New-onset diabetes mellitus developing in Asian adult living donor liver transplant recipients: a single-center experience

Background

New-onset diabetes mellitus (NODM) after liver transplantation is a common complication with a potentially negative impact on patient outcome.

Methods

To evaluate the incidence of NODM and its impact on Asian adult living donor liver transplant (LDLT) recipients, we investigated 369 adult LDLT cases in our institute.

Results

Preoperative diabetes mellitus (DM) was diagnosed in 38 (9 %) patients. NODM was observed in 128/331 (38 %) patients, 56 (44 %) with persistent NODM and 72 (56 %) with transient NODM. The mean interval between LDLT and the development of NODM was 0.6 ± 1.8 (range 0–1.4) months. Multivariate analyssis revealed that older age, being male and having a higher body mass index were independent risk factors among recipients for developing NODM, while hepatitis C virus infection was not a significant risk factor, and DM had no impact on patient outcome.

Conclusions

Although the long-term effect of DM on outcome remains to be investigated, the presence of DM after liver transplant, whether it was NODM or preexisting DM, had no impact on LDLT recipients’ outcomes in mid-term.     

Strategies to treat interferon-induced graft dysfunction after living donor liver transplantation for hepatitis C

Purpose

Interferon-induced graft dysfunction (IGD) is a poorly defined, unrecognized, but potentially serious condition for patients receiving antiviral drugs after liver transplantation for hepatitis C.

Methods

We evaluated the characteristics of 80 patients who received pegylated interferon-based antiviral treatment for hepatitis C after living donor liver transplantation (LDLT).

Results

Eight patients experienced IGD either during (n = 6) or after completing (n = 2) antiviral treatment. Pathological diagnosis included acute cellular rejection (ACR, n = 1), plasma cell hepatitis (PCH, n = 2), PCH plus ACR (n = 3), and chronic rejection (CR, n = 2). One patient with CR initially presented with PCH plus ACR and the other presented with ACR; both had apparent cholestasis. The six patients with ACR or PCH without cholestasis were successfully treated by discontinuing antiviral treatment and increasing immunosuppression, including steroids. By contrast, both of the patients with CR and cholestasis experienced graft loss, despite aggressive treatment. Univariate analysis showed that pegylated interferon-α2a-based treatment (75 vs. 26.4 %, p < 0.01) was the only significant factor for IGD, and was associated with decreased 5-year graft survival (93.4 vs. 71.4 %, p = 0.04).

Conclusions

IGD is a serious condition during or even after antiviral treatment for hepatitis C after LDLT. Early recognition, diagnosis, discontinuation of interferon, and introduction of steroid-based treatment may help to save the graft.     

Circulating IL-1β levels, polymorphisms of IL-1B, and risk of cervical cancer in Chinese women

Purpose

Long-term human papillomavirus (HPV) infection is a prerequisite for cervical cancer. IL-1β and IL-1Ra expression levels play an important role in cervical carcinogenesis. Several functional genetic variants in IL1B and IL-RN have been reported to be associated with IL-1β expression and cancer susceptibility. In the current study, we hypothesized that plasma IL-1β levels, IL-1B and IL-RN polymorphisms were candidate biomarkers for cervical cancer.

Methods

We measured plasma IL-1β levels and genotyped IL-1B and IL-RN polymorphisms in a case–control study of 404 cervical cancer cases and 404 controls in Chinese women.

Results

The mean plasma IL-1β levels in cervical cancer cases (42.19 ± 31.55 pg/ml) was significantly higher than those in controls (34.86 ± 22.68 pg/ml, P = 0.0002), and plasma IL-1β levels above the 75% quartiles in controls (IL-1β ≥ 46.94 pg/ml) were associated with a 1.74-fold significantly increased risk of cervical cancer [95% confidence interval (CI), 1.28–2.36], compared with those of lowest quartile. Multivariate logistic regression analyses revealed that the variant genotypes, IL-1B T-31C TC/CC and C-511T CT/TT, were associated with a significantly increased risk of cervical cancer [adjusted odds ratio (OR), 1.60; 95% CI, 1.16–2.21 for ?31TC/CC, and adjusted OR, 1.52; 95% CI, 1.10–2.09 for ?511CT/TT, respectively), especially among subjects having higher levels of IL-1β. However, IL-RN VNTR polymorphism was not associated with cervical cancer risk in the current study. Furthermore, the significant differences of IL-1β concentration between cervical cancer cases and controls were observed only among subjects carrying T-31C or C-511T variant genotypes.

Conclusion

Functional IL-1B genotypes may modify plasma IL-1β concentrations to contribute to the etiology of cervical cancer in Chinese women; however, further perspective studies are warranted to test the causal effects of IL-1β concentration in cervical carcinogenesis.     

Long-term outcome of ABO-incompatible living-donor liver transplantation: a single-center experience

Purpose

We report the long-term outcome of ABO-incompatible living donor liver transplantation (LDLT) performed in our hospital.

Methods

We started the LDLT program in 1991 and from that year up to now (2008) 11 patients have received an ABO-incompatible graft.

Results

Nine out of the 11 cases have survived from 3.7 years to 13.9 years (mean 7.3 years) and they are in good conditions at present. Seven patients were subjected to preoperative apheresis. Eight patients experienced acute rejection and of them, 6 experienced steroid-resistant rejection that was treated with deoxyspergualin and apheresis. One patient who suffered rapidly progressing rejection died due to liver failure. Three patients who were administered rituximab did not suffer severe rejection nor adverse effects. During the long-term follow up 5 recipients had major complications such as postoperative lymphoproliferative disease, post-transplantation diabetes mellitus, portal vein occlusion and biliary stenosis. But those complications were controlled under stable conditions.

Conclusions

We concluded that long-term survival can be expected after ABO-incompatible LDLT provided perioperative complications such as humoral rejection are overcome.     

Concomitant iguratimod therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate: a randomized, double-blind, placebo-controlled trial

Objectives

To investigate the efficacy and safety of iguratimod (T-614) in Japanese patients with active rheumatoid arthritis who had inadequate response to stable background methotrexate (MTX) alone.

Methods

In this multicenter, double-blind, controlled trial, a total of 253 patients were randomized at 2:1 ratio to either the iguratimod group or the placebo group. Iguratimod was orally administered at dosages of 25 mg/day for the first 4 weeks (25 mg once daily) and 50 mg/day for the subsequent 20 weeks (25 mg twice daily). MTX at dosage of 6 or 8 mg/week was administered to patients in both groups.

Results

The rate of 20 % improvement in American College of Rheumatology criteria (ACR20) at week 24 was 69.5 % in the iguratimod group compared with 30.7 % in the placebo group (P < 0.001). Significant improvements in the ACR50, ACR70, Health Assessment Questionnaire Disability Index, Disease Activity Score 28 <3.2, and rheumatoid factor were also observed. The most commonly reported adverse events (AEs) were blood iron decrease, nasopharyngitis, and lymphocyte decrease. These AEs were mild or moderate in severity. No deaths occurred.

Conclusion

The study results suggest that iguratimod in combination with MTX was efficacious and had a manageable safety profile.     

The Outcomes of Patients with Severe Hyperbilirubinemia Following Living Donor Liver Transplantation

Background

Prolonged hyperbilirubinemia (HB) following living donor liver transplantation (LDLT) can be a risk factor for early graft loss and mortality. However, some recipients who present with postoperative hyperbilirubinemia do recover and maintain a good liver function.

Aim

The purpose of this study was to investigate the risk factors for hyperbilirubinemia following LDLT and to identify predictors of the outcomes in patients with post-transplant hyperbilirubinemia.

Methods

A total of 107 consecutive adults who underwent LDLT in Nagasaki University Hospital were investigated retrospectively. The patients were divided into two groups according to postoperative peak serum bilirubin level (HB group: ≥30 mg/dl; non-HB group: <30 mg/dl). These two groups of patients and the prognosis of patients in the HB group were analyzed using several parameters.

Results

Seventeen patients (15.9 %) presented with hyperbilirubinemia, and their overall survival was significantly worse than patients in the non-HB group (n = 90). Donor age was significantly higher in the HB group (P < 0.05). Of the 17 patients in the HB group, nine survived. The postoperative serum prothrombin level at the time when the serum bilirubin level was >30 mg/dl was significantly higher in surviving patients (P < 0.01).

Conclusions

The use of a partial liver graft from an aged donor is a significant risk factor for severe hyperbilirubinemia and a poorer outcome. However, those patients who maintain their liver synthetic function while suffering from hyperbilirubinemia may recover from hyperbilirubinemia and eventually achieve good liver function, thus resulting in a favorable survival.     

Cost analysis of adult�Cadult living donor liver transplantation in Tokyo University Hospital

Background and purpose

Living donor liver transplantation (LDLT) is now a well established treatment modality for end-stage liver diseases, but the financial aspects of LDLT have not yet been fully investigated. The purpose of this study was to determine the overall direct cost of adult?Cadult LDLT in Japan and to identify the factors associated with the high cost.

Materials and methods

The direct cost of initial admission for LDLT was determined in a retrospective analysis of data from hospital charts and databases. The records for 100 consecutive adults who underwent LDLT from January 2004 to February 2006 at our center were reviewed, and clinical and financial data of all recipients and donors were analyzed.

Results

The median direct total cost for LDLT was $82,017 (range $51,189?C438,295). Of this, the median cost for donors was $15,011 (range $12,354?C23,251). A multivariate stepwise logistic regression model for overall cost of transplantation revealed that donor age [odds ratio (OR)?=?1.1, p?=?0.02], acute renal failure (OR?=?24, p?=?0.007), and posttransplant plasma exchange (OR?=?72, p?=?0.01) were associated with higher cost. When the models were repeated with preoperative patient and donor factors alone, donor age (OR 1.1, p?=?0.008) and model for end stage liver disease score (OR 1.2, p?=?0.003) were associated with higher cost.

Conclusions

Donor age, acute renal failure, and posttransplant plasma exchange were independent risk factors for the high cost of LDLT in Japan.     

Significance of serum ��-d-glucan levels in recipients of living donor liver transplantation

Background/purpose

Early identification and treatment of fungal infections is essential for recipients of liver transplants, but the sensitivity of surveillance culture is insufficient. Measurement of the serum level of ??-d-glucan is a rapid diagnostic strategy for invasive fungal infection. We aimed to evaluate the significance of serum ??-d-glucan levels in transplant recipients after living donor liver transplantation (LDLT).

Methods

We retrospectively analyzed the clinical and laboratory data of 100 consecutive adult transplant recipients after LDLT performed between August 1997 and August 2009.

Results

Seventy-one had high serum ??-d-glucan levels (>20?pg/ml) after LDLT. Nearly half (47.2%) of the episodes of increase occurred within the first 5?days after surgery. The mortality rate of the recipients with high serum ??-d-glucan levels was similar to that of the recipients without high levels. However, in terms of the time line of increase, the recipients with high serum ??-d-glucan levels from 15?days onward after surgery showed a significantly higher mortality rate than those with high levels before 15?days after surgery (33.3 and 4.3%, respectively; p?Conclusions High serum levels of ??-d-glucan at late time points after LDLT indicate established fungal infection and higher mortality.     

Interleukin-10 Promoter 1082/−819/−592 Polymorphisms are Associated with Asthma Susceptibility in Asians and Atopic Asthma: A Meta-Analysis

Background

Although interleukin-10 (IL-10) is a potent inhibitor of allergic diseases, the association between promoter ?1082/?819/?592 polymorphisms and asthma susceptibility remains inconclusive. We sought to determine if IL-10 promoter ?1082/?819/?592 polymorphisms contribute to asthma susceptibility and are associated with phenotypes of atopic asthma.

Methods

Systematic computerized searches were performed. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by using random-effect and fixed-effect models, based on between-study heterogeneity. Subgroup analyses were performed according to age, ethnicity, and atopy. Publication bias was detected by funnel plot using Egger’s test.

Results

A total of 4,716 asthmatic patients and 5,093 controls were included. The asthma susceptibility correlated significantly with IL-10 promoter gene ?1082 polymorphism [OR (95 % CI) 1.26 (1.02, 1.55) for AA vs. AG + GG] and ?592 polymorphism [OR (95 % CI) 1.12 (1.07, 1.34) for AC + AA vs. CC] (both P < 0.05), but not with ?819 polymorphism (P > 0.05). Subgroup analyzes suggested that the AA versus AG + GG genotype of ?1082A/G polymorphism and AC + AA versus CC genotype of ?592A/C polymorphism contributed significantly to increased asthma susceptibility in adults [OR (95 % CI) 1.39 (1.03, 1.87) for ?1082A/G and 1.53 (1.25, 1.87) for ?592A/C polymorphism]. The Asian population [OR (95 % CI) 1.35 (1.1, 1.7) for ?1082A/G and 1.4 (1.12, 1.64) for ?592A/C polymorphism] and subjects with atopic asthma [OR (95 % CI) 1.49 (1.18, 1.88) for ?1082A/G and 1.23 (1.01, 1.48) for ?592A/C polymorphism] also had an increased susceptibility of asthma. No publication bias was detected.

Conclusions

IL-10 promoter ?1028A/G, ?592A/C polymorphisms and their haplotypes, but not ?819T/C polymorphism, correlate with asthma susceptibility.     

TNFRSF11B gene polymorphisms increased risk of peripheral arterial occlusive disease and critical limb ischemia in patients with type 2 diabetes

Aims

Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. OPG has been hypothesized to modulate vascular functions; however, its role in mediating atherosclerosis is controversial. Epidemiological data in patients with cardiovascular disease (CVD) indicate that OPG serum levels are associated with several inflammatory markers, myocardial infarction events, and calcium scores, suggesting that OPG may be causative for CVD.

Methods

The present study aimed to evaluate whether the OPG gene (TNFRSF11B) polymorphisms are involved in the development of peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI) in patients with type 2 diabetes. This genetic association study included 402 diabetic patients (139 males and 263 females) with peripheral arterial occlusive disease and 567 diabetic subjects without peripheral arterial occlusive disease (208 males and 359 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism.

Results

We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (27.9 vs. 12.2 %, P < 0.01; 33.6 vs. 10.4 %, P < 0.01 and 24.4 vs. 12.7 %, P < 0.01, respectively) and independently (adjusted OR 4.97 (3.12–6.91), OR 7.02 (4.96–11.67), and OR 2.85 (1.95–4.02), respectively) associated with PAOD. We also found that these three polymorphisms act synergistically in patients with PAOD and are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes carried concomitantly by a given individual.

Conclusion

The TNFRSF11B gene polymorphisms under study are associated with PAOD, and synergistic effects between these genotypes might be potential markers for the presence and severity of atherosclerotic disorders.     

A meta-analysis of the relation of polymorphism at sites −1082 and −592 of the IL-10 gene promoter with susceptibility and clearance to persistent hepatitis B virus infection in the Chinese population

Background

Up to now, many publications about the Chinese population have evaluated the correlation between interleukin-10 (IL-10) ?1082 and ?592 polymorphisms and persistent hepatitis B virus (HBV) infection. However, the results remain inconclusive. In order to resolve this conflict, a meta-analysis was performed.

Methods

Seven studies were included and dichotomous data are presented as the odds ratio (OR) with a 95% confidence interval (CI).

Results

The results of our study suggest that carriers of the IL-10 ?592A allele were more likely to clear HBV spontaneously in the Chinese pooled population (A vs. C: OR = 0.799, 95% CI = 0.678–0.941, P = 0.007; AC vs. AA: OR = 1.343, 95% CI = 1.017–1.684, P = 0.011; AA vs. AC + CC: OR = 0.736, 95% CI = 0.594–0.912; AA + AC vs. CC: OR = 0.588, 95% CI = 0.408–0.848, P = 0.004) and the IL-10 ?1082A allele was associated with significantly reduced persistent HBV infection risk in Chinese (A vs. G: OR = 0.701, 95% CI = 0.494–0.996, P = 0.047; AA vs. GG + GA: OR = 0.684, 95% CI = 0.476–0.982, P = 0.040).

Conclusions

Persistent HBV infection susceptibility is associated with the gene polymorphism IL-10 ?1082GA in the Chinese population and the clearance of HBV is associated with the gene polymorphism IL-10 ?592CA in the Chinese population.     

Pre-transplant Left Ventricular Diastolic Dysfunction Is Associated with Post Transplant Acute Graft Rejection and Graft Failure

Introduction

Acute cellular rejection (ACR) is a significant cause of morbidity and graft failure in liver transplant recipients (LTR). Diastolic dysfunction (DD) is frequently present in patients with cirrhosis undergoing liver transplantation. However, it is unclear if DD leads to ACR.

Methods

Data was collected retrospectively for consecutive LTR between January 2000 and December 2010. Demographic data and mortality related data was obtained from social security index. Primary outcome was biopsy proven ACR. Graft failure and all-cause mortality were also evaluated. DD was evaluated as a predictor of these outcomes. Other echocardiographic indices were also assessed as predictors of ACR by using Cox proportional hazard modeling adjusted for covariates.

Results

A total of 970 LTR (mean age 53.2 ± 10 years, women 34.6 % and white 64.5 %) were followed for 5.3 ± 3.4 years. Patients with DD (n = 145, 14.9 %) were significantly more likely to develop ACRs (HR 10.56; 95 % CI 6.78–16.45, p value = 0.0001) as well as graft failure (HR 2.09; 95 % CI 1.22–3.59, p value = 0.007) and all-cause mortality (HR 1.52; 95 % CI 1.08–2.13, p = 0.01). There was an increase in the risk of these outcomes with worsening of DD, when adjusted for various risk factors such as donor and recipient age, gender, race, Framingham risk score, pre-transplant MELD, transplant etiology and cold ischemia time.

Conclusion

Pre-transplant DD is significantly associated with increased risk of allograft rejection, graft failure and mortality. This signifies the importance of cardiac evaluation during the pre-transplant period.     

Liver transplantation for hepatocellular carcinoma: the Kyoto experience

Background/purpose

The results of living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) at Kyoto University were analyzed.

Methods

Between February 1999 and December 2006, 136 patients with HCC underwent LDLT. Of these, 74 patients met the Milan criteria, while 62 patients did not. Treatment for HCC had been previously performed prior to LDLT for 101 patients (74%).

Results

According to the results of multivariate analysis of risk factors for recurrence among preoperative tumor variables, we have defined new Kyoto criteria as ≤10 tumors all ≤5 cm in diameter and protein induced by vitamin K absence or antagonist-II (PIVKA-II) ≤400 mAU/ml. The 5-year recurrence rate was significantly lower for the 85 patients who met the Kyoto criteria than for the 45 patients who exceeded them (3 vs. 54%, p < 0.0001). Similarly, patients who met the Kyoto criteria showed a significantly better 5-year survival rate (87%) than those who did not (36%, p < 0.0001). Survival rates did not differ between pretreated and primary groups, and recurrence rates were similarly low when limited to patients who met the Kyoto criteria.

Conclusions

The proposed Kyoto criteria are expected to serve efficiently as expanded selection criteria for LDLT in patients with HCC. History of previous treatments did not affect outcomes after LDLT.     

Readmission after living donor liver transplantation: Predictors,causes, and outcomes

Background

Complications following liver transplantation requiring readmission may be serious and potentially life threatening. Most reports on readmission have been about after deceased donor liver transplantation (DDLT). We hypothesized that readmission after living donor liver transplantation (LDLT) is due to different reasons and analyzed our experience.

Methods

We retrospectively analyzed the records of 172 consecutive patients who underwent liver transplantation at our institute between January 2010 and June 2012. The primary outcome measure was readmission. We classified readmission into early (<3 months after discharge) and late (>3 months).

Results

The study population was 140 after excluding pediatric patients (12), DDLT recipients (2), and those who died during the index admission (18). Their median age was 42 years, and there were 117 males and 23 females. Thirty-eight patients were readmitted (56 episodes) after LDLT. There were 35 early and 21 late readmission episodes. The most common cause for early readmissions was infection (46 %) and that for late readmissions was biliary stricture (62 %). On univariate analysis, pretransplant portal vein thrombosis, more than one bile duct in the liver graft, revised arterial anastomosis or two arteries in the graft, and higher serum alkaline phosphatase levels at discharge were significantly associated with readmission. Readmission was also significantly associated with a higher overall mortality than non-readmission in which there was no mortality.

Conclusion

Pretransplant portal vein thrombosis, more than one bile duct in the liver graft, revision of the arterial anastomosis or two arteries in the graft, and higher serum alkaline phosphatase levels at discharge were significantly associated with readmission. Infective and biliary complications were the commonest causes of early and late readmission after LDLT.     

TNF superfamily gene polymorphism as prognostic factor in early breast cancer

Purpose

Since apoptosis may play a role in the prognosis of breast cancer, the present study analyzed the polymorphisms of apoptosis-related genes and their impact on the survival of 240 patients with early invasive ductal breast cancer.

Methods

The genomic DNA was extracted from paraffin-embedded tumor-free tissue or blood, and 12 single nucleotide polymorphisms (SNPs) of 11 apoptosis-related genes in the apoptosis pathway determined using a Sequenom MassARRAY system.

Results

During the median follow-up of 53.4 (range 2.9–205.9) months, 37 relapses and 22 deaths occurred. Among the target polymorphisms, the tumor necrosis factor superfamily member 10 gene polymorphism (TNFSF10 rs1131532) in a recessive model of the T allele and prostaglandin-endoperoxide synthase 2 gene polymorphism (PTGS2 rs5275) in a dominant model of the C allele were associated with survival in a log-rank test. The TT genotype of TNFSF10 (rs1131532) was also significantly correlated with a lower disease-free, distant disease-free, and overall survival in a multivariate analysis (HR = 3.304, 4.757, and 6.459; P = 0.002, 0.001, and 0.009, respectively), while PTGS2 rs5275 was only associated with a higher distant disease-free survival (HR = 0.302; P = 0.041). No clinicopathologic difference was observed according to the genotypes of these two polymorphisms.

Conclusion

The TNFSF10 (rs1131532) polymorphism was identified as a possible prognostic factor of survival in patients with operated invasive breast cancer.     

Tacrolimus-related adverse effects in liver transplant recipients: Its association with trough concentrations

Background

Tacrolimus is an important immunosuppressant administered to patients following liver transplantation (LT), with a recommended trough concentration of 8 to 11 ng/mL to prevent allograft rejection. We retrospectively examined our data to identify the tacrolimus trough concentration that combined efficacy with minimal adverse effects.

Methods

The case records of LT recipients, who were nondiabetic, nonhypertensive, and with normal renal parameters prior to LT were retrospectively examined for acute cellular rejection (ACR) episodes and three major adverse effects of tacrolimus, i.e. neurotoxicity, nephrotoxicity, and new onset diabetes mellitus (NODM).

Results

Thirty-two LT recipients fulfilled the criteria for the study. The mean (±SD) tacrolimus level for the 290 troughs (after 10 days) was 8.5?±?3.8 ng/mL. At 10 days, 1 month, 3 months, and 6 months, the trough values were 7.3?±?2.9, 9.7?±?3.4, 7.9?±?3.3, and 7.6?±?2.6 ng/mL, respectively. The mean time taken for stabilization of the blood pressure and biochemical parameters was 7?±?2 days. Overall, a trough window with the least adverse effect was 7 to 7.9 ng/mL. Neurotoxicity was least in the trough range 5 to <8 ng/mL. Symptoms included headache in four, tremors in three, seizure in one, confusion and psychosis in two, and combination in three. Nephrotoxicity was least in trough 8 to <11 ng/mL. One patient progressed to chronic kidney disease at 6 months. NODM was present in 11 % to 18 % across the various trough range, including the extremes (mean trough level, 8.4?±?4.4 ng/dL). At 6 months, five recipients were on treatment for NODM. Three recipients developed ACR, two within the first month and one at 7 weeks. The trough levels were 8.5, 9, 15.2 ng/mL, respectively. All recovered with three pulse doses of methylprednisolone.

Conclusion

Tacrolimus concentration of 5 to <8 ng/mL was associated with least overall toxicity, neurotoxicity, and ACR.     

Combinations of simple baseline variables accurately predict sustained virological response in patients with recurrent hepatitis C after liver transplantation

Background

The efficacy of antiviral therapy in patients with hepatitis C recurrence after liver transplantation (LT) is far from optimal and a careful selection of candidates with the best chances to achieve sustained virological response (SVR) is relevant. Moreover, investigating the effects of sustained viral clearance on clinical outcomes is particularly significant. We aimed to identify and combine the best baseline predictors of SVR and to assess the clinical outcomes of antiviral therapy after LT.

Methods

We studied 144 hepatitis C virus (HCV)-infected LT recipients who underwent antiviral therapy following transplantation. Baseline predictors of SVR including donor and recipient interleukin IL28B (IL28B) rs12979860 genotype were evaluated, and the long-term effects of antiviral therapy on clinical outcomes were assessed.

Results

The presence of an IL28B CC genotype with either low viral load (VL), young donor age, or cyclosporine A (CsA)-based immunosuppression identified individuals with 69–80 % probabilities of SVR. In contrast, only 20 % of recipients with a CT/TT IL28B genotype and either high VL, old donor age, or non-CsA immunosuppression achieved an SVR (p = 0.004). Regarding clinical outcomes, the 5-year cumulative probability of graft loss was 2 % for the SVR patients and 48 % for non-responders (p < 0.001).

Conclusions

The use of simple combinations of baseline variables including IL28B polymorphisms identifies HCV-infected LT recipients with different probabilities of response to antiviral treatment. SVR is associated with improved clinical outcomes.     

Impact of Anti-Thymocyte Globulin During Immunosuppression Induction in Patients with Hepatitis C After Liver Transplantation

Background

Induction immunosuppression with anti-thymocyte globulin (ATG) provides potential benefits after liver transplantation (LT). However, its use in patients with LT and hepatitis C (HCV) is controversial.

Aim

To evaluate the 1- and 2-year patient survival and HCV recurrence rate in patients receiving ATG during the induction phase of immunosuppression (IPI) after LT.

Methods

A total of 49 patients undergoing their first LT for HCV were randomized to receive ATG during IPI. Patient survival and HCV recurrence were determined at 1 and 2 years. The frequency of acute cellular rejection (ACR), infections, and neoplasms was also evaluated.

Results

Twenty-six patients were randomized to receive ATG (Arm-1) and 23 to standard induction therapy (Arm-2). Those given ATG had lower HCV recurrence (26.9 vs 73.9 %, p = 0.001). The 1- and 2-year patient survival rates were similar for both arms (p = 0.33). Infections occurred in 46.1 % subjects in Arm-1 and 34.7 % in Arm-2 (p = 0.562). There was a greater proportion of fungal infections in Arm-1 (19.2 vs 0 %, p = 0.032).

Conclusions

ATG during the IPI was associated with lower frequency of recurrence of HCV in patients undergoing LT. This, however, did not affect the 1- and 2-year survival and the frequency of ACR, infections, or neoplasms.     

Occult hepatitis B virus infection as a cause of posttransfusion hepatitis in patients with cancers

Background

Prevalence of hepatitis B virus (HBV) infection is increased in patients of cancer with increased mortality. Multiple transfusions of blood and blood-related products are a potential source.

Aims

This study aims to assess the incidence of hepatitis B surface antigen (HBsAg) seroconversion in cancer patients receiving transfusion of blood or blood-related products and identify possible reasons for infection in these patients.

Material and Methods

Patients of cancer receiving blood products, who were HBsAg-, anti-hepatitis B core (HBc)-, and HBV DNA-negative prior to transfusion, were tested for HBsAg by ELISA at 6, 12, and 24 weeks after the last transfusion. Blood donors were screened for HBsAg by ELISA.

Results

Twenty of 3,600 (0.56 %) blood donors tested positive for HBsAg and were rejected. Nine of 150 (6 %) cancer patients became HBsAg-positive posttransfusion which included seven patients who presented with acute hepatitis B and other two patients who remained HBsAg-positive without hepatitis. In 6/9 (66.6 %) patients, HBsAg positivity was related to blood transfusion as their corresponding blood donors on retesting the stored samples were positive for anti-HBc antibody and HBV DNA. In other three patients, the cause of their HBsAg positivity could not be ascertained.

Conclusion

Occult HBV infection in blood donors is a potential source of posttransfusion HBV infection in recipients. Anti-HBc antibody and HBV DNA should be tested in blood donors especially when blood is given to cancer patients receiving chemotherapy.     

Branched-chain amino acid-enriched nutrients improve nutritional and metabolic abnormalities in the early post-transplant period after living donor liver transplantation

Background/purpose

Malnutrition and metabolic disorder of patients undergoing living donor liver transplantation (LDLT) can affect post-transplant prognosis. The aim of this study was to establish whether perioperative usage of branched-chain amino-acid (BCAA)-enriched nutrients improve metabolic abnormalities of patients undergoing LDLT.

Methods

We designed a randomized pilot study (UMIN registration number; 000004323). Twenty-five consecutive adult elective LDLT recipients were enroled and divided into two groups: the BCAA group (BCAA-enriched nutrients, n?=?12) and the control group (standard diet, n?=?13). Metabolic and nutritional parameters, including BCAA-to-tyrosine ratio (BTR), retinol binding protein (RBP), and prealbumin were regularly measured from 1?week before to 4?weeks after LDLT. Non-protein respiratory quotient (npRQ) was measured before and 4?weeks after LDLT.

Results

BTR and RBP improved considerably in the BCAA group compared with the controls. npRQ significantly increased from 1?week before LDLT to 4?weeks after LDLT in the BCAA group (0.77?±?0.05 to 0.84?±?0.06, P?=?0.002), but not in the control group (0.78?±?0.04 to 0.81?±?0.05).

Conclusions

Supplementation with BCAA-enriched nutrients might improve persistent nutritional and metabolic disorders associated with end-stage liver disease in the early post-transplant period, and consequently shorten the post-transplant catabolic phase after LDLT. A larger multicenter trial is needed to confirm these findings.