• YAKHAK HOEJI
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• v.40 no.5
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• pp.550-557
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• 1996

One of therapeutics in liver disease (morbus wilson) is D-penicillamin (D-pen: D-3-mercapto-valin). Especially the cross-linking of collagen molecules could be inhibited by D-pe n in extracellular space. In this study we investigated the antifibrotic effects of D-pen in rats that were induced the liver fibrosis by bile duct ligation and scission (BDL/S). Rats were treated for 4 weeks with D-pen after BDL/S operation or sham operation. The balance between fibrogenesis-marker (PNIIIP) and the fibrolysis-maker (PNIVP) were observed in sera by RIA (radioimmunoassay), and the parameter of collagen deposition in liver tissue (hydroxyproline: HYP) was measured by colorimetry. The weight of liver in BDL/S operated group was increased significantly in compared with sham operation group (15.2g${\pm}$1.1, vs 11.9g${\pm}$3.9: p<0.005, p<0.05). The rats group treated by D-pen showed the lower level of PNIIIP (6.7ng/ml${\pm}$1.5, vs 9.5ng/ml${\pm}$2.8) and the higher value of PIVCP (14.0ng/ml${\pm}$1.9, vs 7.9ng/ml${\pm}$1.5) in sera that compared to untreated rats. The content of HYP was decreased by 141% in BDL/S with D-pen treated group than that of it in BDL/S group. No correlation was revealed between collagen parameters in sera and HYP in liver tissue of BDL/S operated and D-pen treated rats. The group treated with D-pen showed the lower value of clinical biochemistry parameters (GOT: glutamate oxalacetate transaminase, Total-Bilirubin) in compared with only BDL/S operated rats, but the value of GPT (glutamate pyruvate transaminase) and Alkaline phosphatase in two BDL/S groups was nearly same. In the histological finding, we observed mild bile duct proliferation, weak inflammation and fibrosis in BDL/S with D-pen treated group, but BDL/S operated group showed the formation of septum (island of hepatocytes), massive bile duct proliferation. This result represents that the BDL/S operation induces liver fibrosis (cirrhosis) in 4 weeks, and D-pen inhibits the synthesis of collagen weakly and stimulates the degradation of collagen in the extracellular space. We conclude that the monitoring of PNIIIP, PIVCP in sera is useful parameter for screening of antifibrotic effect, and D-pen delay the liver fibrosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7211-7217
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• 2015

Background: The aims of this study were to evaluate the diagnostic and prognostic roles of serum osteopontin (OPN) and single nucleotide polymorphisms (SNPs) in the OPN promoter in patients with hepatitis B-related hepatocellular carcinoma (HCC). Materials and Methods: Four groups were studied, which included 157 patients with HCC, 73 with liver cirrhosis (LC) and 97 with chronic hepatitis (CH), along with 80 healthy subjects. Serum OPN and alpha-fetoprotein (AFP) levels were measured. The SNPs -66 T/G, -156 G/${\Delta}G$ and -433 C/T within the OPN promoter were determined by direct sequencing. Results: Serum OPN levels were significantly higher in patients with HCC than in the other groups. Area under receiver operating characteristics curves in distinguishing HCC from chronic liver disease (CLD; CH and LC) were 0.782 (95% CI; 0.729-0.834) for OPN and 0.888 (95% CI; 0.850-0.927) for AFP. Using the optimal cut-off value (70 ng/mL), OPN had sensitivity and specificity of 72% and 71%, respectively. Serum OPN was superior to AFP in detecting early-stage HCC (68% vs. 46%). A combination of both markers yielded an improved sensitivity for detecting early HCC to 82%. A high OPN level was significantly correlated with advanced BCLC stage and was an independent prognostic factor for HCC. The SNPs -156 and -443 were associated with susceptibility to HCC, but were not related to overall survival. Conclusions: Serum OPN is a useful diagnostic and prognostic marker for HCC. The combined use of serum OPN and AFP improved the diagnosis of early HCC. Genetic variation in the OPN promoter is associated with the risk, but not the prognosis of HCC.

• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.265-271
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• 2016

Recently, liver damage contributes to big percentage of the morbidity and mortality rates worldwide. Excessive intake of alcohol is one of the major causes of liver injury. When liver injury is repeated and becomes chronic, it leads to development of fibrosis and cirrhosis. In the liver, TGF-${\beta}$ is a profibrogenic cytokine, which participates in various critical events cause liver fibrosis. Seahorse (Hippocampus abdominalis) is a common traditional Chinese medicine and has been widely used for centuries. Seahorse has been known to have a variety of bioactivities, such as anti-oxidant, anti-fatigue, and anti-tumor. Peptide is one of the main compounds of seahorse. In this study, we isolated enzymatic hydrolysate from seahorse H. abdominalis by alcalase hydrolysis and investigated the effect of the hydrolysate on liver injury. In the present in vitro studies, the hydrolysate increases cell viability of Chang cells and protects Huh7 cells from ethanol toxicity. In addition, the hydrolysate inhibits TGF-${\beta}$-induced responses. In vivo studies show that the pretreatment of hydrolysate reduces alcohol-induced increases of serum Glutamic oxaloacetic acid transaminase and Glutamic pyruvate transaminase activities and increases liver weight and body weight. These results suggest that seahorse may have a hepatoprotective effect.

• Journal of Preventive Medicine and Public Health
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• v.40 no.1
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• pp.23-28
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• 2007

Objectives : Chronic infections with hepatitis B or C and alcoholic cirrhosis are three well-known major risk factors for liver cancer. Diabetes has also been suggested as a potential risk factor. However, the findings of previous studies have been controversial in terms of the causal association. Therefore, the aim of this study was to evaluate the association between serum glucose levels and liver cancer development in a Korean cohort. Methods : Thirty-six liver cancer cases were identified in the Korean Multi-Center Cancer Cohort (KMCC). Baseline information on lifestyle characteristics was obtained via questionnaire. Serum glucose levels were measured at the study's enrollment. Relative risks (RRs) were estimated using a Cox proportional hazard regression model. The adjusting variables included age, gender, smoking history, alcohol consumption, body mass index, and hepatitis B surface antigen (HBsAg) seropositivity. Results : The RRs of serum glucose for liver caner were 1.20 (95% CI = 0.48-2.99) for the category of 100 to 125 mg/dL of serum glucose and 2.77 (95% CI = 1.24-6.18) for the >126 mg/dL serum glucose category (both compared to the <100 mg/dL category). In a subgroup analysis, the RR of serum glucose among those who were both HBsAg seronegative and non-drinkers was 4.46 (95% CI = 1.09-18.28) for those with glucose levels >100 mg/dL. Conclusions : The results of this study suggest that a high level of serum glucose can increase liver cancer risk independently of hepatitis infection and drinking history in Koreans. This study implies that glucose intolerance may be an independent risk factor for liver cancer.

• Korean Journal of Radiology
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• v.23 no.12
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• pp.1269-1280
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• 2022

Objective: This study aimed to evaluate the usefulness of quantitative indices obtained from deep learning analysis of gadoxetic acid-enhanced hepatobiliary phase (HBP) MRI and their longitudinal changes in predicting decompensation and death in patients with advanced chronic liver disease (ACLD). Materials and Methods: We included patients who underwent baseline and 1-year follow-up MRI from a prospective cohort that underwent gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance between November 2011 and August 2012 at a tertiary medical center. Baseline liver condition was categorized as non-ACLD, compensated ACLD, and decompensated ACLD. The liver-to-spleen signal intensity ratio (LS-SIR) and liver-to-spleen volume ratio (LS-VR) were automatically measured on the HBP images using a deep learning algorithm, and their percentage changes at the 1-year follow-up (ΔLS-SIR and ΔLS-VR) were calculated. The associations of the MRI indices with hepatic decompensation and a composite endpoint of liver-related death or transplantation were evaluated using a competing risk analysis with multivariable Fine and Gray regression models, including baseline parameters alone and both baseline and follow-up parameters. Results: Our study included 280 patients (153 male; mean age ± standard deviation, 57 ± 7.95 years) with non-ACLD, compensated ACLD, and decompensated ACLD in 32, 186, and 62 patients, respectively. Patients were followed for 11-117 months (median, 104 months). In patients with compensated ACLD, baseline LS-SIR (sub-distribution hazard ratio [sHR], 0.81; p = 0.034) and LS-VR (sHR, 0.71; p = 0.01) were independently associated with hepatic decompensation. The ΔLS-VR (sHR, 0.54; p = 0.002) was predictive of hepatic decompensation after adjusting for baseline variables. ΔLS-VR was an independent predictor of liver-related death or transplantation in patients with compensated ACLD (sHR, 0.46; p = 0.026) and decompensated ACLD (sHR, 0.61; p = 0.023). Conclusion: MRI indices automatically derived from the deep learning analysis of gadoxetic acid-enhanced HBP MRI can be used as prognostic markers in patients with ACLD.

• Journal of the Korean Society of Radiology
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• v.84 no.3
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• pp.666-675
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• 2023

Purpose This study aimed to determine whether the attenuation coefficient (AC) from attenuation imaging (ATI) was correlated with visual US assessment in patients with hepatic steatosis. Moreover, it aimed to assess whether the patient's blood chemistry results and CT attenuation were correlated with AC. Materials and Methods Patients who underwent abdominal US with ATI between April 2018 and December 2018 were included in this study. Patients with chronic liver disease or cirrhosis were excluded. The correlation between AC and other parameters, such as visual US assessment, blood chemistry results, liver attenuation, and liver-to-spleen (L/S) ratio, were analyzed. AC values according to visual US assessment grades were compared using analysis of variance. Results A total of 161 patients were included in this study. The correlation coefficient between US assessment and AC was 0.814 (p < 0.001). The mean AC values for the normal, mild, moderate, and severe grades were 0.56, 0.66, 0.74, and 0.85, respectively (p < 0.001). Alanine aminotransferase levels were significantly correlated with AC (r = 0.317, p < 0.001). The correlation coefficients between liver attenuation and AC and between L/S ratio and AC were -0.702 and -0.626, respectively (p < 0.001). Conclusion Visual US assessment and AC showed a strong positive correlation with the discriminative value between the groups. Computed tomography attenuation and AC showed a strong negative correlation.

• Journal of Yeungnam Medical Science
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• v.14 no.1
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• pp.155-167
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• 1997

The identification of serum HBV DNA is very important for the assessment of the disease activity in persistent infection, for the evaluation of the infectivity of an individuals blood. The dot blot, however, has limited sensitivity and sometimes inconsistent with other serological markers and clinical settings. Using the most important recent advance in molecular biology, the polymerase chain reaction(PCR), specific DNA sequences can be amplified more than a million-fold in a few hours and with this technique the detection of the extreme low level of DNA is possible. This study was to determine sensitivity of the PCR for the detection of serum HBV DNA in comparison with dot blot analysis and to investigate the serum HBV DNA status and clinical significance of PCR in patients with chronic HBsAg positive liver disease. The subjects of this study were 17 patients with asymptomatic HBsAg carriers(9 HBeAg positive patients, 8 anti-HBe positive patients), 91 chronic hepatitis B(50 HBeAg positive patients, 41 anti-HBe positive patients), 57 liver cirrhosis(21 HBeAg positive patients, 36 anti-HBe positive patients), 27 hepatocellular carcinoma(10 HBeAg positive patients, 17 anti-HBe positive patients). The results were summerized as following; The detection rates of HBV DNA by dot blot, PCR were 58.9%, 72.2% in HBeAg positive patients, 34.3%, 53.9% in anti-HBe positive patients. The detection rates of HBV DNA by PCR in HBeAg negative patients were 25.0% in asymptomatic HBsAg carriers, 61.0% in chronic hepatitis B, 52.8% in liver cirrhosis, 52.9% in hepatocellular carcinoma. The positive rate for HBV DNA is a significant difference between HBeAg positive and negative asymptomatic HBsAg carriers, but not significantly difference in other groups. In conclusions, this study confirmed that the PCR is much more sensitive than the dot blot analysis in detecting the HBV DNA in the sera of patients with chronic liver disease. The presence of HBV DNA in the serum was detected by PCR with higher sensitivity and it suggested that active viral replication is still going on in most patients with chronic HBsAg positive liver disease irrespective of HBeAg/anti-HBe status, and PCR may be used as a prognostic factor in asymptomatic HBsAg carriers.

• Proceedings of the Korean Society of Sericultural Science Conference
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• 2003.10a
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• pp.28-33
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• 2003

Over 100 million people worldwide are chronic carriers of hepatitis C virus (HCV)(1). Chronic viral infections of the liver can prouess to cirrhosis, which may ultimately lead to hepatic failure or the development of hepatocellular carcinoma. There are a limited number of antiviral drugs on the market approved fur clinical management of chronic HCV infections; interferon-alpha (IFN$\alpha$) and the nucleoside analog ribavirin. However, whether used as monotherapy or in combination, adverse side-effects are associated with each drug and better therapeutic regimens are needed. (omitted)

• BMB Reports
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• v.36 no.1
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• pp.138-143
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• 2003

Of many viral causes of human cancer, few are of greater global importance than the hepatitis B virus (HBV). Over 250 million people worldwide are persistently infected with HBV. A significant minority of these develop severe pathologic consequences, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Earlier epidemiological evidence suggested a link between chronic HBV infection and HCC. Further, the existence of related animal viruses that induce acute and chronic infections of the liver, and eventually HCC, confirms the concept that HBV belongs to one of the few human oncogenic viruses. Although it is clear that chronic HBV infections are major risk factors, relatively little is understood about how the viral factors contribute to hepatocarcinogenesis. This review will introduce molecular aspects of the viral infection, and highlight recent findings on the viral contribution to hepatocarcinogenesis.

• Journal of Chest Surgery
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• v.18 no.1
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• pp.128-139
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• 1985

Seven patients [six women and one man] with obstruction of hepatic portion of inferior vena cava was operated on, from May, 1969 to January, 1985. Of seven patients, six were undergone corrective operation for IVC obstruction and another one was not operated because of far advanced liver cirrhosis. The occlusions were found at or close to the level of diaphragm and they were membranous or diffuse with or without thrombi. Most of their symptoms were referable to either inferior vena caval or hepatic venous obstruction and onset of the symptoms was usually gradual, beginning between the age of their thirties and forties. Most of the patients showed marked elevation of peripheral venous pressure of lower extremity [29-40 cm H2O] preoperatively, which decreased significantly after corrective operation [17-30 cm H2O]. Venous catheterization for pressure study and venography were essential for confirming the diagnosis. Of six cases, in which corrective operations were done, Transatrial membranotomy with or without IVC dilatation were performed in five cases [case 1, 2, 3, 5, 6], using cardiopulmonary bypass and in another one case, bypass operation between IVC, distal to obstruction, and RA was done using Dacron tube graft under the thoracoabdominal incision. All survived and their conditions were improved.