Current status of hepatopulmonary syndrome in liver transplantation in Japan: a Japanese multicenter analysis.

BACKGROUND: Hepatopulmonary syndrome (HPS) negatively affects the outcomes of deceased donor liver transplantation (LT). METHODS: We retrospectively reviewed the clinical records of patients with HPS who underwent LT and studied the impact of risk factors on clinical outcomes to determine strategies to overcome complications. Patients with symptoms of hypo-oxygenemia and a shunt ratio >15% on 99mTc-MAA lung perfusion scintigraphy were defined as having HPS. RESULTS: Forty-eight patients in 10 centers were enrolled. Diseases included biliary atresia, liver cirrhosis, non-alcoholic steatohepatitis, congenital hepatic fibrosis, and others. The length of ICU stay was 2-170 days. The respirator was used for 41.6% of patients on post-operative day (POD) 3 and 20.8% on POD 14. The patient survival rate was 87% at 1 year and 82% at 5 years. The causes of hospital mortality were sepsis, thrombotic microangiopathy, intracranial bleeding, pulmonary fibrosis, and transplant rejection. An amount of shunt ratio prior to LT was a significant risk factor for hospital mortality. Hypoxia from POD 3 to POD 14 was a risk factor for biliary stenosis. The shunt ratio of all surviving patients significantly improved. CONCLUSION: Although LT is feasible for patients with HPS, early transplantation and avoiding hypo-oxygenemia immediately after transplantation are important.

Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.

Impact of age older than 60 years in living donor liver transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) was extended to adults in recent years and more recently to older patients. The impact of donor age, analysis of preoperative risk factors for older LDLT recipients, and comparison of the complication rate between older and younger recipients were analyzed. METHODS: Subjects included patients who underwent LDLT at Kyoto University Hospital from October 1996 to December 2005. Twenty-three donors were 60 years of age or older, and 411 were younger than 60 years of age. Fifty-two recipients were 60 years of age or older and 410 were younger than 60 years of age. RESULTS: Postoperative recovery of liver function for donors and recipient/graft survival were not influenced by donor age. Hospital stay was longer in the donors 60 years of age or older than those younger than 60 years of age (P=0.02). The 5-year survival rates were 78.7% in recipients 60 years of age or older and 69.3% in younger recipients (P=0.26). Among preoperative risk factors for recipient survival rate, fulminant hepatic failure and preoperative status in the intensive care unit were significant (P<0.05). There were no significant differences in the incidence of postoperative complications for recipients. CONCLUSIONS: Selected right lobe donors from individuals who were 60 years of age or older showed a similar postoperative course compared with younger donors. Moreover, LDLT is feasible for patients 60 years of age or older who do not require care in the intensive care unit or do not have fulminant hepatic failure.

Serum-derived hepatitis C virus infectivity in interferon regulatory factor-7-suppressed human primary hepatocytes.

BACKGROUND/AIMS: The development of an efficient in vitro infection system for HCV is important in order to develop new anti-HCV strategy. Only Huh7 hepatocyte cell lines were shown to be infected with JFH-1 fulminant HCV-2a strain and its chimeras. Here we aimed to establish a primary hepatocyte cell line that could be infected by HCV particles from patients' sera. METHODS: We transduced primary human hepatocytes with human telomerase reverse transcriptase together with human papilloma virus 18/E6E7 (HPV18/E6E7) genes or simian virus large T gene (SV40 T) to immortalize cells. We also established the HPV18/E6E7-immortalized hepatocytes in which interferon regulatory factor-7 was inactivated. Finally we analyzed HCV infectivity in these cells. RESULTS: Even after prolonged culture HPV18/E6E7-immortalized hepatocytes exhibited hepatocyte functions and marker expression and were more prone to HCV infection than SV40 T-immortalized hepatocytes. The susceptibility of HPV18/E6E7-immortalized hepatocytes to HCV infection was further improved, in particular, by impairing signaling through interferon regulatory factor-7. CONCLUSIONS: HPV18/E6E7-immortalized hepatocytes are useful for the analysis of HCV infection, anti-HCV innate immune response, and screening of antiviral agents with a variety of HCV strains.