A risk score and a flowchart for liver retransplantation.

Rates of overall graft survival after liver retransplantation (RETX) are still 20% lower than those after primary liver transplantation (TX). On the basis of previous mathematical approaches from other authors who tried to identify prognostic variables for survival and prognostic risk scores for liver RETX, we studied 12 categorical and 17 continuous variables from the donor, the recipient, and the surgical procedure, among patients who underwent liver retransplantation. Data were retrieved in a retrospective study over the last 12 years, in order to overcome the possible gap of other series that often included RETX performed many years ago. We considered 394 consecutive cadaveric liver TXs in adult patients, namely, 351 primary TXs and 43 RETXs. Using multivariate logistic regression, we calculated the following equation for 1-year risk of death for patients undergoing liver RETX: log(Odds)= -4.81+2.23 x Recipient Sex + 1.86 x Donor Age + 1.60 x MELD Score (where: Recipient Sex: F=0, M=1; Donor Age (years): <40=0, 40-59=1; 60+ =2; MELD Score: <26=0, 26+ =1). With this formula, we built a decision tree to predict the individual risk of death based on the subject's profile. Keeping in mind that mathematical models can only help our decisional process and are not conclusive, our data needs to be validated on a larger scale.

Liver Transplantations and Brain Dead Donors With Alcohol Abuse.

BACKGROUND AND AIM: Liver grafts from donors with chronic and active history of alcohol abuse are usually immediately ruled out for use in liver transplantation (LT). The aim of our study is to evaluate the use of those grafts. METHODS: From 2011 to 2016, a study group (Group 1) composed of 5 adult LT patients transplanted with livers from donors with alcohol abuse, was compared with a control group (Group 2) of 10 randomly matched patients who received liver transplants. Preoperative, intraoperative, and postoperative data were compared. RESULTS: Among donors, serum gamma-glutamyl transferase values were significantly higher in Group 1. In recipients, post-LT laboratory exams showed significantly higher peak values of aspartate transaminase and alanine transaminase in Group 1; higher values of aspartate aminotransferase, alanine aminotransferase, and total bilirubin in Group 1 were also recorded on day 0. Early allograft dysfunction occurred at higher rates in Group 1 (80% vs 20%, P = .025), with no differences in early rejection episodes or early surgical repeat interventions. All patients from both groups were alive after 20 ± 10 (range 6-35) months from LT. CONCLUSION: Despite higher rates of early allograft dysfunction, selected liver grafts from donors with alcohol abuse can be accepted for LT with good clinical results.

Sent Liver Grafts Do Not Have a Detrimental Impact on Post-transplant Outcome.

INTRODUCTION: "Sent livers" (SL) (interregional allocated organs) are considered extended donor criteria grafts. These grafts influence post-transplant outcome. In our donor allocation program, the number of allocated SLs is increasing. The aim of our study is to provide data supporting the possibility to enlarge the use of SLs through adequate donor-to-recipient matching. METHODS: A retrospective analysis was carried out from our prospective-collected database during 2014. RESULTS: Fifty-seven liver transplantations (LTs) were included: 22 SLs and 35 grafts procured by us (nSLs). Only donor risk index among donor characteristics showed a trend toward significant values (SL 1.901 vs nSL 1.726, P = .07). Among LT variables, the number of patients who received interleukin-2 inhibitor induction (SL 7 vs nSL 20, P < .05) and the presence of hepatocellular carcinoma (SL 50% vs nSL 34%, P < .05) reached statistical significance. One case of primary nonfunction occurred in the nSL group. No major retrieval injuries were observed. Retransplantation was performed in 6 cases (2 SLs and 4 nSLs). One patient in the SL group died after retransplantation. Graft survival rates at 1, 3, 6, and 12 months were 100%, 100%, 90%, 86% and 91%, 86%, 86%, 86% (P = .79) in SL and nSL groups, respectively. DISCUSSION: SL performance did not differ from that of nSL. SLs were usually allocated to noncritical candidates, and nSLs were transplanted more frequently in decompensated recipients. Despite this peculiar donor-recipient match, grafts survival was similar in the 2 groups of patients.

Holmium Intraductal Laser Lithotripsy of Biliary Stones in Liver Grafts.

BACKGROUND: Biliary stones after liver transplantation (LT) rarely occur but a focus on those complications and their treatment is needed. PATIENTS AND METHODS: In total, 390 adult patients who underwent an LT from July 2004 to July 2014 entered the study. Biliary complications and notably biliary stones after LT were identified. RESULTS: In total, 365 LT were analyzed. Biliary stones were identified in 14 patients (3.8%). Predictive factors for the onset of biliary stones after LT were hepatocellular diseases (P = .038; OR = 9.7) and biliary stenosis (P = .000; OR = 11.9). Treatments consisted of percutaneous transhepatic procedures (4 patients), endoscopic retrograde procedures (9 patients), and in open surgery (1 case); in 2 cases, due to a failure of previous treatments, holmium intraductal laser lithotripsy (HILL) was used: the first patient, a 35-year-old woman developed multiple intrahepatic biliary stones after LT. Percutaneous transhepatic cholangiography (PTC) was ineffective and a HILL was performed, clearing the right common bile duct but leaving residual stones in the left duct. The patient underwent a retransplantation due to recurrent hepatitis C virus infection but died 3 months later because of graft failure. The second patient, a 42-year-old 14 years after retransplantation, developed biliary sludge and stones; after several attempts with PTC and endoscopic retrograde cholangiopancreatography, a HILL was performed. All stones except one big one were treated. The patient is alive and well. CONCLUSIONS: When usual treatments are unsuccessful and biliary stones are large, their fragmentation and treatment could be done with HILL, a promising procedure after LT.

A "steroid-free" tacrolimus and low-dose mycophenolate mofetil primary immunosuppression does not prevent early acute rejection after liver transplantation.

To assess the efficacy and safety of a primary immunosuppressive regimen with tacrolimus (Tac) and low-dose mycophenolate mofetil (MMF) without steroids and to determine the exposure to mycophenolic acid (MPA) in the early postoperative period, we performed a single-center, randomized 1:1, open-label, controlled study planned to be 60 liver transplantation patients randomized into 2 groups: group A, tacrolimus + MMF (750 mg orally twice a day); and group B, tacrolimus + MMF (750 mg orally twice a day) + steroids. After an interim analysis by the ethical committee patient enrollment was stopped. Data from 30 patients (12 in group A and 18 in group B with a mean follow-up period of 31 +/- 7 months) showed a patient survival rate of 91.7% in group A and 100% in group B and a graft survival rate of 91.7% and 88.9%, respectively. Nine patients (75%) in group A suffered an acute rejection episode, whereas in group B only 3 patients (16.7%) showed acute rejection (P = .002). All rejection episodes occurred in both groups at 1 week after transplantation. The difference in histological grading was statistically significant (P = .021). The toxicity profiles were similar in both groups. A primary immunosuppressive regimen based on Tac and low-dose MMF without steroids is safe but unable to prevent acute rejection at 1 week after transplantation even if early acute rejection does not affect the outcome in terms of morbidity and graft or patient survival.

Long-term outcome of right split in situ grafts in adults.

In situ split liver transplants represent a technical progression from ex situ split procedures conceived to retrieve grafts for pediatric recipients. The transection line runs along the falciform ligament, so the main artery to the right graft is the right proper artery, whereas the left graft retains the main arterial axis with the celiac trunk. Although the major advantages are for pediatric recipients, due to the expanded pool of grafts available, for adult recipients the results of right split in situ grafts must be compared with whole grafts. We considered two groups of consecutive grafts transplanted since 1993 as first grafts: 20 of the former and 261 of the latter. Groups were comparable for donor gender, recipient age and gender, perfusion solution, ischemia time, and follow-up time, but not for donor age and for the number of arterial anastomoses. Although there were more major surgical complications in the former compared with the latter group (40% vs 25%), the only statistically significant difference was found in retransplantation rate for arterial complications (15% vs 2.2%). No statistical difference was observed in graft or patient actuarial survival rates at 1, 3, or 6 years after transplantation; for right split grafts these were 85%, 69%, and 69% and 95%, 79%, and 79%, respectively.

Back-table arterial reconstructions in liver transplantation: single-center experience.

Anatomic variations of the arterial supply to donor liver grafts often require complex hepatic artery reconstructions on the back table. Therefore, because of the additional anastomoses, there is a greater risk of arterial thrombosis and graft loss. Among the 620 orthotopic liver transplantations (OLT) in 549 adult and pediatric patients performed from June 1983 through August 2004, the rates and types of donor hepatic artery variations (HAV) and the type of reconstructions were reviewed as well as the 1- and 5-year grafts and patient survival rates after OLT. At least 1 HAV was present in 133 liver grafts (21.4%). The most frequent variations were as follows: right hepatic artery (RHA) from superior mesenteric artery (SMA) (44 cases); RHA from aorta (4 cases); and RHA from SMA, combined with a left hepatic artery (LHA) from left gastric artery (3 cases). No graft was discarded. Fifty-six of 133 (42%) HAV required arterial reconstructions, generally a termino-terminal (TT) anastomosis between RHA and splenic artery (26 cases, 46.4%). Less frequently performed anastomoses were the "fold-over" technique (15 cases, 26.8%) and the anastomosis between the RHA and the gastro-duodenal artery (6 cases, 10.6%); rare reconstructions were performed in 9 cases (16.0%). The rate of hepatic artery thrombosis was 5.4% (3 of 56 OLT) in complex hepatic artery reconstructions and 2.2% in other grafts. One- and 5-years graft and patient actuarial survival rates have been respectively 73.2%- 71.4% in hepatic artery reconstructions and 78.6%-76.8% in the absence of an artery reconstruction, respectively.

Unusual peripheral T cell lymphoma presenting as acute liver failure and reappearing in the liver allograft.

A 25-year-old man presented with fulminant hepatic failure from an unusual peripheral T cell lymphoma involving the liver and spleen without lymphadenopathy. He underwent liver transplantation before establishing a definitive diagnosis and 21 days later, died from liver allograft failure because of recurrent lymphoma. In both the native liver and hepatic allograft, the lymphoma presented as a sparse cytologically atypical malignant infiltrate intermixed with numerous reactive macrophages, which showed marked angio- and epitheliotropism and irregular areas of coagulative necrosis. The malignant cells were CD3+/ granzyme B+/TIA1+/CD8-/CD56-/S100-- with variable staining for beta F1, CD5, and CD7. Multiplex polymerase chain reaction (PCR) showed rearrangement of the T cell receptor gamma chain gene in the native and transplanted liver and spleen. Even in the absence of a mass lesion or lymphadenopathy, peripheral T cell lymphoma should be included in the differential diagnosis of fulminant hepatic failure in young patients who show no evidence of viral or autoimmune diseases.

Hepatitis C virus infection in liver allograft recipients.

The impact of HCV infection after liver transplantation remains a topic of discussion. The aims of this study were to define the prevalence of anti-HCV antibodies in liver donors; the risk of acquired HCV infection and HCV re-infection according to the pre-transplant anti-HCV status; the prevalence of HCV infection in post-transplant chronic hepatitis. Sera from 42 recipients with follow up longer than 6 months and their donors were tested for anti-HCV. By results at pre-transplant time patients were classified as follows: donor (D) negative and recipient (R) negative (D-/R-) 31; D-/R+ 9; D+/R- 1; D+/R+ 1. Twenty-one patients with sustained hepatic dysfunction underwent liver biopsy. In group D-/R-, 5 patients showed anti-HCV positivity and 3 (9.7%) of them had acquired HCV hepatitis. In group D-/R+, 6 patients showed persistent anti-HCV positivity and 4 (44.4%) of them had recurrent HCV hepatitis; of these 2 died due to liver failure. The 2 patients of groups D+/R- and D+/R+ had normal liver function. Anti-HCV negative hepatitis was found in 2 patients. The prevalence of anti-HCV positivity in liver donors appeared low (3.2%). Acquired HCV infection rate was 9.7%. Pre-transplant HCV infection led to a high incidence of recurrence (44.4%). HCV was the major etiological agent in post-transplant chronic hepatitis (77.8%).

[Hepatitis B and D recurrence after liver transplantation]. / Ricorrenza epatitica da HBV-HDV dopo trapianto di fegato.

In Italy, many patients with B-virus (HBV) and Delta-virus (HDV) end-stage liver disease, are potential candidates to liver transplantation. Several authors have reported 70 to 100% hepatitis recurrence rates. From june 1983 to may 1989, 72 transplants on 60 patients were performed at Liver Transplantation Department of the Maggiore-Policlinico Hospital of Milan. The results in 26 HBsAg positive patients (19 with HDV infection), that underwent liver transplantation, are reported. A detailed report of 17 of these patients with a follow-up longer 7 months, and the clinical course of 4 patients with HBV reinfection, 3 of which had hepatitis recurrence, is also presented. The occurrence of HDV-RNA in the serum of 5 patients, that were negative for HBsAg and also other HBV-HDV replication markers after transplantation is discussed, together with the observation that in these patients no hepatitis recurrences or alteration of the clinical course were evident.

Left lung allotransplantation in pig feasibility and transplanted lung function. Experimental Lung Transplant Group of Ospedale Maggiore of Milan.

Changing attitudes to animals in research and practical considerations prompted the authors to evaluate whether the pig might be a suitable substitute for dog and baboons for single left lung transplants. Twenty-nine paired pigs were used. The first transplants on 13 pairs (group 1) were done to adapt the lung transplant technique to pigs; later transplants on 16 pig pairs (group 2) were done to evaluate operative survival, and function and histological modifications of the transplanted lung in the absence of immunosuppressive treatment. Surgical and anesthetic techniques for both donor and recipient are described in detail. The survival rate in group 2 was 68%. Hemodynamic and blood gas changes were assessed during operation. PaO2 did not drop significantly after occluding the right pulmonary artery by an inflatable cuff placed around it; this suggests that the function of the transplanted lung was preserved. The pigs were put down on the third postoperative day. Vascular and bronchial anastomoses were patent and intact, but the transplanted lung was macroscopically and microscopically altered. Lung transplants can be performed in pigs and the transplanted lung seems to be capable of functioning immediately after the operation. Alteration in the lung after 3 days is probably due to rejection.

[Major surgical complications after 73 consecutive liver transplantations]. / Complications chirurgicales majeures après 73 transplantations hépatiques consécutives.

In order to evaluate the incidence of postoperative surgical complications requiring additional surgery, we report 73 consecutive liver orthotopic transplantations performed in 60 patients from June 1983 through June 1989. Transplantations were performed in 54 adults and 6 children for the following reasons: postnecrotic cirrhosis in 31, biliary diseases in 16, hepatobiliary malignancy in 7; Wilson's diseases in 3 and fulminant hepatitis in 3. Surgical complications requiring additional surgery occurred in 35 (58%) patients with 53 operations. Twenty-two patients (36%) had postoperative bleeding complications, 5 (8%) biliary complications, one had a late artery thrombosis and 16 (26%) had miscellaneous complications. The latter group included 6 abdominal hernias, 3 bowel perforations, 2 bowel obstructions, 2 cases of pneumothorax, 2 cases of chylous ascitis, one liver necrosis, one hepatic artery kinking, one peritonitis and one cardiac tamponade. The incidence of surgical complications was not significantly different in patients who underwent retransplantation as compared to those who had a single transplantation. We did not find a significant difference in surgical complication rate according to the preoperative liver disease. In comparison with the literature, in our series, we had a higher rate of abdominal hernia but a lower rate of biliary complications.

[Current therapeutic indications and possibilities in prolonged respiratory insufficiency (collective review) ]. / Attuali indicazioni e possibilità terapeutiche sulla insufficienza respiratoria prolungata (Rassegna sintetica).

The article provides a synthetic review of the most current problems of treatment of acute respiratory insufficiency refractory to standard and conventional therapeutic remedies using extracorporal membrane gas exchangers. On the basis of a review of the literature on the subject, the advantages and disadvantages of each main type of oxygenator are considered and critically evaluated with regard to metabolic, haemodynamic and circulatroy activity and the repercussions of each resuscitation technique on haemocoagulation.

[Problems of anesthesia and resuscitation in drepanocytic anemia]. / Problemi di anestesia e rianimazione nelle anemie drepanocitiche.

A study was made of anesthesiological and resuscitation problems in 18 patients suffering from drepanocytic anemia. An examination of the results showed that the anesthesiological problems do not so much concern selection of the anesthetic as a knowledge of the physiopathology of this disease, i.e. the tendency to bronchopulmonary complications as a result of the increased viscosity of the blood, the increased mechanical fragility of the erythrocytes, and erythrostasis, with consequent rise of ischaemic necrosis and damage to the various parenchymas. It was also observed that pulmonary complications occurred more frequently in preoperatively transfused patients.

[Renal resistance in ethrane anesthesia]. / Le resistenze renali in anestesia etranica.

The indices of renal functionality are studied during the course of ether anesthesia in order to ascertain the behaviour of the kidney subjected to narcosis with this drug. A sharp reduction in the minute volume of F.G. and P.R.E. is evidenced, together with an increase in renal resistances, especially as regards the efferent sector. These changes, which are established at the start of anesthesiological treatment, tend to decrease in intensity as narcosis continues. This picture is interpreted as being due to the concomitant action of two factors: a decrease in cardiac output on the one hand, and an increased incretion of catecholamines leading to renal arteriolar vasoconstriction on the other.

[Circulatory flow during anesthesia with enflurane]. / La portata circolatoria in anestesia con enflurane.

The rebreathing technique was used to study the behaviour of the circulatory flow in patients operated under ether anesthesia. It was observed that during ether narcosis the circulatory flow values show a fair drop at the readings made 30' and 45' after the inductive period. 60' after the start of ether narcosis the circulatory flow values show a tendency to increase, and these observations are accentuated in the readings taken at 75' and 90'.

Ischemia time and liver transplantation, today.

The aim of our study was to retrospectively evaluate the impact of ischemia time and other clinical factors on the development of liver allograft primary nonfunction (PNF). We enrolled 531 consecutive liver transplantations from 1998 to 2013, identifying 10 PNF (1.9%). PNF was found to be statistically related to 4 different variables: donor age>60 years (P=.01), female donor gender (P=.01), total ischemia time>10 hours (P=.03) and infusion of more than 30 fresh frozen plasma units during surgery (P=.02). The study focused on the clinical impact of total ischemia time. We grouped total ischemia time into 4 groups (Group 1: ≤7.5 hours; Group 2: between 7.5 and 10 hours; Group 3: between 10 and 12 hours; Group 4: >12 hours) and 2 groups (assigning a cut-off value of 10 hours): both these grouping systems significantly influenced the development of PNF and 1-year graft survival, with limited impact on long-term survival. We split total ischemia time in a "technical time," "hepatectomy time," and "warm ischemia time." Only the first 2 components were found to be statistically related to PNF development with P=.02 and P=.003, respectively. Further studies should focus on these aspects of PNF.

Arterial anastomosis in liver transplantation for Rendu-Osler-Weber disease: two case reports.

Liver transplantation (LT) in patients with hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber, disease is a problematic procedure. In patients with hepatic involvement due to clinically significant arterovenous malformations, there is high risk of intraoperative bleeding and intra- or perioperative complications. Some surgical corrections have been proposed for venous problems, concerning the vena caval anastomosis. A common finding in HHT is arterial enlargement of the celiac trunk and of the common hepatic artery. We report 2 cases of LT in HHT where the arterial anastomosis was successfully performed using the splenic artery of the recipient, which shows less tendency for enlargement than the celiac trunk.

Hyperbilirubinemia after liver transplantation: the role of coupled plasma filtration adsorption.

Hyperbilirubinemia often accompanies liver failure; therefore, artificial liver support devices are currently used as a bridge to more definitive treatments to eliminate water-soluble and albumin-bound toxins. We report 2 patients, of which, after liver transplantation, the first experienced early allograft dysfunction and the other hyperbilirubinemia linked to chronic rejection. After 3 cycles of coupled plasma filtration adsorption (CPFA), the bilirubin promptly decreased in both cases. CPFA is an extracorporeal therapy that uses plasma filtration associated with an adsorbent cartridge and hemofiltration to remove cytokines and inflammatory mediators associated with septic shock, severe sepsis, and multiple organ dysfunction syndrome. Each cycle of treatment lowered the bilirubin of our patients by ∼40%. CPFA deserves attention as a potential inexpensive short-lasting device to treat hyperbilirubinemia after liver surgery or transplantation. Moreover, the effects of CPFA should be further studied to address inflammatory mediators in chronic rejection after liver transplantation or other immunologic disorders.

Fulminant multiorgan failure due to varicella zoster virus and HHV6 in an immunocompetent adult patient, and anhepatia.

Varicella is a well-known contagious disease of childhood that can also affect both immunodepressed and immunocompetent adults. The present observations concern a previously healthy adult patient who presented with a fulminant hepatitis evolving in multiorgan failure (MOF), associated with an atypical papulo-ethemateous cutaneous rash without fever. An hepatic biopsy showed massive necrosis. Because of the persistent MOF and severe hemodynamic instability, total hepatectomy was performed as a bridge to urgent liver transplantation (OLT). Despite temporary improvement, the patients condition progressively deteriorated and he died 11 hours after the hepatectomy, i.e. 7 days after admission to the intensive care unit. High viral loads of varicella zoster virus (VZV) and human herpes virus 6 (HHV6) were demonstrated in the blood and in DNA at post mortem examination of the liver, kidneys, lung, and heart. We hypothesize that VZV infection may occasionally occur in immunocompetent patients due to extremely virulent strains that can be rapidly fatal. The clinical influence of simultaneous infection with HHV6 is not clear. Moreover, the role of a previous steroid treatment as a trigger for a temporary immunodepressed state must be considered. The diagnosis of liver disease from VZV should always be clinically suspected in the presence of concurrent atypical skin lesions and a temporarily immunocompromised state. Therapy with acyclovir was ineffective in our patient. Based on the wide spectrum of VZV infections, fulminant MOF in immunocompetent adults must raise the possibility of VZV with simultaneous HHV6 infection with early listing of the patient for a urgent OLT, possibly with a total hepatectomy as a bridge, due to the therapeutic uncertainty of medical treatments.