Fungal infections after liver transplantation: outcomes and risk factors revisited in the MELD era.

Antifungal prophylaxis is recommended in high-risk patients, but risk criteria remain unclear and the predictive value of Model of End-Stage Liver Disease (MELD) score is unknown. In a retrospective, single-center analysis of 667 liver transplants, potential risk factors for fungal infection were assessed, including MELD score. Antifungal prophylaxis was administered in 198 patients (29.4%). During follow-up (mean 43.6 ± 29.6 months), 263 patients (39.4%) developed ≥ 1 episode of fungal infection, and 187 (28.0%) patients developed a probable or proven invasive fungal infection requiring systemic antifungal treatment. Patients receiving antifungal prophylaxis had a lower incidence of fungal infection (29.8% vs. 43.5% without prophylaxis, p < 0.001) and invasive fungal infection (17.7% vs. 32.4%, p < 0.001). One-yr patient survival was 91%, 85% and 69%, respectively, in patients with no fungal infection, fungal colonization and treated invasive fungal infection (p < 0.001); graft survival was 88%, 85% and 66% (p < 0.001). Multivariate analysis indicated that MELD score of 20-30 or ≥ 30 was associated with a 2.0-fold or 4.3-fold increase in relative risk of fungal infection, respectively, and a 2.1-fold or 3.1-fold increase in relative risk of invasive fungal infection. In conclusion, liver transplant patients with a MELD score ≥ 20, and particularly patients with a score ≥ 30, are candidates for antifungal prophylaxis.

Outcomes associated with amphotericin B lipid complex (ABLC) prophylaxis in high-risk liver transplant patients.

Antifungal prophylaxis with liposomal amphotericin B in high-risk liver transplant recipients is recommended, but experience with amphotericin B lipid complex (ABLC, Abelcet(®)) in this setting is limited. Data from 615 liver transplants performed during 1999-2005 were analyzed retrospectively. High-risk patients (n = 146) received a mean cumulative ABLC dose of 955 ± 609 mg (mean duration of 23.3 ± 11.9 days). Low-risk patients (n = 469) received no prophylaxis. During a mean follow-up of 43.8 ± 29.2 months, fungal infections occurred in 32.2% of ABLC patients versus 43.5% of non-prophylaxis patients (P = 0.015). The overall rate of invasive fungal infection was 12.3% in the ABLC group versus 15.6% in the non-prophylaxis patients (P = 0.34). Any Candida infection (ABLC 29.5%, non-prophylaxis 41.2%, P = 0.011), probable or proven invasive Candida infection requiring systemic antifungal treatment (ABLC 18.5%, non-prophylaxis 32.4%, P = 0.001) and invasive abdominal candidiasis during the first 3 months (ABLC 4.1%, non-prophylaxis 9.2%, P = 0.049) were significantly less frequent in the ABLC group. There was no significant difference between groups in the incidence of Aspergillus infections. The ABLC group showed no evidence of nephrotoxicity. In conclusion, the marked and significant differences in infection rates and requirement for systemic treatment in this large population suggest that targeted use of low-dose ABLC therapy to high-risk patients is a valid prophylactic strategy following liver transplantation.

Acute liver failure due to antitubercular therapy: Strategy for antitubercular treatment before and after liver transplantation.

The standard antitubercular treatment (ATT), which consists of isoniazid (INH), rifampicin (RIF), ethambutol, and pyrazinamide (PZA), is the best available treatment for tuberculosis (TB). However, the hepatotoxicity of INH and PZA can be severe, and even after drug withdrawal, patients may require liver transplantation (LT). In these cases, the strategy for the treatment of TB is poorly defined. Between 1986 and 2008, 14 patients presented at our department with severe hepatitis secondary to INH and PZA treatment. Four of these patients were immunosuppressed: 2 after renal transplantation and 2 because of human immunodeficiency virus infection. In seven of the 14 patients an alternative ATT was begun on admission, which was well tolerated. Hepatitis improved spontaneously in 5 patients, and alternative ATT was continued for 9.3 ± 4.2 months; 1 patient deteriorated and underwent LT, and 1 patient died. ATT was stopped definitively in 2 patients. Six patients required urgent LT, and alternative ATT was started after transplantation and was successful. Five patients receiving RIF had an episode of acute rejection. In conclusion, hepatitis secondary to ATT can be successfully treated with alternative anti-TB regimens. The use of RIF in LT patients may lead to acute rejection. RIF should therefore be avoided in these patients.

Escape hepatitis B virus mutations in recipients of antibody to hepatitis B core antigen-positive liver grafts receiving hepatitis B immunoglobulins.

A variety of prophylactic strategies are used to prevent the risk of hepatitis B virus (HBV) transmission from antibody to hepatitis B core antigen (anti-HBc)-positive donors. The mechanisms underlying the failure of HBV immunoglobulin monoprophylaxis have been poorly evaluated. Seventy-seven anti-HBc-positive grafts were used in 21 hepatitis B surface antigen (HBsAg)-positive recipients and 56 HBsAg-negative recipients. HBsAg-positive recipients received prophylaxis comprising hepatitis B immunoglobulins (HBIG) and antiviral agents, 45 HBsAg-negative recipients received a modified HBIG regimen, and 11 HBsAg-negative recipients received no prophylaxis. Both donors and recipients were screened for HBsAg, antibody to HBsAg (anti-HBs) and anti-HBc in their sera and for HBV DNA in both their sera and liver. S gene mutations were investigated after HBV reinfection. HBV infection occurred in 15 HBsAg-negative recipients (19.4%) at a median interval of 16 months (range = 6-67 months) post-transplant and in none of the HBsAg-positive recipients. HBV infections were observed in 31.6% of HBV-naive recipients and 7.7% of HBV-immune recipients receiving HBIG prophylaxis versus 100% of HBV-naive recipients (P = 0.0068) and 33% of HBV-immune recipients (P = 0.08) with no such prophylaxis. S gene mutations were identified in 9 recipients. In conclusion, priority should be given to using anti-HBc positive grafts for HBsAg-positive or HBV-immune recipients. Our study has confirmed the high risk of HBV transmission to naive recipients. HBIG monoprophylaxis was associated with a significant risk of de novo HBV infection and HBV escape mutations. In these patients, we therefore recommend prophylaxis with lamivudine or new nucleos(t)ides analogues. The potential benefits of HBIG prophylaxis combined with antiviral drugs require further evaluations. Long-term prophylaxis is needed because of the long interval of de novo HBV infection post-transplant in some patients.

Hepatitis C virus therapy in liver transplant recipients: response predictors, effect on fibrosis progression, and importance of the initial stage of fibrosis.

Antiviral therapy after liver transplantation (LT) using interferon (IFN) and ribavirin (RBV) can achieve a sustained virological response (SVR) rate ranging from 20% to 45%. The aims of our study were to assess efficacy and tolerability of therapy, effect on fibrosis progression and the importance of the initial fibrosis stage to outcome. A total of 113 hepatitis C virus (HCV)-infected LT patients received 133 courses of IFN (standard, n = 29, pegylated IFN [pegIFN], n = 104) and RBV (75% genotype 1). Early virological response (EVR), end-of-treatment (EOT), and SVR were obtained in 74%, 55%, and 38%, respectively. EVR, completion of treatment, viral load before therapy, genotype non-1, and use of pegIFN were predictive of SVR, but only EVR remained in the multivariate analysis. SVR was obtained in 45% patients who received a second course of therapy. Paired biopsies at baseline, at EOT and at long-term were available in 42 patients. The mean fibrosis stage remained stable in patients with SVR and increased in patients without response. Rejection episodes were observed in 6% of patients. Tolerability of therapy decrease in patients with fibrosis stage > or =3 on baseline liver biopsy. A total of 20% of them died or were retransplanted due to liver failure as opposed to 1% of patients who had fibrosis stage <3. In conclusion, IFN and RBV achieved SVR in 38% of patients. EVR is independently associated with SVR. Fibrosis stage remained stable in patients with SVR and increased in nonresponders. Fibrosis stage > or =3 was associated with a high rate of liver failure, arguing for an early introduction of antiviral therapy.

3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome.

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.

Liver retransplantation: a model for determining long-term survival.

BACKGROUND: Because of the worse results from retransplantation in relation to the initial liver transplantation, there is a need to refine the indication for retransplantation, such that fair distribution of this benefit is obtained. METHODS: This was a study of 139 patients who underwent liver retransplantation. Thirty variables were studied: 18 relating to the recipient and 12 to the donor. All the independent variables were initially compared with the length of survival using univariate analyses. Variables presenting significance were compared with the dependent variable of length of survival, to determine which factors were related to longer survival among patients, when evaluated together. RESULTS: A multivariate model for determining long-term survival among patients with retransplants was built up using the following variables: recipient's age, creatinine, urgency of retransplantation and early failure of the first graft. Through this multivariate model it was possible to determine a score that was categorized according to tertile distributions (below the 33rd percentile, score <24; 33rd to 66th percentile, 24 < or = score < or = 32; above the 66th percentile, score > 32). One-year, 3-year, and 5-year patient survival rates following retransplantation were respectively 85%, 82%, and 77% for scores <24; 69%, 66%, and 61% for scores between 24 and 32; and 21%, 19%, and 16% for scores >32 (P < 0.0001). CONCLUSION: The variables of recipient's age, creatinine, urgency of retransplantation, and early failure of the initial transplantation were factors that were independently related to the long-term survival of patients with liver retransplants.

Predictive factors for survival and score application in liver retransplantation for hepatitis C recurrence.

AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus (HCV) recurrence and to apply a survival score to this population. METHODS: We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers (seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis (FCH) post-first graft presenting with hepatic decompensation. RESULTS: Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease (MELD) score < 25 when replaced on the waiting list, and a retransplantation donor age < 60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patients who underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andrés score was applied to 102 patients for whom all score variables were available, producing a mean score of 43.4 (SD = 6.6). Survival rates after the date of the first decompensation post-first liver transplantation (LT1) in the liver retransplantation (reLT) group (94 patients decompensated) at 3, 5, and 10 years were 62%, 59%, and 51%, respectively, among 78 retransplanted individuals with advanced cirrhosis, and 42%, 32%, and 16% among 16 retransplanted individuals with FCH. In the non-reLT group with hepatic decompensation, survival rates were 27%, 18%, and 9% at 3, 5, and 10 years, respectively (P < 0.0001). Compared with non-retransplanted patients, retransplanted patients were younger at LT1 (mean age 48 ± 8 years compared to 53 ± 9 years in the no reLT group, P < 0.0001), less likely to have human immunodeficiency virus (HIV) co-infection (4% vs 14% among no reLT patients, P = 0.005), more likely to have received corticosteroid bolus therapy after LT1 (25% in reLT vs 12% in the no reLT group, P = 0.01), and more likely to have presented with sustained virological response (SVR) after the first transplantation (20% in the reLT group vs 7% in the no reLT group, P = 0.028). CONCLUSION: Antiviral therapy before and after retransplantation had a substantial impact on survival in the context of retransplantation for HCV recurrence, and with the new direct-acting antivirals now available, outcomes should be even better in the future.

Quality of life in adult survivors beyond 10 years after liver, kidney, and heart transplantation.

BACKGROUND: 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. METHODS: A sample of 126 liver recipients (Liver-R), 229 kidney recipients (Kidney-R), and 113 heart recipients (Heart-R) with more than 10 years posttransplant follow-up were included in the study with a response rate of 86%. Respondents were matched with healthy subjects recruited from general population (GP). The three groups of recipients and GP subjects completed a French version of the questionnaire used by the National Institute of Diabetes and Digestive and Kidney Disease, Pittsburgh, PA, and were compared for each score, with adjustments for age and sex. RESULTS: Personal function and measures of disease by the transplant recipients were significantly worse than in the GP (P<0.0001), with the worst score in Kidney-R. No difference, either between organs or between organs and GP, was found regarding the perceived social and role function. However, for psychologic status and general health perception, Kidney-R had the least favorable performance when compared with GP (P<0.01) and also when compared with Liver-R (P<0.05). With the exception of Kidney-R, the well-being index of Liver-R and Heart-R was significantly better than the GP (P<0.001 and P<0.05, respectively). CONCLUSIONS: The QOL beyond 10 years after liver, heart, and kidney transplantation is quite similar to the GP, with Kidney-R starting out as the worst, Heart-R as intermediate, and Liver-R the best.

Beneficial effect of pentoxifylline on microvesicular steatotic livers submitted to a prolonged cold ischemia.

BACKGROUND: The deleterious effect of steatosis on transplanted livers is mainly related to a microcirculation impairment. We investigated the effect of preservation duration on the recovery of isolated perfused rat steatotic livers and tested the effect of pentoxifylline (PTX), known to have a beneficial effect on hepatic microcirculation. MATERIALS AND METHODS: Fatty rat livers were obtained using a diet able to induce an 80% to 100% microvesicular steatosis within 7 days. We studied the effect of the duration of preservation (12 hr, 18 hr, and 24 hr) on fatty and normal isolated perfused rat liver. PTX was added to University of Wisconsin solution during cold storage (30 mM/kg of weight) and at reperfusion (3 mM) (n=5 livers in each group). Lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, bile production, and vascular resistance were evaluated. The liver injury at the end of perfusion was assessed by optical and electron microscopy. RESULTS: For a 24-hr preservation period, fatty livers demonstrated increased enzymatic release (aspartate aminotransferase: 42+/-16 vs. 17+/-5 IU/L/g of liver, P<0.005; alanine aminotransferase: 32+/-13 vs. 13+/-3 IU/L/g of liver, P<0.005; lactate dehydrogenase: 1,207+/-497 vs. 291+/-195 IU/L/g of liver, P<0.001). Vascular resistance (0.32 vs. 0.15 cm H(2)O/min/mL, P<0.0005) and bile output (67+/-24 vs. 141+/-61 mg/g of liver, P<0.05) were decreased. Peliosis appeared after an 18-hr preservation period for fatty livers compared with a 24-hr preservation period for controls. All these negative effects were suppressed by PTX. CONCLUSION: Diffuse microvesicular steatosis became deleterious only after long preservation times (24 hr). PTX prevented this effect.

Quality control of the European Liver Transplant Registry: results of audit visits to the contributing centers.

BACKGROUND: 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. METHODS: The European Liver Transplant Registry (ELTR) cocoordinating committee appointed an independent team to check the reliability of data contained in ELTR. Centers were selected at random. Ten percent of each center's files were selected at random, and 25 items per file were checked during the site visits. The rates of completeness and inconsistencies and the agreement between ELTR and charts were established. We also assessed the correlation between the quality of data and the visited centers' activity. RESULTS: Seven hundred thirty-four files from 21 centers have been audited between June 1998 and June 2001. The rate of ELTR completeness was 95%, and the rate of consistency between charts and ELTR was 98%. The agreement between the ELTR and charts review was very good for all conditions (kappa value < or =0.81). However, comparisons of rates between items indicated that specific items, mostly cause of death or graft failure and patient outcome, should be targeted for improvement. No significant correlation was found between the quality of data and the experience of visited centers. The mean (min-max) and median cost per audited file were EUR 60 (8-150) and EUR 44, respectively. CONCLUSION: The results of audit visits indicate that ELTR data are reliable, and the scientific results of ELTR can be considered credible and representative of liver transplantation in Europe. The method could serve as a model for auditing a registry.

Histologic findings predictive of a diagnosis of de novo autoimmune hepatitis after liver transplantation in adults.

BACKGROUND: Autoimmune hepatitis (AIH) after liver transplantation has been defined histologically as a "hepatitic" pattern of injury, characterized by lymphoplasmacytic inflammation with necroinflammatory activity (NIA), comparable with findings seen in native livers. This definition, however, is difficult to apply in practice because specific histologic criteria are not clearly delineated. This study aimed to determine which histologic features correlated best with clinical and serologic features of dAIH. METHODS: Index liver biopsies from patients with autoimmune-like hepatitis transplanted for non-AIH in two centers (n=35 and 20) were reviewed. Histologic features were correlated with the clinical diagnosis of AIH based on a retrospective review of clinical and serologic data, including therapeutic response. RESULTS: A clinical diagnosis of AIH was retrospectively assigned to 24 of 35 (68%) and 18 of 20 (90%) patients, respectively (P=0.10). In multivariate analysis, centrilobular NIA and centrilobular plasma cell (PC) ratio of 30% to 50% were independently discriminating for a clinical diagnosis of AIH (P=0.04 and 0.05, respectively). The best level of predictability (99.6%) was mathematically achieved when severe centrilobular NIA and centrilobular PC ratio of 30% to 50% were both present. CONCLUSION: A histologic pattern of centrilobular injury including increased NIA and increased PC infiltration correlates with measurements of autoimmunity in liver recipients. It could be used to segregate cases for further study and introduced into the AIH scoring systems when applied in the context of liver transplantation.

Is hepatic resection justified after chemotherapy in patients with colorectal liver metastases and lymph node involvement?

PURPOSE: For patients with colorectal liver metastases (CLM), regional lymph node (RLN) involvement is one of the worst prognostic factors. The objective of this study was to evaluate the ability of a multidisciplinary approach, including preoperative chemotherapy and hepatectomy, to improve patient outcomes. PATIENTS AND METHODS: Outcomes for a consecutively treated group of patients with CLM and simultaneous RLN involvement were compared with a cohort of patients without RLN involvement. Univariate and multivariate analysis of clinical variables was used to identify prognostic factors in this high-risk group. Results Of the 763 patients who underwent resection at our institution for CLM between 1992 and 2006, 47 patients (6%) were treated with hepatectomy and simultaneous lymphadenectomy. All patients had received preoperative chemotherapy. Five-year overall survival (OS) for patients with and without RLN involvement were 18% and 53%, respectively (P < .001). Five-year disease-free survival rates were 11% and 23%, respectively (P = .004). When diagnosed preoperatively, RLN involvement had an increased 5-year OS compared with intraoperative detection, although the difference was not significant (35% v 10%; P = .18). Location of metastatic RLN strongly influenced survival, with observed 5-year OS of 25% for pedicular, 0% for celiac, and 0% for para-aortic RLN (P = .001). At multivariate analysis, celiac RLN involvement and age >or= 40 years were identified as independent poor prognostic factors. CONCLUSION: Combined liver resection and pedicular lymphadenectomy is justified when RLN metastases respond to or are stabilized by preoperative chemotherapy, particularly in young patients. In contrast, this approach does not benefit patients with celiac and/or para-aortic RLN involvement, even when patients' disease is responding to preoperative chemotherapy.

Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality?

PURPOSE: Complete clinical response (CCR) of colorectal liver metastases (CLM) following chemotherapy is of limited predictive value for complete pathologic response (CPR) and cure of the disease. The objective of this study was to determine predictive factors of CPR as well as its impact on survival. PATIENTS AND METHODS: From January 1985 to July 2006, 767 consecutive patients with CLM underwent liver resection after systemic chemotherapy. Patients with CPR were compared with patients without CPR. RESULTS: Twenty-nine of 767 (4%) patients had CPR, and none of these 29 patients had CCR. Patients with CPR (mean age, 54 years) had a mean number of 3.3 metastases at diagnosis (mean size, 29.3 mm). Objective response and stable disease were observed in 79% and 21% of cases, respectively. Postoperative mortality rate was 0%. After a median follow-up of 52.2 months (range, 1.1 to 193.0 months), overall 5-year survival was 76% for patients with CPR compared with 45% for patients without CPR (P = .004). Independent predictive factors for CPR were: age

Usefulness of corticosteroids for the treatment of severe and fulminant forms of autoimmune hepatitis.

Immunosuppressive therapy, and particularly corticosteroids with or without azathioprine, can achieve a remission in more than 80% of patients with autoimmune hepatitis (AIH). By contrast, the usefulness of corticosteroid therapy in severe forms of AIH remains a subject of debate. Between 1986 and 2005, 16 patients (14 females, 2 males; mean age: 36.6 +/- 13.1 yr) presenting with acute, severe, or fulminant disease due to type 1 AIH (n = 13) or type 2 AIH (n = 3) were admitted to our liver intensive care unit. At admission, 10 of 16 (62.5%) patients presented with encephalopathy. Median international normalized ratio (INR), bilirubin, alanine aminotransferase (ALT), and creatinine values were 5.36 (range, 1.7-12.2), 425 micromol/L (range, 278-850), 678 IU/L (range, 60-2867), and 72 muicrool/L (range, 52-133), respectively. A total of 12 patients received corticosteroid therapy: 8 had started in the referring center a median of 2.5 days (range, 1-89) previously, and this therapy was initiated in 4 patients at their admission to our unit (median: 2 days; range: 0-5). Four patients were not treated because of a rapid deterioration in their AIH. Before treatment, 4 of 12 patients had been suffering from encephalopathy. The median duration of corticosteroid therapy was 7 days (range: 2-135). Of 16 patients, 13 underwent liver transplantation (LT) (81%), at which time all were encephalopathic. Median values for INR, total bilirubin, and ALT were 7.2 (range: 3.3-15.9), 400 micromol/L (range: 301-550), and 706 IU/L (range: 69-1,932), respectively, at the time of transplantation. All patients treated with corticosteroids had experienced a clinical (encephalopathy) and biochemical (Model for End-Stage Liver Disease [MELD] score) deterioration at the time of transplantation. Histological findings did not reveal any features of underlying chronic liver disease. Of the 13 patients undergoing transplantation, 10 had received prior corticosteroid therapy. Of the 2 nontransplanted patients treated with corticosteroids, a clinical improvement was observed in only 1 patient. Severe septic complications occurred in 3 patients under corticosteroid therapy (gram-negative septicemia n = 2; disseminated aspergillus n = 1). Nine of the treated patients are still alive; 1 died after liver transplantation (LT) (recurrence of AIH, acute pancreatitis, sepsis), 1 survived without LT, and 1 died without LT. Among the untreated patients, 3 survived after LT and 1 died without LT. In conclusion, corticosteroid therapy is of little benefit in severe and fulminant forms of AIH; it may favor septic complications and should not delay LT.

Is liver resection justified for patients with hepatic metastases from breast cancer?

OBJECTIVE: The purpose of this study was to examine our experience with hepatic resection (HR) in a relatively unselected group of patients with breast cancer liver metastases (BCLM). BACKGROUND: Although medical therapies provide limited survival benefit (median survival, 3-15 months), inclusion of HR into the multimodality treatment of patients with BCLM remains controversial. Our approach has been to offer HR to all patients with BCLM, provided that curative hepatic resection was feasible and extrahepatic disease was controlled with medical and/or surgical therapy. METHODS: Outcomes for 85 consecutive patients (all female, median age, 47 years) with BCLM treated with HR from 1984 to 2004 were reviewed. Extrahepatic metastases had been treated prior to HR or were synchronously present in 27 patients (32%). BCLM were solitary in 32 patients (38%) and numbered more than 3 in 26 patients (31%). The prognostic value of each study variable was assessed with log rank tests for univariate analysis and Cox proportional hazard models for multivariate analysis. RESULTS: Within 60 days of major hepatectomy (> or =3 segments, 54 patients) or minor hepatectomy (<3 segments, 31 patients), there was no mortality. The median hospital stay was 9 days with complications occurring in 26% of patients. Microscopically and macroscopically positive margins were present in 18% (R1) and 17% (R2) of patients. Following HR, 28 patients (33%) developed isolated hepatic recurrences, 12 of whom were treated with repeat hepatectomy. At a median follow-up interval of 38 months, 32 patients were alive, yielding median and 5-year overall survivals of 32 months and 37%. Median and 5-year disease-free survivals were 20 months and 21%. Study variables independently associated with poor survival were failure to respond to preoperative chemotherapy (P = 0.008), an R2 resection (P = 0.0001), and the absence of repeat hepatectomy (P = 0.01). CONCLUSIONS: For patients with BCLM, HR is safe and may provide a significant survival benefit over medical therapy alone. Response to preoperative chemotherapy, resection margin, and rehepatectomy for intrahepatic recurrence are key prognostic factors. Importantly, favorable outcomes can be achieved even in patients with medically controlled or surgically resectable extrahepatic disease, indicating that surgery should be considered more frequently in the multidisciplinary care of patients with BCLM.

Longitudinal prospective evaluation of quality of life in adult patients before and one year after liver transplantation.

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.

Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases?

OBJECTIVE: To evaluate the influence of the response to preoperative chemotherapy, especially tumor progression, on the outcome following resection of multiple colorectal liver metastases (CRM). SUMMARY BACKGROUND DATA: Hepatic resection is the only treatment that currently offers a chance of long-term survival, although it is associated with a poor outcome in patients with multinodular CRM. Because of its better efficacy, chemotherapy is increasingly proposed as neoadjuvant treatment in such patients to allow or to facilitate the radicality of resection. However, little is known of the efficacy of such a strategy and the influence of the response to chemotherapy on the outcome of hepatic resection. METHODS: We retrospectively analyzed the course of 131 consecutive patients who underwent liver resection for multiple (> or =4) CRM after systemic chemotherapy between 1993 and 2000, representing 30% of all liver resections performed for CRM in our institution during that period. Chemotherapy included mainly 5-fluorouracil, leucovorin, and either oxaliplatin or irinotecan for a mean of 9.8 courses (median, 9 courses). Patients were divided into 3 groups according to the type of response obtained to preoperative chemotherapy. All liver resections were performed with curative intent. We analyzed patient outcome in relation to response to preoperative chemotherapy. RESULTS: There were 58 patients (44%) who underwent hepatectomy after an objective tumor response (group 1), 39 (30%) after tumor stabilization (group 2), and 34 (26%) after tumor progression (group 3). At the time of diagnosis, mean tumor size and number of metastases were similar in the 3 groups. No differences were observed regarding patient demographics, characteristics of the primary tumor, type of liver resection, and postoperative course. First line treatments were different between groups with a higher proportion of oxaliplatin- and/or irinotecan-based treatments in group 1 (P < 0.01). A higher number of lines of chemotherapy were used in group 2 (P = 0.002). Overall survival was 86%, 41%, and 28% at 1, 3, and 5 years, respectively. Five-year survival was much lower in group 3 compared with groups 1 and 2 (8% vs. 37% and 30%, respectively at 5 years, P < 0.0001). Disease-free survival was 3% compared with 21% and 20%, respectively (P = 0.02). In a multivariate analysis, tumor progression on chemotherapy (P < 0.0001), elevated preoperative serum CA 19-9 (P < 0.0001), number of resected metastases (P < 0.001), and the number of lines of chemotherapy (P < 0.04), but not the type of first line treatment, were independently associated with decreased survival. CONCLUSIONS: Liver resection is able to offer long-term survival to patients with multiple colorectal metastases provided that the metastatic disease is controlled by chemotherapy prior to surgery. Tumor progression before surgery is associated with a poor outcome, even after potentially curative hepatectomy. Tumor control before surgery is crucial to offer a chance of prolonged remission in patients with multiple metastases.

Decision for retransplantation of the liver: an experience- and cost-based analysis.

OBJECTIVE: To determine the patient factors affecting patient outcome of first liver retransplantation at a single center to help in the decision process for retransplantation. SUMMARY BACKGROUND DATA: Given the critical organ shortage, one of the most controversial questions is whether hepatic retransplantation, the only chance of survival for patients with a failing first organ, should be offered liberally despite its greater cost, worse survival, and the inevitable denial of access to primary transplantation to other patients due to the depletion of an already-limited organ supply. The authors' experience of 139 consecutive retransplantations was reviewed to evaluate the results of retransplantation and to identify the factors that could improve the results. METHODS: From 1986 to 2000, 1,038 patients underwent only one liver transplant and 139 patients underwent a first retransplant at the authors' center (first retransplantation rate = 12%). Multivariate analysis was performed to identify variables, excluding intraoperative and donor variables, associated with graft and patient long-term survival following first retransplantation. Lengths of hospital and intensive care unit stay and hospital charges incurred during the transplantation admissions were compared for retransplanted patients and primary-transplant patients. RESULTS: One-year, 5-year, and 10-year graft and patient survival rates following retransplantation were 54.0%, 42.5%, 36.8% and 61.2%, 53.7%, and 50.1%, respectively. These percentages were significantly less than those following a single hepatic transplantation at the authors' center during the same period (82.3%, 72.1%, and 66.9%, respectively). On multivariate analysis, three patient variables were significantly associated with a poorer patient outcome: urgency of retransplantation (excluding primary nonfunction), age, and creatinine. Primary nonfunction as an indication for retransplantation, total bilirubin, and factor II level were associated with a better prognosis. The final model was highly predictive of survival: according to the combination of the factors affecting outcome, 5-year patient survival rates varied from 15% to 83%. Retransplant patients had significantly longer hospital and intensive care unit stays and accumulated significantly higher total hospital charges than those receiving only one transplant. CONCLUSIONS These data confirm the utility of retransplantation in the elective situation. In the emergency setting, retransplantation should be used with discretion, and it should be avoided in subgroups of patients with little chance of success.