Barry G. Rosser

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.

Efficacy of tacrolimus in the treatment of steroid refractory autoimmune hepatitis.

Background Autoimmune hepatitis (AIH) is an immune mediated chronic liver disease with a prevalence of 17 cases/100,000. Resistance to the standard treatment of AIH (prednisone and azathioprine) occurs in 15% to 20%. There is currently no standard treatment of patients with steroid refractory AIH. Goals Determine the efficacy of tacrolimus in the treatment of steroid refractory AIH. Methods This is a retrospective study evaluating the efficacy of Tacrolimus in the treatment of steroid refractory AIH. Results Between October 1998 and February 2002, 11 patients with steroid refractory AIH were treated with tacrolimus. Mean age was 63 years. Median duration of steroid treatment before starting tacrolimus was 9 months. Median duration of tacrolimus treatment was 25 months. Median follow-up period was 16 months. Median baseline ALT, AST were 77 U/L and 68 U/L and became 21 U/L and 32 U/L respectively at end of follow-up (P = 0.005 and 0.01 respectively). Significant weight reduction was seen in all patients (P = 0.02). Tacrolimus treatment was safe and well tolerated. Conclusion Use of low dose tacrolimus led to successful biochemical and histologic remission and weaning off prednisone in patients with steroid refractory AIH. This data supports further studies in evaluating the use of tacrolimus in the treatment of AIH.

Prevalence and natural history of gastric antral vascular ectasia in patients undergoing orthotopic liver transplantation

Goals: To describe the prevalence and natural history of gastric antral vascular ectasia (GAVE) in patients with end-stage liver disease undergoing orthotopic liver transplantation (OLT). Background: GAVE is a well-recognized cause of gastrointestinal hemorrhage. Although 30% of patients with GAVE have liver disease, the prevalence of GAVE in patients with cirrhosis is not known. Study: We reviewed clinical records of patients who underwent OLT at our institution from February 1, 1998 to June 2003. Demographic and clinical details were recorded with attention to findings during upper endoscopy before and after OLT. Results: A total of 597 patients underwent OLT, and 345 were evaluated preoperatively with esophagogastroduodenoscopy (EGD). Eight (2.3%) were found to have GAVE before OLT. Three of these eight underwent EGD after OLT, and GAVE was absent in all three. None of the patients with GAVE experienced gastrointestinal bleeding postoperatively. Conclusions: GAVE was present in nearly 1 in 40 patients with end-stage liver disease who underwent EGD before OLT at our institution and appears to resolve after transplant. These findings are consistent with a previous report documenting resolution of GAVE after OLT.

Kidney allocation to liver transplant candidates with renal failure of undetermined etiology: Role of percutaneous renal biopsy

The feasibility, value and risk of percutaneous renal biopsy (PRB) in liver transplant candidates with renal failure are unknown. PRB was performed on 44 liver transplant candidates with renal failure of undetermined etiology and glomerular filtration rate (GFR) <40 mL/min/1.73 m2 (n = 37) or on renal replacement therapy (RRT) (n = 7). Patients with ≥30% interstitial fibrosis (IF), ≥40% global glomerulosclerosis (gGS) and/or diffuse glomerulonephritis were approved for simultaneous‐liver‐kidney (SLK) transplantation. Prebiopsy GFR, urinary sodium indices, dependency on RRT and kidney size were comparable between 27 liver‐transplant‐alone (LTA) and 17 SLK candidates and did not relate to the biopsy diagnosis. The interobserver agreement for the degree of IF or gGS was moderate‐to‐excellent. After a mean of 78 ± 67 days, 16 and 8 patients received LTA and SLK transplants. All five LTA recipients on RRT recovered kidney function after transplantation and serum creatinine was comparable between LTA and SLK recipients at last follow‐up. Biopsy complications developed in 13, of these, five required intervention. PRB is feasible in liver transplant candidates with renal failure and provides reproducible histological information that does not relate to the pretransplant clinical data. Randomized studies are needed to determine if PRB can direct kidney allocation in this challenging group of liver transplant candidates.

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.

Use of liver grafts from donation after cardiac death donors for recipients with hepatitis C virus

Hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation in the United States. Although studies have addressed the use of expanded criteria donor organs in HCV+ patients, to date the use of liver grafts from donation after cardiac death (DCD) donors in HCV+ patients has been addressed by only a limited number of studies. This retrospective analysis was undertaken to study the outcomes of DCD liver grafts used in HCV+ recipients. Seventy‐seven HCV+ patients who received DCD liver grafts were compared to 77 matched HCV+ patients who received donation after brain death (DBD) liver grafts and 77 unmatched non‐HCV patients who received DCD liver grafts. There were no differences in 1‐, 3‐, and 5‐year patient or graft survival among the groups. Multivariate analysis showed that the Model for End‐Stage Liver Disease score [hazard ratio (HR) = 1.037, 95% confidence interval (CI) = 1.006‐1.069, P = 0.018] and posttransplant cytomegalovirus infection (HR = 3.367, 95% CI = 1.493‐7.593, P = 0.003) were significant factors for graft loss. A comparison of the HCV+ groups for fibrosis progression based on protocol biopsy samples up to 5 years post‐transplant did not show any difference; in multivariate analysis, HCV genotype 1 was the only factor that affected progression to stage 2 fibrosis (genotype 1 versus non‐1 genotypes: HR = 2.739, 95% CI = 1.047‐7.143, P = 0.040). In conclusion, this match‐controlled, retrospective analysis demonstrates that DCD liver graft utilization does not cause untoward effects on disease progression or patient and graft survival in comparison with DBD liver grafts in HCV+ patients. Liver Transpl 17:641‐649, 2011.

Hepatitis C recurrence is not associated with allograft steatosis within the first year after liver transplantation

The natural history of allograft steatosis in hepatitis C (HCV)‐infected patients after liver transplantation (LT) is poorly understood. The aim of our study was to determine the relationship of allograft steatosis to HCV recurrence after LT. All patients undergoing LT at our center from March 1998 to December 2001 were included in the study. Explanted liver tissue and liver biopsies performed at 1 week, 4 months, and 12 months were scored for degree of allograft steatosis (0–4), fibrosis (0–6), and modified histological activity index (0–18). One hundred sixty‐seven HCV and 235 non–HCV‐infected patients (control group) underwent LT. Of these patients, 122 HCV and 154 non‐HCV patients had a viable graft at 1 year and were analyzed. Allograft steatosis was present in 40% of HCV patients at 4 months and 36% at 1 year. The incidence of allograft steatosis after LT was similar in HCV‐infected and non–HCV‐infected patients (P not significant). Age of the donor (P = .041), or higher recipient body mass index (BMI) at the time of LT (P = .015) or at 12 months after LT (P = .041) predicted a higher degree of allograft steatosis at 12 months in the HCV group. Degree of allograft steatosis was not associated with higher fibrosis or necroinflammatory score. In conclusion, there is a similar high incidence of allograft steatosis in HCV and non–HCV‐infected patients after LT. A high BMI of the HCV‐infected recipient is the best predictor for high degree of allograft steatosis after LT. Allograft steatosis does not predict the severity of HCV recurrence in the first 12 months after LT. (Liver Transpl 2004;10:599–606.)

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.

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.