Familial Amyloidotic Polyneuropathy Patients Research Articles

Cerebrovascular regulation in patients with vasovagal syncope and autonomic failure due to familial amyloidotic polyneuropathy.

While there is strong evidence for autonomic involvement in cerebrovascular function acutely, long-term role of autonomic nervous system in cerebrovascular function has been controversial. We assessed autoregulation in 10 healthy individuals, nine patients with vasovagal syncope (VVS), and nine with Familial Amyloidotic Polyneuropathy (FAP), in response to head-up tilt test (HUTT). Arterial blood pressure heart rate, cardiac output, and bilateral cerebral blood flow velocity (CBFV) at the M1 segment of middle cerebral artery (transcranial Doppler ultrasound) were recorded during supine rest and 70° HUTT. Autoregulation was quantified using a validated nonlinear and nonparametric approach based on projection pursuit regression. Plasma adrenaline and noradrenaline were also measured at rest and during HUTT. During supine rest and HUTT, plasma noradrenaline content was lower in FAP patients. During HUTT, VVS patients had a hyperadrenergic status; CBFV decreased in all groups, which was greater in FAP patients (p<0.01). Healthy controls responded to HUTT with a reduction in CBFV responses to increases (p=0.01) and decreases (p<0.01) in arterial pressure without any change in the range or effectiveness of autoregulation. VVS patients responded to HUTT with a reduction in falling (p=0.02), but not rising slope (p=0.40). Autoregulatory range (p<0.01) and effectiveness increased (p=0.09), consistent with the rapid increase in levels of catecholamines. In FAP patients, the level of increase in range of autoregulation was significantly related to the magnitude of increase in plasma noradrenaline in response to HUTT (R2=0.26, p=0.05). Autonomic dysfunction affects the cerebral autoregulatory response orthostatic to challenge.

MMP-14 overexpression correlates with the neurodegenerative process in familial amyloidotic polyneuropathy.

ABSTRACTLevels of matrix metalloproteases (MMPs) can be differentially regulated in response to injury or neurological diseases. For instance, it is known that selective and short-term inhibition of MMP-14, a membrane-type 1 MMP, accelerates axon regeneration. Because axon growth and regeneration is impaired in familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by misfolding and deposition of mutant transthyretin (TTR) in the peripheral nervous system (PNS), we presently investigated the expression levels and the potential role for MMP-14 in this condition. By using cell culture studies, a mouse model of disease and human clinical samples, we observed that MMP-14: (i) is overexpressed in FAP nerves, correlating with TTR deposition; (ii) is upregulated in sciatic nerves from a preclinical transgenic mouse model, increasing with TTR deposition; (iii) levels in the PNS and plasma are rescued upon treatment of mice with anakinra or TTR siRNA, drugs acting over the IL-1 signaling pathway or TTR liver synthesis, respectively; (iv) increases in Schwann cells upon incubation with amyloid-like aggregates; and, finally, (v) is increased in plasma of FAP patients, correlating with disease progression. These results highlight the relevance of MMP-14 in the pathophysiology of FAP, suggesting not only a potential role for this molecule as a novel biomarker for therapy follow up, but also as a new potential therapeutic target.

In vitro modelling of familial amyloidotic polyneuropathy allows quantitative detection of transthyretin amyloid fibril-like structures in hepatic derivatives of patient-specific induced pluripotent stem cells.

The transthyretin protein is thermodynamically destabilised by mutations in the transthyretin gene, promoting the formation of amyloid fibrils in various tissues. Consequently, impaired autonomic organ function is observed in patients suffering from transthyretin-related familial amyloidotic polyneuropathy (FAP). The influence of individual genetic backgrounds on fibril formation as a potential cause of genotype-phenotype variations needs to be investigated in order to ensure efficient patient-specific therapies. We reprogrammed FAP patient fibroblasts to induced pluripotent stem (iPS) cells and differentiated these cells into transthyretin-expressing hepatocyte-like cells (HLCs). HLCs differentiated from FAP iPS cells and healthy control iPS cells secreted the transthyretin protein in similar concentrations. Mass spectrometry revealed the presence of mutant transthyretin protein in FAP HLC supernatants. In comparison to healthy control iPS cells, we demonstrated the formation of transthyretin amyloid fibril-like structures in FAP HLC supernatants using the amyloid-specific dyes Congo red and thioflavin T. These dyes were also applicable for the quantitative determination of in vitro formed transthyretin fibril-like structures. Moreover, we confirmed the inhibition of fibril formation by the TTR kinetic stabiliser diclofenac. Thioflavin T fluorescence intensity measurements even allowed the quantification of amyloid fibril-like structures in 96-well plate formats as a prerequisite for patient-specific drug screening approaches.

Differential expression of Cathepsin E in transthyretin amyloidosis: from neuropathology to the immune system

BackgroundIncreasing evidence supports a key role for inflammation in the neurodegenerative process of familial amyloidotic polyneuropathy (FAP). While there seems to be an overactivation of the neuronal interleukin-1 signaling pathway, the immune response is apparently compromised in FAP. Accordingly, little immune cell infiltration is observed around pre-fibrillar or fibrillar amyloid deposits, with the underlying mechanism for this phenomenon remaining poorly understood. Cathepsin E (CtsE) is an important intermediate for antigen presentation and chemotaxis, but its role in the pathogenesis of FAP disease remains unknown.MethodsIn this study, we used both mouse primary macrophages and in vivo studies based on transgenic models of FAP and human samples to characterize CtsE expression in different physiological systems.ResultsWe show that CtsE is critically decreased in bone marrow-derived macrophages from a FAP mouse model, possibly contributing for cell function impairment. Compromised levels of CtsE were also found in injured nerves of transgenic mice and, most importantly, in naïve peripheral nerves, sensory ganglia, murine stomach, and sural nerve biopsies derived from FAP patients. Expression of CtsE in tissues was associated with transthyretin (TTR) deposition and differentially regulated accordingly with the physiological system under study. Preventing deposition with a TTR small interfering RNA rescued CtsE in the peripheral nervous system (PNS). In contrast, the expression of CtsE increased in splenic cells (mainly monocytes) or peritoneal macrophages, indicating a differential macrophage phenotype.ConclusionAltogether, our data highlights the potential of CtsE as a novel FAP biomarker and a possible modulator for innate immune cell chemotaxis to the disease most affected tissues—the peripheral nerve and the gastrointestinal tract.

Somatic mosaicism with reversion to normality of a mutated transthyretin allele related to a familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is a progressive neuropathy, with onset in adulthood and high mortality. It is related to an altered transthyretin (TTR) plasma protein, mainly produced by the liver and responsible for amyloid deposit in the peripheral nervous system. SNPs in the TTR gene were associated with FAP, and the G>C substitution (NM_000371.3:c.325G>C) in the 109th codon (GAG vs CAG; NP_362.1:p.E109Q) was previously described in Sicily (Italy). Here, we report on a Sicilian family with several patients affected by FAP related to the E109Q mutation, which displayed a somatic mosaicism with the reversion to normality of the c.325G>C mutation. After exclusion of isodisomy and allele deletion, this event seems to be due to a rare, post-zygotic interallelic gene conversion with the wild-type allele serving as a donor. Further investigations will be necessary to better understand the molecular basis of this phenomenon, and could help determine if this can be induced in a targeted manner in the context of natural gene therapy to treat TTR-related FAP patients, as previously proposed for other diseases. Moreover, our results confirm the need to perform DNA-based diagnostic tests with at least a second tissue when a suspected germline mutation in a candidate gene is not identified in the first tissue.

Minor salivary gland biopsy for the diagnosis of familial amyloid polyneuropathy.

The diagnosis of Val30Met familial amyloidotic polyneuropathy (FAP) is based on genetic tests, clinical manifestations, familial history and biopsy of peripheral tissues (e.g. rectum, abdominal fat pad, sural nerve, and minor salivary gland) to confirm the presence of amyloid deposits. The aim of this study was to determine the frequency of amyloid deposits in minor salivary glands biopsied from FAP patients and to investigate whether an association exists between the presence of these deposits and clinical features. Seventeen patients with FAP were submitted to minor salivary gland biopsy to confirm the presence of amyloid deposits. The histopathology of the salivary glands confirmed glandular amyloid deposits in nine symptomatic patients (sensitivity of 75.0%). In general, FAP patients who tested positive for glandular amyloid deposits exhibited significantly higher frequencies of sensorimotor and dysautonomic dysfunctions (p=0.001) compared with those who tested negative. None of the patients reported xerostomia. Minor salivary gland biopsy may help confirm the diagnosis of FAP in symptomatic cases, as it is noninvasive, easy to execute, and causes minimal discomfort to patients.

Tissue remodeling after interference RNA mediated knockdown of transthyretin in a familial amyloidotic polyneuropathy mouse model

Transthyretin (TTR) deposition in the peripheral nervous system is the hallmark of familial amyloidotic polyneuropathy (FAP). Currently, liver transplantation is the only available treatment to halt the progression of clinical symptoms; however, due to the limitations of this procedure, development of alternative therapeutic strategies is of utmost importance. In this regard, interference RNA (RNAi) targeting TTR is currently in phase III clinical development. To dissect molecular changes occurring in dorsal root ganglia (DRG) upon RNAi-mediated knockdown of TTR, we treated both chronically and acutely an FAP mouse model, in different stages of disease. Our data show that inhibition of TTR expression by the liver with RNAi reverse TTR deposition in DRG, decrease matrix metalloproteinase-2 (MMP-2) protein levels in plasma, inhibit Mmp-2 gene expression and downregulate MMP-9 activity in DRG, indicating extracellular matrix remodeling. Furthermore, protein levels of MMP-2 were found upregulated in plasma samples from FAP patients indicating that MMP-2 might be a novel potential biomarker for FAP diagnosis. Collectively, our data show that silencing TTR liver synthesis in vivo can modulate TTR-induced pathology in the peripheral nervous system and highlight the potential of MMP-2 as a novel disease biomarker.

Tissue remodeling after RNAi-mediated knockdown of TTR in a Familial Amyloidotic Polyneuropathy mouse model

Background Transthyretin (TTR) deposition in the peripheral nervous system (PNS) is the hallmark of Familial Amyloidotic Polyneuropathy (FAP). Mice expressing human TTR with the V30M mutation in a heterozygous heat shock factor 1 (Hsf-1) background show extensive TTR deposits in PNS and gastrointestinal tract, as well as extracellular matrix (ECM) remodeling, similar to those seen in human FAP patients. Currently, liver transplantation is the only available treatment to halt the progression of clinical symptoms in FAP. Due to the limitations of this procedure, it is of utmost importance to develop alternative therapeutic strategies. In this regard, an RNAi therapeutic targeting TTR for the treatment of FAP is currently in Phase 3 clinical development. An ongoing phase 2 clinical trial in FAP patients demonstrated promising results as a mean plasma TTR reduction of 80%, sustained for over nine months, led to a decrease in neuropathy progression compared to historical data.

Long-term Results of Domino Liver Transplantation for Hepatocellular Carcinoma Using the "Double Piggy-back" Technique: A 13-Year Experience.

The aim of this study was to evaluate the long-term outcome of liver transplantation (LT) for hepatocellular carcinoma (HCC) with Domino LT (DLT) using the "Double Piggy-back" technique. DLT using livers from familial amyloidotic polyneuropathy (FAP) patients is a well-described technique and useful for expanding the donor pool. However, data on long-term results for HCC are limited, particularly regarding the use of the "Double Piggy-back" technique. Between 2001 and 2014, a total of 260 patients undergoing LT for HCC were analyzed from a prospective database. Of those, 114 were submitted to DLT. Comparisons between groups were performed using propensity score matching. Median follow-up was 34 months (1-152). Overall and disease-free 5-year survival rates for the whole population were 58% and 56%, respectively. There were 177 (68%) patients within Milan Criteria and an additional 26 (10%) within University of California San Francisco (UCSF) criteria. Patients older than 50 years were more likely to receive an FAP liver [odds ratio (OR) 1.94, confidence interval (CI) 1.02-3.69]. DLT patients had more major complications (23.7% vs 13.0%, P = 0.025). Only patients undergoing DLT presented with piggy-back syndrome (7% vs 0%, P = 0.001). After adjusting for potential confounders, DLT and cadaveric LT had a similar 5-year survival rate (59% vs 44%, respectively, P = 0.117). Thirteen patients (11.4%) evidenced FAP disease but not before 6 years after DLT. DLT for HCC is feasible and achieves equivalent results to cadaveric LT. The benefit of expanding the donor pool must be balanced against higher morbidity and a real risk of disease transmission.

Impact of liver transplantation on the natural history of oculopathy in Portuguese patients with transthyretin (V30M) amyloidosis

Purpose: Evaluation of the impact of liver transplantation in the natural history of ocular disorders in familial amyloidotic polyneuropathy (FAP) amyloidosis TTR V30M related (ATTR V30M) patients.Design: A clinical, retrospective and cross-sectional study of 64 Portuguese FAP ATTR V30M patients was carried out between January 2005 and December 2011.Methods: Thirty-two liver transplanted patients (both eyes) aged 39.6–53.8 years old, 32/32 male/female, were paired with an equal number of non-transplanted patients, matching for age, gender, age at onset, disease duration and gender of transmitting parent. Intervention or observation procedure: Routine ophthalmological observation. Main outcome measures: Slit-lamp observation for abnormal conjunctival vessels (ACV), tears break-up time, iris, lens; fundus observation for vitreous, retina and optic disc; Schirmer test.Results: Liver transplantation had no influence on tears break-up time, deposition of amyloid on the iris and retinal amyloid angiopathy. Slight, non-statistically significant protective effects of liver transplantation were noted in the first years for some ocular manifestations (ACV and scalloped iris), except for the abnormal Schirmer test, which was significantly more prevalent in non-transplanted patients’ eyes (81% versus 56%, p = 0.002). On the other hand, deposition of amyloid on the lens, vitreous amyloidosis and glaucoma were apparently more common in transplanted patients. Those differences tended to disappear with time.Conclusions: Ocular manifestations of FAP were not influenced by liver transplantation in a meaningful way. Both transplanted and non-transplanted FAP patients need similar regular follow-up due to long-term risk of serious ocular disease.

Outflow reconstruction with arterial patch in domino liver transplantation: a new technical option

Domino liver transplantation (LT), using livers from familial amyloidotic polyneuropathy (FAP) patients, is a well described technique useful to expand donor pool. One of the main difficulties of this type of LT arises from the necessity to share the vascular pedicles between the graft and the donor. The most important challenge resides in restoring a proper hepatic venous outflow in the FAP-liver recipient. This is specially challenging when using the piggy-back technique, because the hepatic stumps may be too short. To overcome this issue, surgeons explored several techniques using different types of venous grafts. We describe a new technical option by using an arterial graft from the deceased donor. By using both iliac arteries a long graft is created and sutured as needed to the hepatic vein stump. We describe herein this new technique employed in a domino liver recipient who underwent retransplantation for ischemic cholangitis. The procedure was performed using the piggy-back technique; the venous stump of the FAP liver was reconstructed with the arterial graft. The patient had uneventful postoperative and mid-term hepatic function, and anastomosis was patent 24 months after LT.

Transthyretin Aggregate-Specific Antibodies Recognize Cryptic Epitopes on Patient-Derived Amyloid Fibrils

Amyloidosis involves the extracellular deposition of proteinaceous amyloid fibrils and accessory molecules in organ(s) and/or tissue(s), and is associated with a host of human diseases, including Alzheimer disease, diabetes, and heart disease. Unfortunately, the amyloidoses are currently incurable, and there is an urgent need for less invasive diagnostics. To address this, we have generated 22 monoclonal antibodies (mAbs) against aggregates formed by a blood transport protein, transthyretin (TTR), which primarily forms amyloid fibrils in a patient's heart and/or peripheral nerves. Four of the mAbs, 2T5C9, 2G9C, T1F11, and TB2H7, demonstrated diagnostic potential in enzyme-linked immunosorbent assays (ELISA) by their low to sub-nanomolar cross-reactivity with recombinant wild-type (WT) and mutant TTR aggregates and lack of binding to native TTR or amyloid fibrils formed by other peptides or proteins. Notably, in the presence of normal human sera, three of the four mAbs, 2T5C9, 2G9C, and T1F11, retained low nM binding to TTR amyloid fibrils derived from two patients with familial amyloidotic polyneuropathy (FAP). The two most promising mAbs, 2T5C9 and 2G9C, were also shown by immunohistochemistry to have low nM binding to TTR amyloid deposits in cardiac tissue sections from two FAP patients. Taken together, these findings strongly support further investigations on the diagnostic utility of TTR aggregate specific mAbs for patients with TTR amyloidoses.

Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells

Familial amyloidotic polyneuropathy (FAP) is a hereditary amyloidosis induced by amyloidogenic transthyretin (ATTR). Because most transthyretin (TTR) in serum is synthesized by the liver, liver transplantation (LT) is today the only treatment available to halt the progression of FAP, even though LT is associated with several problems. Despite the urgent need to develop alternatives to LT, the detailed pathogenesis of FAP is still unknown; also, no model fully represents the relevant processes in patients with FAP. The induction of induced pluripotent stem (iPS) cells has allowed development of pluripotent cells specific for patients and has led to useful models of human diseases. Because of the need for a tool to elucidate the molecular pathogenesis of FAP, in this study we sought to establish heterozygous ATTR mutant iPS cells, and were successful, by using a Sendai virus vector mixture containing four transcription factors (Oct3/4, Sox2, Klf4, and c-Myc) to reprogram dermal fibroblasts derived from FAP patients. Moreover, FAP-specific iPS cells had the potential to differentiate into hepatocyte-like cells and indeed expressed ATTR. FAP-specific iPS cells demonstrated the possibility of serving as a pathological tool that will contribute to understanding the pathogenesis of FAP and development of FAP treatments.

Transthyretin Proteins Regulate Angiogenesis by Conferring Different Molecular Identities to Endothelial Cells

Familial amyloidotic polyneuropathy (FAP) has a high prevalence in Portugal, and the most common form of hereditary amyloidosis is caused by an amyloidogenic variant of transthyretin (TTR) with a substitution of methionine for valine at position 30 (V30M). Until now, the available efficient therapy is liver transplantation, when performed in an early phase of the onset of the disease symptoms. However, transplanted FAP patients have a significantly higher incidence of early hepatic artery thrombosis compared with non-FAP transplanted patients. Because FAP was described as an independent risk factor for early hepatic artery thrombosis, more studies to understand the underlying mechanisms involved in this outcome are of the utmost importance. Knowing that the liver is the major site for TTR production, we investigated the biological effects of TTR proteins in the vasculature and on angiogenesis. In this study, we identified genes differentially expressed in endothelial cells exposed to the WT or V30M tetramer. We found that endothelial cells may acquire different molecular identities when exposed to these proteins, and consequently TTR could regulate angiogenesis. Moreover, we show that V30M decreases endothelial survival by inducing apoptosis, and it inhibits migration. These findings provide new knowledge that may have critical implications in the prevention of early hepatic artery thrombosis in FAP patients after liver transplantation.

Usefulness of plasma B-type natriuretic peptide as a prognostic marker of cardiac function in senile systemic amyloidosis and in familial amyloidotic polyneuropathy

Objective: In senile systemic amyloidosis (SSA), a common age-related amyloidosis, wild-type transthyretin accumulates in tissues, with a primary result being cardiac dysfunction. Here, we aimed to clarify the usefulness of B-type natriuretic peptide (BNP) as a prognostic marker of cardiac function in SSA and in familial amyloidotic polyneuropathy (FAP).Methods and results: We studied 13 patients with severe SSA and 14 patients with FAP. SSA patients, but not FAP patients, demonstrated a significant correlation of log BNP with the echocardiographic diastolic marker E/e′ ratio (r = 0.78, p < 0.01). SSA patients also showed significant correlations between log BNP and log C-reactive protein or log high-sensitive troponin T (r = 0.70, p < 0.01; r = 0.64, p < 0.05). FAP patients, however, had significant correlations between log BNP and left ventricular wall thickness (intraventricular septum thickness diastole and posterior wall thickness diastole) (r = 0.73, p < 0.01; r = 0.77, p < 0.01). The mean log BNP level in the follow-up period was significantly higher than that in the diagnostic period in SSA patients (2.65 ± 0.45 versus 2.36 ± 0.40, p < 0.01) but not in FAP patients (1.91 ± 0.56 versus 1.93 ± 0.45, p = 0.87). An especially notable phenomenon was the high plasma BNP level (≥180 pg/ml) in SSA patients.Conclusion: Plasma BNP levels may be a useful prognostic marker of cardiac function in SSA.

TECHNICAL IMPROVEMENTS IN DOMINO LIVER TRANSPLANTATION

TECHNICAL IMPROVEMENTS IN DOMINO LIVER TRANSPLANTATION (Abstract): A new modality of liver transplantation was introduced in 1997: the sequential or domino live transplantation. In this kind of transplantation, the FAP (familial amyloidotic polyneuropathy) patients’ livers are used as grafts especially for recipients older than 55—60 years. The obvious inconvenience is that the FAP liver can continue to provide transthyretin, with the probability of later development of neuropathy in the new recipient.

Thrombolysis in ischemic stroke in a familial amyloidotic polyneuropathy patient — /INS;Is there an increased risk of hemorrhagic complication?

Thrombolysis in ischemic stroke in a familial amyloidotic polyneuropathy patient — /INS;Is there an increased risk of hemorrhagic complication?

Fibroblasts endocytose and degrade transthyretin aggregates in transthyretin-related amyloidosis

Transthyretin (TTR)-related amyloidosis is a fatal disorder characterized by systemic extracellular deposition of TTR amyloid fibrils. Mutations in the TTR gene cause an autosomal dominant form of the disease—familial amyloidotic polyneuropathy (FAP). Wild-type (WT) TTR can also form amyloid fibrils in elderly patients with senile systemic amyloidosis. Regression of amyloid deposits in FAP patients who undergo liver transplantation to remove the main source of mutant TTR suggests the existence of mechanisms for the clearance of TTR deposits from the extracellular matrix (ECM), but the precise mechanisms are largely unknown. Because fibroblasts are abundant, playing a central role in the maintenance of the ECM and because the skin is one of the major sites of soluble TTR catabolism, in the present study, we analyzed their role in clearance of TTR aggregates. In vitro studies with a fibroblast cell line revealed that fibroblasts endocytosed and degraded aggregated TTR. Subcutaneous injection of soluble and aggregated TTR into WT mice showed internalization and clearance over time by both fibroblasts and macrophages. Immunohistochemical studies of skin biopsies from V30M patients, asymptomatic carriers, recipients of domino FAP livers as well as transgenic mice for human V30M showed intracellular TTR immunoreactivity in fibroblasts and macrophages that increased with clinical status and with age in transgenic mice. Overall, the present in vitro and in vivo data show that fibroblasts endocytose and degrade TTR aggregates. The function or dysfunction of TTR clearance by fibroblasts may have important implications for the development, progression, and regression of TTR deposition in the ECM.

Marked cardiomegaly in a patient with familial amyloidotic polyneuropathy after orthotopic liver transplantation: a case study

Hepatocyte-derived mutant amyloidogenic transthyretin (ATTR) causes familial amyloidotic polyneuropathy (FAP), for which orthotopic liver transplantation is an established curative treatment. However, some patients with FAP have cardiac amyloidosis after transplantation. Here, we describe a man with an autonomic disorder diagnosed as FAP ATTR Val30Met and marked cardiomegaly after liver transplantation. He underwent orthotopic liver transplantation at 49 years of age and was prescribed prednisolone to prevent graft rejection. Two years later, autonomic dysfunction and severe heart failure gradually developed. He died suddenly at 59. The autopsy revealed marked cardiomegaly (heart weight: 1020 g). Histological and ultrastructural examinations demonstrated massive amyloid deposition and unusual myocardial hypertrophic injury associated with nuclear translocation of the glucocorticoid receptor (GR). No other FAP patients without heart failure showed GR nuclear translocation. GR is a nuclear transcription factor that leads to myocardial hypertrophy, and cumulative prednisolone doses may promote marked cardiomegaly and severe cardiac amyloidosis.

Peritransplant Gastrointestinal Symptoms in Familial Amyloidotic Polyneuropathy

Gastrointestinal dysfunction is a common complication in familial amyloidotic polyneuropathy, and gastrointestinal symptoms are associated with a patient's nutritional status. The object of this study was to evaluate changes in peritransplant gastrointestinal symptoms and the nutritional status of familial amyloidotic polyneuropathy patients using the modified body mass index following a living-donor liver transplant. In a retrospective analysis, we compared 17 Japanese familial amyloidotic polyneuropathy patients who underwent living-donor liver transplant in Kumamoto University Hospital between 2000 and 2009 with a control group of 28 patients with chronic liver disease. We analyzed the peritransplant gastrointestinal symptoms, nutritional status, duration of central venous catheterization, and postoperative hospital stay. The Mann-Whitney U test and Fisher exact test were used to analyze relations between the familial amyloidotic polyneuropathy group and control group, and the Wilcoxon signed-rank test, to analyze the relation of perioperative modified body mass index, with a value for P < .05 considered statistically significant. The duration of central venous catheterization and postoperative hospital stay were significantly longer in the familial amyloidotic polyneuropathy group than they were in the control group. There was no significant difference between modified body mass index preoperatively and 1 year after living-donor liver transplant. Although gastrointestinal symptoms were typically mild before living-donor liver transplant, the familial amyloidotic polyneuropathy group experienced a temporary deterioration in gastrointestinal symptoms after receiving the living-donor liver transplant but recovered after approximately 2 months. Although familial amyloidotic polyneuropathy patients experienced temporary exacerbations of gastrointestinal symptoms, their nutritional status was not affected during the peritransplant period, and they generally recovered within 2 months.