Abstract: After liver transplantation (LT), hepatic veno-occlusive disease (VOD), which is also known as sinusoidal obstruction syndrome (SOS), has been reported initially in relation to azathioprine use and subsequently in relation to acute rejection (AR). Isolated veno-occlusive disease (iVOD)/SOS raises some questions about its significance and especially its treatment. From the post-LT biopsy samples of 1364 patients (2000-2008), 31 patients with index biopsy samples showing VOD/SOS (2.3%) were identified. After a review of the index biopsy samples and previous biopsy samples, those patients not exposed to azathioprine therapy were subdivided into 2 groups according to the absence or presence of AR. Fifteen of the 31 patients had no previous evidence of AR, whereas 16 experienced episodes of AR (before or concurrently with VOD). The 2 groups were similar in terms of demographic and clinical data and the range of histological centrilobular changes. AR episodes were characterized by an endothelial predilection. iVOD/SOS occurred later than acute rejection-related veno-occlusive disease (AR-VOD)/SOS (mean times of 65 and 4.4 months, respectively, P = 0.0098). There was a tendency for iVOD/SOS to progress less frequently to chronic rejection in comparison with AR-VOD/SOS (3/15 versus 9/15, P = 0.06). The histological resolution of iVOD/SOS was significantly more frequent in patients who benefited from increased immunosuppression in comparison with those who did not (5/7 versus 2/8, P = 0.05). When the groups were considered together, the same result was obtained (14/18 versus 4/12, P = 0.024). In conclusion, despite a constant overall prevalence of VOD/SOS, the proportion of iVOD/SOS has increased. The histological resolution of iVOD/SOS after increase in immunosuppression suggests an immune-mediated origin. Better optimization of immunosuppression may be a curative treatment.
Abstract: Liver transplantation is an established lifesaving treatment for patients with severe protoporphyric liver disease, but disease recurrence in the graft occurs for the majority of recipients. Severe burn injuries may occur when protective light filters are not used with surgical luminaires. Motor neuropathy with an unclear pathogenesis is a frequent complication. We retrospectively studied 35 transplants performed for protoporphyric liver disease in 31 European patients between 1983 and 2008. Most of the patients were male (61.3%), and the mean age at the time of primary transplantation was 39 years (range = 9-60 years). The overall patient survival rates were 77% at 1 year and 66% at 5 and 10 years. The overall rate of disease recurrence in the graft was 69%. Forty-three percent of the patients experienced recurrence within a year, but this was often a transient finding that was associated with other graft complications. Phototoxic injuries due to surgical luminaires were seen in 25.0% of the patients who were not protected by filters, but these injuries were not seen in the 9 patients who were protected by filters. Significant motor neuropathies requiring prolonged ventilation complicated the postoperative course for 5 of the 31 patients (16.1%). Hematopoietic stem cell transplantation was performed for 3 patients to prevent graft loss due to disease recurrence. Prognostic markers are needed to identify patients prone to severe protoporphyric liver disease so that curative stem cell transplantation can be offered to select patients instead of liver transplantation.
Abstract: The lack of use of a common grading system in reporting morbidity impedes estimation of the true risk to a right lobe living donor (RLLD). We report outcomes in 91 consecutive RLLD's using the validated 5-tier Clavien grading and a quality of life (QOL) questionnaire. The median follow-up was 79 months. The donors were predominantly female (66%), 22 (24%) received autologous blood transfusions. Fifty-three complications occurred in 43 donors (47% morbidity), 19 (37%) were ≥ Grade III, biliary fistula (14%) was the most common. There was no donor mortality. Two intraoperative complications could not be graded and two disfiguring complications in female donors were graded as minor. Two subgroups (first 46 vs. later 45 donors) were compared to study the presence if any, of a learning curve. The later 45 donors had lesser autologous transfusions, lesser rehospitalization and no reoperation and a reduction in the proportion of ≥ Grade III (major) complications (24% vs. 50%; p = 0.06). In the long term, donors expressed an overall sense of well being, but some sequelae of surgery do restrain their current lifestyle. Our results warn against lackadaisical vigilance once RLLD hepatectomy becomes routine.
Abstract: BACKGROUND & AIMS: Most liver transplant centres have discontinued the practice of protocol liver biopsies (LB), mainly because of the perceived lack of therapeutic benefit. This study aimed to examine the usefulness of 20-year LBs. METHODS: Ten, 15, and 20-year protocol LBs from 147 patients surviving for >20years were reviewed. Twenty-year biopsy findings were correlated with clinical data. RESULTS: Twenty-year-biopsy patients (N=91) and 20-year-non-biopsy patients (N=56) were similar in terms of transplant data, adverse events, and liver function tests (LFTs). Twenty-year LBs revealed a 90% prevalence of abnormalities, among which viral chronic hepatitis (VCH) was the most common (46%). Between 15 and 20years, hepatic structural abnormalities were the only disorder to increase (p=0.008). An individual progression of abnormalities occurred in 56% of patients. At 20years, the negative and positive predictive values (PV) of LFTs with respect to histological abnormalities were 95% and 18%, respectively; In VCH, Fibrotest and transient elastography displayed poor discriminative ability for fibrosis (80% and 81% discordance, respectively), but were satisfactory regarding significant fibrosis (negative PV of 77.7% and 80%, respectively). A decrease in immunosuppression was less frequent (14/91 vs. 20/56, p=0.008) while an increase was more common (15/91 vs. 2/56, p=0.017) in 20-year-biopsy patients than in non-biopsy patients. Antiviral therapy was administered in seven of the 20-year biopsy patients, but in none of the non-biopsy patients (p=0.04). CONCLUSIONS: Twenty-year LBs provided important histological information on graft function that was available to a limited degree from LFTs and non-invasive markers. They exerted an impact on immunosuppressive and antiviral therapies.
Abstract: The principal aim of this study was to compare the probability of and potential risk factors for death and graft loss after primary adult and pediatric liver transplantation in patients undergoing transplantation for autoimmune hepatitis (AIH) to those in patients undergoing transplantation for primary biliary cirrhosis (PBC; used as the reference group) or alcoholic cirrhosis (used as an example of a nonautoimmune liver disease). The 5-year survival of patients undergoing transplantation for AIH (n = 827) was 0.73 [95% confidence interval (CI) = 0.67-0.77]. This was similar to that of patients undergoing transplantation for alcoholic cirrhosis (0.74, 95% CI = 0.72-0.76, n = 6424) but significantly worse than that of patients undergoing transplantation for PBC (0.83, 95% CI = 0.80-0.85, n = 1588). Fatal infectious complications occurred at an increased rate in patients with AIH (hazard ratio = 1.8, P = 0.002 with PBC as the reference). The outcome of pediatric AIH patients was similar to that of adult patients undergoing transplantation up to the age of 50 years. However, the survival of AIH patients undergoing transplantation beyond the age of 50 years (0.61 at 5 years, 95% CI = 0.51-0.70) was significantly reduced in comparison with the survival of young adult AIH patients (0.78 at 18-34 years, 95% CI = 0.70-0.86) and in comparison with the survival of patients of the same age group with PBC or alcoholic cirrhosis. In conclusion, age significantly affects patient survival after liver transplantation for AIH. The increased risk of dying of infectious complications in the early postoperative period, especially above the age of 50 years, should be acknowledged in the management of AIH patients with advanced-stage liver disease who are listed for liver transplantation. It should be noted that not all risk factors relevant to patient and graft survival could be analyzed with the European Liver Transplant Registry database.
Abstract: Alcohol-related liver disease (ALD) is one of the most common indications for liver transplantation (LT). Long-term outcome after LT for ALD versus other etiologies is still under debate. The aim of this study was to compare outcome after LT of patients with ALD, viral (VIR), and cryptogenic cirrhosis. Donor, graft and recipient ELTR variables were analysed in transplants for alcoholic and nonalcoholic cirrhosis (1988-2005) and were correlated with patient survival. Causes of death and/or graft failure were compared between groups. Nine thousand eight hundred eighty ALD, 10,943 VIR, 1478 ALD+VIR and 2410 cryptogenic (CRYP) liver transplants were evaluated. One, 3, 5 and 10 years graft survival rates after LT in ALD patients were 84%, 78%, 73%, 58%, significantly higher than in VIR and CRYP (p=0.04, p=0.05). By multivariate analysis, ALD+VIR (RR 1.14) and viral alone (RR 1.06) were significant risk factors for mortality. De novo tumors, cardiovascular and social causes were causes of death/graft failure in higher percentage in ALD groups versus other etiologies. LT for ALD cirrhosis has a favorable outcome, however, hepatitis C virus co-infection seems to eliminate this advantage. Screening for de novo tumors and prevention of cardiovascular complications are essential to provide better long-term results.
Abstract: Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up.
Abstract: During the past 3 decades, more than 2,250 liver transplants were performed at Paul Brousse Hospital. Overall patient survival was 82% at one year, 71% at 5 years and 64% at 10 years. Our group has developed a variety of approaches to liver transplantation, including: 1. Anti HBs immunoglobulin prophylaxis for the prevention of HBV recurrence. Combination prophylaxis with lamivudine and anti HBs immunoglobulins reduced the rate of HBV re-infection to 20%. 2. Transplantation of HIV-HCV and HIV-HBV infected patients. These transplants are feasible and we achieved 2- year survival rates of 70% and 90%, respectively. The main problem was HCV recurrence which was more severe in HIV co-infected patients. 3. Transplantation for hepatocellular carcinoma on a cirrhotic liver with a single tumor <5 cm or <3 tumors <3 cm. 4. Transplantation for familial amyloidotic polyneuropathy (FAP). The 5- and 10-year survival rates were 76% and 72%, respectively. More than 100 livers obtained after hepatectomy from FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with a 5-year survival rate of 64%. In some domino recipients, symptoms of FAP disease occurred more rapidly than expected and this could be an indication for a second transplantation of a non FAP-liver. 5. Split-liver transplantation for pediatric patients. This has increased the number of transplantable livers for children by 28%. 6. Split-liver transplantation for 2 adults. The grafts were prepared by ex-vivo or in-situ splitting and the overall 5-year survival rate was 56%. 7. Adult -to-adult living-related liver transplantation. There has been no mortality nor late complications in donors and the overall 5-year survival rate among recipients was 73%. 8. Liver retransplantation with good results in the elective situation. Retransplantation should be used with discretion in the emergency setting.
Abstract: This study aims to compare the results of living donor (LDLT), cadaveric split (SLT) and domino (DO) liver transplantation which are currently available alternatives to the conventional cadaveric full-size liver transplantation (CAD).
Abstract: BACKGROUND: Mortality after liver transplantation depends on heterogeneous recipient and donor factors. Our aim was to assess risk of death and to develop models to help predict mortality after liver transplantation. METHODS: We analysed data from 34,664 first adult liver transplants from the European Liver Transplant Registry to identify factors associated with mortality at 3-months (n=21,605 in training dataset) and 12-months (n=18,852 in training dataset) after transplantation. We used multivariable logistic regression models to generate mortality scores for each individual, and assessed model discrimination and calibration on an independent validation dataset (n=9489 for 3-month model and n=8313 for 12-month model). FINDINGS: 2540 of 21,605 (12%) individuals in the 3-month training sample had died by 3 months. Compared with those transplanted in 2000-03, those transplanted earlier had a higher risk of death. Increased mortality at 3-months post-transplantation was associated with acute liver failure (adjusted odds ratio 1.61), donor age older than 60 years (1.16), compatible (1.22) or incompatible (2.07) donor-recipient blood group, older recipient age (1.12 per 5 years), split or reduced graft (1.96), total ischaemia time of longer than 13 h (1.38), and low United Network for Organ Sharing score (score 1: 2.43; score 2: 1.67). However, cirrhosis with hepatocellular carcinoma, alcohol cirrhosis, hepatitis C or primary biliary cirrhosis, donor age 40 years or younger, or less, hepatitis B, and larger size of transplant centre (> or = 70 transplants per year) were associated with improved early outcomes. The 3-month mortality score discriminated well between those who did and did not die in the validation sample (C statistic=0.688). We noted similar findings for 12-month mortality, although deaths were generally underestimated at this timepoint. INTERPRETATION: The 3-month and 12-month mortality models can be effectively used to assess outcomes both within and between centres. Furthermore, the models provide a means of assessing the risk of post-transplantation mortality, giving clinicians important data on which to base strategic decisions about transplant policy in particular individuals or groups.
Abstract: Caroli's disease (CD) or syndrome (CS) are rare inherited disorders which may cause severe, life-threatening, cholangitis or which may lead to hepatobiliary degeneration. The typical cystic biliary anomalies are often associated to congenital hepatic fibrosis (CHF) and, less frequently, to cystic renal disease especially autosomic recessive polycystic kidney disease (ARPKD). The place of liver transplantation (LT) in the treatment of CD or CS is evaluated based on our own experience of three successfully transplanted patients, the literature review of 19 patients and the European experience with 110 patients collected in the European Liver Transplant Registry. LT should be proposed as a definitive therapeutic option once severe cholangitis or (suspicion of) malignant transformation is present. The frequently used radiological, endoscopical or surgical biliary drainage procedures carry a high morbidity and mortality rate. In case of concomitant symptomatic CHF and renal failure, combined or sequential hepatorenal transplantation should be carried out, dependent on the evolution of the hepatic and renal disease. In case of associated ARPKD, renal transplantation is often indicated early on because of the more rapid progression of the renal component of the disease.
Abstract: Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a rare disease characterized by the presence of arteriovenous malformations. Hepatic involvement can lead to life-threatening conditions.
Abstract: Preoperative chemotherapy for colorectal liver metastases (CLM) can produce histologic changes in the nontumor-bearing liver (NTBL) that may impact on surgical outcomes.
Abstract: A histologic pattern comprising centrilobular cholestasis and portal changes including edema, predominantly neutrophil polymorph infiltration, cholangiolar proliferation, and cholangiolitis is well known to correspond to biliary obstruction. This pattern, referred as biliary tract pathology (BTP) in this text, remains unclear in terms of its clinical significance. We aimed to assess the incidence, timing, and diagnostic accuracy of BTP after liver transplantation. All 248 liver biopsies and clinical records, from 94 patients, including 30 living donor, 17 split, 15 domino, and 32 cadaveric full-size primary liver transplantation, were reviewed. BTP was diagnosed in 21% of biopsies from 31% of patients at a median of 28 days after transplantation (range, 5-763 days). When radiologic imaging of the biliary tree was taken as the gold standard, biopsy was found to have a sensitivity of 87% (95% confidence interval, 73%-100%) and a specificity of 87% (95% confidence interval, 80%-95%) for the diagnosis of biliary complications. An underlying clinical condition was found in 86% of cases, which included biliary complications (69%), arterial thrombosis (3%), sepsis (10%), and recurrent disease (3%). In 14% of cases, BTP remained unexplained. In conclusion, BTP after liver transplantation has clinical significance in most cases, with a particular emphasis for true biliary complications. This pattern must incite radiographic verification of the biliary tract.
Abstract: We report 5 cases of acute liver failure related to herpes simplex (HSV) infection in 1 immunocompetent and 4 immunosuppressed patients. One patient was too ill for liver transplantation indication. Three patients, among the 4 listed, underwent liver transplantation. Three patients died 11 days to 1 year after transplantation and 2 patients died 2 to 3 days after admission. All presented with fever and none with skin lesions. The diagnosis of HSV-related hepatitis was made antemortem in only 2 patients on the basis of positive blood cultures and/or immunohistochemic findings. In the remaining patients, HSV diagnosis was made retrospectively on further histologic and virologic investigations. Primary HSV infection was certain or likely in all cases, including an HSV2 superinfection of an anti-HSV1-positive patient and two HSV superinfections of hepatitis B virus (HBV)-related chronic liver disease. In these latter patients, HSV diagnosis was totally unsuspected, despite fever. HSV superinfection has significantly contributed to liver dysfunction aggravation and death. In conclusion, the diagnosis of HSV hepatitis is difficult to establish in the absence of specific clinical signs. This may suggest the need for early administration of acyclovir in patients with suspected HSV hepatitis, without waiting for virologic confirmation. Diagnosis methods providing fast results (real-time polymerase chain reaction [PCR]) should be implemented.
Abstract: Factors influencing the long-term histological outcome of liver graft are not known. We conducted a prospective study based on a 10-year liver biopsy in order to identify the main factors influencing long-term graft histology.
Abstract: Autoimmune hepatitis (AIH) has been reported to recur after orthotopic liver transplantation (OLT) in 10-35% of patients in small series with a short follow up. The aim of the present study was to examine the clinical and histological outcome more than 10 years after OLT for AIH.
Abstract: We assessed the impact of liver transplantation (LT) on the quality of life (QOL) of French recipients 1 year after surgery. A French version of the questionnaire used by the National Institute of Diabetes and Digestive and Kidney Disease-Pittsburg, USA (NIDDK), was validated by the back-translation method. Five QOL domains were evaluated: measures of disease, psychological distress, personal function, social function, and general health perception. Patients enrolled onto the waiting list completed the questionnaire before and 1 year after LT. Respondents were age- and gender-matched with healthy subjects recruited from the general population (GP). One year after LT, the analysis of data from 67 consecutive patients showed dramatic improvement in the five domains. Compared with baseline, patients noted fewer disease-related symptoms (P <.0001) and lower level of distress overall (P <.001). However, levels of distress caused by excess appetite (P <.01), trembling (P <.05), and headaches (P =.06) were more likely to increase than decrease. Twenty-five percent of patients prevented by their disease from going to work before LT were no longer so limited at 1-year follow-up. General health perception improved remarkably, with seven times as many recipients reporting improved health as reporting worse health. A correlation was found between the pretransplantation severity of cirrhosis and the social and role function after LT (P <.05). In summary, the French version of the NIDDK questionnaire seems to be reliable. The results of transplant recipients were generally close to those of the general population. Although it is not a true return to normal status, it approaches it.
Abstract: The yearly increasing survival rates testify to the success of transplantation, but questions remain relating to the quality of life (QOL) associated with long-term survival.
Abstract: The number of registries is increasing, but few of them perform reliability audits by comparing the data contained in the database with data contained in hospital charts.
Abstract: To identify the outcomes and risks of split-liver transplantation (SLT) for two adult recipients to determine the feasibility of more widespread use of this procedure to increase the graft pool for adults.
Abstract: To reappraise the results of auxiliary partial orthotopic liver transplantation (APOLT) compared with those of standard whole-liver transplantation (OLT) in terms of postoperative death and complications, including neurologic sequelae.
Abstract: No model exists for liver transplantation to estimate the mortality risk in a given patient, and no standard by which to assess performance in different centres. We investigated the intrinsic mortality risk in the absence of known mortality risk factors.
Abstract: During the past 16 years, more than 1,500 liver transplants were performed at Paul Brousse Hospital. The overall patient survival rates were 83% at one year and 65% at 10 years. Our group has pioneered a variety of new approaches to liver transplantation, including: 1. Anti-HBs (HBIG) prophylaxis for the prevention of HBV recurrence. To date more than 270 patients have received long-term treatment and the overall 10-year recurrence rate was 27%. 2. Transplantation for hepatocellular carcinoma of the cirrhotic liver in patients with uni- or binodular HCC (< 3 cm). Survival for transplanted patients was 83% compared with 18% if the liver was resected. 3. Transplantation for familial amyloidotic polyneuropathy (FAP). More than 60 patients had 5- and 10-year survival rates of 85% and 83%, respectively. Ten livers obtained after hepatectomy from these FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with satisfactory short-term results. 4. Reduced-size liver grafts have been used successfully to reduce pretransplant mortality and posttransplant morbidity and mortality by shortening the wait for our pediatric patients. 5. Split-liver transplantation has increased the number of transplantable livers by 28%. 6. Split-liver transplantation for 2 adults. Using optimal livers we have transplanted 34 adults with grafts prepared by ex-vivo or in-situ splitting with good survival rates. 7. Adult-to-adult living-related donor liver transplantation. In 2000, 7 adult-to-adult living donor transplants were performed with no complications from the donor surgeries. One recipient was retransplanted for arterial thrombosis, but all 7 recipients are alive at home. The Paul Brousse Hospital is committed to exploring new technologies to improve the outcome of and expand the indications for liver transplantation. We have taken a surgical approach to the organ shortage, finding new ways to serve the most patients with the limited number of livers available.
