• Title/Summary/Keyword: cirrhosis of liver

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Joint model of longitudinal data with informative observation time and competing risk (결시적 자료에서 관측 중단을 모형화하기 위해 사용되는 경쟁 위험의 적용과 결합 모형)

  • Kim, Yang-Jin
    • The Korean Journal of Applied Statistics
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    • v.29 no.1
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    • pp.113-122
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    • 2016
  • Longitudinal data often occur in prospective follow-up studies. Joint model for longitudinal data and failure time has been applied on several works. In this paper, we extend it to the case where longitudinal data involve informative observation time process as well as competing risks survival times. We use a likelihood approach and derive an EM algorithm to obtain maximum likelihood estimate of parameters. A suggested joint model allows us to make inferences for three components: longitudinal outcome, observation time process and competing risk failure time. In addition, we can test the association among these components. In this paper, liver cirrhosis patients' data is analyzed. The relationship between prothrombin times measured at irregular visiting times and drop outs is investigated with a joint model.

The Prevalence of Chronic Degenerative Disease and Utilization of Medical Facility in Rural Population (농촌지역(農村地域) 주민(住民)의 만성퇴행성질환(慢性退行性疾患) 유병률(有病率) 및 이용의료기관(利用醫療機關))

  • Ann, Kil-Soo;Chun, Byung-Yeol;Yeh, Min-Hae
    • Journal of agricultural medicine and community health
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    • v.21 no.2
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    • pp.209-220
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    • 1996
  • This study was performed to investigate the prevalence of chronic disease and utilization of medical facility in rural area. 5,797 persons were randomly selected from 28,883 rural residents who were over 30 years old and living in Moonkyung city in Kyungsangpook Province during the period October 1 1983 to February 28 1994. The person prevalence rate was 336 per 1,000. The prevalence rate in men(278 per 1,000) was higher than that(388 per 1,000) in women. The spell prevalence rate in men(367) was significantly higher than that(429) in women (p<0.05). The prevalence was increased with the age, 106 in the 30's. 223 in the40's, 336 in the 50's, 407 in the 60's, and 457 in the age group of 70 above. Of all chronic diseases, the prevalence of neuralgia ranked first(128), chronic gastrointestinal disorders(64), degenerative arthritis(54). hypertension (44) and diabetes (14) were followed in descending order. In men, the prevalence of neuralgia ranked first, chronic gastrointestinal disorders, degenerative arthritis, hypertension and bronchial asthma were followed in descending order. In women, the prevalence of neuralgia ranked first, degenerative arthritis, chronic gastrointestinal disorders, hypertension and diabetes were followed in descending order. The prevalences of neuralgia, degenerative arthritis and hypertension were significantly higher in women than those in men, however, those of cardiovascular disease, pulmonary tuberculosis and liver cirrhosis in men were significantly higher than those in women(p<0.05). Most patients with chronic diseases were more likely to utilize hospital and/or local clinics than public health facility or community health providers. Patients with neuralgia, degenerative arthritis and bronchial asthma tended to utilizing local clinics initially, however, they were changed to visit public health facility or community health providers afterwards. Patients with hypertension or pulmonary tuberculosis were more likely to visit public health facility, however, those with diabetes, cancer, heart failure, CVD, liver cirrhosis were more likely to visit hospital.

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Analysis of Linear Growth in Children after Living-related Liver Transplantation (소아 생체 부분 간이식 후의 성장 분석)

  • Rim, Sun-Hee;Yun, Hye-Jin;Suh, Young-Mee;Choi, Bo-Hwa;Kim, Kyung-Mo;Lee, Young-Joo;Lee, Sung-Gyu
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.4 no.1
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    • pp.63-70
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    • 2001
  • Purpose: The aim of this study is to evaluate the effective role of living-related liver transplantation (LRLT) on posttransplant linear growth in children. Methods: Thirty six children were enrolled who received LRLT at Asan Medical Center from December, 1994 to February, 1999 and showed more than one-year postoperative survival. Mean height standard deviation score (zH) was analyzed according to medical records including heights during pretransplant and posttransplant follow-up periods. Results: zH of total children showed significant linear growth after LRLT from -1.58 to 0.33 at 24 posttransplant month (p<0.05). zH in children under 6 years of age, to exclude the effect of adolescent linear growth spurt, showed increment in height (p<0.05). Linear growth of children with liver cirrhosis improved and that with fulminant hepatitis was matained same. While stunted children (mean zH=-2.30) achieved good catch-up growth after transplantation, children with normal growth remained same. Children with significant hepatic dysfunction after LRLT such as chronic rejection or posttransplant lymphoproliferative disorder showed retarded posttrasplant linear growth. There was no statistical difference according to the type of immunosuppressants. Conclusion: LRLT resulted in adequate or catch-up linear growth in children with acute, chronic and metabolic liver disease. Successful LRLT suggested to be a promising option not only in long term survival but also in normal linear growth.

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A Study on the Estimation of Limits to Life Expectancy (한국인 기대여명의 한계추정에 관한 연구)

  • 천성수;김정근
    • Korea journal of population studies
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    • v.16 no.2
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    • pp.65-83
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    • 1993
  • The purpose of this study is estimate limits of Korean life expectancy at birth by 'Gompertz growth curse Model', 'Cause-Elimination Model' and Multidimensional models of Senescencee and Mortality'. Data used in Gompertz curve were obtained from all life tables published from 1905 to 1990 in Korea, and life expectancies at birth of eighteen groups were selected at five-year interval in consideration of time-series changes. Data used in Cause-Elimination Model are 'Cause of Death statistics in 1991' published in 1992 by National Bureau of Statistics of Korea and 'life table of 1989' published in 1990 by National Bureau of Statistics, Economic Planning Board of Korea. The materials are all classifiable death data, 119, 253 cases of male and 82, 420 cases of female, which is from 1991 Causes of Death statistics. The cases of death analyzed belong to one of 8 categories; i.e., Infectious and Parasitic Diseases(001-139; with notation of Infectious Diseases), Malignant Neoplasms(140-208), Hypertensive Diseases(401-405), Ischemic Heart Dieases and Diseases of Pulmonary Circulation and Other Forms of Heart Diseases(410-429;with notation of Heart Disease), Cerebrovascular Diseases(430-438), Chronic Liver Diseases and Cirrhosis(571; with notation of Liver Diseases), Injury and Poisoning(800-999) and all other disease. Data used in 'Multidimensional models of senescence and mortality' were life table of 1989 published by National Bureau of statistics, Economic Planning Board of Korea and life table of 1970, 1978-79, 1983, 1985 and 1987. The major findings may be summarised as follows: 1. Estimate equations of Gompertz growth curve using life expectancy at birth during the 1905-1990 period are as the following. Male : y = 88.047697 $\times$ $0.199690^{0.903381x}$ Female : y = 95.632828 $\times$ $0.199690^{0.903381x}$ Limits of life expectancy at birth, which were estimated by Gompertz growth curve, are 88.05 for male and 95.63 for female. 2. The effect on life expectancy at birth eliminationg all causes death is 14.04 years(for male) and 10.86 years(for female). Astonishingly, eliminating the malignant neoplasms increase life expectancy at birth by 2.85 years for male 2.03 years for female in 1991. In table 8 we show the effect on life expectancy at birth of separately eliminating each of the 8 categorical causes of death. The theoretical limit to life expectancy by Cause-Elimination Model is 80.96 for male and 85.82 for female. 3. If the same rate of delay [0.376 year(male), 0.435 year(femable) per calendar year] continued, then life expectancy at birth would reach 74.82(male) years and 84, 10(female) years in 2010. With 14.04-years(male) and 10.86-years(female) effect attributable in 2010 would be 88.86 years(male) and 94.96(femable) years. 4. 'Multidimensional models of senescence and death' permits calculations of the value of the attribution coefficient (B), percent of loss per year of physiologic function. The results of Ro and B during the 1970-1989 period are listed in table 9. Estimate of limit to Korean life expectancy at birth by 'Multidimensional models of senescence and death' is 99.47 years for male and 104.74 years for female in 1989.

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Hepatitis B Virus DNA Negativity Acts as a Favorable Prognostic Factor in Hepatocellular Carcinoma Patients

  • Li, Xing;Zhong, Xiang;Chen, Zhan-Hong;Xing, Yan-Fang;Wu, Dong-Hao;Chen, Jie;Ma, Xiao-Kun;Lin, Qu;Wen, Jing-Yun;Wei, Li;Wang, Tian-Tian;Ruan, Dan-Yun;Lin, Ze-Xiao;Wu, Xiang-Yuan;Dong, Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9635-9641
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    • 2014
  • Background: This retrospective study was aimed to investigate the efficacy of prophylactic agents in hepatocellular carcinoma (HCC) patients receiving TACE and compare the difference between lamivudine and entecavir. Materials and Methods: A consecutive series of 203 HBV-related HCC patients receiving TACE were analyzed including 91 patients given prophylactic agents. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 IU/ml higher than the nadir level, hepatitis flares due to HBV reactivation and progression free survival (PFS) were the main endpoints. Results: Some 48 (69.6%) reached virologic response. Prophylaxis significantly reduced virologic events (8.8% vs 58.0%, p=0.000) and hepatitis flares (1.1% vs 13.4%, p=0.001). Patients presenting undetectable HBV DNA levels displayed a significantly improved PFS as compared to those who never achieved undetectable HBV DNA. Prophylaxis and e-antigen positivity were the only significant variables associated with virologic events. In addition, prophylaxis was the only independent protective factor for hepatitis flares. Liver cirrhosis, more cycles of TACE, HBV DNA negativity, a lower Cancer of the Liver Italian Program score, non-metastasis and no hepatitis flares were protective factors for PFS. Prophylactic lamivudine demonstrated similar efficacy as entecavir. Conclusions: Prophylactic agents are efficacious for prevention of HBV reactivation in HCC patients receiving TACE. Achievement of undetectable HBV DNA levels displayed a significant capability in improving PFS. Moreover, persistent tumor residual lesions, positive HBV DNA and hepatitis B flares might be causes of tumor progression in these patients.

Fine Needle Aspiration Cytology of Hepatocellular Carcinoma - A Study on 247 Cases - (간세포암종의 세침흡인 세포학적 소견 - 247예에 대한 연구 -)

  • Lee, Kwang-Gil;Lee, Jong-Tae;Choi, Soo-Im;Park, Chan-Il
    • The Korean Journal of Cytopathology
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    • v.1 no.1
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    • pp.1-17
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    • 1990
  • Hepatocellular carcinoma (HCC) is malignant tumor frequently occurring in Koreans. There have been few reports regarding the cytologic findings of fine needle aspiration (FNA) of HCC. Most have suggested a diagnostic problem in the cytology distinguishing HCC from some benign hepatic lesions-for example, a regeneration nodule in cirrhosis and liver cell adenoma. In spite of its high frequency in Korea, no cytologic study has been reported, concerning the FNA of HCC. In an attempt to achieve cytologic criteria for the diagnosis of HCC, the authors studied retrospectively cytopathologic findings of 247 cases of HCC. These cases were confirmed either by histoiogic examination including lobectomy, biopsy, or ceil block material, or, when tissue diagnosis was unavailable, by a high serum alpha-fetoprotein level (over 400 I. U.). All aspiration smears were stained by the Papanicolaou method. In each case, the smears were analyzed for cell patterns and various cytomorphology of the tumor cells. The smear background was assessed for the presence of tumor cell necrosis and inflammatory components and compared to that of metastatic carcinomas. The cell patterns were classified as trabecular, acinar, dispersed, and irregular. The cytologic parameters analyzed included the degree of nuclear atypia and the presence of mitoses, intranuclear cytoplasmic inclusions, nucleolar prominency, endothelial lining, multinucleated giant cells, eosinophiic globules, bile, and Mallory body. Most of the FNA of HCC showed markedly cellular smears. The tumor cells were most frequently arranged in a trabecular pattern (80.3%). The irregular (12.6%), the acinar (5.5%), and the dispersed patterns (1.7%) followed in decreasing frequency. Individual hepatoma cells were larger than normal liver cells. However, they had morphologic features characteristic of the hepatic cells the cells were round or polygonal, their cytoplasm was abundant and granular with eosinophilic or amphophilic stainability, and their nuclei were round to oval, located centrally, and tended to have prominent nucleoli. Anaplasia and pleomorphism of tumor cells were generally mild to moderate. These findings existed even in very well differentiated cases. Mitotic figures were present in about 85% of the cases. Prominent nucleoli were observed only in about half the cases. The frequency of other cytologic features was as follows intranuclear cytoplasmic inclusion in 86.8% : endothelial lining in 56.1% : bile in 19.8% : and giant cells in 60.1%. Clear cells were often present in 11.7%, Most aspiration smears of HCC displayed clean background without necrosis or inflammatory material in contrast to the dirty, necrotic background of metastatic cancers and cholangiocarcinomas. Based on the above mentioned features, it is suqqested that the cytologic critieria most important for the diagnosis of HCC include a markedly cellular smear, trabecular pattern, hepatocytoid appearance of tumor cells, endothelial lining, the presence of bile, giant cells, intranuclear cytoplasmic inclusions, and prominent nucleoli, Among these, trabecular pattern, endothelial lining, giant cells and clean smear background are points to be considered in differentiating HCC from metastatic and cholangiocellular carcinoma.

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Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

  • Shi, Liang;Wu, Li-Li;Yang, Jian-Rong;Chen, Xiao-Fei;Zhang, Yi;Chen, Zeng-Qiang;Liu, Cun-Li;Chi, Sheng-Ying;Zheng, Jia-Ying;Huang, Hai-Xia;Yu, Fu-Jun;Lin, Xiang-Yang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.2979-2986
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    • 2014
  • Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.

Suppressive Activity of Extract of Termialia chebula Retz. on Hepatic Fibrosis (가자(Terminalia chebula Retz.) 추출물의 간섬유화 억제활성)

  • Lee, Hyun-Sun;Koo, Yun-Chang;Lee, Kwang-Won
    • Korean Journal of Food Science and Technology
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    • v.41 no.5
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    • pp.597-601
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    • 2009
  • Activation of hepatic stellate cells (HSCs) is known to be responsible for hepatic fibrosis and cirrhosis. When round-shape quiescent HSCs go to activation by liver injury, production of extracellular matrix is increased, and its shape becomes myofibroblast-like shape. The activated HSCs are characterized by the high rate of proliferation and the increased production of extracellular matrix. One way of the regeneration of activated HSCs is an apoptosis induction followed by removing the activated myofibroblast-like cells. The effect of extract of Terminalia chebula Retz. (TCE) on cytotoxicity was evaluated using the rat primary hepatocyte, HepG2 and T-HSC/Cl-6 by incubating these cells with TCE up to the dose of $1,000{\mu}g/mL$. At the maximum dose of TCE, no cytotoxicity was found on primary hepatocyte and HepG2, but cytotoxic effect of TCE was found on activated HSCs, and T-HSC/Cl-6 in a U-shaped dose-response manner with the highest effect at $500{\mu}g/mL$ of TCE. Finally, we confirmed the occurrence of apoptotic cell death by annexin-V/PI double staining. The population of annexin-V positive cells was increased in a dose dependent manner.

Core Promoter Mutation of ntC1731T and G1806A of Hepatitis B Virus Increases HBV Gene Expression (B형 간염 바이러스의 ntC1731T 및 G1806A의 core 프로모터 돌연변이에 의한 HBV 유전자 발현 증가 분석)

  • Cho, Ja Young;Yi, Yi Kyaw;Seong, Mi So;Cheong, JaeHun
    • Journal of Life Science
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    • v.32 no.2
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    • pp.94-100
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    • 2022
  • Chronic infection by hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype, adaptive mutations, and environmental factors. The pregenomic RNA transcription of HBV for their replication is regulated by the core promoter activation. Core promoter mutations have been the reason for acute liver failure and are associated with HCC development. We obtained HBV genes from a patient in Myanmar who was infected with HBV and identified gene variations in the core promoter region. For measuring the relative transactivation activity of the core promoter, we prepared the core-promoter reporter construct. Among the gene variations of the core promoter, the mutations of C1731T and G1806A were associated with increase in the transactivation of the HBV core promoter. Through computer analysis for searching for a tentative transcription factor binding site, we showed that the mutations of C1713T and G1806A newly created C/EBPβ and XBP1-responsive elements of the core promoter, respectively. The ectopic expression of C/EBPβ largely increased the HBV core promoter containing the C1713T mutation and that of XBP1 activated the M95 promoter containing the G1806A mutation. Our efforts to treat and prevent HBV infections are hampered by the emergence of drug-resistant mutations and vaccine-escape mutations. Our results provide the biological properties and clinical significance of specific HBV core promoter mutations.

Post HCV Infection Due to MX Gene Stimulation Produced Post Treatment with Imported and Locally Produced Egyptian Biosimilar IFN

  • Mohamed, Shereen H;Mahmoud, Nora F;Mohamed, Aly F;Kotb, Nahla S
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5635-5641
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    • 2015
  • Background: Cirrhosis is regarded as a possible end stage of many liver diseases, including viral infection. It occurs when healthy liver tissue becomes damaged and is replaced by scar tissue and finally may lead to hepatocellular carcinoma. Interferons (IFNs)are two general categories, type I and II. Type I includes one beta interferon and over 20 different alpha interferons. Alpha interferons are very similar in how they work, interacting with other proteins on cells like receptors. The main objective of this study was to compare Mx gene productivity post different cell line treatment with imported and Egyptian biosimilar locally produced IFNs, as well as the efficacy of those tested IFNs. Also, an assessment was made of sensitivity of different cell lines as alternatives to that recommended for evaluation of antiviral activity. Materials and Methods: Different cell lines (Vero, MDBK and Wish) were employed to evaluate cytotoxicity using the MTT assay. Antiviral activity was evaluated compared with standard IFN against VSV, Indiana strain -156, on tested rh-IFNs (imported; innovated and Egyptian biosimilar locally produced IFNs) in the pre-treated cell lines previously mentioned. The virus was propagated in the Wish cell line as recommended. Finally we estimated up-regulation of the Mx gene as a biomarker. Results: Data recorded revealed that test IFNs were safe in test cell lines. Viability was around 100%. Locally tested interferon did not realize the international potency limits, while the imported one was accepted compared with the standard IFN. These results were the same either using infectivity titer reduction assay or crystal violet staining of residual non- infected cells. Mx protein production was cell type related and confirmed by the detected Mx gene expressed in imported and locally produced IFN pre-treated cell lines. The expression of the gene was arranged in the order of Vero> wish > MDBK for the imported IFN, while for the Egyptian biosimillar locally produced one it was MDBK> Vero> wish. With regard to the antiviral activity there was a significant difference of imported IFN potency compared with the locally produced IFN (P<0.05), the IFN potential (antiviral activity) was not cell line related and showed non-significant difference for each separate product. Conclusions: Vero cells can be used as an alternative cell line for evaluation of IFN potency in case of unavailable USP recommended cell lines. Alternative potency evaluation assay could be used and proved significant difference in IFN potency in case of local and imported agents. Evaluation of antiviral activity could be used in parallel to viral infectivity reduction assay for better accuracy. Mx gene can be used as a marker for IFN potential.