Winston R. Hewitt

Donor age affects fibrosis progression and graft survival after liver transplantation for hepatitis C

Background. The use of liver allografts from an older donor (OD) (age >50 years) is a widespread strategy to manage the disparity between supply and demand of organs for liver transplantation. This study determines the effect of OD allografts on fibrosis progression and graft survival after liver transplantation in patients with and without infection caused by hepatitis C virus (HCV). Methods. All patients undergoing liver transplantation at our center from March 1998 to December 2001 were analyzed. Protocol liver biopsies were performed at 1, 16, and 52 weeks after transplantation and yearly thereafter. One liver pathologist scored all biopsy specimens for modified hepatic activity index (0–18) and fibrosis (0–6). Results. A total of 402 patients (167 with HCV and 235 without HCV) underwent liver transplantation during the study period. Among patients with HCV, baseline characteristics of OD recipients were similar to younger donor (YD) (age <50 years) recipients. In patients with HCV, graft survival was shorter in OD graft recipients than in YD recipients (P <0.001). In patients without HCV, graft survival was independent of donor age. In patients with HCV, a fibrosis score of 3 or greater was present in 17% of OD recipients at 4 months and in 26% at 12 months after transplantation, compared with 8% of YD recipients at 4 months and 13% at 12 months (P <0.001). Conclusions. Liver transplantation with OD grafts is associated with rapid progression of fibrosis and decreased graft survival in patients with HCV, but not in patients without HCV. OD grafts should be considered preferentially for patients without HCV.

Liver Transplantation Using Controlled Donation After Cardiac Death Donors: An Analysis of a Large Single-Center Experience

The use of donation after cardiac death (DCD) donors may provide a valuable source of organs for liver transplantation. Concerns regarding primary nonfunction (PNF) and intrahepatic biliary stricture (IHBSs) have limited the enthusiasm for their use. A retrospective analysis of 1436 consecutive deceased donor liver transplants performed between December 1998 and October 2006 was conducted. These included 108 DCD liver transplants, which were compared to 1328 transplants performed with organs from donors meeting the criteria for donation after brain death (DBD). The median follow‐up was 48 months. The 1‐, 3‐, and 5‐year patient survival and graft survival for DCD donors were 91.5%, 88.1%, and 88.1% and 79.3%, 74.5%, and 71.0%, respectively. The 1‐, 3‐, and 5‐year patient survival and graft survival for DBD donors were 87.3%, 81.1%, and 77.2% and 81.6%, 74.7%, and 69.1%, respectively. Patient survival and graft survival were not significantly different between DCD donors less than 60 years old, DCD donors greater than 60 years old, and DBD donors. Causes of graft loss included IHBSs (n = 9), PNF (n = 4), recurrent hepatitis C virus (n = 4), hepatic artery thrombosis (n = 1), rejection (n = 2), and patient death (n = 13). Contrary to previously published data, excellent long‐term patient survival and graft survival can be obtained with DCD allografts, and in our experience, they are equivalent to those obtained from DBD allografts. Liver Transpl 15: 1028–1035, 2009.

Long-term outcomes of donation after cardiac death liver allografts from a single center.

Abstract:  Organ shortage continues to be a major challenge in transplantation. Recent experience with controlled non‐heart‐beating or donation after cardiac death (DCD) are encouraging. However, long‐term outcomes of DCD liver allografts are limited. In this study, we present outcomes of 19 DCD liver allografts with follow‐up >4.5 years. During 1998–2001, 19 (4.1%) liver transplants (LT) with DCD allografts were performed at our center. Conventional heart‐beating donors included 234 standard criteria donors (SCD) and 214 extended criteria donors (ECD). We found that DCD allografts had equivalent rates of primary non‐function and biliary complications as compared with SCD and ECD. The overall one‐, two‐, and five‐yr DCD graft and patient survival was 73.7%, 68.4%, and 63.2%, and 89.5%, 89.5%, and 89.5%, respectively. DCD graft survival was similar to graft survival of SCD and ECD in non hepatitis C virus (HCV) recipients (p > 0.370). In contrast, DCD graft survival was significantly reduced in HCV recipients (p = 0.007). In conclusion, DCD liver allografts are durable and have acceptable long‐term outcomes. Further research is required to assess the impact of HCV on DCD allograft survival.

Excellent Renal Allograft Survival in Donor-Specific Antibody Positive Transplant Patients—Role of Intravenous Immunoglobulin and Rabbit Antithymocyte Globulin

Background. Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients. Methods. A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses. Results. Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups. Conclusions. Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.

Gallbladder carcinosarcoma: A case report and literature review

Carcinosarcoma of the gallbladder is a rare malignancy characterized by both malignant epithelial and mesenchymal components. The clinical behavior of this tumor is extremely aggressive. Only 26 cases have been reported in the world literature to date. We report the case of a 64-year-old woman who had fever associated with a right upper quadrant mass. An exploratory laparotomy through a right upper quadrant incision was performed at another institution, and the patient was thought to have severe acute cholecystitis that would require additional antibiotic therapy before attempted resection. She was referred to our center, where abdominal CT showed a 6.4 × 8.2 cm pericholecystic mass involving the hepatic flexure of the colon. The patient underwent cholecystectomy and hepatic wedge resection, pancreaticoduodenectomy, and right hemicolectomy. Pathologic examination of the surgical specimen revealed two histologic components consisting of squamous cell carcinoma and spindle cell sarcoma of gallbladder origin, consistent with carcinosarcoma. All seven lymph nodes in the pancreaticoduodenectomy specimen were negative for tumor. We present this case and a review of the literature and current treatment recommendations.

Surgical site infection after liver transplantation: risk factors and association with graft loss or death.

Background. Risk factors for surgical site infection (SSI) after liver transplantation and outcomes associated with these infections have not been assessed using consensus surveillance and optimal analytic methods. Methods. A cohort study was performed of patients undergoing first liver transplantation at Mayo Clinic, Jacksonville, Florida, in 2003 and 2004. SSIs were identified by definitions and methods of the National Nosocomial Infections Surveillance System. Measures of known or suspected risk factors for SSI, graft loss, or death were collected on all patients. Associations of SSI with these factors and also with the primary composite endpoint of graft loss or death within 1 year of liver transplantation were examined using Cox proportional hazards models; relative risks (RRs) were estimated along with 95% confidence intervals (CIs). Results. Of 370 patients, 66 (18%) had SSI and 57 (15%) died or sustained graft loss within 1 year after liver transplantation. Donor liver mass-to-recipient body mass ratio of less than 0.01 (RR 2.56; 95% CI 1.17–5.62; P=0.019) and increased operative time (RR 1.19 [1-hr increase]; 95% CI 1.03–1.37; P=0.018) were associated with increased SSI risk. SSI was associated with increased risk of death or graft loss within the first year after liver transplantation (RR 3.06; 95% CI 1.66–5.64; P<0.001). Conclusion. SSI is associated with increased risk of death or graft loss during the first year after liver transplantation. Increased operative time and decreased donor liver-to-recipient body mass ratio showed evidence of association with SSI.

Peritonitis after liver transplantation: Incidence, risk factors, microbiology profiles, and outcome

Peritonitis occurring after liver transplantation (PLT) has been poorly characterized to date. The aims of this study were to define the incidence, risk factors, microbiology profiles, and outcome of nonlocalized PLT. This was a retrospective study of 950 cadaveric liver transplantation (LT) procedures in 837 patients, followed for a mean of 1,086 days (range, 104‐2,483 days) after LT. PLT was defined as the presence of at least one positive ascitic fluid culture after LT. There were 108 PLT episodes in 91 patients occurring at a median of 14 days (range, 1‐102 days) after LT. Significant risk factors associated with the development of PLT by multivariate analysis included pre‐LT model for end‐stage liver disease score, duration of LT surgery, Roux‐en‐Y biliary anastomosis, and renal replacement therapy after LT. Biliary complications, intra‐abdominal bleeding, and bowel leak/perforation were associated with 34.3%, 26.9%, and 18.5% of episodes, respectively. Multiple organisms, gram‐positive cocci, fungus, and multidrug‐resistant bacteria were isolated in 61.1%, 92.6%, 25.9%, and 76.9% of ascitic fluid cultures, respectively. The 28 fungal PLT episodes were associated with bowel leak/perforation and polymicrobial peritonitis. Patients who developed PLT after their first LT had a significantly greater risk of graft loss or mortality compared to unaffected patients. Parameters significantly associated with these adverse outcomes by multivariate analysis were recipient age at LT and bowel leak or perforation after LT. In conclusion, PLT is a serious infectious complication of LT, associated with significant intra‐abdominal pathology and reduced recipient and graft survival. Liver Transpl 12:1244‐1252; 2006.

Polycystic Liver Disease and Liver Transplantation: Single-Institution Experience

Adult polycystic liver disease (PLD) can cause massive hepatomegaly leading to pain, caval obstruction, and hemorrhage. Many surgical techniques including aspiration, fenestration, and resection have been used to treat PLD. In addition to substantial morbidity and mortality, conservative surgery may have limited success, and palliation may be temporary. With improved results of liver transplantation, it has become the definitive treatment for PLD. We retrospectively reviewed our experience in patients with PLD between 1998 and 2007. Thirteen patients underwent liver only or liver-kidney transplantation. All surgical procedures were performed with preservation of the recipient inferior vena cava and without venovenous bypass (piggyback technique). Our patients experienced a high rate of perioperative morbidity. However, long-term patient and graft survival were excellent.

Liver retransplantation of patients with hepatitis C infection is associated with acceptable patient and graft survival

Infection with hepatitis C virus (HCV) is the leading cause of liver transplantation (LT), while liver retransplantation (RT) for HCV is controversial as a result of concerns over poor outcomes. We sought to compare patient and graft survival after RT in patients with and without HCV. We performed a retrospective chart review of all patients undergoing RT at our center between February 1998 and April 2004. Indications for RT, HCV status, patient, and donor characteristics, laboratory values, and hospitalization status at RT were collected. A total of 108 patients (48 HCV and 60 non‐HCV) underwent RT during the study period, with mean post‐RT follow‐up of 1,096 days (range, 0‐2,888 days). Grafts from donors aged >60 years were used less frequently in HCV patients at RT (6%) compared with LT (47%), P < 0.001. There was no difference between HCV vs. non‐HCV patients in 1‐ and 3‐year patient survival (respectively, 79% vs. 63%, and 71% vs. 63%) and graft survival (respectively, 67% vs. 66%, and 59% vs. 56%). Post‐RT mortality and graft failure in HCV patients occurred within the first year in 89% of patients, and 83% were unrelated to HCV recurrence. We conclude that patients should not be excluded from consideration for retransplantation solely on the basis of a diagnosis of HCV. Liver Transpl 13:1717–1727, 2007.

Immunosuppression in pediatric liver transplant recipients: Unique aspects.

Pediatric liver transplantation has experienced improved outcomes over the last 50 years. This can be attributed in part to establishing optimal use of immunosuppressive agents to achieve a balance between minimizing the risks of allograft rejection and infection. The management of immunosuppression in children is generally more complex and can be challenging when compared with the use of these agents in adult liver transplant patients. Physiologic differences in children alter the pharmacokinetics of immunosuppressive agents, which affects absorption, distribution, metabolism, and drug excretion. Children also have a longer expected period of exposure to immunosuppression, which can impact growth, risk of infection (bacterial, viral, and fungal), carcinogenesis, and likelihood of nonadherence. This review discusses immunosuppressive options for pediatric liver transplant recipients and the unique issues that must be addressed when managing this population. Further advances in the field of tolerance and accommodation are needed to relieve the acute and cumulative burden of chronic immunosuppression in children. Liver Transplantation 23 244–256 2017 AASLD