• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6019-6026
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• 2015

Background: The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. Materials and Methods: We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. Results: No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. Conclusions: Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.

• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.307-311
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• 1992

Anorexia, nausea, and vomiting are one of the most frequent symptoms in viral hepatits patients. These may be due to poorly detoxified substances by dysfunctioned hepatocytes or by gastritis, but the pathophysiology is not totally understood. The symptoms interfere with adequate nutrient intake and are managed by metoclopramide, which accelerates gastric emptying. Thus delayed gastric emptying may well be a contributing factor to such symptoms. To determine such a relationship, we measured gastric emptying time in 11 normal subjects,9 acute (AVH), and 12 chronic B viral hepatitis (CVH) patients. All were males with a mean age of 23 years. An egg was labeled with 0.5 mCi of $^{99m}Tc-sulfur$ colloid, fried, then eaten between 2 slices of bread with 100 cc of water. Anterior and posterior images were taken at 20 minute intervals over a 2 hour period. A geometric mean of activity pertaining to the gastric region was measured, and $T_{1/2}$ was calculated from the time activity curve. $T_{1/2}$ for normal the group was $57.8{\pm}6.3$ minutes while that for the AVH and CVH group was $58.2{\pm}8.2$ (p=0.40) and $64.1{\pm}10.5$ (p=0.09), respectively. There was 1 AVH Patient and 4 CVH patients with prolonged $T_{1/2}$. Anorexia and nausea was seen in 71% and 46% of the patients, respectively. 80% and 60% of the patients with prolonged $T_{1/2}$ had anorexia and nausea, respectively.

• Korean Journal of Microbiology
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• v.47 no.4
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• pp.342-347
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• 2011

T cells play a key role in viral infection. However, in patients with chronic hepatitis C virus (HCV) infection, HCV-specific T cells are dysfunctional and impaired in the liver, which is the primary site for HCV replication. There are multiple potential mechanisms for HCV-specific T cell dysfunction including induction of immune inhibitory pathways (program death-1; PD-1, cytotoxic t lymphocyte associated antigen-4; CTLA-4) and immune tolerance induced specific for the liver. However, the interaction between hepatocytes and HCV-specific CD8 T cells has not clearly established. In this study, we confirmed huh (human hepatoma) 7.5 cells expressing HLA (human leukocyte antigen) A2 presented antigen to activate HCV-specific CD8 T cells in HLA A2-restricted manner and expression of PD-L (program death ligand) 1 on huh7.5 cells reduced HCV-specific CD8 T cell activation, suggesting an immune modulatory activity. Loss of HCV-specific tetramer responses following antigenic stimulation correlated with increased caspase-3 activity. In addition, PD-L1 on huh7.5 cells rescued HCV-specific CD8 T cells from apoptosis. Our results suggest that the interaction between PD-L1 and PD-1 can recover the function of HCV-specific CD8 T cells in the liver, which could be applied in therapy of HCV chronic infection.

• Korean Journal of Radiology
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• v.22 no.7
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• pp.1066-1076
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• 2021

Objective: To evaluate the performance of the 2018 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) Practice Guidelines (hereafter, PG) for the diagnosis of hepatocellular carcinoma (HCC) using gadoxetic acid-enhanced MRI, compared to the Liver Imaging-Reporting and Data System (LI-RADS) version 2018 (hereafter, v2018). Materials and Methods: From January 2013 to October 2015, treatment-naïve hepatic lesions (≥ 1 cm) on gadoxetic acid-enhanced MRI in consecutive patients with chronic hepatitis B or cirrhosis were retrospectively evaluated. For each lesion, three radiologists independently analyzed the imaging features and classified the lesions into categories according to the 2018 KLCA-NCC PG and LI-RADS v2018. The imaging features and categories were determined by consensus. Generalized estimating equation (GEE) models were used to compare the per-lesion diagnostic performance of the 2018 KLCA-NCC PG and LI-RADS v2018 using the consensus data. Results: In total, 422 lesions (234 HCCs, 45 non-HCC malignancies, and 143 benign lesions) from 387 patients (79% male; mean age, 59 years) were included. In all lesions, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity and lower specificity than LR-5 (LI-RADS v2018) (87.2% [204/234] vs. 80.8% [189/234], p < 0.001; 86.2% [162/188] vs. 91.0% [171/188], p = 0.002). However, in lesions of size ≥ 2 cm, the definite HCC had a higher sensitivity than the LR-5 (86.8% [164/189] vs. 82.0 (155/189), p = 0.002) without a reduction in the specificity (80.0% [48/60] vs. 83.3% [50/60], p = 0.15). In all lesions, the sensitivity and specificity of the definite/probable HCC (2018 KLCA-NCC PG) and LR-5/4 did not differ significantly (89.7% [210/234] vs. 91.5% [214/234], p = 0.204; 83.5% [157/188] vs. 79.3% [149/188], p = 0.071). Conclusion: For the diagnosis of HCC of size ≥ 2 cm, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity than LR-5, without a reduction in specificity. The definite/probable HCC (2018 KLCA-NCC PG) had a similar sensitivity and specificity to that those of the LR-5/4.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7825-7829
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• 2015

Background: Egypt has the highest prevalence of HCV infection in the world (~14.7%). Around 10-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. The incidence of HCC is expected to grow in the next two decades, largely due to HCV related cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. No simple reliable non-invasive marker has been available till now. B2M, a non-glycosylated polypeptide composed of 99 amino acids, is one of the components of HLA class I molecules on the surfaces of all nucleated cells. It has been reported that the level of serum B2M is elevated in patients with chronic hepatitis C and HCV-related HCC when compared to HCV-negative patients or healthy donors. Determining the clinical utility of serum B2M as a marker for disease progression in Egyptian patients with HCV related chronic hepatitis, cirrhosis and hepatocellular carcinoma was the aim of the present study. Materials and Methods: In this analytical cross sectional study 92 participants were included in 4 equal groups: Group (1) non cirrhotic chronic HCV; Group (2) HCV related liver cirrhosis; Group (3) HCC on top of HCV,; and Group (4) healthy controls. History taking, clinical examination, routine labs and abdominal ultrasound were conducted for all patients, PCR and Metavir scores for group (1) patients, and triphasic CT abdomen and AFP for Group (3) patients. B2M levels were measured in serum with a fully-automated IMX system. Results: The mean serum B2M level of Group (1) was $4.25{\pm}1.48{\mu}g/ml$., Group (2) was $7.48{\pm}3.04$, Group (3) was $6.62{\pm}2.49$ and Group (4) was $1.62{\pm}0.63$. Serum B2M levels were significantly higher in diseased than control group (p<0.01) being significantly higher in cirrhosis ($7.48{\pm}3.04$) and HCC groups ($6.62{\pm}2.49$) than the HCV group ($4.25{\pm}1.48$) (p<0.01). There was a significant correlation between B2M Level and ALK, total and direct bilirubin and INR (p<0.05), and a significant inverse correlation between B2M level and albumin, total proteins, HB andWBCS values (p<0.05). There was no significant correlation between B2M level and viral load or Metavir score, largest tumour size or AFP (p>0.05). The best B2M cut-off for HCV diagnosis was 2.6 with a sensitivity of 100%, a specificity of 92%, a positive predictive value (PPV) of 97% and a negative predictive value (NPV) of 100%. The best B2M cut-off for HCC diagnosis was 4.55 which yielded sensitivity, specificity, positive predictive value, negative predictive values of 74%, 62%, 39.5, 87.8% respectively (p-value <0.01) while best cut-off for cirrhosis was 4.9, with sensitivity 74 % and specificity 74%.The sensitivity for HCC diagnosis increased upon B2M and AFP combined estimation to 91%, specificity to 79%, NPV to 95% and accuracy to 83%. Conclusions: Serum B2M level is elevated in HCV related chronic liver diseases and may be used as a marker for HCV disease progression towards cirrhosis and carcinoma.

• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.49-56
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• 1999

Purpose: Heart to liver ratio on T1-201 per rectal scintigraphy (shunt index) is known to be useful in the assessment of portal systemic shunt. We assessed T1-201 uptake pattern and early liver/heart uptake rate of T1-201 and correlated with shunt index in patients with chronic active hepatitis (CAH) and liver cirrhosis (LC). Materials and Methods: Fifty eight patients with biopsy-proven chronic liver disease (35 with CAH, 23 with LC) underwent T1-201 per rectum scintigraphy after instillation of 18.5 MBq of T1-201 into the upper rectum. We evaluated hepatic uptake (type 1 : homogeneous, 2: inhomogeneous segmental, 3: inhomogeneous nonsegmental) and extrahepatic uptake of spleen, heart and kidney (grade 0: no uptake, 1: less than liver, 2: equal to liver, 3: greater than liver). We measured the early liver/heart uptake rate (the slope of the liver to heart uptake ratio for 10 min) and shunt index (heart to liver uptake ratio). T1-201 uptake pattern and early liver/heart uptake rate of T1-201 was correlated with the pathologic diagnosis and shunt index. Results: Hepatic uptake patterns of type 1 and 2 were dominant in CAH (CAH: 27/35, LC. 8/23), and type 3 in LC (CAH: 8/35, LC: 15/23)(p<0.005). The grades of extrahepatic uptake were higher in LC than in CAH (spleen: p<0.001, other soft tissue: p<0.005). The early liver/heart uptake rate of CAH ($0.110{\pm}0.111$) was significantly higher than that of LC ($0.014{\pm}0.090$)(p<0.001). The sensitivity and specificity of the early liver/heart uptake rate were 77.7% and 67.7% in differentiating LC from CAH. There was negative correlation between early liver/heart uptake rate and shunt index (r=-0.3347, p<0.01). Conclusion: Hepatic and extrahepatic uptake pattern and early liver/heart uptake rate on T1-201 per rectum scintigraphy are useful in the assessment of portal systemic shunt in patients with chronic liver disease.

• Korean Journal of Biological Psychiatry
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• v.2 no.1
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• pp.100-106
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• 1995

Antibodies to hepatitis C drew attention because of high morbidity to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV was known to be transmitted by transfusion, sexual behavior and parenteral drug use. However, some kind of autoimmune mechanism was suggested to be involved in the genesis of HCV-induced liver diseases. We hypothesized the prevalence of having anti-HCV might be higher in psychiatric patients rather than general population because of the characteristic route of transmission. Using Abbott HCV BA kit, anti-HCV was detected in the sera of 113 psychiatric inpatients from early December in 1992 to late May in 1994. The Positivity of anti-HCY was significantly(P<0.05) higher among psychiatric inpatients(10.6%) than in healthy controls(3.0%). There were no disease specificity among psychiatric inpatients who had anti-HCV, though alcoholics tended to have more anti-HCV. We couldn't find any significant correlation of anti-HCV with age, seasons of birth, lymphocytes (%) and liver function.

• 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.

• Clinical and Experimental Pediatrics
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• v.50 no.4
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• pp.348-354
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• 2007

Purpose : Perinatal hepatitis B viral infection is decreasing; however, 10% of babies to HBeAg positive mothers still become chronic carriers despite perinatal prophylaxis. Although, the cause of prophylaxis failure is still unclear, an importance of maternal HBV-DNA level at the delivery time has been suggested. This study was established to certify if it would be a useful predictable factor for the outcome of perinatal prophylaxis. Methods : Twenty-nine HBeAg positive mothers whose babies had known outcomes of prophylaxis were selected. To determine the amount of maternal HBV-DNA, a quantitative PCR was performed with the WHO International Standard for HBV DNA NAT assays. Results : The mean logarithm HBV-DNA level of mothers with failed outcomes was significantly higher than that of mothers with succeessful outcomes (7.99 vs. 6.72, P=0.015). The predictable maternal HBV-DNA cut-off level to prophylaxis outcome was $2.83{\times}10^7copies/mL$ (100 pg/mL). None out of the case 16 (0%) who had below this level, and 5 out of 13 (38.5%) who had above this level of maternal HBV-DNA failed in perinatal prophylaxis. Conclusion : Mothers with higher levels of HBV-DNA at delivery time would be prone to a worse outcome of prophylaxis using the conventional approach. Perinatal prophylaxis failure rate can be reduced, if we try to introduce more potent prophylactic treatment into the cases with this risk factor.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.37-46
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• 2018

Objectives : Liver disease is an inflammatory reaction caused by oxidative stress, viral, alcohol, and drug properties. Inflammatory reaction causes hepatitis and chronic hepatitis is persistent, it progresses to liver fibrogenesis and liver cancer. The aim of this study was to confirm the hepatoprotective effect of Tongyuhwalhyeol-tang(Tongqiaohuoxue Decoction) (TH) and Gamtongyuhawlhyeol-tang(GTH) in TAA-induced liver injury animal model. Methods : The antioxidant activities were evaluated through in vitro experiments, such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, total polyphenol and total flavonoid content measurement. To confirm the liver protective effect, induced by Thioacetamide (TAA) for 3 days injection at 200 mg/kg rats. TH and GTH were treated 3 days at 200 mg/kg/day. The changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$), alanine aminotransferanse (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, expression of anti-inflammation, anti-oxidant related proteins were investigated by western blot analysis. Results : TH was inhibited the antioxidant activities. In the TAA-induced rat, TH decreased ROS, $ONOO^-$, ALT, AST level in serum. Inflammation related protein expressions increased in TAA-induced rat compared to normal rat. However, TH group inhibited the down expression of these proteins. Also, anti-oxidant related protein expressions increased in TH group compared TAA-induced rat. Conclusion : Therefor, these results suggested that TH provided hepatoprotective effects on the hepatic injury leading to the reduction of inflammatory response. In addition, the effect of TH was superior to that of GTH.