Koichiro Hata

Impact of Sarcopenia on Survival in Patients Undergoing Living Donor Liver Transplantation

Skeletal muscle depletion, referred to as sarcopenia, predicts morbidity and mortality in patients undergoing digestive surgery. However, the impact on liver transplantation is unclear. The present study investigated the impact of sarcopenia on patients undergoing living donor liver transplantation (LDLT). Sarcopenia was assessed by a body composition analyzer in 124 adult patients undergoing LDLT between February 2008 and April 2012. The correlation of sarcopenia with other patient factors and the impact of sarcopenia on survival after LDLT were analyzed. The median ratio of preoperative skeletal muscle mass was 92% (range, 67–130%) of the standard mass. Preoperative skeletal muscle mass was significantly correlated with the branched‐chain amino acids to tyrosine ratio (r = −0.254, p = 0.005) and body cell mass (r = 0.636, p < 0.001). The overall survival rate in patients with low skeletal muscle mass was significantly lower than in patients with normal/high skeletal muscle mass (p < 0.001). Perioperative nutritional therapy significantly increased overall survival in patients with low skeletal muscle mass (p = 0.009). Multivariate analysis showed that low skeletal muscle mass was an independent risk factor for death after transplantation. In conclusion, sarcopenia was closely involved with posttransplant mortality in patients undergoing LDLT. Perioperative nutritional therapy significantly improved overall survival in patients with sarcopenia.

Posttransplant Bacteremia in Adult Living Donor Liver Transplant Recipients

Infectious complications such as bacteremia after living donor liver transplantation (LDLT) are associated with significant morbidity and mortality. We retrospectively analyzed the frequency and characteristics of posttransplant bacteremia in 181 adult LDLT recipients between April 2006 and November 2009, and we evaluated the risk factors for posttransplant bacteremia. One hundred seventeen episodes of bacteremia occurred in 62 of 181 recipients (34.3%) within 12 days (median) after transplantation (range = 1‐71 days). The most frequently isolated pathogens were Pseudomonasaeruginosa (26 episodes), methicillin‐resistant coagulase‐negative staphylococci (22 episodes), and Enterococcus sp. (11 episodes). The overall survival rate at 1 year for patients with bacteremia (n = 62) was significantly lower than the rate for patients without bacteremia (n = 119; 69.6% versus 92.3%, respectively, P < 0.0001). Multivariate analysis showed that Child‐Pugh class C (P = 0.0002), preoperative massive pleural effusion or ascites requiring drainage (P = 0.0384), postoperative cytomegalovirus infection (P = 0.0014), ABO incompatibility (P = 0.0188), and older donor age (P = 0.015) were independent risk factors for postoperative bacteremia. In conclusion, bacteremia occurred at a high rate after adult LDLT and induced a higher mortality rate in those who developed it. Infection control may play a pivotal role in improving early outcomes after LDLT. Liver Transpl 16:1379–1385, 2010.

Density of Helicobacter pylori Infection in Patients with Peptic Ulcer Perforation

BACKGROUND A lack of change in prevalence of severe ulcer complications requiring emergency operation has been reported, despite the common use of histamine-2 (H2)-receptor antagonists and proton pump inhibitors. This may be attributable to use of ulcerogenic drugs or Helicobacter pylori (HP) infection, or both. In this study, HP infection was evaluated semiquantitatively in patients with peptic ulcer who required surgery, and the severity of histologic change was investigated. METHODS We reviewed a total of 113 consecutive patients (98 men and 15 women) operated on for perforation, hemorrhage, or stenosis of gastroduodenal ulcer between January 1986 and December 1995. Detection of HP was carried out by immunohistochemical staining. We graded the density of HP infection according to the number of individual HP bacteria counted in a highly magnified visual field (x 1,000 of light microscopy). The grade of HP infection was defined as follows: (0) = 0; (1+) = 1-9; (2+) = 10-29; (3+) = 30-99; (4+) > or = 100. The severity of gastritis was evaluated by histologic examination using the criteria of Rauws. RESULTS Although the number of operations for gastroduodenal ulcer declined significantly, the rate of emergency operation for gastroduodenal ulcer increased from 60% to 90%, with the result that the frequency of operations for perforation or bleeding remained virtually constant and that for stenosis significantly decreased. HP infection was more prevalent in perforated ulcer (92%) than hemorrhagic ulcer (55%) or stenotic ulcer (45%). The grades of HP infection were 3.0 +/- 0.14 (mean +/- SEM) in perforated ulcer, 2.3 +/- 0.34 in hemorrhagic ulcer, and 2.5 +/- 0.22 in stenotic ulcer. Perforated ulcer was associated with significantly more severe HP infection and gastritis changes than hemorrhagic ulcer or stenotic ulcer. CONCLUSIONS This study indicates that patients with perforated ulcer were infected with HP more severely than those with hemorrhagic ulcer or stenotic ulcer at the time of surgery. A close relationship was observed between the perforated ulcer and the density of HP infection determined semiquantitatively using immunohistochemical stain.

Lower Limit of the Graft-to-Recipient Weight Ratio Can Be Safely Reduced to 0.6% in Adult-to-Adult Living Donor Liver Transplantation in Combination with Portal Pressure Control

INTRODUCTION The goal of this study was to examine whether the lower limit of the graft-to-recipient weight ratio (GRWR) can be safely reduced to make better use of a left-lobe graft in adult-to-adult living donor liver transplantation (LDLT) in combination with portal pressure control. PATIENTS AND METHODS Beginning in December 2007, our institution actively selected left-lobe grafts for use in liver transplantation seeking to minimize the risks to healthy donors. We gradually decreased the lower limit of the GRWR to preferentially select a left-lobe over a right-lobe graft: from ≥0.7% beginning in December 2007 to ≥0.6% beginning in April 2009. A portal pressure control program, targeting final portal pressures below 15 mm Hg, was also introduced to overcome small-for-size graft problems. The ratio of left-lobe grafts among all adult-to-adult LDLT grafts and the donor complication rate (defined as Clavien grade ≥ III, excluding wound infection) were compared between two time periods: June 1999 to November 2007 (period 1, n = 541) and December 2007 to February 2010 (period 2, n = 119). Overall survival rates were also compared between those recipients of a GRWR < 0.8% and those with a GRWR ≥ 0.8% in 198 recipients who underwent LDLT at our institution between April 2006 and February 2010. RESULTS Left-lobe grafts use increased from period 1 (65/541 recipients; 12.0%) to period 2 (50/119 recipients; 42.0%; P < .001). The donor complication rate tended to decrease from 13.8% in period 1 to 9.3% in period 2 (P = .115). The overall survival rate in 52 recipients with a GRWR < 0.8% did not differ from that in 146 recipients with a GRWR ≥ 0.8%. CONCLUSIONS The lower limit of the GRWR can be safely reduced to 0.6% in adult-to-adult LDLT in combination with portal pressure control.

Pre- and perioperative factors affecting infection after living donor liver transplantation.

OBJECTIVE Infectious complications, including sepsis, that often occur after liver transplantation (LT) comprise the most frequent causes of in-hospital death. This study investigated the predictors of post-transplantation infectious complications to establish a strategy with which to improve short-term outcomes after LT. METHODS We used univariate and multivariate analyses to assess pre- and perioperative risk factors for post-transplantation infectious complications in 100 consecutive patients who underwent living donor LT from February 2008 through February 2010 at our institute. RESULTS Multivariate analysis showed that low preoperative body cell mass and the absence of preoperative supplementation with branched-chain amino acids were of prognostic significance for post-transplantation sepsis. In addition, Child-Pugh classification C and massive operative blood loss were independent risk factors for post-transplantation bacteremia, and preoperative low body cell mass was an independent risk factor for in-hospital death from infection. CONCLUSION Pretransplantation nutritional intervention and decreases in operative blood loss would help prevent post-transplantation infectious complications from developing during living donor LT. Branched-chain amino acid supplementation before LT affects the occurrence of infectious complications.

Efficacy and safety of prophylaxis with entecavir and hepatitis B immunoglobulin in preventing hepatitis B recurrence after living‐donor liver transplantation

Aim:  Hepatitis B recurrence after liver transplantation can be reduced to less than 10% by combination therapy with lamivudine (LAM) and hepatitis B immunoglobulin (HBIG). The aim of this study was to evaluate the efficacy and safety of prophylaxis with entecavir (ETV), which has higher efficacy and lower resistance rates than LAM, combined with HBIG in preventing hepatitis B recurrence after living‐donor liver transplantation (LDLT).

Spontaneous perforation of the rectum with possible stercoral etiology: Report of a case and review of the literature

Stercoral perforation of the colon or rectum is a rare cause of acute abdomen, with fewer than 70 cases documented in the literature. We report herein the case of a 60-year-old man who presented with anuria and epigastric pain with physical signs of peritonitis. An abdominal X-ray showed bilateral subphrenic free air accumulation, and an emergency laparotomy subsequently revealed perforation of the rectum, suggestive of a stercoral cause, which was treated by simple closure after debridement. Following an uneventful postoperative course, he was discharged from the hospital 3 weeks after his operation and is now doing well without having suffered any further gastrointestinal problems. The clinical features, diagnosis, and treatment of the disease are reviewed following the presentation of this case. Surgeons should be aware of the possibility of this fatal disease, despite its rare incidence. Furthermore, it is important to recognize the condition at an early stage because it has a significantly high mortality if not treated early. Conversely, the surgical outcome is satisfactory provided surgery is performed in due time.

Pediatric Liver Transplantation Using Reduced and Hyper-Reduced Left Lateral Segment Grafts: A 10-Year Single-Center Experience

Few studies have examined the long‐term outcomes and prognostic factors associated with pediatric living living‐donor liver transplantation (LDLT) using reduced and hyper‐reduced left lateral segment grafts. We conducted a retrospective, single‐center assessment of the outcomes of this procedure, as well as clinical factors that influenced graft and patient survival. Between September 2000 and December 2009, 49 patients (median age: 7 months, weight: 5.45 kg) underwent LDLT using reduced (partial left lateral segment; n = 5, monosegment; n = 26), or hyper‐reduced (reduced monosegment grafts; n = 18) left lateral segment grafts. In all cases, the estimated graft‐to‐recipient body weight ratio of the left lateral segment was more than 4%, as assessed by preoperative computed tomography volumetry, and therefore further reduction was required. A hepatic artery thrombosis occurred in two patients (4.1%). Portal venous complications occurred in eight patients (16.3%). The overall patient survival rate at 1, 3 and 10 years after LDLT were 83.7%, 81.4% and 78.9%, respectively. Multivariate analysis revealed that recipient age of less than 2 months and warm ischemic time of more than 40 min affected patient survival. Pediatric LDLT using reduced and hyper‐reduced left lateral segment grafts appears to be a feasible option with acceptable graft survival and vascular complication rates.

Urinary neutrophil gelatinase-associated lipocalin: A useful biomarker for tacrolimus-induced acute kidney injury in liver transplant patients

Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication of liver transplantation. For early detection of AKI, various urinary biomarkers such as monocyte chemotactic protein-1, liver-type fatty acid-binding protein, interleukin-18, osteopontin, cystatin C, clusterin and neutrophil gelatinase-associated lipocalin (NGAL) have been identified. Here, we attempt to identify urinary biomarkers for the early detection of tacrolimus-induced AKI in liver transplant patients. Urine samples were collected from 31 patients after living-donor liver transplantation (LDLT). Twenty recipients developed tacrolimus-induced AKI. After the initiation of tacrolimus therapy, urine samples were collected on postoperative days 7, 14, and 21. In patients who experienced AKI during postoperative day 21, additional spot urine samples were collected on postoperative days 28, 35, 42, 49, and 58. The 8 healthy volunteers, whose renal and liver functions were normal, were asked to collect their blood and spot urine samples. The urinary levels of NGAL, monocyte chemotactic protein-1 and liver-type fatty acid-binding protein were significantly higher in patients with AKI than in those without, while those of interleukin-18, osteopontin, cystatin C and clusterin did not differ between the 2 groups. The area under the receiver operating characteristics curve of urinary NGAL was 0.876 (95% confidence interval, 0.800–0.951; P<0.0001), which was better than those of the other six urinary biomarkers. In addition, the urinary levels of NGAL at postoperative day 1 (p = 0.0446) and day 7 (p = 0.0006) can be a good predictive marker for tacrolimus-induced AKI within next 6 days, respectively. In conclusion, urinary NGAL is a sensitive biomarker for tacrolimus-induced AKI, and may help predict renal event caused by tacrolimus therapy in liver transplant patients.

Thrombotic microangiopathy-like disorder after living-donor liver transplantation: a single-center experience in Japan.

AIM To investigate thrombotic microangiopathy (TMA) in liver transplantion, because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated, and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered, the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells, the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD, the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD, such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies, must be decided according to each case. CONCLUSION The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.