De Novo Autoimmune Hepatitis Following Liver Transplantation.

INTRODUCTION: De novo autoimmune hepatitis, also known as plasma cell hepatitis, is an increasingly recognized entity following liver transplantation. The aim of this study is to investigate the long-term outcomes of patients with de novo autoimmune hepatitis. METHODS: Using transplant liver biopsy database, we identified all patients showing plasma cell hepatitis following liver transplantation between 2008 and 2013. The diagnosis of plasma cell hepatitis was based on the histologic features from liver biopsies. RESULTS: A total of 30 patients with plasma cell hepatitis were identified. Underling liver disease were hepatitis C virus (n = 11) and non-hepatitis C virus-related disease (n = 19). The interval period from liver transplantation to development of plasma cell hepatitis was 20 (2-246) months during 6 (1.5-25.8) years after liver transplantation. The mean international autoimmune hepatitis score and frequency of acute cellular rejection episode prior to the diagnosis of plasma cell hepatitis were lower in the patients with hepatitis C virus than those underlying non-hepatitis C virus-related disease. Twenty-seven patients (90.0%) showed complete biochemical response to plasma cell hepatitis treatment, but 10 (37.0%) patients relapsed. During the median 72 months' follow-up after liver transplantation, 9 (30.0%) patients progressed to cirrhosis (median 37 months) and 10 (33.3%) patients died or were retransplanted. CONCLUSIONS: This long-term clinical observation shows that de novo autoimmune hepatitis represents one cause of graft loss in patients with or without hepatitis C virus. Although most patients exhibit a good response to medical therapy, de novo autoimmune hepatitis is likely to recur and progress to liver cirrhosis.

Concurrent Umbilical Hernia Repair at the Time of Liver Transplantation: A Six-Year Experience from a Single Institution.

BACKGROUND: Umbilical hernias are common in patients with end-stage liver disease undergoing liver transplantation. Management of those persisting at the time of liver transplantation is important to define. OBJECTIVE: To evaluate the long-term results of patients undergoing simultaneous primary umbilical hernia repair (UHR) at the time of liver transplantation at a single institution. METHODS: Retrospective chart review was performed on patients undergoing simultaneous UHR and liver transplantation from 2010 through 2016. 30-day morbidity and mortality outcomes and long-term hernia recurrence were investigated. RESULTS: 59 patients had primary UHR at the time of liver transplantation. All hernias were reducible with no overlying skin breakdown or leakage of ascites. 30-day morbidity and mortality included 5 (8%) superficial surgical site infections, 1 (2%) deep surgical site infection, and 7 (12%) organ space infections. Unrelated to the UHR, 10 (17%) patients had an unplanned return to the operating room, 16 (27%) were readmitted within 30 days of their index operation, and 1 (2%) patient died. With a mean follow-up of 21.8 months, 7 (18%) patients experienced an umbilical hernia recurrence. CONCLUSION: Despite the high perioperative morbidity associated with the transplant procedure, concurrent primary UHR resulted in an acceptable long-term recurrence rate with minimal associated morbidity.

Adenosine Increases Hepatic Artery Flow in Liver Transplant Recipients: A Pilot Study.

BACKGROUND: The aim of this study was to assess the effect of low-dose adenosine on hepatic artery flow (HAF) when administered intraoperatively by continuous infusion. MATERIALS AND METHODS: Between January 2009 and August 2009, 74 patients underwent orthotopic liver transplantation (OLT). Ten patients were enrolled for adenosine treatment, and 64 non-study patients served as controls. After arterial reperfusion, a 16-G central venous catheter was placed in the gastroduodenal artery, and adenosine was continuously infused at doses ranging from 0.7 to 2.8 µg/kg/min for 30 min. HAF and portal vein flow were measured using a transit time flow meter before adenosine infusion, during infusion, and 10 min after infusion. Liver function tests were monitored routinely, duplex ultrasonography was performed on postoperative day 1, and the hepatic artery resistive index measured. The patients were followed for 1 year. RESULTS: Adenosine significantly increased HAF at doses from 0.7 to 2.8 µg/kg/min. The smallest increase in HAF was 24% above the baseline; in 80% of patients, the increase in HAF was >50% of the baseline values. In 2 patients, HAF was increased by >300%. The dosing started at 0.7 µg/kg/min, and 6 of 10 patients responded. Three patients required an increase to 1.4 µg/kg/min. Doses >2.8 µg/kg/min did not further increase HAF. One patient showed a minimal response regardless of the dose. There were no differences between the adenosine group and control group with respect to liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and International Normalized Ratio), platelet count on POD2, hepatic artery resistive index, and post-transplant length of stay, intensive care days, or 1-year patient survival rates. CONCLUSIONS: This pilot study established that adenosine administered directly into the hepatic artery produces a similar effect on HAF in cadaveric liver transplant recipients to that found in the laboratory without producing systemic side effects.

Sofosbuvir and Simeprevir for the Treatment of Recurrent Hepatitis C with Fibrosing Cholestatic Hepatitis after Liver Transplantation.

Fibrosing cholestatic hepatitis (FCH) is an aggressive form of hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT), which frequently results in graft failure and death. Treatment of FCH remains challenging, and the optimal antiviral therapy is yet to be determined. Between November 2013 and early 2015, 62 patients with HCV cirrhosis underwent OLT at our transplant center, of whom, 5 patients developed recurrence HCV in the form of severe FCH and were treated with sofosbuvir and simeprevir (SOF-SMV) for 24 weeks. All patients achieved significant improvement of HCV viral load and had undetectable viral PCR at 6-8 week of treatment. The HCV RNA remained undetectable throughout treatment course. The first two patients achieved SVR at week 12 after completion of the treatment. There were significant histologic and biomarkers improvements after initiation of the treatment. One patient developed refractory pruritus and acute pancreatitis. The second, fourth and fifth patients had very benign treatment courses with no side effects recorded. The third patient was starting the treatment with multiple comorbid conditions. His course was complicated with hepatic artery thrombosis, and later developed sepsis and renal failure. Therefore, it seems that the combination of SOF-SMV is an efficacious oral regimen in OLT recipient with recurrent hepatitis C and FCH. However, safety profile needs to be carefully evaluated.

En Bloc Multivisceral and Kidney Transplantation in an HIV Patient: First Case Report.

The continual improvement in outcome with highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection and visceral transplantation for gut failure stimulated our interest in lifting HIV infection as a contraindication for intestinal and multivisceral transplantation. This report is the first to describe visceral transplantation in a patient with HIV infection. A HAART regimen was introduced in the setting of short-gut syndrome with successful suppression of HIV viral load. The indication for en bloc multivisceral and kidney transplantation was end-stage liver failure with portomesenteric venous thrombosis and chronic renal insufficiency. The underlying hepatic pathology was alcoholic and home parenteral nutrition-associated cirrhosis. Surgery was complicated due to technical difficulties with excessive blood loss and long operative time. The complex posttransplant course included multiple exploratory laparotomies due to serious intra-abdominal and systemic infections. Heavy immunosuppression was required to treat recurrent episodes of severe allograft rejection. Posttransplant oral HAART successfully sustained undetectable viral load. Unfortunately, the patient succumbed to sepsis 3 months posttransplant. With new insights into the biology of gut immunity, mechanisms of allograft tolerance, and HIV-associated immune dysregulation, successful outcome is anticipated, particularly in patients who are in need of isolated intestinal and less-organ-contained visceral allografts.

Hepatocellular Carcinoma in the Setting of Chronic Hepatitis B Virus Infection: Tumor Recurrence and Survival Rates After Liver Transplantation.

BACKGROUND: Higher rates of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in patients with chronic hepatitis B virus (HBV) infection have been reported. This can influence their selection for LT and post-LT monitoring. OBJECTIVE: The aim of this work was to compare the rates of post-LT HCC recurrence and survival in HBV and non-HBV patients with the use of the United Network for Organ Sharing (UNOS) database. METHODS: After accessing the UNOS database, we analyzed patients with HCC stage T2 who underwent LT from cadaveric donors on or after August 24, 1998. Propensity score matching based on age, Model for End-Stage Liver Disease (MELD), and donor risk index was used to match HBV-HCC patients to HCC patients with other underlying liver diseases: hepatitis C virus (HCV), alcoholic liver disease (ALD), both HCV + ALD, and nonalcoholic steatohepatitis (NASH). Kaplan-Meier plots and multivariable analysis (with the use of propensity score, age, sex, and race) were used to assess post-LT HCC recurrence and overall survival. RESULTS: A total of 4,480 HCC patients were matched. Their average age was 57 ± 7.8 years and average calculated MELD score was 13. Within 5 years of LT, 5.5% of patients had HCC recurrence and 20% died. HBV-HCC patients had 1.9 and 1.8 times higher hazard of tumor recurrence compared with ALD and NASH patients, respectively, and a 32% lower hazard of death than patients with HCV + ALD. There was no evidence of any other significant difference in HCC recurrence or survival among the etiology groups. CONCLUSIONS: HCC recurrence and survival rates following LT for HCC patients with chronic HBV infection are similar to those of HCC patients with other underlying liver diseases. These findings support LT as a viable option for HCC-HBV patients.

Treatment of Recurrent Hepatitis C Genotype-4 Post-Liver Transplantation with Sofosbuvir plus Simeprevir.

Hepatitis C virus (HCV) infection remains a leading indication for orthotopic liver transplantation (OLT) worldwide. Recurrence of HCV following OLT is universal. There is scarcity of data on the post-OLT treatment of HCV genotype-4-the predominant genotype in North Africa and the Middle East. Herein, we present three patients who have experienced HCV genotype-4 recurrence post-OLT. All three patients were interferon-naive and were treated with simeprivir (SIM) and sofosbuvir (SOF) combination therapy for 12-24 weeks. The data from this case series show that SIM+SOF are well-tolerated and effective for achieving viral clearance in HCV genotype-4 post-OLT patients. Given the limited nature of a case series, further research must be pursued regarding post-OLT HCV genotype-4 responses to direct-acting anti-viral therapy.

Split liver transplantation using Hemiliver graft in the MELD era: a single center experience in the United States.

Under the "sickest first" Model for End-Stage Liver Disease (MELD) allocation, livers amenable to splitting are most often allocated to patients unsuitable for split liver transplantation (SLT). Our experience with SLT using hemilivers was reviewed. From April 2004 to June 2012, we used 25 lobar grafts (10 left lobes and 15 right lobes) for adult-sized recipients. Twelve recipients were transplanted with primary offers, and 13 were transplanted with leftover grafts. Six grafts were shared with other centers. The data were compared with matched whole liver grafts (n = 121). In 92% of donors, the livers were split in situ. Hemiliver recipients with severe portal hypertension had a greater graft-to-recipient weight ratio than those without severe portal hypertension (1.96% vs. 1.40%, p < 0.05). Hemiliver recipients experienced biliary complications more frequently (32.0% vs. 10.7%, p = 0.01); however, the 5-year graft survival for hemilivers was comparable to whole livers (80.0% vs. 81.5%, p = 0.43). The secondary recipients with leftover grafts did not have increased incidences of graft failure (p = 0.99) or surgical complications (p = 0.43) compared to the primary recipients. In conclusion, while routine application is still controversial due to various challenges, hemiliver SLT can achieve excellent outcomes under the MELD allocation.

Combined intestine and kidney transplantation in a patient with encapsulating peritoneal sclerosis: case report.

Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis characterized by fibrosis and calcification of the intestine that, in severe cases, can progress to intestinal failure and total parenteral nutrition dependency. Medical and surgical interventions carry a poor prognosis in these patients. We describe a case of a 36-year-old female with end-stage kidney disease and severe EPS not amenable to surgical intervention who underwent a combined intestinal and kidney transplantation. At 3 years posttransplantation, the patient has normal intestinal and kidney function. This represents, to our knowledge, the first report of severe EPS and end-stage kidney disease treated with a combined transplant.

The incidence and risk factors of de novo skin cancer in the liver transplant recipients.

BACKGROUND: Liver transplantation (LT) increases the risk of de novo malignancies including skin cancers. However, risk factors for this type of cancers have not been well studied. OBJECTIVE: To determine the incidence of skin cancer in LT recipients, and to identify the risk factors of this type of cancer. METHODS: We identified all adult patients who underwent LT and developed de novo skin cancer post-LT at our institution between 1996 and 2009. We excluded the patients with history of skin cancer prior to LT. We also studied a control group of patients who underwent LT during the same period but did not develop skin cancer; the control group was matched (1:2) for age, gender and geographical place of residence. RESULTS: Over a median (IQR) follow-up of 41.5 (18.0, 98.6) months, 23 (2.3%) of 998 patients developed skin cancer post-LT, of whom 10 were identified with squamous cell carcinoma, 9 with basal cell carcinoma and 4 with melanoma. After adjusting the confounding variables, subjects who had combined liver/kidney transplant had 22 (95% CI: 5.1-99) times higher hazard of skin cancer compared to subjects with LT alone. Furthermore, patients who had non-skin cancer prior to LT had 23 (95% CI: 8.6-60) times higher hazard developing skin cancer after the transplant. Patients with history of alcohol consumption, as the underlying etiology of liver disease, had 4 (95% CI: 1.2-12.9) times higher hazard of developing skin cancer after transplantation. Type or duration of immunosuppression was not associated with increased risk of skin cancer post-LT. The post-LT survival outcome was not affected by the development of de novo skin cancer post-LT. CONCLUSION: Skin cancer is relatively common in LT recipients and should be monitored, particularly in patients with a history of pretransplant malignancy, recipients of combined liver and kidney transplant or having alcoholic cirrhosis as the underlying cause of liver disease.

Recurrence of Disease Following Liver Transplantation: Nonalcoholic Steatohepatitis vs Hepatitis C Virus Infection.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an increasing indication for orthotopic liver transplantation (OLT) in the United States and other countries. However, the incidence of disease recurrence and natural course following OLT remains incompletely understood. OBJECTIVE: To estimate the incidence of recurrent disease, outcome and identify risk factors associated with disease recurrence in patients undergoing OLT for NASH as compared to those undergoing OLT for HCV cirrhosis. METHODS: We identified all patients with end-stage liver disease secondary to NASH (n=53) or HCV (n=95) cirrhosis who underwent OLT at our institution between 1998 and 2005. Protocol liver biopsies were performed (Day 7, Month 4 and yearly) after OLT, and as clinically indicated. Kaplan-Meier survival analysis was performed to assess the fibrosis progression and survival. Cox regression analysis was performed to identify factors associated with disease recurrence. RESULTS: Five-year survival was 90.5% in NASH vs 88.4% in HCV group (p=0.97). The median (25%ile, 75%ile) follow-up to last available biopsy was 12.7 (5.9, 26.3) months, during which 17 (32%) of NASH patients developed persistent fatty infiltration in their graft, 8 (15%) of whom had accompanying histologic features of recurrent NASH. There was no difference in the prevalence of post-OLT steatosis between HCV and NASH patients after adjusting for time of histologic follow-up (p=0.33). Patients with HCV infection were more likely to develop hepatic fibrosis post-OLT than those with NASH (62.1% vs 18.9%, p<0.001). Multivariate analysis identified post-OLT diabetes (HR=2.0, 95% CI: 1.2-3.2, p=0.007) as an independent risk factor for fibrosis development. Additionally, NASH subjects who received steroids had a significantly higher risk of developing hepatic fibrosis post-OLT than NASH patients who did not receive steroids and all HCV subjects (p<0.001). CONCLUSION: Recurrence of steatosis post-OLT is common. Corticosteroid use may contribute to fibrosis progression in this population.

Use of tissue plasminogen activator in liver transplantation from donation after cardiac death donors.

Ischemic-type biliary stricture (ITBS) occurs in up to 50% after liver transplantation (LT) from donation after cardiac death (DCD) donors. Thrombus formation in the peribiliary microcirculation is a postulated mechanism. The aim was to describe our experience of tissue plasminogen activator (TPA) administration in DCD-LT. TPA was injected into the donor hepatic artery on the backtable (n = 22). Two recipients developed ITBS including one graft failure. Although excessive postreperfusion bleeding was seen in 14 recipients, the amount of TPA was comparable between those with and without excessive bleeding (6.4 ± 2.8 vs. 6.6 ± 2.8 mg, p = 0.78). However, donor age (41 ± 12 vs. 29 ± 9 years, p = 0.02), donor BMI (26.3 ± 5.5 vs. 21.7 ± 3.6 kg/m(2) , p = 0.03), previous laparotomy (50% vs. 0%, p = 0.02) and lactate after portal reperfusion (6.3 ± 4.6 vs. 2.8 ± 0.9 mmol/L, p = 0.005) were significantly greater in recipients with excessive bleeding. In conclusion, the use of TPA may lower the risk of ITBS-related graft failure in DCD-LT. Excessive bleeding may be related to poor graft quality and previous laparotomy rather than the amount of TPA. Further studies are needed in larger population.

IL-2 Receptor Antagonist (Basiliximab) Is Associated with Rapid Fibrosis Progression in Patients with Recurrent Hepatitis C after Liver Transplantation Using Serial Biopsy Specimens.

BACKGROUND: Recurrence of hepatitis C virus (HCV) infection following orthotopic liver transplantation (OLT) is universal. There is paucity of data on the safety and efficacy of interleukin (IL)-2 receptor antagonist (IL-2RA) when added to the standard immunosuppression regimen in OLT recipients with recurrent HCV infection. OBJECTIVES: To evaluate the efficacy of IL-2RA (Basiliximab) in preventing acute cellular rejection (ACR) in patients with recurrent HCV infection after OLT and to assess the impact of IL-2RA in promoting fibrosis progression in post-OLT recurrent HCV infection. METHODS: Using an electronic pathology database, we identified all OLT/HCV patients with at least 2 post-OLT liver biopsies (1998-2006). Standard immunosuppression consisted of steroids and calcineurin inhibitor with and without mycophenolate mofetil. All patients who were transplanted after May 2004 received IL-2RA induction therapy. The Ludwig-Batts system was used to stage all biopsies (593 biopsies from 124 patients). The first biopsy that showed post-OLT fibrosis or the last follow-up biopsy was used for time-to-progression analysis. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify factors associated with the progression of fibrosis. RESULTS: ACR was significantly (p<0.001) lower in patients who received IL-2RA (20 of 70, 29%) compared to those who did not (33 of 54, 61%). The median (25%ile, 75%ile) follow-up was 12.1 (6.1, 23.9) months during which 61% of patients had progression of fibrosis. Univariate analysis revealed that a higher HCV RNA load at 4 months post-OLT (p=0.002), cytomegalovirus (CMV) infection (p<0.001), use of steroid therapy for ACR (p=0.043), and use of IL-2RA (p<0.001) were associated with higher hazards for the progression of fibrosis. Viral load at 4 months post-OLT was significantly (p=0.025) higher in patients who had IL-2RA therapy (median [25%ile, 75%ile]: 2.9 [1.0, 5.0] ×10(6) vs. 1.4 [1.0, 2.3] ×10(6)). In multivariate analysis, patients who received IL-2RA therapy were 3.1 (95% CI: 1.8-5.3) times more likely to develop fibrosis than those who did not treated with IL-2RA. Steroid therapy for ACR remained significantly (Hazard Ratio=2.9, p=0.002) associated with the progression of fibrosis. CONCLUSION: IL-2RA (Basiliximab) decreases the rate of ACR. However, it may be associated with more rapid histological progression of the disease in post-OLT recurrent HCV.

Characteristics of oral abnormalities in liver transplant candidates.

BACKGROUND: Several oral mucosal abnormalities have been reported to occur more frequently in patients with liver disease. It has, however, not been determined if these conditions are related to the disease or are manifestations of extraneous factors not associated with the liver pathology. OBJECTIVE: To identify and quantify oral abnormalities in candidates for liver transplantation, and to determine whether these conditions were correlated with the type of liver disease or were the result of other patient variables. METHODS: Oral examinations were performed on 300 candidates for liver transplantation to assess their oral health and to record the presence and types of oral mucosal pathologies. Abnormalities most frequently encountered were analyzed for significant associations with classification of liver disease, hyposalivation, diuretic therapy, edentulism, or smoking. RESULTS: Among these subjects, 175 (58%) had one or more abnormalities. The anomalies most frequently found were fissured tongue (37%), atrophy of the papillae of the tongue (18%), angular cheilitis (4%) and manifestations of clinical candidiasis (2%). Clinical hyposalivation was found in 28.7% of all patients and 70% of those who were on diuretic therapy. Fissured tongue and atrophy of the tongue papillae were significantly associated with hyposalivation (p<0.001); hyposalivation was correlated to diuretic therapy (p=0.028). Pathologies suggestive of candidiasis were significantly associated with hyposalivation and total edentulism. CONCLUSION: Several oral mucosal abnormalities that have previously been linked with liver diseases were found to be primarily associated with diuretic-induced hyposalivation, smoking, and total edentulism.

Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C.

Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.

Livers transplanted from donors after cardiac death occurring in the ICU or the operating room have excellent outcomes.

BACKGROUND: Increasing donor hospital cooperation with donation after cardiac death (DCD) requires the organ procurement organization (OPO) to use current withdrawal of life support (WLS) protocols. Hospital ICU nurses/physicians are comfortable performing the emotionally draining procedure of WLS in the ICU while OPOs are reluctant to accept these donors due to increased warm ischemia (WI). In our area, several hospitals will only allow WLS to occur in the ICU. This study compares liver outcomes from DCD donors where death occurred in the ICU (DCDICU) vs the OR (DCDOR). METHODS: From March 2003 to June 2004, 34 DCD donors were recovered by our OPO. WLS occurred in the ICU for 26 donors (76%) and in the OR for 8 donors (24%). Thirteen of 26 DCDICU and 5 of 8 DCDOR livers were transplanted. Donor demographics, warm ischemic time, cold ischemic time, distance shipped, and recipient functions were analyzed. RESULTS: Eighteen livers were transplanted both locally and at distant transplant centers. Results are outlined in the . CONCLUSIONS: Although DCDICU donors averaged approximately 4 minutes longer WI than DCDOR donors, short-term results for both groups were equivalent. These findings support using DCDICU livers. DCDICU donors have the potential to significantly improve donor hospital cooperation.

Tacrolimus for primary liver transplantation: 12 to 15 years actual follow-up with safety profile.

BACKGROUND: Tacrolimus has been increasingly used for liver transplantation during the last decade. The drug has immunological advantages in short- to medium-term follow-up. However, data on longitudinal follow-up are lacking. AIM: The aim of the present report was to examine the impact of tacrolimus in primary adult and pediatric liver transplantation (LTx) patients. MATERIAL AND METHOD: One thousand consecutive primary LTx patients were performed under tacrolimus between August 1989 and December 1992 were followed up until August 2004. Mean follow-up was 13.4 +/- 0.92 (range, 11.7-15) years. There were 600 males and 400 females with a mean age of 42.6 +/- 20.2 years. There were 166 children (age 18 years or younger) and 834 adults, of whom 204 were older than 60 years (seniors). RESULTS: Four hundred ninety-seven (49.7%) patients died in the follow-up period. The overall 15-year actuarial patient survival rate was 51.4%. The survival rate for children was significantly better (81.3%) compared with adults (47.5%) and seniors (36.4%) (P = .0001). One hundred fifty-one patients received a second LTx, 22 patients received a third LTx, and 4 patients received a fourth LTx. Over all 15 years the actuarial graft survival rate was 46.1%. At last follow-up, 69.1% of patients were off steroids. The majority of late deaths were due to age-related complications, recurrence of disease, and De novo cancers. CONCLUSION: The data on longitudinal follow-up have shown actuarial survival for children to be significantly better than in adults and seniors. Graft loss from immunological causes are rare even with long-term follow-up.

Review article: current status of liver transplantation in HIV-infected patients.

The increases in survival of patients infected with human immunodeficiency virus is attributed to the introduction of combination human immunodeficiency virus antiviral therapy, better known as highly active anti-retroviral therapy. In fact, survival statistics have improved such that individuals often succumb to other disease entities, notably liver failure and not from acquired immunodeficiency syndrome complications. Liver transplantation has been introduction in this patient population in several centres around the world. This review will discuss the current clinical status of liver transplantation in individuals suffering from human immunodeficiency virus infection.

Recurrent hepatitis C in liver allografts: prospective assessment of diagnostic accuracy, identification of pitfalls, and observations about pathogenesis.

RATIONALE AND DESIGN: The accuracy of a prospective histopathologic diagnosis of rejection and recurrent hepatitis C (HCV) was determined in 48 HCV RNA-positive liver allograft recipients enrolled in an "immunosuppression minimization protocol" between July 29, 2001 and January 24, 2003. Prospective entry of all pertinent treatment, laboratory, and histopathology results into an electronic database enabled a retrospective analysis of the accuracy of histopathologic diagnoses and the pathophysiologic relationship between recurrent HCV and rejection. RESULTS: Time to first onset of acute rejection (AR) (mean, 107 days; median, 83 days; range, 7-329 days) overlapped with the time to first onset of recurrent HCV (mean, 115 days; median, 123 days; range, 22-315 days), making distinction between the two difficult. AR and chronic rejection (CR) with and without co-existent HCV showed overlapping but significantly different liver injury test profiles. One major and two minor errors occurred (positive predictive values for AR = 91%; recurrent HCV = 100%); all involved an overdiagnosis of AR in the context of recurrent HCV. Retrospective analysis of the mistakes showed that major errors can be avoided altogether and the impact of unavoidable minor errors can be minimized by strict adherence to specific histopathologic criteria, close clinicopathologic correlation including examination of HCV RNA levels, and a conservative approach to the use of additional immunosuppression. In addition, histopathologic diagnoses of moderate and severe AR and CR were associated with relatively low HCV RNA levels, whereas relatively high HCV RNA levels were associated with a histopathologic diagnosis of hepatitis alone, particularly the cholestatic variant of HCV. CONCLUSIONS: Liver allograft biopsy interpretation can rapidly and accurately distinguish between recurrent HCV and AR/CR. In addition, the histopathologic observations suggest that the immune mechanism responsible for HCV clearance overlap with those leading to significant rejection.