitant hepatic artery complications were excluded, as were those who underwent urgent retransplantation or died within 1 week after transplantation. Finally, the study group comprised 743 patients. RESULTS The overall BC rate was 9.8% (73 patients), including stricture in 19 patients (2.6%) and bile leakage in 39 patients (5.2%). After univariate analysis, significant risk factors for BCs were surgery time >5 hours, arterial ischemia time >30 minutes, use of a classic transplant technique, transfusion of red blood cells ≥5 units, anti-cytomegalovirus treatment, and period of transplantation between 1996 and 2002. Stepwise logistic regression study was performed, including those variables with a value of P <.200. Multivariate analysis showed that pretransplant serum creatinine (odds ratio = 1.27; 95% confidence interval [CI], 1.03-1.57; P = .025) and arterial ischemia time >30 minutes (odds ratio = 2.44; 95% CI, 1.45-4.12; P = .001) were the only independent risk factors related to the development of BCs after biliary reconstruction with the T-tube. CONCLUSIONS The performance of different variables in predicting occurrence of BCs was assessed with the use of receiver operating characteristic analysis. The area under the receiver operating characteristic curve of our model was 0.637 (95% CI, 0.564-0.710), and therefore we must conclude that other variables not included in our model may have influence in the development of BCs after OLT with an EE-CC with a T-tube as the procedure for biliary reconstruction.