• Parasites, Hosts and Diseases
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• 제52권6호
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• pp.695-699
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• 2014

Chronic Opisthorchis viverrini-induced hepatobiliary disease is associated with significant leukocyte infiltration, including activated macrophages; however, the polarization of infiltrating macrophages remains to be fully characterized. In this study, we characterized macrophage polarization and phenotype in chronic O. viverrini-induced hepatobiliary disease in humans and hamsters using gene expression and histochemical analysis. Chronic O. viverrini infection and associated hepatobiliary diseases were associated with iron loaded M2-like macrophages in both humans and hamsters. This study provides suggestive evidence that iron loaded M2-like macrophages promote hepatobiliary disease in chronic O. viverrini infection.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제21권4호
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• pp.306-314
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• 2018

Purpose: The objective of this study was to describe the clinical phenotypes of children and adolescents with cystic fibrosis (CF); and to assess the role of pancreatic insufficiency and neonatal screening in diagnosis. Methods: A cross-sectional study was conducted, which included 77 patients attending a reference center of CF between 2014 and 2016. Epidemiological data, anthropometric measurements, and the presence of pulmonary, pancreatic, gastrointestinal and hepatobiliary manifestations were evaluated based on clinical data and complementary examinations. Results: Of the 77 patients, 51.9% were male, with a median age of 147 months (7.0-297.0 months), and the majority showed adequate nutritional status. The most common phenotype was pulmonary (92.2%), followed by pancreatic (87.0%), with pancreatic insufficiency in most cases. Gastrointestinal manifestation occurred in 46.8%, with constipation being the more common factor. Hepatobiliary disease occurred in 62.3% of patients. The group with pancreatic insufficiency was diagnosed earlier (5.0 months) when compared to the group with sufficiency (84.0 months) (p=0.01). The age of diagnosis was reduced following implementation of neonatal screening protocols for CF (6.0 months before vs. 3.0 months after, p=0.02). Conclusion: The pulmonary phenotype was the most common, although extrapulmonary manifestations were frequent and clinically relevant, and should mandate early detection and treatment. Neonatal screening for CF led to earlier diagnosis in patients with pancreatic failure, and therefore, should be adopted universally.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• Parasites, Hosts and Diseases
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• 제59권4호
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• pp.363-368
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• 2021

Despite the synergistic effect of Opisthorchis viverrini and Helicobacter pylori co-infection on pathogenesis of severe hepatobiliary abnormalities (HBA) including advanced periductal fibrosis and replace with cholangiocarcinoma (CCA) have been established, the immune response to H. pylori in O. viverrini infected population has never been explored. Hence, this study aimed to investigate the antibody responses to 2 immunogenic H. pylori proteins in O. viverrini-infected patients with HBA and CCA. The risk analysis by multinomial logistic regression revealed that GroEL seropositivity was associated with higher risks of hepatobiliary abnormalities and CCA with adjusted odds ratios (95% confidence intervals) of 2.11 (95% CI=1.20-3.71, P=0.008) and 2.13 (95% CI=1.21-3.75, P=0.009), respectively. These findings indicate that GroEL seropositivity might be a biomarker for early detection of O. viverrini associated HBA and CCA.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4131-4136
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• 2016

Background: The population in northeast Thailand continues to present with hepatobiliary abnormalities, particularly periductal fibrosis (PDF) which is the result of chronic infection with liver fluke (Opisthorchis viverini; OV) and may lead to the development of cholangiocarcinoma (CCA). Although the prevalence of OV infection has been decreased due to a liver fluke control program over decades, the prevalence of PDF remains high. This study aimed to investigate demographic factors associated with PDF risk based on ultrasonography (US) screening. Materials and Methods: This cross-sectional study is part of the Cholangiocarcinoma Screening and Care Program (CASCAP), a prospective cohort study. Multiple logistic regression was used for data analysis. Results: In 55,246 subjects, the overall prevalence of PDF was 33.0% (95%CI: 32.6 - 33.4). Males (33.9 %) were at higher risk for developing PDF than females (32.2 %) (ORcrude = 0.93; 95%CI: 0.89 - 0.96; p-value < 0.001). Factors associated with an increased PDF risk, in addition to OV infection, included old age (${\geq}70$ years) (ORadj = 1.28, 95% CI: 1.14 - 1.44, p < 0.001) and hepatitis B infection (ORadj = 1.31, 95% CI: 1.11 - 1.55, p = 0.001). In contrast, number of praziquantel treatments (> 2 times) (ORadj = 0.54, 95% CI: 0.47 - 0.63, p < 0.001) and diabetes mellitus (ORadj = 0.57, 95% CI: 0.49 - 0.65, p < 0.001) were significantly associated with a decreased PDF risk. Conclusions: Future US screening should closely examine older people and hepatitis B subjects for the purpose of PDF surveillance among high risk groups for CCA. However, the results of inverse associations require further investigation in order to confirm our findings.

• Parasites, Hosts and Diseases
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• 제55권3호
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• pp.295-304
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• 2017

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, IFN-${\gamma}$, LT-${\alpha}$, and TNF-${\alpha}$ were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-$1{\beta}$-511C/T, IL-6-174G/C, IFN-${\gamma}$+874T/A, LT-${\alpha}$+252A/G, and TNF-${\alpha}$-308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-${\alpha}$+252A/G and TNF-${\alpha}$-308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-${\gamma}$+874T/A were significantly higher than the variants in CCA cases. IFN-${\gamma}$+874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6-174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

• Advances in pediatric surgery
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• 제3권1호
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• pp.6-14
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• 1997

본 저자들은 1992년 3월부터 1996년 4월까지 신생아 울체성 황달의 감별진단, 특히 신생아담도폐쇄증과 신생아 간염의 감별진단에 있어 Tc-99m DISIDA 간담도주사와 경피간침생검을 시행하여 다음과 같은 결과를 얻었다. 질환별로 볼 때 전체 60예의 환아 중에서 담도패쇄증이 23예, 신생아 감염이 34예였으며 경정맥고영양법으로 인한 황달이 2예, Alagille 증후군이 1예였다. Tc-99m DISIDA 간담도주사는 60명의 환아를 대상으로 실시하였다. BA 진단에 대한 민감도와 특이도는 각각 96%와 32%로서 높은 민감도를 보인 반면 특이도는 낮게 나타났으며 전체적인 진단 정확도는 57%였다. 경피간침생검은 Tc-99m DISIDA 간담도주사를 실시한 60명의 환아중 장관내 방사능이 나타나지 않았던 38명의 환아에서 40회 실시하였는데, 경피간침생검에 BA 진단에 대한 민감도는 88%, 특이도는 96%로 모두 높았으며 전체적인 진단 정확도는 93%였다. 본 연구를 요약하면 Tc-99m DISIDA 간담도주사는 특이도 32%, 양성예측율 47%로서 Tc-99m DlSIDA 간담도주사에서 장관내 방사능이 배설이 되지 않을 때는 경피간침생검이 반드시 필요하리라 생각되며, 일단 장관내 방사능이 배출되면 BA는 배제할 수 있으리라 생각된다. 경피간침생검은 전체적인 진단율이 93%로 높으나, BA 환아에서 8주전에 경피간침생검시는 NH와 감별이 어려울 수 있으며, 또 일부 NH, 경정맥고영양법 관련 울체성 황달에서는 경피간침생검시 BA와 감별이 어려울 수 있으므로, 임상경과를 보아서 의심스러우면 재 경피간침생검을 시행하던지 타 진단법을 응용해서 참고하여야 할 것으로 생각된다.

• 대한영상의학회지
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• 제83권5호
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• pp.991-1002
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• 2022

담도폐쇄증은 신생아 담즙 정체의 드물지만 중요한 원인이다. 적절한 치료와 예후를 위해서는 정확한 조기 진단이 중요하다. 본 종설에서는 초음파 검사, MRI, 간담도 핵의학스캔, 담관조영술 등의 영상 검사에서 담도폐쇄증의 영상 소견을 검토하였다. 지금까지 알려진 주요 영상의학적 소견들은 담낭의 비정상적인 모양과 크기, 간문맥 주변의 비후를 나타내는 'triangular cord' sign, 총담관이 보이지 않고, 간동맥 혈류가 증가하는 소견 등과 함께 동반된 기형의 유무들을 보이는 것이다. 담도폐쇄증의 진단을 위해 초음파 검사, MRI, 간담도 핵의학 스캔, 담관조영술 등의 여러 영상 검사들을 시행하며, 1차 영상 검사로 초음파 검사가 중요하다. 본 종설에서는 각 영상 검사들에서 지금까지 알려진 담도폐쇄증의 소견들과 함께 조기 신생아기에서 담도폐쇄증 진단의 어려움, 그리고 간 섬유화를 예측하기 위한 영상의 역할도 검토하였다. 본 종설이 담도폐쇄증 진단에 도움이 되길 바란다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제2권2호
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• pp.262-266
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• 1999

Obstruction of the extrahepatic bile ducts is the most common cause of conjugated hyperbilirubinemia in early infancy. More than 90% of such obstructive lesions are accounted for by extrahepatic biliary atresia. A rare lesion is obstruction of the common duct by impacted, thickened secretions and bile. Bile plug syndrome is defined as extrahepatic obstruction of the bile ducts by bile sludge in term infants without anatomic abnormalities, congenital chemical defects of bile, or hepatocellular lesions. Obstruction of extrahepatic ducts by plugs of biliary material apperas to be due to the inspissation and precipitation of bile and mucus within the lumen of the ducts. Cholestasis and precipitation of bile develop in association with abnormal composition of bile in cystic fibrosis, hepatocellular damage, prolonged erythroblastic jaundice, altered biliary dynamics with total parenteral nutrition, gut dysfunction, diuretic therapy, exchange transfusions and perinatal hemolysis. In those cases, the term inspissated bile syndrome is used. The clinical and laboratory findings in bile plug syndrome are identical to those observed in biliary atresia and choledochal cyst. The diagnosis can be suspected based on the findings of clinical and laboratory examinations together with hepatobiliary imaging, ultrasonography, radionuclide scan and liver biopsy. We experienced a case of spontaneous resolution of bile plug syndrome in a 4-year-old girl. We report this case with brief review related literatures.

• Parasites, Hosts and Diseases
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• 제57권4호
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• pp.379-387
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• 2019

Clonorchis sinensis is a carcinogenic human liver fluke that promotes hepatic inflammatory environments via direct contact or through their excretory-secretory products (ESPs), subsequently leading to cholangitis, periductal fibrosis, liver cirrhosis, and even cholangiocarcinoma (CCA). This study was conducted to examine the host inflammatory responses to C. sinensis ESPs and their putative protein components selected from C. sinensis expressed sequenced tag (EST) pool databases, including $TGF-{\beta}$ receptor interacting protein 1(CsTRIP1), legumain (CsLeg), and growth factor binding protein 2 (CsGrb2). Treatment of CCA cells (HuCCT1) with the ESPs or bacterial recombinant C. sinensis proteins differentially promoted the secretion of proinflammatory cytokines ($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$) as well as anti-inflammatory cytokines (IL-10, $TGF-{\beta}1$, and $TGF-{\beta}2$) in a time-dependent manner. In particular, recombinant C. sinensis protein treatment resulted in increase (at maximum) of ~7-fold in $TGF-{\beta}1$, ~30-fold in $TGF-{\beta}2$, and ~3-fold in $TNF-{\alpha}$ compared with the increase produced by ESPs, indicating that CsTrip1, CsLeg, and CsGrb2 function as strong inducers for secretion of these cytokines in host cells. These results suggest that C. sinensis ESPs contribute to the immunopathological response in host cells, leading to clonorchiasis-associated hepatobiliary abnormalities of greater severity.