Although organ transplants have been applied for decades, outcomes of somatic cell transplants remain disappointing, presumably due to lack of appropriate supporting stromal cells. Thus, cotransplantation with liver stromal cells, hepatic stellate cells (HSC), achieves long-term survival of islet allografts in mice by way of induction of effector T cell apoptosis and generation of regulatory T (Treg) cells. In this study we provide evidence both in vitro and in vivo that HSC can promote generation of myeloid-derived suppressor cells (MDSC). HSC-induced MDSC demonstrate potent immune inhibitory activity. Induction of MDSC is dependent on an intact interferon gamma signaling pathway in HSC and is mediated by soluble factors, suggesting that the specific tissue stromal cells, such as HSC, play a crucial role in regulating immune response by way of inflammation-induced generation of MDSC. Large amounts of MDSC can be propagated in vitro from bone marrowderived myeloid precursor cells under the influence of HSC. Conclusion: Cotransplantation with in vitro generated MDSC can effectively protect islet allografts from host immune attack. Local delivery of potent immune suppressor cells for cell transplants holds great clinical application potential. (HEPATOLOGY 2011;53:1007-1019
Background: An increase in the incidence of hepatocellular carcinoma (HCC) in Japan since the 1980s suggests an imminent outbreak in other countries where viral spread occurred more recently. Interferon therapy for chronic hepatitis C, in general, has been shown to prevent HCC. Aims: To determine the scale of benefit in individual patients. Subjects: Histologically proven chronic hepatitis C patients in the Inhibition of Hepatocarcinogenesis by Interferon Therapy (IHIT) cohort (Ann Intern Med 1999;131:174), as updated in March 2003. Methods: The lifetime risk for HCC was calculated based on HCC incidence rates, stratified by sex, age, fibrosis stage, and outcome of interferon therapy. The gain in HCC free survival was defined as the difference between expected HCC free survival with sustained virological response and that without. Results: The gain in HCC free survival was greater when a patient was younger and fibrosis was more advanced. For example, a 30 year old male with F3 fibrosis gained 12.4 years by attaining sustained response while a patient with F1 fibrosis older than 60 years gained less than one year. For a treatment protocol with a given sustained response rate, prior estimation of the gain can be obtained by multiplying the calculated HCC free survival for responders by the response rate. Conclusions: The gain in HCC free survival may serve as an indicator of the benefit of interferon therapy in terms of HCC prevention and be useful in the consideration of indication and selection of treatment protocol for individual patients.
Seventy-five cirrhotic patients with hyperammonemia in ing number of patients with compensated or noncompenthe past or at the time of the study were randomly divided sated cirrhosis are managed in outpatient clinics over a long into two groups (treated with lactulose or nontreated) in 14 period. In these patients, prevention of the above complicahospitals in Japan. Thirty-six cirrhotic patients were diag-tions is necessary in long-term home care to improve the nosed as having subclinical hepatic encephalopathy (SHE), quality of life (QOL). and 39 were diagnosed as non-SHE. SHE was diagnosedIn hepatic encephalopathy, psychoneurological symptoms when the results of all three of the quantitative psychometric are clinically absent before the onset and during the interval tests used (number connection test, and symbol digit and period of encephalopathic episodes. However, subclinical heblock design tests of the Wechsler adult intelligence scale patic encephalopathy (SHE), in which behavior abnormali-[revised]) were abnormal as compared with age-matched ties and impairment in cognitive functions can be shown by normal values. The mean number of abnormal psychometric quantitative psychometric (neuropsychologic) tests, has been test results and the prevalence of SHE were used for a quanti-reported recently in cirrhotic patients who have no history tative evaluation of the efficacy of the lactulose treatment. of encephalopathy, and clinically appear to be free of encephTwenty-two of the SHE patients were treated with lactulose alopathy.1,2 Moreover, recent imaging analysis of the brain (45 mL/d) for 8 weeks, and the other 14 SHE patients did in cirrhotic patients with and without encephalopathy has not receive lactulose. In the SHE patients administered lactu-shown brain atrophy on computed tomography, 3 abnormal lose, the results of the quantitative psychometric evaluation regional cerebral blood flow on single photon emission comwere significantly improved at 4 and 8 weeks after the begin-puted tomography, 4 and high signals in the basal ganglia on ning of the lactulose administration. The SHE had disap-T1-weighted magnetic resonance imaging. Therefore, it is important for the long-term management it persisted in 11 (85%) of the untreated 13 patients. We of cirrhotic patients to understand the presence of these morconcluded that lactulose treatment in cirrhotic patients with phological changes and functional impairments of the brain, SHE is effective with respect to psychometric tests. (HEPA-and to pay attention to changes in daily behavior and sleep. TOLOGY 1997;26:1410-1414.)This approach would be useful for maintaining the compensated stage of cirrhosis over a long period and for reversing Because the treatment for complications of cirrhosis such as hepatic encephalopathy, jaundice, ascites, and gastrointes-the noncompensated cirrhosis to compensated cirrhosis. tinal bleeding has improved, the survival period of cirrhotic Lactulose has been used worldwide for the treatment of patients has been markedly prolonged. Th...
The extended application of living donor liver transplantation (LDLT) has revealed the problem of graft size mismatching called "small-for-size (SFS) graft syndrome." The initial trials to resolve this problem involved increasing the procured graft size, from left to right, and even extension to include a right lobe graft. Clinical cases of living right lobe donations have been reported since then, drawing attention to the risks of increasing the liver volume procured from a living donor. However, not only other modes of increasing graft volume such as auxiliary or dual liver transplantation, but also control of the increased portal pressure caused by an SFS graft, such as a portosystemic shunt or splenectomy, have been trialed with some positive results. To establish an effective strategy for transplanting SFS grafts and preventing SFS graft syndrome, it is essential to have precise knowledge and tactics to evaluate graft quality and graft volume, when performing these LDLTs with portal pressure control. We reviewed the updated literature on the pathogenesis of and strategies for using SFS grafts.
These results revealed that impaired liver regeneration was due to aging, which was expressed by decreased cell cycle and increased autophagy and apoptosis. Therefore, understanding the molecular basis for aged liver regeneration might provide a new therapeutic option for old patients.
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