Fulminant hepatic failure is a clinical syndrome associated with a high mortality rate. Orthotopic liver transplantation is the only clinically proven effective treatment for patients with end-stage liver disease who do not respond to medical management. A major limitation of this treatment modality is the scarcity of donor organs available, resulting in patients dying while waiting for a donor liver. An extracorporeal bioartificial liver (BAL) device containing viable hepatocytes has the potential to provide temporary hepatic support to liver failure patients, serving as a bridge to transplantation while awaiting a suitable donor. In some patients, providing temporary hepatic support may be sufficient to allow adequate regeneration of the host liver, thereby eliminating the need for a liver transplant. Although the BAL device is a promising technology for the treatment of liver failure, there are several technical challenges that must be overcome in order to develop systems with sufficient processing capacity and of manageable size. In this overview, the authors describe the critical issues involved in developing a BAL device. They also discuss their experiences in hepatocyte culture optimization within the context of a microchannel flat-plate BAL device.
Hyperthroidism in known to alter the activity of a number of enzymes involved in the catabolism of histidine to CO2. 10-Formyltetrahydrofolate dehydrogenase(EC 1.5, 1.6, 10-formyl-THE dehydrogenase) catalyzes the NADP-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. In previous studies, 10-formyl-THF dehydrogenase purified from rat and pig liver was coidentified with the cytosolic folate-binding protein. In this study, we investigated the effects of feeding thyroid powder (TP) and thiouracil(TU) on the folate-binding properties of 10-formyl-THE dehydrogenase, the uptake of an injected dose of [3H] folate, and the metabolism of labeled folate to pteroylopoly-${\gamma}$-glutamate in rat liver. The initial hepatic uptake(24hr) of the labeled folate dose was higher in TU-rats and slightly higher in TP-rats in controls. With longer time periods, decreased hepatic uptake of labeled folate was observed in TP-animals compared to euthroid animals, and high levels of hepatic uptake of labeled folate were maintained in TU-animals. This data shows that high levels of thyroid hormone decreased the retention of folate in rat liver. Folate polygutamate chain length was shorter in TU-rats than controls, which suggests that thyroid states do not affect the ability to synthesize pteroylpolyglutamates and that folate polyglutamate might be modulated by altered folate pool size. The ability of 10-formyl-THE dehydrogenase to bind folate in rat liver was similar in both TP-and TU-rats although dehydrogenase activity was changed by thyroid sates.
This study was concerned with assessment of dietynitrosamine (DEN) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. The changes of hepatic morphology in rats(Sprague-Dawley) were detected by hematoxylin-eosin stain and immunohistochemistry(PCNA). The results were as follows ; 1. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake. were observed in rats 7 weeks after DEN administration. 2. Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. 3. Numerous vacuoles were showed on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were showed. 4. Several proliferative small round cells were shown on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. 5. PCNA-positive cells were showed on the vacuolated portal areas and peripheral areas of hepatic lobules. Maximal positivity was 23.6% in the areas of small round cells. In conclusion, this result confirmed that the DEN was one of the potent hepatocarcinogens. In histopathological analysis, the altered foci, hyperplastic nodules, neoplastic nodules, adenomas and carcinomas were observed in liver tumors induced by administration of DEN in rats.
Kim, Ju-Yeon;Choi, Haena;Kim, Hyeon-Ji;Jee, Yelin;Noh, Minsoo;Lee, Mi-Ock
Biomolecules & Therapeutics
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v.30
no.5
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pp.391-398
/
2022
Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.
Infantile hepatic hemangioendothelioma (IHHE) is the most common benign vascular hepatic tumor in children. We analyzed the 17-year experience of IHHE. The medical records of 16 patients (M:F=8:8) treated at the Department of Pediatric Surgery and the Department of Pediatrics Seoul National University Children's Hospital between January 1991 and January 2008 were reviewed retrospectively. Mean age at presentation was 87 days (1 day - 551 days). Seventy five percent of patients were diagnosed with imaging study and 25 % with biopsy. Major symptoms were hepatomegaly (N=5), palpable abdominal mass (N=4) and congestive heart failure (N=3). Six patients had no symptoms. Kasabach-Merritt syndrome was combined in one patient. Nine patients (56.3 %) underwent operation and 2 patients (12.5 %) underwent only medical treatment. Clinical observation was tried on 5 patients (31.3 %) without any treatment. Operation was performed on the patient with clinical symptoms or on patients where the differentiation between begin and malignant could not be determined. Patients who had clinical symptoms but tumor was unreresectabile were treated medically. Among the 5 patients who had been observed for their clinical course, 2 patients showed complete regression and the tumors of the remaining 3 patients were regressing. Clinical symptoms, the age at presentation, the size of tumor and ${\alpha}$-FP, all had no significant statistical relationship with the time required for complete tumor regression. There was no relationship between the size change of the tumor and the change of ${\alpha}$-FP level. Only the size of tumor was related with clinical symptoms. One patient died of post-operatvie bleeding. Treatment plan was determined by the extent of the tumor and the presence of clinical symptoms. Observation was enough for the patients without clinical symptoms and complete resection was curative for patients with clinical symptoms. Medical treatment is an alternative for the patient whose tumor is unresectable.
Jung, In Ah;Cho, Won Kyoung;Jeon, Yeon Jin;Kim, Shin Hee;Cho, Kyoung Soon;Park, So Hyun;Jung, Min Ho;Suh, Byung-Kyu
Clinical and Experimental Pediatrics
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v.58
no.6
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pp.234-237
/
2015
Hepatic glycogenosis in type 1 diabetes mellitus (DM) can be caused by poor glycemic control due to insulin deficiency, excessive insulin treatment for diabetic ketoacidosis, or excessive glucose administration to control hypoglycemia. Mauriac syndrome, which is characterized by hepatomegaly due to hepatic glycogenosis, growth retardation, delayed puberty, and Cushingoid features, is a rare diabetic complication. We report a case of hepatic glycogenosis mimicking Mauriac syndrome. A 14-year-old girl with poorly controlled type 1 DM was admitted to The Catholic University of Korea, Seoul St. Mary's Hospital for abdominal pain and distension. Physical examination revealed hepatomegaly and a Cushingoid face. The growth rate of the patient had decreased, and she had not yet experienced menarche. Laboratory findings revealed elevated liver enzyme levels. A liver biopsy confirmed hepatic glycogenosis. Continuous glucose monitoring showed hyperglycemia after meals and frequent hypoglycemia before meals. To control hyperglycemia, we increased insulin dosage by using an insulin pump. In addition, we prescribed uncooked cornstarch to prevent hypoglycemia. After strict blood glucose control, the patient's liver functions and size normalized. The patient subsequently underwent menarche. Hepatic glycogenosis is a complication of type 1 DM that is reversible with appropriate glycemic control.
Ye, J.Z.;Miao, Z.G.;Wu, F.X.;Zhao, Y.N.;Ye, H.H.;Li, L.Q.
Asian Pacific Journal of Cancer Prevention
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v.13
no.5
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pp.1771-1777
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2012
The impact of anatomic resection (AR) as compared to non-anatomic resection (NAR) for hepatocellular carcinoma (HCC) as a factor for preventing intra-hepatic and local recurrence after the initial surgical procedure remains controversial. A systematic review and meta-analysis of nonrandomized trials comparing anatomic resection with non-anatomic resection for HCC published from 1990 to 2010 in PubMed and Medline, Cochrane Library, Embase, and Science Citation Index were therefore performed. Intra-hepatic recurrence, including early and late, and local recurrence were considered as primary outcomes. As secondary outcomes, 5 year survival and 5 year disease-free survival were considered. Pooled effects were calculated utilizing either fixed effects or random effects models. Eleven non-randomized studies including 1,576 patients were identified and analyzed, with 810 patients in the AR group and 766 in the NAR group. Patients in the AR group were characterized by lower prevalence of cirrhosis, more favorable hepatic function, and larger tumor size and higher prevalence of macrovascular invasion compared with patients in the NAR group. Anatomic resection significantly reduced the risks of local recurrence and achieved a better 5 years disease-free survival. Also, anatomic resection was marginally effective for decreasing the early intra-hepatic recurrence. However, it was not advantageous in preventing late intra-hepatic recurrence compared with non-anatomic resection. No differences were found between AR and NAR with respect to postoperative morbidity, mortality, and hospitalization. Anatomic resection can be recommended as superior to non-anatomic resection in terms of reducing the risks of local recurrence, early intra-hepatic recurrence and achieving a better 5 year disease-free survival in HCC patients.
The objective of this study was to investigate the effects of supplementation of an antiobese functional formula (FC-GT) on body weight and lipid metabolism in rats fed a high-fat diet. Three groups of male Sprague-Dawley rats were fed different diets for 6 weeks: normal control (NC), high-fat (HF), and high-fat supplemented with powdered antiobese functional formula (FC-GT) (5% wt/wt) groups. Although body weight was not significantly different among the groups, relative weights of epididymal and perirenal white adipose tissues were significantly lower in the FC-GT group than in the HF group. FC-GT supplementation significantly lowered the plasma total cholesterol and triglyceride concentrations, whereas it elevated the ratio of HDL-C/total-C and improved the atherogenic index. Hepatic cholesterol and triglyceride concentrations were significantly lowered in the FC-GT group compared to the HF group. The accumulation of hepatic lipid droplets and the epididymal white adipocyte size of the FC-GT group were diminished compared to the HF group. Hepatic HMG-CoA reductase activity was significantly lower in the FC-GT group than in the HF group. Plasma GPT activity was significantly lowered in the FC-GT group compared to the HF group. Additionally, fecal weight was significantly increased in the FC-GT group than in the HF group. In addition, contents of fecal triglyceride and cholesterol were significantly higher in the FC-GT group compared to the other groups. The antioxidant activities of hepatic SOD, CAT, and GR were significantly increased in the FC-GT group compared to the HF group. Hepatic mARS and plasma mARS levels were significantly lowered in the FC-GT group compared to the NC group. Accordingly, we conclude that supplementation of FC-GT improves plasma and hepatic lipid levels in high-fat fed rats.
A 37 year old female presented with epigastric pain and weight loss over a period of 3 months. Her abdominal CT finding showed a 4.5 cm size hepatic mass and 4.3 cm size pancreatic head mass with multiple macronodules in the liver. At the same time, her chest CT revealed a 5 cm size necrotic mass in the left lower lobe of the lung with multiple bilateral pulmonary nodules. We diagnosed these lesions as tuberculosis through multiple biopsies. She was treated with anti-tuberculous medication. After taking the medications, her symptoms were improved. Twelve months later, imaging studies indicated an improvement in the patient's health. Here we report a case report of multi-organ macronodular tuberculosis in lung, liver and pancreas.
Kim, Eun-Hee;Koh, Kyung-Nam;Park, Mee-Rim;Kim, Bo-Eun;Im, Ho-Joon;Seo, Jong-Jin
Clinical and Experimental Pediatrics
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v.54
no.6
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pp.260-266
/
2011
Purpose: Infantile hepatic hemangioendothelioma (IHHE) is the most common type of hepatic vascular tumor in infancy. We conducted this study to review our clinical experience of patients with IHHE and to suggest management strategies. Methods: We retrospectively analyzed the medical records of 23 IHHE patients (10 males, 13 females) treated at the Asan Medical Center between 1996 and 2009. Results: Median age at diagnosis was 38 days (range, 1 to 381 days). Seven patients (30%) were diagnosed with IHHE based on sonographically detected fetal liver masses, 5 (22%) were diagnosed incidentally in the absence of symptoms, 5 (22%) had congestive heart failure, 3 (13%) had skin hemangiomas, 2 (9%) had abnormal liver function tests, and 1 (4%) had hepatomegaly. All diagnoses were based on imaging results, and were confirmed in three patients by histopathology analysis. Six patients were observed without receiving any treatment, whereas 12 received corticosteroids and/or interferonalpha. One patient with congestive heart failure and a resectable unilobar tumor underwent surgical resection. Three patients with congestive heart failure and unresectable tumors were managed by hepatic artery embolization with/without medical treatment. At a median follow-up of 29 months (range, 1 to 156 months), 21 (91%) patients showed complete tumor disappearance or >50% decrease in tumor size. One patient died due to tumor-related causes. Conclusion: IHHE generally has a benign clinical course with low morbidity and mortality rates. Clinical course and treatment outcome did not differ significantly between medically treated and non-treated groups. Surgically unresectable patients with significant symptoms may be treated medically or with hepatic artery embolization.
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