Assessing bone status in patients awaiting liver transplantation.

UNLABELLED: Osteoporosis is common in liver transplant recipients as a result of both iatrogenic factors and preexisting hepatic osteodystrophy. OBJECTIVES: To assess the prevalences of osteoporosis and fractures and to identify risk factors for these two abnormalities in patients awaiting liver transplantation for end-stage liver disease. METHODS: Between January 2006 and December 2007, patients on a liver transplant waiting list underwent a routine evaluation comprising the identification of risk factors for osteoporosis, radiographs of the spine, bone mineral density measurements (BMD), and laboratory tests (phosphate and calcium levels, hormone assays, liver function tests, and bone turnover markers). RESULTS: We studied 99 patients (70 males and 20 females; mean age, 55 ± 8 years) including 75% with alcohol-induced cirrhosis with or without hepatocarcinoma. Among them, 36% had radiographic vertebral fractures, 38% had osteoporosis, 35% had osteopenia, and 88% had vitamin D insufficiency or deficiency (25(OH)vitamin D3<20 ng/mL). Lower BMD values were associated with vertebral fractures; the odds ratios and 95% confidence intervals for each BMD decrease of 1 SD were as follows: spine, 1.45 (95%CI, 1.1-1.9); total hip, 2.1 (95%CI, 1.3-3.2); and femoral neck, 2 (95%CI, 1.3-3.1) (P<0.05). Levels of bone resorption markers correlated negatively with BMD at the spine and hip. The Model for End-Stage Liver Disease score correlated negatively with hip BMD. CONCLUSION: Our findings suggest high prevalences of low BMD values and vertebral fractures among patients awaiting liver transplantation. Bone status should be evaluated routinely in candidates to liver transplantation.

Assessing renal function with daclizumab induction and delayed tacrolimus introduction in liver transplant recipients.

BACKGROUND: Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection. METHODS: This open, randomized, multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months; an observational study was continued for 18 months. Liver transplant patients with a 12-hr serum creatinine (SrC) level less than 180 micromol/L received either delayed Tac with daclizumab induction (n=98) or standard Tac (n=101) both combined with mycophenolate mofetil and steroids. The primary endpoint was the incidence of SrC level more than 130 micrommol/L at 6 months. RESULTS: The incidence was 22.4% with delayed Tac and 29.7% with standard Tac (P=ns), which remained unchanged at 12 months (21.6% and 23.9%) but increasing slightly at 24 months (29.0% and 32.9%), respectively. A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr (100 micromol/L) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 micromol/L in the delayed Tac group. Biopsy-proven acute rejection was similar at 6 months (17.5% and 18.75%), 12 months (23.5% and 23.8%), and 24 months (24.5% and 25.7%), respectively. Patient and graft survival in both groups were comparable and good. Similar types and incidences of adverse events were reported in both groups at all time. CONCLUSIONS: Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline.

Aerobic capacity in patients with chronic liver disease: Very modest effect of liver transplantation.

INTRODUCTION: Aerobic capacity is commonly impaired in patients with liver cirrhosis, as demonstrated by their low oxygen consumption at peak exercise (peak VO(2)). This impairment is correlated with the severity of the liver disease. We investigated the effect of orthotopic liver transplantation (OLT) alone on exercise capacity in this prospective study of patients with liver cirrhosis. METHOD: Twenty liver transplant candidates, aged 27 to 61years, underwent resting pulmonary function tests, echocardiography, and incremental cardiopulmonary exercise testing (CPET) before OLT and 16.3 + or - 1.6months after OLT. RESULTS: Following OLT, peak VO(2) increased by a mean of only 7.7% (from 63.4 to 71.1% of predicted value), and decreased in one-quarter of the patients. Cardiac function was normal before OLT and no changes in respiratory indicators followed OLT. Change in peak VO(2) after OLT (Delta peak VO(2)) was related to changes in hemoglobin level (r(2)=0.45, p=0.04), the stopping of beta-blocker therapy, and muscle impairment, as suggested by the correlation between Delta peak VO(2) and peak lactate concentration before OLT (r(2)=0.64, p<0.01). DISCUSSION: Our study provides evidence of a very modest and inconsistent increase in aerobic capacity in liver transplant candidates after liver transplantation alone. This persistent impairment of exercise tolerance was principally of peripheral origin but anemia and beta-blocker treatment should be considered as major aggravating factors. Rehabilitation programs before and after transplantation may increase its benefits to these deconditioned liver transplant recipients in their daily lives.

Primary graft function, metabolic control, and graft survival after islet transplantation.

OBJECTIVE To investigate the influence of primary graft function (PGF) on graft survival and metabolic control after islet transplantation with the Edmonton protocol. RESEARCH DESIGN AND METHODS A total of 14 consecutive patients with brittle type 1 diabetes were enrolled in this phase 2 study and received median 12,479 islet equivalents per kilogram of body weight (interquartile range 11,072-15,755) in two or three sequential infusions within 67 days (44-95). PGF was estimated 1 month after the last infusion by the beta-score, a previously validated index (range 0-8) based on insulin or oral treatment requirements, plasma C-peptide, blood glucose, and A1C. Primary outcome was graft survival, defined as insulin independence with A1C < or =6.5%. RESULTS All patients gained insulin independence within 12 days (6-23) after the last infusion. PGF was optimal (beta-score > or =7) in nine patients and suboptimal (beta-score < or =6) in five. At last follow-up, 3.3 years (2.8-4.0) after islet transplantation, eight patients (57%) remained insulin independent with A1C < or =6.5%, including seven patients with optimal PGF (78%) and one with suboptimal PGF (20%) (P = 0.01, log-rank test). Graft survival was not significantly influenced by HLA mismatches or by preexisting islet autoantibodies. A1C, mean glucose, glucose variability (assessed with continuous glucose monitoring system), and glucose tolerance (using an oral glucose tolerance test) were markedly improved when compared with baseline values and were significantly lower in patients with optimal PGF than in those with suboptimal PGF. CONCLUSIONS Optimal PGF was associated with prolonged graft survival and better metabolic control after islet transplantation. This early outcome may represent a valuable end point in future clinical trials.

[Daily life, pregnancy, and quality of life after liver transplantation]. / Vie quotidienne, grossesse, qualité de vie après transplantation hépatique.

It is now accepted that patients with a liver transplantation regain the ability to lead a normal life within months of surgery, but at the price of lifetime immunosuppressive treatment and specific regular surveillance. A balanced and diversified diet, together with regular physical activity is necessary to prevent, limit, or delay the development of the cardiovascular complications that determine the prognosis for long-term survival. Attenuated live vaccines are contraindicated in patients treated with immunosuppressants to avoid the risk of reversion of the attenuation of the virus or bacteria. Travel abroad is possible to places with good sanitary conditions, if the patient increases his or her vigilance for any contagious infection. The global incidence of cancer is higher than in the general population, justifying specific and regular testing and clinical monitoring. A planned pregnancy is possible in patients stabilized after liver transplantation, and prognosis is most often good for mother and child. Early multidisciplinary management is essential because of the elevated risks of fetal growth restriction and preterm delivery. The global perception of quality of life increases after liver transplantation, but remains lower than in healthy subjects.

Primary sarcoma of the liver and transplantation: a case study and literature review.

Primary sarcomas of the liver are rare tumors and their diagnosis is difficult to assess, particularly on percutaneous liver biopsy. Epithelioid hemangioendothelioma (EHE) is an infrequent indication for liver transplantation, and angiosarcoma (AS) is a widely recognized contraindication because of its poor prognosis. We report the case of a young woman who underwent liver transplantation (LT) for an infiltrative hepatic tumor with several features suggestive of EHE, although the analysis of the native liver revealed AS. Everolimus was used as the main immunosuppressive drug. More than two years after LT, her physical condition remained stable despite a local recurrence at 10 months. In this setting, the ranking of new immunosuppressive agents belonging to the family of the proliferation signal inhibitors will need to be precise, but their intrinsic properties suggest a potential use in treatments after LT for atypical malignancies.

Impact of impaired aerobic capacity on liver transplant candidates.

BACKGROUND: Oxygen consumption at peak exercise (peak VO2) is the most accurate index of aerobic capacity (AC), which reflects the physical condition of an individual and is currently considered the gold standard for cardiorespiratory fitness. Evaluation of peak VO2 to identify high-risk candidates for liver transplantation (LT) may represent an interesting approach. The aims of this study were (a) to describe AC and identify factors independently associated with peak VO2; (b) to analyze the prognostic value of peak VO2 in patients referred for preliminary evaluation of LT; and (c) to provide preliminary data on the influence of peak VO2 on length of hospitalization and the need for oxygen support after LT. RESULTS: Peak VO2 was determined in patients referred for preliminary evaluation for LT. One hundred thirty-five candidates were included. More than half had severe alterations in peak VO2. Age, gender, model-for-end-stage liver disease (MELD) score, tobacco use, and hemoglobin were independently associated with peak VO2. Candidates with severe alterations in peak VO2 had a lower 1-year survival than others. Model-for-end-stage liver disease score and peak VO2 were independently associated with survival. In patients with a MELD above 17, those with severe alterations of peak VO2 AC had lower 1-year survival than the others. Among patients who underwent LT, those with severe impairment of peak VO2 showed a trend toward a higher mean length of hospitalization after LT and had significantly longer need for oxygen support. CONCLUSIONS: Peak VO2 is severely impaired in candidates for LT and affects survival and post-LT course. Perioperative respiratory rehabilitation programs validated in lung and heart transplantation must be tested.

Comparison of two techniques of transarterial chemoembolization before liver transplantation for hepatocellular carcinoma: a case-control study.

Supraselective transarterial chemoembolization (STACE) more efficiently targets chemotherapy delivered via the feeding arterial branches of the tumor than does conventional transarterial chemoembolization (TACE). However, the hypothesis of its greater efficacy compared with the latter is subject to controversy. The aim of the present study was to compare STACE to conventional TACE in a controlled study of candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC). Patients were matched for factors associated with HCC recurrence and survival. Sixty patients were included: 30 who were treated with STACE and 30 treated with conventional TACE. The 2 groups were similar in terms of matched criteria. In the overall population (uni- and multinodular HCC), there was no marked difference between the 2 groups in 5-year disease-free survival: 76.8% vs. 74.8%. In sensitivity analysis of patients considered to be the best candidates for TACE (uninodular HCC < or =5 cm), there was a trend toward significance between STACE and TACE in 5-year disease-free survival: 87% vs. 64% (P = 0.09). The only factor associated with complete tumor necrosis was STACE in the overall population (30.8% vs. 6.9%, P = 0.02), with a similar trend in the subgroup of patients with a single nodule (33.3% vs. 6.7%, P = 0.06), whereas the mean number of procedures was similar in the 2 groups (mean, 1.3 procedures; range 1-5 procedures; P = NS). STACE is more efficient at inducing complete tumor necrosis in the liver. This study observed trends toward improvement in the disease-free survival of patients with uninodular HCC < or =5 cm. Future studies focusing on such patients are warranted.

Conversion to sirolimus: a useful strategy for recalcitrant cutaneous viral warts in liver transplant recipient.

Dermatological complications following transplantation are very common and the majority of immunosuppressed transplant recipients develop some to many warts due to human papillomavirus (HPV) infection. In the setting of immunosuppression, therapeutic management may be disappointing because of the extent of the lesions in patients unable to develop a sufficient immune response directed against HPV. We report here a case of a young liver transplant recipient who developed diffuse recalcitrant HPV-induced warts leading to an impairment of her quality of life. Taking into account the antiproliferative and cytostatic properties of the target-of-rapamycin (TOR) inhibitors, a new class of immunosuppressive drug, we significantly modified the immunosuppressive regimen. Conversion to sirolimus was followed by a rapid improvement of cutaneous state suggesting that this strategy may be useful for recalcitrant cutaneous viral warts in transplant recipient.

Long-term results of percutaneous management for anastomotic biliary stricture after orthotopic liver transplantation.

The purpose of this study was to evaluate the results of percutaneous transhepatic management (PTM) of anastomotic biliary strictures (BS). Among 168 liver transplant adult recipients, BS was identified in 30 patients. In 6 patients, narrowing of the anastomosis was found early, and in all cases disappeared spontaneously with prolonged draining of the bile tube. Within a mean time of 14 months after transplantation, 24 patients had symptomatic BSs, revealed by cholestasis (n = 17) or cholangitis (n = 7). Twenty-two patients underwent PTM as first treatment of BS (balloon dilatation or stent placement). We evaluated the primary and secondary patency rate of PTM. In 1 patient, PTM failed because the stricture could not be passed with the guide wire, necessitating conversion to a Roux-en-Y choledochojejunostomy (CDJ). Fourteen patients were treated by percutaneous balloon dilatation from which 8 patients (57.2%) were recurrence-free with a mean follow-up of 61 months. One patient with a patent biliary anastomosis underwent retransplantation for acute rejection. Twelve patients received metallic expandable stent placement as their primary treatment (n = 7) or after failure of balloon dilatation (n = 5). Recurrent stricture was found in 7 cases (58%) and was treated by PTM (n = 6) or surgery (n = 1). The primary patency rate for PTM was 58.8% at 12 months and the secondary patency rate 88.4%, with a mean follow-up of 47 months (median: 44 months). The mortality rate was 3.5% (one death). PTM with balloon dilatation, stent placement, or both, represent a safe method to treat anastomotic BSs after orthotopic liver transplantation (OLT) resulting in a secondary patency rate of 88% at 5 years.