bluuebunny/crossref_metadata_2025 huggingface dataset:
Reexamining the role of the humoral immune response in control of hepatitis C virus infection
Authors: Dustin Lynn B. , Jaeshke Hartmut , Tucson A Z , Mullen Kevin , Cleveland O H
Published: August 2004

Immunoglobulin GM and KM allotypes—genetic markers of γ and κ chains, respectively—are associated with immune responsiveness to several infectious pathogens and with survival in certain viral epidemics. We hypothesized that GM and KM allotypes affect the outcome of hepatitis C virus (HCV) infection. To test this hypothesis, we serologically allotyped 100 persons with well-documented clearance of HCV infection and 198 matched persistently infected persons. None of the GM or KM phenotypes by itself was associated with the clearance or persistence of HCV infection. Particular combinations of these phenotypes, however, were significantly associated with the outcome of HCV infection. Subjects with GM 1,17 5,13 and KM 1,3 phenotypes were over three times (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.44-8.87) as likely to clear the infection as the subjects who lacked these phenotypes. This GM phenotype had a similar association with clearance in the absence of KM 3 (OR, 2.75; 95% CI, 1.21-6.23). The presence of GM 1,3,17 23 5,13 phenotype (in the absence of KM 3) was associated with persistence (OR, 0.21; 95% CI, 0.06-0.77), while its absence (in the presence of KM 1,3) was associated with the clearance of infection (OR, 2.03; 95% CI, 1.16-3.54). These results show epistatic interactions of genes on chromosomes 14 (GM) and 2 (KM) in influencing the outcome of an HCV infection. Further investigations involving candidate genes (GM, KM, HLA, and Fcγ receptors) and cellular and humoral immune responses to HCV epitopes are needed to understand the mechanisms underlying these associations.
A novel IgM class autoantibody to a hepatocyte-related 190 kDa molecule in patients with type 1 autoimmune hepatitis
Authors: Yamauchi Katsumi , Yamaguchi Naoko , Furukawa Takaji , Takatsu Kazuko , Nakanishi Toshimi , Sasaki Mina , Isono Etsuko , Tokushige Katsutoshi , Komatsu Tatsuji , Shiratori Keiko
Published: August 2004

It has been reported that autoantibodies to hepatocytes are frequently found in patients with autoimmune hepatitis (AIH). To elucidate the nature of these hepatocyte-specific autoantibodies, we attempted to generate a hepatocyte-specific monoclonal antibody (MoAb) from Epstein-Barr virus-transformed peripheral blood mononuclear cells obtained from a patient with AIH. We established a single clone, 2E3, that continued to produce an immunoglobulin M (IgM) antibody (λ-type). This MoAb had the following properties: it reacted mainly with hepatocyte-derived cell lines, rather than with other cell lines, and it reacted with liver tissue but not with other tissues. By immunoblot analysis, we found that this MoAb recognized a 190 kDa molecule on hepatocytes. The MoAb was able to kill hepatocyte-derived cell lines in the presence of fresh human serum. This cytotoxic effect was completely abrogated by heat inactivation of human serum prior to its addition to cell lines. In addition, an IgM autoantibody that recognized a 190 kDa molecule was also found in patients with AIH but not in those with chronic hepatitis C; its titer correlated significantly with serum alanine aminotransferase (ALT) levels in patients with AIH. In conclusion, we generated a human MoAb that recognizes a 190 kDa molecule on hepatocytes. Because of its ability to mediate complement-dependent cytotoxicity and the presence of similar IgM autoantibody in patients with AIH, we hypothesize this autoantibody may play a role in the immunopathogenesis of AIH. (Hepatology 2004;40:687-692.)
Hepatology highlights
Authors: Elias Elwyn
Published: August 2004

In accordance with increasing demands for evidence-based practice for ethical, fiscal, and medico-legal reasons Hepatology provides a rich source of material that can justly guide the hepatologist’s day-to-day clinical activity. The first four articles highlighted below constitute such confidence building data.
Biased fragment distribution in MC simulation of protein folding
Authors: Martineau Eric , L'Heureux Pierre‐Jean , Gunn John R.
Published: August 2004

Monte Carlo (MC) methods play an important role in simulations of protein folding. These methods rely on a random sampling of moves on a potential energy surface. To improve the efficiency of the sampling, we propose a new selection of trial moves based on an empirical distribution of three‐residue (triplet) conformations. This selection is compared to random combinations of the preferred conformations of the three amino acids, and it is shown that the new trial moves lead to finding structures closer to the native conformation. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1895–1903, 2004
Positively curved cubic plane graphs are finite
Authors: Sun Liang , Yu Xingxing
Published: August 2004

Let G be an infinite plane graph such that G is locally finite and every face of G is bounded by a cycle. Then G is said to be positively curved if, for every vertex x of G, ${1-{d{(x)}\over 2}+\sum _{x\in F}{1\over |F|}>0}$, where the summation is taken over all facial cycles F of G containing x and |F| denotes the number of vertices in F. Note that if G is positively curved then the maximum degree of G is at most 5. As a discrete analog of a result in Riemannian geometry, Higuchi conjectured that if G is positively curved then G is finite. In this paper, we establish this conjecture for cubic graphs. © 2004 Wiley Periodicals, Inc. J Graph Theory 47: 241–274, 2004
Effect of p75 neurotrophin receptor antagonist on disease progression in transgenic amyotrophic lateral sclerosis mice
Authors: Turner Bradley J. , Murray Simon S. , Piccenna Loretta G. , Lopes Elizabeth C. , Kilpatrick Trevor J. , Cheema Surindar S.
Published: August 2004

Neurotrophin level imbalances and altered p75 neurotrophin receptor (p75NTR) expression are implicated in spinal motor neuron degeneration in human and mouse models of amyotrophic lateral sclerosis (ALS). Recently, elevated reactive astrocyte‐derived nerve growth factor (NGF) was linked to p75NTR‐expressing motor neuron death in adult transgenic ALS mice. To test the role of NGF‐dependent p75NTR‐mediated signalling in ALS, we examined the effects of a cyclic decapeptide antagonist of p75NTR ligand binding by using neurotrophin‐stimulated cell death assays and transgenic ALS mice. Murine motor neuron‐like (NSC‐34) cell cultures expressed full‐length and truncated p75NTR, tyrosine receptor kinase B (TrkB), and the novel neurotrophin receptor homolog‐2 (NHR2) but were TrkA deficient. Accordingly, treatment of cells with NGF induced dose‐dependent cell death, which was significantly blocked by the cyclic decapeptide p75NTR antagonist. Application of brain‐derived neurotrophic factor, neurotrophin‐3, or neurotrophin‐4 to cultures increased cell proliferation, and such trophic effects were abolished by pretreatment with the tyrosine kinase inhibitor K‐252a. Systemic administration of a modified cyclic decapeptide p75NTR antagonist conjugated to the TAT4 cell permeabilization sequence to presymptomatic transgenic SOD1G93A mice affected neither disease onset nor disease progression, as determined by hindlimb locomotor, grip strength, and survival analyses. These studies suggest that disrupting NGF‐p75NTR interactions by using this approach is insufficient to alter the disease course in transgenic ALS mice. Thus, alternate ligand‐independent pathways of p75NTR activation or additional NGF receptor targets may contribute to motor neuron degeneration in ALS mice. © 2004 Wiley‐Liss, Inc.
Increased diisopropylfluorophosphate‐induced toxicity in μ‐opioid receptor knockout mice
Authors: Tien Lu‐Tai , Fan Lir‐Wan , Ma Tangeng , Loh Horace H. , Ho Ing‐Kang
Published: August 2004

The potential involvement of μ‐opioid receptors in mediating the changes of toxic signs and muscarinic receptor bindings after acute administration of irreversible antiacetylcholinesterase diisopropylfluorophosphate (DFP) was investigated. DFP‐induced chewing movement and tremors were monitored for a period of 180 min in μ‐opioid receptor knockout and wild‐type mice. The autoradiographic studies of total, M1, and M2 muscarinic receptors were conducted using [3H]quinuclidinyl benzilate, [3H]pirenzepine, and [3H]AF‐DX384 as ligands, respectively. Saline‐treated μ‐opioid receptor knockout and wild‐type mice did not show chewing movement or tremors. Although DFP (1, 2, or 3 mg/kg, subcutaneous injection, s.c.)‐induced chewing movement and tremors were shown in a dose‐dependent manner, there were no significant differences in tremors induced by 1 or 2 mg/kg of DFP between μ‐opioid receptor knockout and wild‐type mice. There were also no significant differences in chewing movement induced by all doses of DFP between μ‐opioid receptor knockout and wild‐type mice. However, DFP (3 mg/kg)‐induced tremors in μ‐opioid receptor knockout mice were significantly increased over those in wild‐type controls. Acetylcholinesterase activity in the striatum of saline‐treated μ‐opioid receptor knockout mice was significantly higher than that of the wild‐type controls. After administration of DFP, acetylcholinesterase activity in the striatum of both μ‐opioid receptor knockout and wild‐type mice was significantly decreased (more than 36%, 58%, and 94% reduced at the doses of 1, 2, and 3 mg/kg, respectively) than that of their respective saline controls. M2 muscarinic receptor binding in saline‐treated μ‐opioid receptor knockout mice was significantly lower than that of the wild‐type controls in the striatum. However, there were no significant differences in total, M1, or M2 muscarinic receptor binding in the cortex, striatum, or hippocampus of μ‐opioid receptor knockout and wild‐type mice after DFP administration. Our data show increased DFP‐induced tremors, compensatory up‐regulation of acetylcholinesterase activity, and compensatory down‐regulation of M2 muscarinic receptors in the striatum of mice lacking μ‐opioid receptor gene. These results suggest that the enhancement of DFP‐induced tremors may be associated with the compensatory up‐regulation of acetylcholinesterase activity and compensatory down‐regulation of M2 muscarinic receptors in the striatum of μ‐opioid receptor knockout mice. © 2004 Wiley‐Liss, Inc.
Astrocytes and oligodendrocytes express different STOP protein isoforms
Authors: Galiano M.R. , Bosc C. , Schweitzer A. , Andrieux A. , Job D. , Hallak M.E.
Published: August 2004

Many cell types contain subpopulations of microtubules that resist depolymerizing conditions, such as exposure to cold or to the drug nocodazole. This stabilization is due mainly to polymer association with STOP proteins. In mouse, neurons express two major variants of these proteins, N‐STOP and E‐STOP (120 kDa and 79 kDa, respectively), whereas fibroblasts express F‐STOP (42 kDa) and two minor variants of 48 and 89 kDa. N‐ and E‐STOP induce microtubule resistance to both cold and nocodazole exposure, whereas F‐STOP confers microtubule stability only to the cold. Here, we investigated the expression of STOP proteins in oligodendrocytes and astrocytes in culture. We found that STOP proteins were expressed in precursor cells, in immature and mature oligodendrocytes, and in astrocytes. We found that oligodendrocytes express a major STOP variant of 89 kDa, which we called O‐STOP, and two minor variants of 42 and 48 kDa. The STOP variants expressed by oligodendrocytes induce microtubule resistance to the cold and to nocodazole. For astrocytes, we found the expression of two STOP variants of 42 and 48 kDa and a new STOP isoform of 60 kDa, which we called A‐STOP. The STOP variants expressed by astrocytes induce microtubule resistance to the cold but not to nocodazole, as fibroblast variants. In conclusion, astrocytes and oligodendrocytes express different isoforms of STOP protein, which show different microtubule‐stabilizing capacities. © 2004 Wiley‐Liss, Inc.
Molecular adsorbent recirculating system for acute and acute-on-chronic liver failure: A meta-analysis
Authors: Khuroo Mohammed S. , Khuroo Mehnaaz S. , Farahat Karim L.C.
Published: August 2004

Molecular adsorbent recirculating system (MARS) is an important option for patients with liver failure to give them additional time for recovery or to serve as a “bridge” to transplantation. However, its effect on survival for such patients is not well known. Our aim was to assess the treatment effects of MARS on patients with acute and acute-on-chronic liver failure. The outcomes measure evaluated was survival. We searched Medline (1966-2002) and EMBASE (1974-2002) using the terms liver failure, liver support systems, and MARS. Our search was extended to the Cochrane Controlled Trials Registry Database, published abstracts from 5 international conferences, Teraklin (the manufacturer of MARS), known contacts, and bibliographies from each full-published report. We included trials published in English and non-English languages. Eligible studies were randomized and nonrandomized controlled trials, which compared the treatment effects of MARS with standard medical treatment. Of the 206 articles screened, 4 randomized controlled trials including 67 patients were analyzed. Two nonrandomized trials with 61 patients were used for explorative analysis. The methodology, population, intervention, and outcomes of each selected trial were evaluated by duplicate independent review. Disagreements were resolved by consensus. In the primary meta-analysis, MARS treatment did not appear to reduce mortality significantly compared with standard medical treatment [relative risk (RR), 0.56; 95% confidence interval (CI), 0.28-1.14; P = .11]. Only 1 of the 4 randomized trials analyzed showed significant reduction in mortality. Sensitivity analysis of 3 peer-reviewed trials did not reduce mortality significantly with MARS treatment (RR, 0.72; 95% CI, 0.37-1.40; P = .33). Subgroup analysis of 2 trials for acute liver failure and another 2 trails for acute-on-chronic liver failure also did not reveal any benefit to survival with MARS treatment. In contrast, explorative analysis of 2 nonrandomized trials showed a significant survival benefit with MARS treatment (RR, 0.36; 95% CI, 0.17-0.76; P = .007). This was possibly related to bias in the selection of patients in the nonrandomized trials. In conclusion, MARS treatment had no significant survival benefit on patients with liver failure when compared with standard medical therapy. However, we found only a few trials with a small number of patients for the analysis, allowing for the possibility of false negative and erroneous conclusions. Well-conducted randomized trials are strongly recommended to define the role of MARS in the treatment of patients with liver failure. (Liver Transpl 2004;10:1099-1106.)
Orthotopic liver transplantation for portosystemic encephalopathy in an adult with congenital absence of the portal vein
Authors: Wojcicki Maciej , Haagsma Elizabeth B. , Gouw Annette S.H. , Slooff Maarten J.H. , Porte Robert J.
Published: August 2004

Congenital absence of the portal vein (CAPV) is a very rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. There is no portal perfusion of the liver and no portal hypertension. This abnormality is usually coincidentally discovered in children, the majority of whom have no signs of encephalopathy and only slightly abnormal liver function tests. Additional anomalies common in CAPV are cardiovascular abnormalities and hepatic tumors. To date, only 5 adult patients (>18 years) with CAPV have been described, none of whom underwent liver transplantation. We describe a 45-year-old man with CAPV and end-stage renal insufficiency due to focal segmental glomerulopathy, who developed therapy-resistant encephalopathy with intermittently high ammonia levels. The patient underwent a combined liver and kidney transplantation and is doing well at 2.5 years of follow-up. Histopathological examination of the native liver showed no portal vein branches in the portal tracts. In conclusion, our experience suggests that, although children with CAPV usually have no symptoms of encephalopathy, this may still develop at a later stage in adult life. When encephalopathy becomes refractory to medical therapy, orthotopic liver transplantation (OLT) can be successfully performed with restoration of normal cerebral function. (Liver Transpl 2004;10:1203-1207.)
Revisiting liver transplant immunology: From the concept of immune engagement to the dualistic pathway paradigm
Authors: Reding Raymond , Davies Hugh F.S.
Published: August 2004

Ever since the demonstration that allografts are rejected through immune reactions of the host, clinical therapies for organ allografts have relied on immune suppression to prevent these destructive events. A growing body of clinical and experimental data suggests that allografts elicit multiple, interactive immune responses. The result is not inevitably graft rejection, and “spontaneous” acceptance of fully allogeneic liver grafts occurs in rodents without immunosuppression. A spectrum of results range from spontaneous acceptance without immunosuppression to rejection with immunosuppression. The “dualistic pathway paradigm” aims to reconcile apparently conflicting observations in liver transplantation and proposes that: (1) immune engagement between the host and the allograft is instrumental in both rejection and acceptance; (2) there exist in all mammalian species congruent interactive pathways of immune activation whereby the fate of the allograft is determined by the quantitative results of these interactions; (3) the dualistic effect of immunosuppressive drugs on pathways of immune activation, conferring the capacity for favorable or unfavorable graft outcome should be investigated in experimental models in which organ allografts are spontaneously accepted. In conclusion the design of clinical strategies based on this research may contribute to protocols resulting in allograft acceptance without chronic immunosuppression. (Liver Transpl 2004;10:1081-1086.)
Evolution of hepatitis C virus quasispecies immediately following liver transplantation†
Authors: Feliu Anna , Gay Eugeni , García-Retortillo Montserrat , Saiz Juan Carlos , Forns Xavier
Published: August 2004

Liver cirrhosis caused by chronic hepatitis C virus (HCV) infection is the main indication for liver transplantation (LT). There is little information on HCV genetic evolution following transplantation. The aim of this study was to carefully assess early evolution of HCV quasispecies in a cohort of 18 liver transplant recipients followed prospectively. Quasispecies analysis was performed by sequence analysis of the hypervariable region 1 (HVR1) before transplantation and at day 4 and week 4 following LT. A predominant variant was present in 12 (67%) of the 18 patients before transplantation and the same variant was propagated and remained predominant after LT in 6 (50%) of these patients. In the remaining individuals, there were major changes in the quasispecies composition, mostly occurring during the first days after LT. There was a progressive decrease in the nonsynonymous (dN)/synonymous (dS) ratios from baseline (1.2) to day 4 (.6) (P = .08) and to week 4 after LT (.3) (P = .015). Similarly, genetic distance (GD) declined from baseline (.1) to day 4 (.03) (P = .07) and to week 4 (.04) (P = .04). We did not find any differences in HCV genetic evolution between patients with mild (n = 10) or severe (n = 8) disease recurrence. In conclusion, during the first days following transplantation, HCV quasispecies becomes more homogenous, even after major changes in its composition. Importantly, these changes persist and even increase during the 1st month after transplantation. The “bottleneck” effect caused by the implantation of a new graft and the lack of selective pressure due to the strong immunosuppression most likely explain this particular pattern of genetic evolution. (Liver Transpl 2004;10:1131-1139.)
Glutathione S-transferase T1 mismatch constitutes a risk factor for de novo immune hepatitis after liver transplantation
Authors: Aguilera Isabel , Sousa Jose M. , Gavilán Francisco , Bernardos Angel , Wichmann Ingeborg , Nuñez-Roldán Antonio
Published: August 2004

A new form of autoimmune hepatitis referred to as de novo, has been reported after liver transplantation during the past 5 years. The features are identical to those of classical autoimmune hepatitis (AIH), but the facts involved in the onset and outcome of this type of graft dysfunction are still unclear. The identification of antibodies directed to glutathione S-transferase T1 (GSTT1) in the sera of patients with de novo immune hepatitis led us to the description of an alloimmune reaction due to a GSTT1 genetic incompatibility between donor and recipient. We analyzed a cohort of 110 liver transplant patients treated in the liver transplant unit of our hospital during a period of 1 year, from September 2002 to October 2003. We found the following distribution of the GSTT1 genotypes (recipient/donor): +/+ = 66, +/− = 23, −/+ = 15, −/− = 6. Six of these patients were diagnosed with de novo immune hepatitis; all of them belong to the group of negative recipients with positive donors, and all produced anti-GSTT1 antibodies. This genetic combination is associated with a statistically significant increased risk of de novo immune hepatitis (IH) in liver transplant patients (P < .0001 by the Fisher exact test). In conclusion, our results clearly establish the importance of the GSTT1 genotype from donor and recipient of a liver transplant as a predictive marker for de novo IH. At the same time, we confirmed our initial results that only this particular donor/recipient combination triggers the anti-GSTT1 antibody production. (Liver Transpl 2004;10:1166-1172.)
Mycophenolate mofetil monotherapy in liver transplant recipients: A single center experience
Authors: Fairbanks Kyrsten D. , Thuluvath Paul J.
Published: August 2004

The long-term use of calcineurin inhibitors (CIs) is associated with significant morbidity in liver transplant recipients. Although mycophenolate mofetil (MMF) is well tolerated, two small studies reported an unacceptable rate of acute allograft rejection in liver transplant recipients receiving MMF monotherapy. In this study, we retrospectively investigated the safety and efficacy of MMF monotherapy in liver transplant recipients. We reviewed the medical records of all patients who underwent liver transplant at our institution. Sixteen patients were identified who received MMF either as monotherapy (n = 13) or with corticosteroids (n = 3; 2 of them for other comorbid conditions), and these patients were studied to determine the efficacy and complications. Fifteen (15/16) patients were converted from a CI to MMF because of renal insufficiency. Patients were converted to MMF monotherapy after a median of 2,056 days (range, 606-5,893) after liver transplantation. The median postconversion follow-up was 668 days (range, 60-1,509). Four patients required dialysis despite conversion; of those patients not requiring dialysis, serum creatinine stabilized and showed a trend toward improvement (2.51 ± 1.12 mg/dL to 1.85 ± .58 mg/dL, P = .1). However, there were 3 episodes (47, 107, and 1,203 days after conversion) of severe, irreversible allograft rejection after conversion resulting in death in 2 patients and necessitating retransplantation in 1 patient. There were no patient characteristics, except perhaps African-American race, that predicted the development of rejection. In conclusion, MMF monotherapy was associated with a significant risk (19%) of unpredictable, severe, and irreversible allograft rejection even among long-term transplant survivors. Caution should be exercised before converting patients to MMF monotherapy. (Liver Transpl 2004;10:1189-1194.)
Long-term results and modeling to predict outcomes in recipients with HCV infection: Results of the NIDDK liver transplantation database†
Authors: Charlton Michael , Ruppert Kris , Belle Steven H. , Bass Nathan , Schafer Daniel , Wiesner Russell H. , Detre Katherine , Wei Yuling , Everhart James
Published: August 2004

Hepatitis C virus (HCV)-associated liver disease is the most common indication for liver transplantation (LT). There are, however, no long-term (>5 year) studies of comparative outcomes for recipients with HCV infection, and no models capable of identifying recipients with HCV infection at greatest risk for adverse outcomes. We prospectively determined: 1) long-term outcomes, and 2) whether pretransplant patient or donor variables can be used to predict death and/or graft loss in recipients with HCV infection. A total of 165 HCV-infected recipients were eligible for this study. Pretransplant donor and recipient characteristics and patient and graft survival data were prospectively collected. Model building for outcomes was carried out using logistic regression. Receiver operating characteristic curves for different models were created and compared. Median follow-up was 8.5 years. Adjusted 10 year graft survival was 64% for recipients with HCV infection and 51% for uninfected recipients. A model incorporating pretransplant HCV ribonucleic acid (RNA), cytomegalovirus immunoglobulin (CMV IgG) serostatus, creatinine, bilirubin, prothrombin time international ratio (INR), recipient age, and donor age was developed to identify recipients at greatest risk of short-term mortality or graft loss (area under receiver operating characteristic curve = .83) In conclusion, long-term outcomes following LT for recipients with HCV infection are comparable to those for recipients undergoing LT for other indications. HCV-infected recipients at greatest risk for short-term mortality and graft loss can be identified using several readily identifiable pretransplant variables. Long-term death and graft loss specifically secondary to recurrence of HCV appears, however, to be determined primarily by factors other than those included in this analysis. (Liver Transpl 2004;10:1120-1130.)
Can liver transplantation improve our understanding of the pathophysiology of iron overload?
Authors: Brandhagen David
Published: August 2004

We observed the development of phenotypic hereditary haemochromatosis in a non-hereditary haemochromatosis liver transplant recipient, following transplantation with a liver from a C282Y heterozygous donor. No cause for secondary iron overload was identified. Subsequent sequencing of the HFE gene of both donor and recipient revealed a strong candidate for a novel pathogenic HFE mutation. In the recipient, heterozygosity for a single base substitution in exon 1, g.18 G>C, resulting in the substitution of arginine by serine at codon 6 (R6S), was detected. This R6S variation is likely to represent a novel pathogenic missense mutation of the HFE gene. An interaction between R6S heterozygosity in the recipient and C282Y heterozygosity in the donor liver is the most likely explanation for the development of iron overload in this patient. The report suggests that an hepatic defect is required for expression of hereditary haemochromatosis and that the intestinal HFE genotype is not the exclusive determinant of iron status. It also raises the possibility that a hereditary haemochromatosis phenotype may result from transplantation of C282Y heterozygous donor livers into recipients with heterozygous pathogenic HFE mutations. This possibility may have significant implications for the common practice of transplanting C282Y heterozygous livers. (Gut 2003;52:433-435).
Herpes zoster after liver transplantation: Incidence, risk factors, and complications
Authors: Herrero Ignacio J. , Quiroga Jorge , Sangro Bruno , Pardo Fernando , Rotellar Fernando , Alvarez-Cienfuegos Javier , Prieto Jesus
Published: August 2004

Herpes zoster is the consequence of the reactivation of latent varicella-zoster infection. Immunosuppression may be a predisposing factor for herpes zoster. We have retrospectively assessed the risk of herpes zoster, the risk factors for its occurrence, and its evolution in a population of 209 consecutive liver transplant recipients. Herpes zoster developed in 25 (12%) of patients. One-, 3-, 5-, and 10-year actuarial rates of herpes zoster were 3%, 10%, 14%, and 18%, respectively. In a case-control study, patients developing herpes zoster were younger, received a higher number of immunosuppressive drugs, and were more frequently receiving mycophenolate mofetil or azathioprine. In multivariate analysis, the only factor related to herpes zoster occurrence was treatment with mycophenolate mofetil or azathioprine. Eight patients (31%) developed postherpetic neuralgia. In conclusion, herpes zoster is a relateively common complication after liver transplantation. It is related to immunosuppressive therapy. Postherpetic neuralgia develops in one third of patients with posttransplant herpes zoster. (Liver Transpl 2004;10:1140-1143.)
Reconstruction of isolated caudate portal vein in left liver graft
Authors: Kokudo Norihiro , Sugawara Yasuhiko , Kaneko Junichi , Imamura Hiroshi , Sano Keiji , Makuuchi Masatoshi
Published: August 2004

The addition of the caudate lobe to a left liver graft is known to increase graft volume by 9% and has been shown to be useful for overcoming borderline graft-recipient size mismatch in adult living donor liver transplantation. To assure full graft viability and regeneration, all of the feeding vessels for the caudate lobe should be preserved or reconstructed. However, more knowledge is needed about portal vein reconstruction for the caudate lobe. From January 1996 to August 2003, 238 living donor liver transplantations were performed at our institution. Of these, 67 donors underwent left hepatectomy with the caudate lobe and the middle hepatic vein. An isolated caudate portal vein originating from the left sidewall of the portal branches for the Spiegelian lobe (P1) was encountered in 9 donors (13.4%). The isolated P1 was reconstructed in 3 of the 9 cases using the pantaloon technique or interposition of an autovein graft. There were no complications related to P1 reconstruction and patency was confirmed by computerized tomography (CT) 1 month after transplantation. In the remaining 6 cases, the isolated P1 was very small (less than .5 mm) and did not require reconstruction. Isolated P1s are relatively rare, but when they are both present and large, it is advisable to undertake reconstruction that assures full graft function of the caudate lobe. (Liver Transpl 2004;10:1163-1165.)
Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center
Authors: Valentín-Gamazo Camino , Malagó Massimo , Karliova Marc , Lutz Juergen T. , Frilling Andrea , Nadalin Silvio , Testa Giuliano , Ruehm Stefan G. , Erim Yesim , Paul Andreas , Lang Hauke , Gerken Guido , Broelsch Christoph E.
Published: August 2004

Adequate selection of donors is a major prerequisite for living donor liver transplantation (LDLT). Few centers report on the entire number of potential donors considered or rejected for living donation. From April 1998 to July 2003, a total of 111 living donor liver transplantations were performed at our institution, with 622 potential donors for 297 adult recipients and 78 potential donors for 52 pediatric recipients evaluated. In the adult group, only 89 (14%) potential donors were considered suitable, with a total of 533 (86%) potential donors rejected. Of these, 67% were excluded either at initial screening or during the first and second steps of the evaluation procedure. In 31% of all cases, the evaluation of donors was canceled because of recipient issues. In the pediatric group, 22 (28%) donors were selected, with the other 56 (72%) rejected. Costs of the complete evaluation process accounted for 4,589 Euro (€) per donor. The evaluation of a potential living donor is a complex and expensive process. We present the results on the evaluation of the largest group of potential donors for adults reported in the literature. Only 14% of potential donors in our series were considered suitable candidates. It has not yet been established who should cover the expenses of the evaluation of all rejected donors. In conclusion, all efforts should be made in order to develop an effective screening protocol for the evaluation of donors with the aim of saving time and resources for a liver transplantation program. (Liver Transpl 2004;10:1087-1096.)
Donor selection for procurement of right posterior segment graft in living donor liver transplantation
Authors: Hwang Shin , Lee Sung-Gyu , Lee Young-Joo , Park Kwang-Min , Kim Ki-Hun , Ahn Chul-Soo , Sung Kyu-Bo , Moon Deok-Bog , Ha Tae-Yong , Kim Keon-Kuk , Kim Yeon-Dae
Published: August 2004

The right posterior segment (RPS) graft was introduced to overcome graft-size mismatch when the donor liver demonstrates a disproportionately small left lobe (LL). As variants of liver anatomy seemed to be related to the feasibility of RPS graft procurement, in 2003, we performed a prospective study to assess its feasibility in 197 consecutive living donors. Variants of the portal vein (PV) were classified as type I (bifurcation), II (trifurcation), and III (independent RPS PV branching from main PV). The right hepatic artery, vein, and bile duct were also classified according to their branching pattern and location. PV variations were type I in 157 (79.7%) donors, type II in 15 (7.6%) donors, and type III in 25 (12.7%) donors. Mean volume proportion of LL plus caudate lobe was 35.3 ± 3.8% (range 24-4) of the whole liver volume (WLV). On exclusion of donors with LL greater than 35% of WLV, there were 14 (7.1%) donors revealing RPS greater than LL by over 3% of WLV. Of these 14 donors, 3 had type I PV with artery or bile duct anatomy not suitable for RPS procurement. One donor with type II PV and 9 out of 10 donors with type III PV met the anatomical conditions for RPS graft procurement. With the exclusion of caudate lobe volume, LL volume became less than 30% of WLV in all of these 14 donors. We successfully procured 3 RPS grafts, all with type III PV, out of 197 consecutive living donors. In conclusion, successful RPS graft procurement is highly possible, only when LL is disproportionately small (<30% of WLV) and the PV variant is type III. (Liver Transpl 2004;10:1150-1155.)
Sharing the middle hepatic vein between donor and recipient: Left liver graft procurement preserving a large segment VIII branch in donor
Authors: Kishi Yoji , Sugawara Yasuhiko , Akamatsu Nobuhisa , Kaneko Junichi , Matsui Yuichi , Kokudo Norihiro , Makuuchi Masatoshi
Published: August 2004

There are few reported techniques to minimize the congestion in the donor after left liver graft procuring. If a large tributary of the middle hepatic vein (MHV) draining segment VIII (V8) converges into the root of the MHV in a donor of left liver, this branch should be preserved on the donor side. The volume of congested area when the V8 was ligated was predicted preoperatively by computed tomography (CT) and examined intraoperatively by the clamp test. Postoperative regeneration of the donor liver was evaluated by CT volumetry. This technique was used in 3 cases. The regeneration rate after 3 months of the right paramedian sector was 27, 38, and 8%, and that of the right lateral sector was 31, 63, and 39% in each donor, respectively. No severe complications occurred in the donors. In conclusion, V8 preservation in donors who underwent left liver resection led to satisfactory regeneration both of the right paramedian and lateral sectors and can minimize congestion in remnant liver. (Liver Transpl 2004;10:1208-1212.)
Permanent access to the portal system for cellular transplantation using an implantable port device
Authors: Darwish Ahmed A. , Sokal Etienne , Stephenne Xavier , Najimi Mustapha , de Ville de Goyet Jean , Reding Raymond
Published: August 2004

A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation. (Liver Transpl 2004;10:1213-1215.)
High hilar dissection: New technique to reduce biliary complication in living donor liver transplantation
Authors: Lee Kwang-Woong , Joh Jae Won , Kim Sung Joo , Choi Seong Ho , Heo Jin Seok , Lee Hwan Hyo , Park Jean Wan , Lee Suk-Koo
Published: August 2004

Biliary complications after living donor liver transplantation (LDLT) continue to be problematic. For reducing the biliary complications, the authors applied an intrahepatic Glissonian approach to the recipient hepatectomy. We called this Glissonian dissection technique at the high hilar level high hilar dissection (HHD). In this study, we introduced this HHD technique and evaluated its outcome in 31 recipients of a living donor liver transplant (LDLT). With total occlusion of hepatoduodenal ligament Glissonia pedicles were divided at the intrahepatic level at the third level of pedicles or beyond. After portal vein and hepatic artery were isolated from the hepatoduodenal ligament, unused bile ducts and bleeding were controlled with continuous suture of the hilar plate. Single duct anastomosis was performed in about 21 and dual duct anastomosis in 10 recipients. Bile leakage of the biliary anastomosis did not occur. There were 6 biliary complications in five patients; 2 bile leaks from the cut liver surface and 4 biliary strictures of which one of unknown etiology. In none of the patients with biliary complications, conversion to a hepaticojejunostomy was necessary. This new HHD technique during recipient hepatectomy may contribute to reduce the biliary complications in duct-to-duct anastomosis by allowing a tension free anastomosis and preserving adequate blood supply to the bile duct. Moreover, it facilitates multiple ductal anastomoses without difficult surgical manipulation. (Liver Transpl 2004;10:1158-1162.)
Prospective evaluation of the role of quantitative Doppler ultrasound surveillance in liver transplantation
Authors: Stell David , Downey Donal , Marotta Paul , Solano Edward , Khakhar Anand , Quan Douglas , Ghent Cam , McAlister Vivian , Wall William
Published: August 2004

Doppler ultrasound (DUS) is able to measure parameters of blood flow within vessels of transplanted organs, and vascular complications are associated with abnormal values. We analyzed the findings of 51 consecutive patients who underwent DUS on 2 occasions in the first postoperative week following liver transplantation for cirrhosis to determine the range of values in patients following liver transplantation. Three patients developed early vascular thromboses that were detected by the absence of a Doppler signal. In patients making an uneventful recovery, the arterial velocity tended to increase and the resistive index (RI) to decrease during the first postoperative week. All recipients were shown to have high-velocity segments within the hepatic artery, without an increase in flow resistance. Assessment of the portal vein revealed narrowing at the anastomosis, associated with a segmental doubling of flow velocity, and the mean portal venous flow decreased by approximately 20% in the first postoperative week. In conclusion, a wide range of abnormalities occurs in the vessels of liver transplant recipients, which were not associated with the development of vascular complications or affect patient management. (Liver Transpl 2004;10:1183-1188.)
Increased prothrombin time and platelet counts in living donor right hepatectomy: Implications for epidural anesthesia
Authors: Siniscalchi Antonio , Begliomini Bruno , De Pietri Lesley , Braglia Vanessa , Gazzi Matteo , Masetti Michele , Di Benedetto Fabrizio , Pinna Antonio D. , Miller Charles M. , Pasetto Alberto
Published: August 2004

The risks and benefits of adult-to-adult living donor liver transplantation need to be carefully evaluated. Anesthetic management includes postoperative epidural pain relief; however, even patients with a normal preoperative coagulation profile may suffer transient postoperative coagulation derangement. This study explores the possible causes of postoperative coagulation derangement after donor hepatectomy and the possible implications on epidural analgesia. Thirty donors, American Society of Anesthesiology I, with no history of liver disease were considered suitable for the study. A thoracic epidural catheter was inserted before induction and removed when laboratory values were as follows: prothrombin time (PT) > 60%, activated partial thromboplastin time < 1.24 (sec), and platelet count > 100,000 mmf£ (mm3). Standard blood tests were evaluated before surgery, on admission to the recovery room, and daily until postoperative day (POD) 5. The volumes of blood loss and of intraoperative fluids administered were recorded. Coagulation abnormalities observed immediately after surgery may be related mostly to blood loss and to the diluting effect of the intraoperative infused fluids, although the extent of the resection appears to be the most important factor in the extension of the PT observed from POD 1. In conclusion, significant alterations in PT and platelet values were observed in our patients who underwent uncomplicated major liver resection for living donor liver transplantation. Because the potential benefits of epidural analgesia for liver resection are undefined according to available data, additional prospective randomized studies comparing the effectiveness and safety of intravenous versus epidural analgesia in this patient population should be performed. (Liver Transpl 2004;10:1144-1149.)
Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: A randomized controlled study
Authors: Sen Sambit , Davies Nathan A. , Mookerjee Rajeshwar P. , Cheshire Lisa M. , Hodges Stephen J. , Williams Roger , Jalan Rajiv
Published: August 2004

The pathophysiological basis of acute-on-chronic liver failure (ACLF) is unclear but systemic inflammatory response is thought to be important. In patients with ACLF, the molecular adsorbents recirculating system (MARS) improves individual organ function, but the effect of MARS on the proposed mediators of systemic inflammatory response is unclear. The present study was designed to determine the effect of MARS on the cytokine profile, oxidative stress, nitric oxide, and ammonia. A total of 18 patients with alcohol-related ACLF due to inflammation-related precipitants were randomized to receive standard medical therapy (SMT) alone, or with MARS therapy over 7 days. Plasma cytokines, malondialdehyde (MDA), free radical production, nitrate / nitrite (NOx), and ammonia were measured. Encephalopathy improved significantly with MARS (P < .01), but not with SMT. Mean arterial pressure and renal function remained unchanged. No significant change of plasma cytokines and ammonia levels were observed in either group. Plasma MDA levels did not change either. There was a fall in NOx (P < .05) with MARS, but not with SMT. In conclusion, in inflammation-related ACLF patients, albumin dialysis using MARS results in improvement of encephalopathy, independent of changes of ammonia or cytokines, without improving blood pressure or renal function. These results should temper the liberal use of MARS until further data is available. (Liver Transpl 2004;10:1109-1119.)
Liver transplantation for hepatocellular carcinoma: Further considerations on selection criteria
Authors: Ravaioli Matteo , Ercolani Giorgio , Cescon Matteo , Vetrone Gaetano , Voci Claudio , Grigioni Walter Franco , D’Errico Antonia , Ballardini Giorgio , Cavallari Antonino , Grazi Gian Luca
Published: August 2004

The selection criteria in liver transplantation for HCC are a matter of debate. We reviewed our series, comparing two periods: before and after 1996, when we started to apply the Milan criteria. The study population was composed of patients with a preoperative diagnosis of HCC, confirmed by the pathological report and with a survival of >1 year. Preoperative staging as revealed by radiological imagining was distinguished from postoperative data, including the variable of tumor volume. After 1996 tumor recurrences significantly decreased (6 out of 15 cases, 40% vs. 3 out of 48, 6.3%, P < .005) and 5-year patient survival improved (42% vs. 83%, P < .005). Not meeting the Milan criteria was significantly related to higher recurrence rate (37.5% vs. 12.7%, P < .05) and to lower 5-year patient survival (38% vs. 78%, P < .005%) in the preoperative analysis, but not in the postoperative one. The alfa-fetoprotein level of more than 30 ng/dL and the preoperative tumor volume of more than 28 cm3 predicted HCC recurrences in the univariate and mutivariate analysis (P < .005 and P < .05, respectively). The ROC curve showed a linear correlation between preoperative tumor volume and HCC recurrence. Milan criteria significantly reduced tumor recurrences after liver transplantation, improving long-term survival. In conclusion, the efficacy of tumor selection criteria must be analyzed with the use of preoperative data, to avoid bias of the postoperative evaluation. Tumor volume and alfa-fetoprotein level may improve the selection of patients. (Liver Transpl 2004;10:1195-1202.)
Insulin in UW solution exacerbates hepatic ischemia / reperfusion injury by energy depletion through the IRS-2 / SREBP-1c pathway
Authors: Li Xian Liang , Man Kwan , Ng Kevin T. , Lee Terence K. , Lo Chung Mau , Fan Sheung Tat
Published: August 2004

Ischemia / reperfusion (I / R) injury is related to tissue graft energy status. Insulin, which is currently used in the University of Wisconsin (UW) preservation solution with insulin (UWI), is an anabolic hormone and was shown to exacerbate the hepatic I / R injury in our previous study. In this study, the energy status and regulation of metabolism genes by insulin were investigated in liver grafts preserved by UW solution. Insulin could significantly decrease adenosine triphosphate (ATP) level after 3 hours of preservation, as well as total adenine nucleotides (TANs) and energy charge (EC) levels. Energy regeneration deteriorated in the grafts preserved by insulin in terms of ATP and EC levels at 24 hours after transplantation. The insulin signal was transduced through the insulin receptor substrate-2 (IRS-2) pathway and the activity of IRS-2 was decreased gradually at the messenger ribonucleic acid (mRNA) level during cold preservation. Downstream targeting genes such as sterol regulatory element-binding protein-1c (SREBP-1c), glucokinase (GKC), and fatty acid synthase (FAS) genes, as well as phospho-glycogen synthase kinase-3β (GSK-3β) were activated and they showed the similar expression profiles during cold preservation. Lipoprotein metabolism was accelerated by insulin through upregulation of the activity of apolipoprotein C-III (Apo C-III) during cold preservation. The insulin-like growth factor-binding protein-1 pathway was inhibited during cold preservation. In conclusion, insulin in UW solution exacerbates hepatic I / R injury by energy depletion as the graft maintains its anabolic activity. The key enzyme activities of the energy-consuming process of glycogen and fatty acid synthesis as well as lipoprotein metabolism were accelerated by insulin through the IRS-2 / SREBP-1c pathway. (Liver Transpl 2004;10:1173-1182.)