Suppressing hepatitis C virus (HCV) before and after liver transplantation (LT) should be a key to prevent clinically significant recurrence (1–3). Occult HCV infection has been described as the presence of detectable HCV RNA in the liver or peripheral blood mononuclear cells with undetectable plasma HCV RNA by PCR assays (4). In that situation, even though HCV RNA seemed to disappear from serum, it would be possible that HCV replicates significantly under posttransplant immunosuppression, leading to clinically significant HCV recurrence. There is a paucity of literature focusing on this population. From 2005 to 2012, all LT patients with HCV at our institution were retrospectively evaluated. Exclusion criteria were as follows: no clinical information for pretransplant HCV RNA level, HCV antibody negative despite a clinical history associated with HCV infection, early mortality (within 30 days after LT), and patients without post-LT biopsy or measurement of HCV RNA. Our standard maintenance immunosuppression regimen consisted of tacrolimus, mycophenolate mofetil, and steroids. Patients also received induction immunosuppression with rabbit anti-thymocyte globulin (0.5–1.0 mg/kg, postoperative day 1, 3, and 5) or basiliximab (20 mg, postoperative day 0 and 4) whereas some patients were given no induction agents, at the surgeon’s discretion. HCV RNA PCR was performed by the Bayer Verant HCV branched DNA assay version 3.0 (the lower limit of detection was 615 IU/mL) or by Roche COBAS Ampliprep and COBAS TaqMan HCV test (the lower limit of detection was 43 IU/mL). Protocol liver biopsy was performed at 6 months post-LT, and additional biopsies done selectively based on clinical findings. Posttransplant antiviral therapy, consisting of pegylated interferon and ribavirin, was considered, when stage 2 or greater fibrosis developed. A total of 22 patients were found to be HCV antibody positive and had undetectable HCV RNA at LT (Table 1). These 22 did not receive HCV positive donor liver grafts. Eight of 22 (36%) showed detectable HCV RNA and 14 (64%) showed sustained negative HCV RNA after LT. Four of six with genotype 1a or 1b developed virologic recurrence, compared to one of five with genotype 3a (P=0.12). Of the nine patients who achieved sustained virologic response (SVR) before LT, only one developed virologic recurrence. However, this patient’s HCV RNA became undetectable without antiviral therapy at 7 months. Conversely, all patients (100%) with detectable HCV RNA at LT (n=162) developed virologic recurrence (P<0.001). Posttransplant antiviral therapy was given in three (cases 6, 10, and 19) in the undetectable group, of whom SVR was achieved in one (case 10), whereas 37 in the detectable group received therapy and 13 achieved SVR (P=0.95).TABLE 1: Patient characteristics and HCV outcome in the group of pretransplant undetectable HCV RNAHistological recurrence and patient survival were compared between the groups of pretransplant undetectable and detectable HCV RNA. There was no difference in terms of patient characteristics between these two groups. Cumulative rate of histological recurrence in these two groups were similar (P=0.31 for F2–4) (Fig. 1A). No patient in the group of undetectable HCV RNA developed fibrosing cholestatic hepatitis, compared to 10 of 162 (6%) in the group of detectable HCV RNA (P=0.23). Overall survival was also comparable (P=0.36) (Fig. 1B), though there were no mortalities secondary to HCV recurrence in the undetectable group.FIGURE 1: Comparison of histological recurrence of HCV and overall survival between the detectable and undetectable HCV RNA before liver transplantation. (A) Endpoint as stage 2 to 4 fibrosis (F2–4). There was no statistically significant difference (P=0.31). (B) Endpoint as overall survival. There was no statistically significant difference (P=0.36), whereas no mortality secondary to HCV recurrence was observed in the undetectable HCV RNA group.According to our experience, pretransplant undetectable HCV RNA did not necessarily lead to persistently negative HCV RNA; rather, half of these patients developed significant histological recurrence (F2–4). This was comparable to those with pretransplant detectable HCV RNA. It is important to acknowledge the fact that HCV potentially exists in the liver or peripheral blood mononuclear cells, or both, even in the setting of undetectable HCV RNA in serum, which could lead to rather high histological recurrence after LT (5, 6). Unfortunately, those tissue samples were not available in our current series. It may be beneficial to measure HCV RNA in the explant liver tissue in this population, so that we can closely monitor possible recurrence of HCV after LT (7). Meticulous peritransplant management is required even in the setting of undetectable HCV RNA. It has been reported that virologic recurrence rates in patients who responded to pretransplant antiviral therapy ranged 33.3% to 80%, emphasizing a positive effect of pre-LT therapy on post-LT outcome (1, 2, 8, 9). Outcomes appear better, when SVR was achieved before LT (only one of nine [11%] developed HCV histological recurrence in this series). Pretransplant antiviral therapy has been shown to be effective at preventing posttransplant recurrence in selected patients (10). The indication and protocol of pretransplant antiviral therapy should be more closely investigated to determine which patients would benefit. Clearly, SVR before LT would be promising to decrease recurrence and improve survival in this population. Shunji Nagai 1 Gabriel T. Schnickel1 Ioannis Theodoropoulos1 David A. Bruno1 Marwan Kazimi1 Kimberly A. Brown2 Atsushi Yoshida1 Marwan S. Abouljoud1 1Division of Transplant and Hepatobiliary Surgery Henry Ford Transplant Institute Henry Ford Hospital Detroit, MI 2Division of Gastroenterology Henry Ford Hospital Detroit, MI
Graft thrombosis and infectious complications are the main early causes of pancreatic allograft loss in recipients of whole vascularized pancreas transplants, resulting in loss rates up to 10 per cent in the first post transplant week. In this study we sought to determine if initiation of a standardized selection criteria and posttransplant chemoprophylaxis regimen could reduce the rate of early allograft loss; we compared the rate of early allograft loss after introduction of these changes. Of the 61 diabetic recipients who underwent these protocols, 50.8 per cent were female. Average age was 42.9 ± 7.4 years of age, average length of stay was 12.7 ± 8.7 days, with all transplants performed heterotopic to the right lower quadrant with venous drainage to the proximal external or common iliac vein. Organ donors were 21.4 ± 4.8 years of age, body mass index was 23.9 ± 2.8 kg/m(2), with a length of stay of 3.7 ± 1.6 days. One-week pancreatic allograft survival for the protocolized versus nonprotocolized patients was 100 per cent versus 96.7 per cent, 1 month was 98.4 per cent versus 93.4 per cent, and 1 year was 96.7 per cent versus 88.5 per cent, respectively. In the protocolized group there were two graft losses due to infectious complications and none due to thrombosis. Before initiation of the protocols patient survival at 1 year was 91.8 per cent and after was 100 per cent. Pancreas transplantation is arguably the most technically demanding organ transplant from a complication and loss standpoint. However, highly successful outcomes can be obtained with standardized protocols beginning pretransplant to reduce the incidence of posttransplant complications.
Introduction:Adequate liver perfusion is critical for allograft function following transplant. Scant flow in the hepatic artery(HA) or portal vein(PV) at implantation suggests a pending thrombosis and risk of graft loss. The implication of different flow volumes has yet to be fully elucidated. We sought to assess the impact of vascular inflow as determined by ultrasonic flow probe on short and long term outcomes. Methods:We analyzed the records of all patients who underwent liver transplant at our institution from Jan. 2000 - June 2012. Hepatic arterial and portal venous flow was measured prior to abdominal closure using ultrasonic vascular flow probes (Transonic System Inc). HA flow was stratified to low(<150ml/min), normal (150-1000 ml/min) and high (>1000ml/min). PV flow was stratified to low(<0.75L/min), normal(7.5-2L/min) and high(>2L/min). Results: 1107 consecutive liver transplants were performed, 757 had vascular flow measurements obtained at transplant. increased hepatocellular injury in the HA-low and PV-low groups demonstrated by significantly higher AST and ALT. Recipient age and true MELD were similar between groups. There were no differences in rates of biliary complications or length of stay between groups. The PV-low group had a higher rate of early re-operation. Patients with low HA or PV flow at transplant had significantly worse short and long-term survival.Table: No Caption available.Conclusion: These data suggest that low PV or HA flow is indicative of morbidity and mortality that continues beyond the perioperative period. In light of this, maneuvers to increase arterial and portal venous flow at the time of transplant may improve long-term graft function. Donor and recipient risk factors that contribute to low vascular flow at the time of transplant should be identified and alleviated.
Despite an increasing demand for liver transplantation in older patients, our understanding of posttransplant outcomes in older recipients is limited to basic recipient and graft survival. Using National Surgical Quality Improvement Program Transplant, we tracked early outcomes after liver transplantation for patients >65.We conducted a retrospective analysis of patients in National Surgical Quality Improvement Program Transplant between March 1, 2017 and March 31, 2019. Recipients were followed for 1 y after transplant with follow-up at 30, 90, and 365 d. Data were prospectively gathered using standard definitions across all sites.One thousand seven hundred thirty-one adult liver transplants were enrolled; 387 (22.4%) were >65 y old. The majority of older recipients were transplanted for hepatocellular carcinoma. The older cohort had a lower lab Model for End-Stage Liver Disease and was less likely to be hospitalized at time of transplant. Overall, older recipients had higher rates of pneumonia but no difference in intensive care unit length of stay (LOS), total LOS, surgical site infection, or 30-d readmission. Subgroup analysis of patients with poor functional status revealed a significant difference in intensive care unit and total LOS. Pneumonia was even more common in older patients and had a significant impact on overall survival.By targeting patients with hepatocellular carcinoma and lower Model for End-Stage Liver Diseases, transplant centers can achieve nearly equivalent outcomes in older recipients. However, older recipients with poor functional status require greater resources and are more likely to develop pneumonia. Pneumonia was strongly associated with posttransplant survival and represents an opportunity for improvement. By truly understanding the outcomes of elderly and frail recipients, transplant centers can improve outcomes for these higher-risk recipients.
