Effects of an exercise training program in physical condition after liver transplantation in familial amyloidotic polyneuropathy: a case report

Introduction

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease that leads to sensory and motor polyneuropathies as well as functional limitations. So far, liver transplantation is the only treatment for FAP because the mutated protein causing the disease is mainly produced in the liver. With the increasing survival of transplant recipients, functional and cardiovascular problems as consequences of immunosuppressant side effects are increasing associated with sedentary lifestyles and/or pretransplantation status. We sought to analyze the impact of exercise training programs on 1 FAP patient's course long-term after liver transplantation.

Methodology

A FAP patient (female; 49 years of age; body mass index = 18.8 kg/m²) underwent a liver transplantation 133 months before assessment. She was assessed for body composition, isometric quadriceps muscle strength, functional capacity, fatigue, and levels of physical activity before and after a 6-month period of combined exercise training.

Results

After the exercise training program, almost all variables were improved, namely, total body skeletal muscle mass, proximal femoral bone mineral density, quadriceps strength, maximal oxygen consumption on 6 minutes walk test (6mwt) or VO_2peak, total ventilation on 6mwt, and fatigue. The improvement in distance on 6mwt (69.2 m) was clinically significant. Preintervention the levels of physical activity were below international recommendations for health; after the program they achieved the recommendations.

Conclusion

The results showed an improvement in functional capacity with a decrease in future disability risk associated with a better lifestyle with respect to physical activity levels in 1 patient.     

Living Donor Liver Transplantation for Acute Liver Failure: A Single Center Experience

Objective

Orthotopic liver transplantation (OLT) is the principal therapy for acute liver failure (ALF). The mortality on the waiting list for deceased donor liver transplantation (DDLT) is high, principally in countries where donation rates are low. Living donor liver transplantation (LDLT) seems an option for the treatment of ALF, although some ethical issues need to be considered. Herein we have evaluated LDLT results among patients with ALF and discussed the ethical aspects of procedures performed in emergency situations.

Patients and Methods

From March 2002 to October 2008, we performed 301 liver transplantations, including 103 from living donors. ALF was responsible for 10.6% of all transplantations; LDLT was only considered for pediatric recipients among whom 7 children displayed ALF.

Results

One patient died on postoperative day 33 due to hepatic artery thrombosis. One patient died at 2 months after transplantation due to biliary sepsis, resulting in an overall survival rate of 71%. The average time for donor discharge was 5 days. No mortality or major complications were observed.

Conclusions

The survival of children with ALF undergoing LDLT was comparable to published data. Furthermore, despite the fact that the available time to prepare the donors was limited, no serious complications were observed in the postoperative period. Thus, using living donors for children with ALF is an effective, safe alternative that can be extremely useful in countries with low donation rates.     

Psychiatric and psychosocial predictors of medical outcome after liver transplantation: a prospective, single-center study

Objective

Recognizing the potential impact of psychiatric and psychosocial factors on liver transplant patient outcomes is essential to apply special follow-up for more vulnerable patients. The aim of this article was to investigate the psychiatric and psychosocial factors predicted medical outcomes of liver transplanted patients.

Methods

We studied 150 consecutive transplant candidates, attending our outpatient transplantation clinic, including 84 who had been grafted 11 of whom died and 3 retransplanted.

Results

We observed that active coping was an important predictor of length of stay after liver transplantation. Neuroticism and social support were important predictors of mortality after liver transplantation.

Conclusion

It may be useful to identify patients with low scores for active coping and for social support and high scores for neuroticism to design special modes of follow-up to improve their medical outcomes.     

Augmentor of liver regeneration ameliorates renal tubular epithelial cell injury after rat liver transplantation

Background

Acute renal insufficiency and dysfunction are common complications after clinical liver transplantation. This study examined whether augmentor of liver regeneration (ALR) played a significant role to ameliorate renal tubular epithelial cell injury after liver transplantation.

Methods

Orthotopic liver transplantation was performed from Sprague-Dawley (SD) to SD rats. Twelve recipients were randomly divided into two groups: ALR group (with recombinated human ALR 100 μg/kg  ·  d intramuscular injection postoperation) versus normal saline-treated group (with the same volume of normal saline injected intramuscularly postoperation). Rats were sacrificed at day 3 posttransplantation. Renal morphological changes in recipients were assessed with light microscopy. The expressions of tumor necrosis factor-α (TNF-α), proliferating cell nuclear antigen (PCNA) and caspase-3 protein and mRNA in the kidney were evaluated by real-time polymerase chain reaction and immunohistochemical staining.

Results

Morphological changes in renal tubular epithelial cells were not significant in either group at day 3 posttransplantation. The intragraft expression of TNF-α and caspase-3 was strikingly promoted in the normal saline-treated group and PCNA attenuated compared to the ALR group.

Conclusion

These data suggested that ALR may play a role to reduce renal damage in liver transplant recipients.     

Applicability of living donor liver transplantation in a program of adult liver transplantation

Introduction

The aim of this study was to investigate the applicability of living donor liver transplantation in a program of adult liver transplantation.

Patients and methods

We studied the outcomes of the evaluation of 71 potential donor candidates for 53 adult candidates to liver transplantation.

Results

Ten of the potential donor candidates did not complete their evaluation. Among the remaining 61 potential donors, 29 (47.5%) were considered to be suitable donors. Only 17 (24% of the 71 initial candidates) underwent donation. The main causes for unsuitability for liver donation were a small remnant liver and vascular anatomic variants.

Conclusion

Fewer than 25% of potential liver donors became effective donors leading us to conclude that adult living donor liver transplantation has a low applicability.     

Bone Disorders in Patients With Chronic Liver Disease Awaiting Liver Transplantation

Background

An important complication of chronic liver disease is osteodystrophy, which includes osteoporosis and the much rarer osteomalacia. Both conditions are associated with significant morbidity through fractures resulting in pain, deformity, and immobility. Liver transplantation may further deteriorate bone metabolism. The aim of the present study was to investigate the frequency and severity of hepatic osteodystrophy among patients with liver cirrhosis who were referred for liver transplantation. We also evaluated modifications in bone metabolism after liver transplantation.

Materials and methods

We recruited 35 consecutive patients with chronic liver disease who were undergoing assessment for transplantation over a 1-year period. Bone mass in the total skeleton and proximal hip was evaluated using a dual-energy X-ray absorptiometry device (Lunar Prodigy Advance, GE Healthcare, USA). According to World Health Organization recommendations, osteoporosis was defined as a T score < −2.5 and osteopenia as T score between −1 and −2.5.

Results

We enrolled in the study 35 patients, including 8 females and 27 males of overall mean age of 57 ± 7, who showed a viral etiology (57%) or alcohol etiology (28%), Child-Pugh 8.7 ± 2.3. The overall prevalence of osteodystrophy was 40% (26% osteopenia and 14% osteoporosis). No difference was evident according to gender, severity of liver disease (Child-Pugh, Model for End-stage Liver Disease), or origin of liver disease. A subgroup of 10 transplanted patients reached 3-month follow-up, showing total body T score with a significant decrease after 3 months while femoral T scores tended to decrease insignificantly.

Conclusions

This study revealed a high prevalence of low bone mineral density among cirrhotic patients before liver transplantation. We suggest that both bone mineral density and biochemical examinations should be considered to be routine tests to identify the status of bone mass and bone metabolism among recipients prior to liver transplantation.     

Impact of Tumor Characteristic on the Outcome of Liver Transplantation in Patients With Hepatocellular Carcinoma

Introduction

Orthotopic liver transplantation (OLT) is a well-established treatment for cirrhotic patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. The aim of this study was to identify predictors of survival among 65 patients with HCC in cirrhotic livers who underwent liver transplantation (OLT).

Methods

From January 2001 to December 2008, we performed 655 OLT in 615 patients. HCC was diagnosed in 58 patients before OLT and in 65 by histological examination of the explanted livers; 74% of the patients met Milan criteria by histological examination.

Results

The median follow-up was 27 months (range = 1-96). We analyzed patient age and gender, etiology of liver disease, Child score at transplantation, rejection episodes, tumor number/size, vascular invasion, and differentiation grade. There was no significant difference in survival among patients grouped according to the Model for End-stage Liver Disease staging system for HCC. The 5-year survival of patients with low differentiated (G3) HCC was significantly worse than that of those with moderately differentiated (G2) or well-differentiated (G1) HCC: 50%, 81%, and 86% respectively, (P < .01). Patients with microvascular invasion displayed a worse 5-year survival than those without vascular invasion (42% vs 80%; P < .01).

Conclusions

The analysis indicated that the histological grade of the tumors and evidences of microscopic vascular invasion were the most useful predictive factors for overall survival among patients with cirrhosis after liver transplantation for HCC.     

Mental health and quality of life in alcoholic liver disease patients after liver transplantation: a prospective controlled study

Objective

Alcoholic liver disease (ALD) is one of the most important indications for liver transplantation. Discordant conclusions have been found concerning quality of life and mental health after transplantation in this particular group. The aim of this work was to investigate improvements in mental health and quality of life among transplanted patients for ALD.

Methods

We studied 45 consecutive transplant candidates with ALD, attending the outpatient clinics. Among these patients we transplanted 24 with the control candidates remaining in wait for transplantation.

Results

There was a significant improvement in all mental health and quality of life dimensions among the transplanted ALD group. We also observed a favorable evolution of coping mechanisms (CM) in this group.

Conclusion

There is a favorable adjustment of ALD patients after transplantation as shown in CM evolution, which might explain the improved mental health and quality-of-life dimensions.     

Reversal of Graft Steatosis After Liver Transplantation: Prospective Study

Objective

To determine the risk factors for reversal of liver graft steatosis.

Patients and Methods

This prospective study included 70 patients (47 men and 23 women) who received steatotic liver grafts between July 2003 and February 2008. No grafts from prisoners were used in the study. Patients were divided into 3 groups according to degree of liver steatosis, as follows: mild (n = 29, group 1), moderate (n = 23, group 2), and severe (n = 18, group 3).

Results

The median (SD) degree of steatosis in liver grafts at transplantation was 15.7% (7.3%) in group 1, 26.3% (10.5%) in group 2, and 45.1% (8.3%) in group 3. Postoperative histologic analysis demonstrated dramatically decreased steatosis in all graft recipients.

Conclusion

Graft steatosis can be decreased substantially after liver transplantation. Factors for reversibility of steatosis include donor age, degree of macrovesicular steatosis, and cold ischemia time.     

Variability of the extrahepatic arterial anatomy in 500 hepatic grafts

Purpose

To review the extrahepatic arterial anatomy in 500 consecutive liver grafts.

Materials and methods

From April 1990 to January 2005 we performed 500 liver transplantations. We received 108 deceased donor liver grafts (21.4%) from other centers. Donor arterial anatomy was recorded as described in the surgical notes of both the donor harvest and the recipient procedures. We used the modified Michels classification scheme proposed by Busuttil. We assessed incidencess of mortality, retransplantation, postreperfusion syndrome, intraoperative arrest, hemorrhagic complications, and primary malfunction, comparing with chi-squared tests.

Results

There were 376 type I (75.2%), 51 type II (10.2%), 32 type III (6.4%), 18 type IV (3.6%), 3 type V (0.6%), 2 type VI (0.4%) and 18 others (3.6%). No significant associations were found between arterial vascular anomalies of the graft and the studied variables.

Conclusion

In our experience, extrahepatic arterial anomalies of the donor graft did not influence the short-term outcomes of liver transplantation.     

Psychosocial Determinants of Quality of Life 6 Months After Transplantation: Longitudinal Prospective Study

Objectives

We sought to investigate the psychosocial determinants of quality of life at 6 months after transplantation.

Methods

A sample of liver transplant candidates (n = 60), composed of consecutive patients (25% with familial amyloid polyneuropathy [FAP]) attending outpatient clinics was assessed in the pretransplant period using the Neo Five Factor Inventory, Hospital Anxiety and depression Scale (HADS), Brief COPE, and SF-36, a quality-of-life, self-rating questionnaire. Six months after transplantation, these patients were assessed by means of the SF-36.

Results

Psychosocial predictors where found by means of multiple regression analysis. The physical component of quality of life at 6 months after transplantation was determined based upon coping strategies and physical quality of life in the pretransplant period (this model explained 32% of variance). The mental component at 6 months after transplantation was determined by depression in the pretransplant period and by clinical diagnoses of patients. Because FAP patients show a lower mental component of quality of life, this diagnosis explained 25% of the variance.

Conclusions

Our findings suggested that coping strategies and depression measured in the pretransplant period are important determinants of quality of life at 6 months after liver transplantation.     

Value of 18-FDG-positron emission tomography/computed tomography before and after transarterial chemoembolization in patients with hepatocellular carcinoma undergoing liver transplantation: initial results

Introduction

Liver transplantation is the treatment of choice for various types of end-stage liver disease and the most appropriate alternative for the treatment of hepatocellular carcinoma (HCC)-associated liver cirrhosis. The aim of this study was to describe our initial experience with the use of 18-FDG positron emission tomography (PET)/computed tomography CT before and after transarterial chemoembolization (TACE) in HCC patients undergoing liver transplantation, seeking to predict the percentage of tumor necrosis achieved by TACE procedures.

Patients and Methods

From January 2007 through December 2009, 39 patients with HCC and liver cirrhosis were included in our liver transplantation program. We selected the 6 subjects who underwent 18-fluorodeoxyglucose PET/CT (18-FDG PET/CT) pre- and post-TACE.

Results

The median SUV (standarized uptake value) in the lesions studied were 4 (range, 2.79-6.95) before TACE with a median post-TACE SUV of 0 (range, 0-4). Among patients whose post-TACE SUV decreased to <3, the percentage of necrosis after studying the hepatectomy was >80%.

Conclusion

Performance of an 18-FDG PET/CT before and after TACE and comparison of SUV in patients with HCC awaiting liver transplantation provided valuable information regarding the effectiveness of TACE.     

Artificial Liver Support System Using Large Buffer Volumes Removes Significant Glutamine and Is an Ideal Bridge to Liver Transplantation

Background

Fulminant hepatitis is an intractable disease of varying etiology. Artificial liver support (ALS) is used to control serious symptoms of fulminant hepatitis, such as brain edema, which may induce postoperative neurological deficits.

Patients and Methods

ALS was evaluated in 12 patients with fulminant hepatitis who had been placed on an ALS system comprising plasma exchange and online hemodiafiltration. Six of 12 patients fell into an ahepatic state, the absolute indication for liver transplantation. The effects of ALS were evaluated on the basis of improvements in clinical symptoms, removal of glutamine (Gln), and brain computed tomography.

Results

All 12 patients regained consciousness with ALS and 5 survived; 7 died despite recovering from hepatic coma. The ALS systems sustained patients in an ahepatic state for more than 2 weeks. The median estimated plasma equivalent volume of removed Gln was 17.9 L (range, 6.7-64.3 L). There was a significant relationship between total buffer volume and the plasma equivalent volume of removed Gln.

Conclusion

Plasma exchange combined with hemodiafiltration using large buffer volumes is a promising and effective bridging method to liver transplantation.     

Extended left hepatectomy of the left and middle hepatic venous drainage areas along the anterior fissure

Background

Extended left hepatectomy including the middle hepatic vein (MHV) may potentially induce right paramedian sector congestion of the remnant liver.

Methods

To prevent venous congestion in the right paramedian sector, we performed extended left hepatectomy including the left hemiliver and anterior segment, which drain into the MHV and left hepatic vein (LHV), for 15 patients.

Results

In 11 of 15 patients (73%), temporary clamping of the common trunk of the MHV and LHV and the proper hepatic artery provided the anterior fissure. Regeneration rate of the middle segment was similar to that of the right lateral sector (10.8% vs 11.2%) on postoperative computed tomography (CT) after 3 months.

Conclusions

This procedure could represent a useful method for preventing postoperative venous congestion.     

Glucocorticoid treatment down-regulates chemokine expression of bacterial cholangitis in cholestatic rats

Background

Postoperative cholangitis is common after operation for biliary atresia. Empirical pulse therapy with glucocorticoid is effective in reversing some detrimental clinical manifestations, but the rationale for such a therapy still is not substantiated.

Methods

Adult male rats were divided into groups according to the treatment: sterile normal saline (NS) or Escherichia coli (EC, 1 mL containing 10⁸ cells of ATCC 25922 strain), 1 mL, were infused into the proximal choledochostomy (PC) tube 2 weeks after ligation of the PC tube (bile duct ligation, BDL), then immediate tube-tube choledocho-choledochostomy (biliary drainage, BD) was constructed. A high dose of dexamethasone (DEX, intraperitoneal injection; 2 mg/kg of body weight) was given after BD in treatment groups. Histopathology of the liver, as well as liver chemokine mRNA expression and serum chemokine levels, were studied 24 hours after treatment.

Results

Inflammatory cell infiltration to the liver was retarded with DEX treatment, which was correlated with a significantly lower expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) mRNA in the liver (P = .006). Serum IL-8 and MCP-1 levels were also significantly down-regulated with DEX treatment (P = 0.008).

Conclusions

Glucocorticoid treatment is effective in modulating IL-8 and MCP-1 expression and ameliorating inflammatory cell infiltration in rat liver with bacterial cholangitis and cholestasis.     

Timing for orthotopic liver transplantation in children with biliary atresia: a single-center experience

Introduction

Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in childhood. The purpose of this study was to determine predictive prognostic factors for children with biliary atresia related to the timing for OLT within 15 months after hepatoportoenterostomy (HPE).

Patients and methods

We retrospectively analyzed the medical records of 25 children (7 boys and 18 girls) who underwent HPE because of biliary atresia between January 1990 and December 2005 at our center. Data examined included age and pathologic findings at HPE, Pediatric End-Stage Liver Disease score at first admission, whether phototherapy was given, liver function test results and total bilirubin level before and 30 days after HPE, and number of cholangitis events.

Results

Twelve children were alive with their native liver, 8 had undergone living donor OLT (all children alive), and 5 had died without OLT. Five- and 10-year survival rates without OLT after HPE were 47.4% and 26.3%, respectively. At univariate analysis, the predictive prognostic factors for children with biliary atresia were total bilirubin level at 30 days after HPE and Pediatric End-Stage Liver Disease score before HPE. At multivariate analysis, the only prognostic factor was total bilirubin level at 30 days after HPE.

Conclusions

In this study, the predictive prognostic factor was total bilirubin level at 30 days after HPE. Orthotopic liver transplantation within 15 months after HPE is needed in children with biliary atresia with a high total bilirubin level at 30 days after HPE.     

Treatment of diaphyseal nonunion of the femur and tibia using an expandable nailing system

Introduction

We evaluated the efficacy of the expandable nailing system for treating femur and tibia shaft nonunions.

Patients and methods

Records of 24 patients (25 fractures) were retrospectively reviewed: 16 with femur and 8 with tibia nonunions. The bones underwent reaming, and the largest possible nail sizes were inserted during re-operation. Bone debris obtained from the reaming was used for bone graft at the site of the nonunion.

Results

The mean age of the patients was 32 years for the tibia group and 49 years for the femur group. The respective intervals between trauma and re-operation were 11 and 13 months, the operation times 60 and 78 min, and the fluoroscopy times 21 and 32 s. Twenty-four of the 25 nonunions healed satisfactorily without requiring additional procedures. In 1 case, demineralised bone matrix was injected percutaneously and the femoral nonunion resolved. Healing time was 23 weeks (6-52) and 17 weeks (6-40) in the tibia and femur groups, respectively. We were able to reduce the need of an autologous bone graft to only two cases by using reamed debris in 17 of the 19 patients who required grafting.

Conclusions

Our results demonstrated satisfactory healing for the treatment of diaphyseal nonunions of the femur and tibia. The expandable nail offers the theoretical advantages of improved load sharing and rotational control without the need for interlocking screws. We recommend expandable nail systems for femur and tibia shaft nonunions and the use of reamed debris in order to decrease the use of autogenous bone graft.     

Biliary complications after orthotopic liver transplantation from donors after cardiac death: broad spectrum of disease

Background

Donation-after-death liver transplantation (DCD-LT) carries higher complication rates compared with donation-after-brain death liver transplantation (DBD-LT). In this report we describe our experience with biliary complications in DCD-LT with emphasis on anatomical patterns and outcomes.

Materials and Methods

We performed retrospective review of patients' medical records from August 2004 to December 2008, during which time total of 26 DCD-LTs were performed. Mean follow-up was 29 months (range 3 to 51 months).

Results

Biliary complications occurred in 12 patients (46%), of whom 9 were related to DCD (35%). Four patients had more than 1 biliary complication, and 4 had concomitant arterial problems (stricture/thrombosis). Treatment of complications included: ERCP (n = 5, 3 resolved), conversion to roux (n = 5, 2 resolved), revision of roux (n = 1), percutaneous transhepatic cholangiography (n = 1), artery revision (n = 3). Three patients with casts had operative extraction of casts depicting a mummified biliary tree; histology showed casts and fibrosis and anastomotic suture material. Six patients underwent retransplantation (23%). Among retransplanted patients, 2 deaths occurred (7.7%).

Conclusion

Our experience with DCD-LT reveals a high prevalence of biliary complications with a new and wide spectrum of clinicopathologic findings. Better strategies for prevention of these unique biliary complications are needed to better justify the added risks and costs for performance of DCD-LT.