• Title/Summary/Keyword: liver fibrosis(cirrhosis)

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Nonalcoholic Fatty Liver Disease Progressing to Cirrhosis in an Obese Boy with Hypopituitarism (청소년기에 간경화증으로 진행된 비알콜성 지방간질환 1예)

  • Park, Ji-Yong;Ko, Jae-Sung;Seo, Jeong-Kee;Lee, Ran;Shin, Choong-Ho;Kang, Gyeong-Hoon;Kim, Woo-Sun
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.11 no.2
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    • pp.204-209
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    • 2008
  • Non-alcoholic fatty liver disease (NAFLD) is typically associated with obesity and insulin resistance. Non-alcoholic steatohepatitis (NASH) is a more serious form of NAFLD. Although fibrosis is common in pediatric NASH, cirrhosis has been rarely reported. Patients with hypothalamic or pituitary dysfunction are at risk for obesity and insulin resistance with subsequent development of NAFLD. We report a case of NAFLD progressing to cirrhosis in an obese 16 year-old boy with hypopituitarism.

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Evaluation of Fibrosis in Liver Cirrhosis by Superparamagnetic Iron Oxide (SPIO)-Enhanced MR Imaging: Does the Radiological Non-Invasive Fibrosis Index Correlate with the Laboratory Non-Invasive Fibrosis Index? (Superparamagnetic Iron Oxide-Enhanced MRI를 이용한 간섬유화의 평가: 영상의학적 비침습적 간섬유화 지표가 AST/혈소판 비와 상관 관계가 있는가?)

  • Kim, Shin-Kee;Lee, Chang-Hee;Kim, Kyeong-Ah;Choi, Jae-Woong;Lee, Jong-Mee;Park, Cheol-Min
    • Investigative Magnetic Resonance Imaging
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    • v.12 no.2
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    • pp.115-122
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    • 2008
  • Purpose : To evaluate the correlation between the radiological non-invasive hepatic fibrosis index (RNHFI), as determined by SPIO-enhanced MRI, and the laboratory non-invasive hepatic fibrosis index. Materials and Methods : Patients (99 total: 61 men and 38 women; mean age: 58 years) who underwent SPIO-enhanced MRI (1.5T) during 5 years included. These patients were subdivided into a liver cirrhosis group (LCG) and a non-liver cirrhosis group (non-LCG). Using PACS view, we measured the RNHFI (mean standard deviation of hepatic signal intensity (SD), noise-corrected coefficient of variation (CV)) of three ROIs in the liver parenchyma by SPIO-enhanced MRI. The laboratory non-invasive hepatic fibrosis index (AST-platelet ratio index (APRI)) of all patients was calculated from the laboratory data. We compared the RNHFI and APRI of LCG with those of non-LC group using Student's t-test. A bivariate correlation was performed to investigate the relationship between the RNHFI and APRI in the LCG. Results : For the LCG, mean values of SD and CV by SPIO-enhanced MRI were $10.3{\pm}3.7$ and $0.19{\pm}0.08$, respectively. For the non-LCG, mean values of SD and CV were $6.5{\pm}1.6$ and $0.08{\pm}0.05$, respectively. The mean APRI of the LCG and the non- LCG were $2.04{\pm}1.7$ and $0.32{\pm}0.32$, respectively. The RNHFI and APRI were significantly different between both groups (p<0.05). For the LCG, the bivariate correlation between SD and APRI revealed a statistically significant positive correlation (r=0.5, p<0.001). In both groups, there was no statistically significant correlation between CV and APRI. Conclusion: A measurement of SD can be a simple and useful method for the evaluation of hepatic fibrosis.

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Pharmacological Analyses of HIMH0021 Extracted from Acer Tegmentosum and Efficacy Tests of Steatohepatitis and Hepatic Fibrosis in NASH/ASH (산겨릅나무로부터 추출된 HIMH0021의 알콜성·비알콜성 지방간염 질환에서의 약리학적 분석 및 지방간염 및 간섬유화 억제능 평가)

  • Ji Hoon Yu;Yongjun Lee
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.5-5
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    • 2021
  • Alcoholic and nonalcoholic steaohepatitis is a leading form of chronic liver disease with few biomakers ad treatment options currently available. a progressive disease of NAFLD may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, we extracted HIMH0021, which is an active flavonoid component in the Acer tegmentosum extract, has been shown to protect against liver damage caused by hepatic dysfunction. Therefore, in this study, we aimed to investigate whether HIMH0021 could regulate steatohepatitis and liver fibrosis during alcoholic or nonalcoholic metabolic process. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

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Pharmacologic therapy for nonalcoholic steatohepatitis focusing on pathophysiology

  • Yoon, In Cheol;Eun, Jong Ryeol
    • Journal of Yeungnam Medical Science
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    • v.36 no.2
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    • pp.67-77
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    • 2019
  • The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.

The Study on the drug pharmacokinetics according to the progression of liver disease

  • Sohn, Soo-Jung;Choi, Hong-Serck;Ahn, Mee-Ryung;Chung, Hye-Joo;Yoo, Tae-Moo;Lee, Min-Ho;Park, Moon-Seung;Shin, In-Chul;Kim, Ju-ll
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.308.1-308.1
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    • 2003
  • We underwent this study to know correlation between the amount of portosysternic shunt/hepatic fibrosis and bioavailability parameters such as AUC, Cmax, Tmax and t1 /2 of high extraction ratio drug, propranolol, in CCl4-induced liver cirrhosis model of rats. This study describes the bioavaility study of propranolol(5 mg/kg), Shunt Index using thallium-201 per rectum scintigraphy to to measure the amount of portosystemic shunt indirectly and intrahepatic hydroxyproline content performed in the CCl4-induced liver cirrhosis model of rats. (omitted)

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Talin-1 and Non-invasive Fibrosis Models in the Assessment of Patients with Hepatocellular Carcinoma

  • Alsebaey, Ayman;Ahmedy, Iman Aly
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.4077-4082
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    • 2016
  • Background: Hepatocellular carcinoma (HCC) is a dreadful complication of end stage liver disease with high morbidity and mortality. Aim: The aim was to assess the role of serum talin-1 and non-invasive fibrosis in patients with HCC. Materials and Methods: A total of eighty seven subjects were enrolled, with 22 two healthy individuals as a control group (n=22), 22 patients in the cirrhosis group and finally 43 in the group with HCC diagnosed with positive triphasic CT abdomen criteria. Serum talin-1 and noninvasive fibrosis parameters were assessed in all subjects. Results: Compared to the cirrhosis group, patients with HCC had higher serum talin-1 ($32.9{\pm}12.6$ vs. $11.1{\pm}2.79ng/ml$), FIB4 ($9.96{\pm}15.3$ vs. $2.90{\pm}1.87$) and $fibro-{\alpha}$ ($10.9{\pm}18.1$ vs. $1.55{\pm}0.28$) but not fibrosis index scores ($4.47{\pm}0.95$ vs. $4.98{\pm}0.96$; p=0.046). Patients with large focal lesions (${\geq}5cm$) had different ALBI scores ($-1.02{\pm}0.63$ vs. $-1.72{\pm}0.59$; p=0.001) serum talin-1 ($9.72{\pm}13.81$ vs. $28.6{\pm}38.89ng/ml$; p=0.007) and fibrosis index scores ($0.85{\pm}0.99$ vs. $4.20{\pm}4.85$; p=0.026). No statistical differences were noted between patients with and without portal vein thrombosis. For detection of HCC, serum talin-1 had 97.7% sensitivity and 100% specificity with a 17.2 ng/ml cutoff. AFP at a 13.7 ng/ml cutoff had 72.1% sensitivity and 6.3.6% specificity. The cutoff for the $fibro-{\alpha}$ score was 1.61 with 81.4% sensitivity and 77.3% specificity. Serum talin-1 (odds=1.08; C.I=1.016-1.150; p=0.014), fibrosis index score (odds=2.35; C.I=1.055-5.217; p=0.037) and the ALBI score (odds=6.9; C.I=1.924-24.708; p=0.003) were predictors of large focal lesions. Conclusions: Serum talin-1, AST/ALT ratio, $fibro-{\alpha}$ score are useful for the assessment of HCC patients.

Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models

  • Sanghwa Kim;Su-Yeon Lee;Haeng Ran Seo
    • BMB Reports
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    • v.56 no.4
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    • pp.225-233
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    • 2023
  • Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an multicelluar tumor spheroid (MCTS) model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases.

Dose-dependent Antifibrotic Effect of Polysaccharide from Mycelium of Ganoderma Lucidum on Liver Biliary Cirrhosis in Rats (담도결찰 흰쥐에서 영지배양 균사체 유래 다당체의 항섬유화 효과 검색 및 용량의존성시험)

  • Park, Eun-Jeon;Ko, Geon-Il;Kim, Jae-Baek;Sohn, Dong-Hwan
    • YAKHAK HOEJI
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    • v.41 no.2
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    • pp.220-224
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    • 1997
  • This study was carried out to investigate the dose dependent antifibrotic effects of polysaccharide from mycelium of Ganoderma lucidum. The experimental hepatic cirrhosis was induced by bile duct ligation/scission (BDL/S) in rats. BDL/S rats in each group were dosed 0.5 mg, 2.0 mg, 5.0 mg or 10.O mg/rat/day orally for 4 weeks after the operation. Antifibrotic effects were evaluated by serum biochemical values, hydroxyproline contents, and light microscopical histology. The results obtained were as follows: 1) Hydroxyproline contents in liver of 5.0 and 10.0mg polysaccharide-treated BDL/S rats were significantly reduced 2) In serum test, ALT, AST, ALP values in polysaccharide from Ganoderma lucidum-treated group were lower than BDL/S control group 3) The hepatic damage such as hepatocellular necrosis, inflammation, bile duct proliferation and fibrosis was less severe in the livers of 2.0 mg and 5.0 mg polysaccharide-treated rats. These results suggest that polysaccharide from mycelium of Ganoderma lucidum to be a promising agent for the inhibition of hepatic cirrhosis.

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GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress

  • Kim, Hyeon Ju;Lee, Yoseob;Fang, Sungsoon;Kim, Won;Kim, Hyo Jung;Kim, Jae-woo
    • BMB Reports
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    • v.53 no.6
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    • pp.317-322
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    • 2020
  • Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. NAFLD can further progress to irreversible liver failure such as non-alcoholic steatohepatitis (NASH) fibrosis and cirrhosis. However, specific regulator of NASH-fibrosis has yet to be established. Here, we found that glutathione peroxidase 7 (GPx7) was markedly expressed in NASH fibrosis. Although GPx7 is an antioxidant enzyme protecting other organs, whether GPx7 plays a role in NASH fibrosis has yet to be studied. We found that knockdown of GPx7 in transforming growth factor-β (TGF-β) and free fatty acids (FFA)-treated LX-2 cells elevated the expression of pro-fibrotic and pro-inflammatory genes and collagen synthesis. Consistently, GPx7 overexpression in LX-2 cells led to the suppression of ROS production and reduced the expression of pro-fibrotic and pro-inflammatory genes. Further, NASH fibrosis induced by choline-deficient amino acid defined, high fat diet (CDAHFD) feeding was significantly accelerated by knockdown of GPx7, as evidenced by up-regulated liver fibrosis and inflammation compared with CDAHFD control mice. Collectively, these results suggest that GPx7 might be a novel therapeutic target to prevent the progression and development of NAFLD.