Impact of the learning curve on the outcome of domino liver transplantation.

Domino liver transplantation (DLT) is a strategy used to increase the number of available grafts. In this procedure, the transplant recipient is a living donor of her own liver. It is mandatory that the graft should be fully functional and the genetic defect should recur with sufficient latency period in the new recipient. Corino-Andrade disease, or familial amyloidotic polyneuropathy (FAP), satisfies these conditions. We retrospectively reviewed our prospective database of DLT. From July 2004 to April 2013, we performed 12 DLTs. We assessed age, sex, real Model for End-Stage Liver Disease (MELD) score, waiting list time, cold and warm ischemia times, intraoperative transfusion requirements, hospital stay, early peritransplantation morbidity (post-reperfusion syndrome, intraoperative cardiac arrest, post-transplantation thrombotic events, and biliary morbidity), acute cellular rejection, retransplantation, mortality, patient and graft survivals. With the intention to study the effect of the learning curve in the global survival results (including both donors and recipients of livers with FAP), we divided our series into 2 periods: the early period (from 2004 to 2008) and the present period (from 2009 to 2013). The crude mortality was 40% vs 0% (P = .042) in the early and present periods, respectively. The cumulative patient survival was also significantly in favor of the present period (P = .049). The graft loss prevalence was 60% vs 7.1% (P = .019) in the early and present periods, respectively. The cumulative graft survival was also significantly in favor of the present period (P = .030; Fig 2). In conclusion, we consider DLT to be a complex procedure, whose initial results are conditioned by the learning curve.

Coping strategies in liver patients as a function of relatives' anxiety level.

OBJECTIVE: To determine whether differences in the coping strategies used by liver patients during the pretransplantation phase were a function of their relatives' level of anxiety. MATERIALS AND METHODS: We assessed 75 pre-liver transplantation patients and 75 relatives (one per patient). To assess relatives' anxiety status, we used the Hospital Anxiety and Depression Scale (HADS), and the Questionnaire of Coping with Stress in Cancer Patients (CAEPO) to study patients' coping strategies. Three subgroups of relatives were established as a function of their scores on the HADS anxiety subscale: normal anxiety (G(1)), dubious anxiety (G2), and clinical anxiety (G(3)). To verify intergroup differences in the coping strategies used by the patients, we used the nonparametric Kruskal-Wallis H test. We also performed pairwise comparisons with nonparametric Mann-Whitney U test (with Bonferroni's correction) and Cohen's d as an effect size index. RESULTS: Focusing on the most relevant effect sizes, the pairwise contrasts indicated the following differences: a) normal anxiety (G(1)) and dubious anxiety (G(2)): seeking social support (d = 0.502); b) normal anxiety (G(1)) and clinical anxiety (G(3)): coping and active fighting (d = 0.607), self-control and emotional control (d = 0.658), and seeking social support (d = 0.944); and c) dubious anxiety (G(2)) and clinical anxiety (G(3)): coping and active fighting (d = 0.743), self-control and emotional control (d = 0.722), and seeking social support (d = 0.515). CONCLUSION: In general, during the pre-liver transplantation study, the liver patients whose relatives showed clinical levels of anxiety used these three healthy coping strategies to a lesser extent: coping and active fighting, self-control and emotional control, and seeking social support.

Monitoring the natural evolution and response to treatment of post liver transplant recurrent hepatitis C using transient elastography: preliminary results.

OBJECTIVES: To perform a prospective analysis of changes in liver stiffness (LS) using transient elastography (TE) in a consecutive series of patients with post-liver transplant (LT) recurrent hepatitis C, either left to their natural evolution or receiving antiviral treatment. METHODS: We examined the results from 17 comparisons of TE (baseline vs follow-up) from 11 patients. We evaluated: (1) upon inclusion in the study: age, sex, genotype, time transpired since LT, and baseline fibrosis (F0-4; Scheuer), and (2) during the follow-up period: time elapsed between the two TE and either specific treatment (B) or absence of treatment (A). RESULTS: Mean patient age was 56.8 ± 7.9 years, with a male/female ratio of 10:1. Ten of the eleven patients had genotype 1b. The median time transpired between the LT and inclusion in the study was 28 months (range: 6-142 months). The mean time transpired between the two TE was 11.3 ± 4.5 months. In the 11 patients from group A (9 F1/2 F2; 13 "paired" TE), a predictable increase in LS was produced in 10 cases and a paradoxical result was produced in 3 cases. In the four patients in group B (3 F2/1 F1; 4 "paired" TE), a decrease in LS was produced in 3 cases and a paradoxical result in 1 case. CONCLUSIONS: In our study of patients left to their natural evolution, a slow increase of LS was normal. However, antiviral treatment appeared to decrease LS. TE can be very useful as a complementary test to biopsy for monitoring post-LT recurrent hepatitis C. A longer follow-up period and larger sample size could confirm these preliminary results.

Prevalence and characteristics of bone disease in cirrhotic patients under evaluation for liver transplantation.

BACKGROUND: We performed a retrospective study to examine the prevalence of bone disease (BD) among cirrhotic patients being evaluated for liver transplantation (OLT) using bone densitometry dual-energy x-ray absorptiometry in the hip/femoral neck and lumbar spine. The associations of BD with demographic and clinical data, disease etiology and liver function were studied by univariate and multivariate logistic regression analyses. Osteopenia and osteoporosis were defined by World Health Organization criteria. RESULTS: We included 486 patients (79% men of mean age, 53 ± 8.8 years (range, 21-69) who included 62.6% smoker and 23.7% diabetic subjects. Body mass index (BMI) was 28.8 ± 5.7 kg/m(2) (range, 16-43). The liver disease was Child-Pugh class A (22%), B (51%), or C (27%); the Model for End-Stage Liver Disease (MELD) score was 14.6 ± 5.4 (range, 7-33). The disease etiology was alcohol (59%), hepatitis C (32%), hepatitis B (10%), primary biliary cirrhosis (PBC) (2.3%), secondary biliary cirrhosis, (2%) or other causes (10%). In all, 350 patients (72%) had BD in the hip/femoral neck and/or lumbar spine: Global hip, 26% (osteopenia, 22%; osteoporosis, 4%); femoral neck, 48% (osteopenia, 43%; osteoporosis, 5%) and lumbar spine, 63% (osteopenia, 40%; osteoporosis, 23%). Univariate analysis showed the BD risk to increase with the following variables: Female gender (odds ratio [OR], 1.88; P = .023) and lower BMI (OR, 0.95; P = .012). Upon multivariate analysis, female gender (OR, 2.43; P = .004), lower BMI (OR, 0.96; P = .016), and tobacco use (OR, 1.59; P = .043) were significant. PBC showed BD in 100% of cases. By adjusting bone mineral density (BMD) values to age (Z-score) in relation to that defined by T-score, we observed a decrease in BD prevalence in both the femoral neck (20% vs 48%) and the lumbar spine (44% vs 63%). CONCLUSION: BD, especially in the lumbar spine, is common among cirrhotic patients under evaluation for OLT. Cirrhosis is a major BD risk factor that remains even when BMD values are adjusted for age. Female gender, lower BMI, and tobacco consumption are major risk factors for BD in cirrhotic patients. Bone densitometry must be included in the OLT evaluation of all patients.

Response to vaccination against hepatitis B virus with a schedule of four 40-µg doses in cirrhotic patients evaluated for liver transplantation: factors associated with a response.

We performed a retrospective study to evaluate the rate of and factors associated with a response to recombinant hepatitis B virus (HBV) vaccination using 4 intramuscular doses (40 µg) administered at 0, 1, 2, and 6 months among 278 cirrhotic patients being evaluated for orthotopic liver transplantation (OLT). We re-vaccinated 57 non-responders with the same schedule. The 39.2% overall response rate to vaccination included 36% after three and 40.7% after four doses, namely, a median anti-HBs level of 100 IU/mL (range, 10 to 1000 IU/mL). The 51% revaccination response rate achieved a median hepatitis B surface antibody (anti-HBs) level of 99 IU/mL (range, 11 to >1000 IU/mL). Upon univariate analysis, variables associated with a higher response were: better liver function (Child-Pugh class [A, 53.8% B, 33.3%, C, 30.1%; P = .002), Model for End-stage Liver-Disease (MELD) score (11.4 versus 13.6; P = .001]), absence of diabetes (43.6% versus 20.8%; P = .002), presence of isolated hepatitis B core antibody (anti-HBc) positivity (80% versus 37.7%; P = .007), and younger age (< 45 years, 52.2%; range, 45 to 55 years, 40.4%; > 55 years, 34.1%; P = .031). Upon multivariate logistic regression analysis, lower MELD score (odds ratio [OR]: 0.922; P = .046), absence of diabetes (OR:0.359; P = .008) and isolated anti-HBc positivity (OR:5.826; P = .034) were associated with a higher response. No differences were observed to be associated with gender, weight, body mass index, etiology or tobacco consumption. Among the same patient cohort (n = 79), the responses after the third and fourth doses were 36.7% and 51.9% respectively. In conclusion, the response rate to HBV vaccination in cirrhotic patients evaluated for OLT reached more than 35% among those who received at least 3 doses. It was higher among patients who showed isolated anti-HBc positivity, better liver function, younger age, and non-diabetic status. The fourth dose only increased the response rate by 24% over that obtained after the first three doses, whereas a revaccination achieved a 50% response rate, which probably accounts for revaccination after no response to 3 doses. Vaccination should be introduced against HBV in the early stages of the disease.

Prevalence of hepatitis B and A virus markers and vaccination indication in cirrhotic patients evaluated for liver transplantation in Spain.

In the absence of immunity, vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic liver disease and those evaluated for liver transplantation (OLT) HAV and HBV infections after OLT which are frequent in this setting, are associated with a worse prognosis. The aim of this study was to estimate the need for vaccination against HBV and HAV among cirrhotic patients who were candidates for OLT and associations with gender, age, and etiologic factors. HBV and HAV serological markers HBsAg, anti-HBc, antiHBs, immunoglobulin G (IgG)-anti-HAV were investigated among 568 patients, including 75% men. The overall mean age was 53.6 ± 8.9 years range 17-69, and 20% were diabetic. This etiologies were alcohol (68%), hepatitis C virus (35%) or other causes (10.4%). Child-Pugh classes were: A (26%), B (44%), and C (30%). In contrast with 359 patients (63.2%) who had negative HBV markers, 209 (36.8%) were positive: HBsAg (+), 43 (7.6%), isolated anti-HBc (+), 57 (10%), isolated anti-HBs (+), 19 (3.3%), anti-HBc (+)/anti-HBs (+), 90 (15.8%). HBV vaccine indication was performed in 416 patients (73.2%) who either had negative HBV markers or isolated anti-HBc (+). It was more frequently performed in women (82.3% versus 70.3%, P = .005), albeit with no differences according to age or etiology. There were only 8.2% (44/538) IgG-anti-HAV-negative, an indication for vaccination against HAV, which was more frequent affecting patients who were younger [≤ 45 years (27.6%), 46-55 (7.2%), >55 (2.6%); P < .0001)]; nondiabetic (9.5% versus 2.8%, P = .023); nonalcoholic (11.4% versus 6.6%, P = .056); and displayed negative HBV markers (10.2% versus 4.6%, P = .023). Only three patients with IgG-anti- HAV (-) were over 60 years. In conclusion, there is a frequent indication for HBV vaccination among cirrhotic and especially HAV vaccine for under 45 year old patients undergoing evaluation for OLT.

Outcomes of domino liver transplantation: a single institution's experience.

AIMS: Domino liver transplantation (DLT) is a strategy to increase the donor pool. Explanted liver from patients with familial amyloidotic polyneuropathy (FAP) are often used as domino grafts, because the liver is normal apart from the production of the mutated transthyretin variant. We present the outcomes for both donors and recipients of DLT. MATERIALS AND METHODS: Retrospective analysis of initial DLT for 16 consecutive adult patients performed between July 2004 and July 2009. All cases of FAP donor to grafts were removed preserving the cava vein with reconstruction of the hepatic veins, except the first and seventh cases, where in we removed the retrohepatic vena cava with the liver without venovenous bypass. The postoperative follow-up period for surviving DLT recipients at the end of September 2009 was 2-62 months (mean, 26). RESULTS: Two patients out of 8 FAP donors died due to pulmonary thromboembolism on the 31st postransplant day, or sepsis at 35 days namely, an overall survival of 75%. One patient out of 8 recipients died namely, an early portal thrombosis on the 22nd postransplant day) with a crude survival of 87.5% in the recipient group (P = no significant [NS]). Four grafts from 8 FAP donors were lost-2 deaths and 2 retransplants due to thrombotic events on the first and second postransplant day-with a crude survival of 50%. Two of 8 recipients lost their grafts: 1 death and 1 retransplantation for an acute Budd-Chiari syndrome on the first postransplant day with a crude survival of 75% in the recipient group (P = not significant [NS]). CONCLUSION: We believe that the FAP liver graft is an excellent option for selected patients. Special care must be taken with thrombotic events.

Switching from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients with gastrointestinal complications.

OBJECTIVE: Our aim was to safely and effectively reduce adverse gastrointestinal (GI) events resulting from the use of mycophenolate mofetil (MMF) in liver transplant patients by switching to enteric-coated mycophenolate sodium (EC-MPS). PATIENTS AND METHODS: We studied 19 patients on maintenance therapy presenting with GI intolerance to MMF whose therapy was switched to EC-MPS. The variables recorded were: calcineurin inhibitor (CNI) dose levels, MMF/EC-MPS dose levels, lipid profile, hematology, renal and hepatic function markers, and rejection episodes. These variables were recorded at the visit prior to the day of conversion, on the day of conversion, and 1, 3, 6, and 9 months thereafter. RESULTS: Of the 19 patients, 16 were men (mean age, 56.6 +/- 15.9 years) and 3 were women (58.3 +/- 12.1 years). While 31.6% were on MMF monotherapy, 52.6% were on combined therapy with tacrolimus and 15.8% with cyclosporine. On the day of conversion, 21% were not on MMF, 36.8% were on 1000 mg/d, 26.3% were on 1500 mg/d, 5.3% were on 750 mg/d, and 10.6% were on 500 mg/d. The starting daily doses of EC-MPS were: 360 mg (26.3%), 720 mg (31.6%), 540 mg (26.3%), 1080 mg (10.5%), and 1440 mg (5.3%). GI complications were significantly reduced from the first month postconversion (P < .01), as 57.2% of patients did not display any symptoms; however, at 9 months, this incidence rose by 12% relative to month 1 (P < .05). There were no changes in the other variables and there were no reported rejection episodes. Treatment was suspended in 2 patients due to dyspnea and nervousness. CONCLUSION: In liver transplant patients with GI complications from chronic MMF use, the use of EC-MPS was safe and efficacious, as it significantly reduced their incidence.

Scoring guide when deciding to accept an organ for a liver transplant.

UNLABELLED: Our objective was establish a scoring system that allows a donor to be evaluated quickly and easily using a set of variables that are evaluated prior to the donation and another set that are evaluated during surgery. MATERIALS AND METHODS: Prior to the donation we analyzed age, medication requirements, natremia, hepatic biochemistry, gas levels, days in ICU, history of hypertension, and weight. A value of 40% was allocated to this group of factors. During the transplant we assessed the characteristics of the organ-shine, consistency, surface, edge, color, presence of steatosis, and atheromatosis. A value of 60% was allocated to this set. We established a scale of 1 to 10, only accepting organs scoring 5 or more points. Those grafts that received a score between 5 and 7.5 points were called suboptimal and those with over 7.5 points, optimal. We prospectively analyzed 133 donors whose organs were implanted. RESULTS: The survival rate at 1 year was 85%, and the rejection rate was 12%. The incidence of primary graft dysfunction was 8.2% (n = 11) and that of primary graft nonfunction 2.2% (n = 3). The incidence of primary graft dysfunction was greater within the group with fewer points (suboptimal). There were no differences between the optimal and suboptimal groups in terms of primary malfunction, survival, or rejection rate. CONCLUSIONS: The score provided a guide to decide whether to accept viable organs for implantation, given that the point system was obtained quickly and easily. When greater than 5, it correlated with low rates of primary nonfunction (<3%) and of primary graft dysfunction (<15%), with acceptable survival at 1 year (>80%) and acute rejections rate (<15%).

Efficacy and safety of mycophenolate mofetil as part of induction therapy in liver transplantation.

AIMS: To report our experience with mycophenolate mofetil (MMF) for induction and maintenance therapy to prevent acute liver transplant rejection. METHODS: A retrospective analysis of 66 elective, noncombined liver transplant patients treated beginning de novo MMF and follow for a minimum of 2 years. Thirty-nine of the 66 cases received MMF, calcineurin inhibitors, and steroids. In 11 cases daclizumab was added; in 16 daclizumab was added without steroids. RESULTS: The global survival rate was 91% at 6 months, 89.4% at 1 year, and 87.9% after 2 years. Acute rejection episodes were observed in six patients (9.1%). All episodes responded to corticoids. Toxicity possibly, probably, or partially related to MMF was observed in 35 patients (53%) with definitive suspension required in 13 cases (20%), with dose reduction or temporary suspension in 22 (33%). Hematological toxicity associated with MMF was observed in 12 patients (18%), leading to definitive suspension in two patients (3.03%), temporary suspension in two cases (3.03%), and dose reduction in eight cases (12%). Opportunistic infection was observed in seven cases (10%). Gastrointestinal toxicity was mild and infrequent (five cases, 7.5%). CONCLUSION: Regimens containing MMF reduce rejection episodes with high survival rates and low toxicity.

Nódulo pulmonar en paciente cirrótico / Pulmonary nodle in a cirrhotic patient

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