Hepatitis B virus genotypes and hepatocellular carcinoma in Thailand

AIM: The role of hepatitis B virus (HBV) genotypes on the clinical features and prognosis of patients with hepatocellular carcinoma (HCC) is currently unknown. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Thai patients.METHODS: HBV genotypes were determined by PCR-RFLP in stored sera of 93 asymptomatic carriers, 103 patients with chronic hepatitis, 60 patients with cirrhosis and 76patients with HCC. The clinical data were analyzed in relation to the HBV genotype.RESULTS: HBV genotypes C and B were predominant in Thailand, accounting for 73% and 21%, respectively. The distributions of genotypes B and C were similar in HCC patients compared to the other groups. Genotype C was significantly more common in HCC patients who were under 40 years old than genotype B (18% vs 0%, P= 0.03), but was significantly less common in patients older than 60 years (26% vs 56.5%, P= 0.01). The positive rate of hepatitis B e antigen (HBeAg) in patients with genotype C was significantly higher than that in patients with genotype B (71.6% vs 44.4%, P = 0.03 in chronic hepatitis; 56.8% vs 11.1%,P = 0.01 in cirrhosis). There were no differences between HCC patients with genotypes B and C regarding tumor staging by CLIP criteria and the overall median survival. Multivariate analyses showed that HBV genotype was not an independent prognostic factor of survival in HCC patients.CONCLUSION: Patients with genotype C had a higher positive rate of HBeAg and exhibited earlier progression of cirrhosis and HCC than those with genotype B. However,there were no differences in the risk of developing HCC and its prognosis between patients with these genotypes.

Interleukin-1β gene polymorphism associated with hepatocellular carcinoma in hepatitis B virus infection

AIM:To examine the effect of interleukin-l-beta (IL-1β)promoter region C-511T and IL-1 receptor antagonist(IL-1RN) polymorphism among the patients with chronichepatitis B virus (HBV) infection (HCC and non-HCC).METHODS:Genomic DNA from 136 Thai patients withchronic HBV infection (HCC=46 and non-HCC=90) and152 healthy individuals was genotyped for IL-1β genepolymorphism (-511) using polymerase chain reactionwith sequence specific primers (PCR-SSP).The variablenumber of tandem repeats (VNTR) of IL-1RN gene wasassessed by a PCR-based assay.The association betweenthese genes and status of the disease was evaluated byX^2 test.RESULTS:IL-1B-511 genotype C/C was found tobe significantly different in patients with HCC whencompared with healthy individuals (P=0.036,OR=2.29,95%CI=1.05-4.97) and patients without HCC (P=0.036,OR=2.52,95%CI=1.05-6.04).Analysis of allelefrequencies of IL-1B-511 showed that IL-1B-511 Callele was also significantly increased in patients withHCC,compared to that in healthy control (P=0.033,OR=1.72,95%CI=1.04-2.84).However,no significantassociation in IL-1RN gene was found between the twogroups.CONCLUSION:IL-1B-511C allele,which may beassociated with high IL-1B production in the liver,is agenetic marker for the development of HCC in chronic hepatitis B patients in Thai population.

Role of serum interleukin-18 as a prognostic factor in patients with hepatocellular carcinoma

AIM:To determine whether serum interleukin-18 (IL-18) levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). METHODS:Serum IL-18,IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls. RESULTS:Serum IL-18,IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (≥ 105 pg/mL) had a poorer survival than those with low serum IL-18 levels (< 105 pg/mL) (4 and 11 mo,respectively,P = 0.015). Multivariate analyses showed that serum IL-18 level,but not IL-6 and IL-12 levels,was a significant and independent prognostic factor of survival. CONCLUSION:These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patients with HCC. Thus,the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.

Diagnostic role of serum interleukin-18 in gastric cancer patients

瞄准：在胃的癌症病人的各种各样的方面决定当前的地位并且在泰国病人与浆液 interleukins 的预示的角色发现临床的关联。方法：68 个病人在 2003 年 4 月期间在楚拉隆克恩国王纪念物医院在这研究被注册到 2005 年 5 月。胃的癌症组织学地在 17 个病人在 51 个病人和胃溃疡被证明。浆液 IL-6， IL-10， IL-12，和 IL-18 层次被连接酶的免疫吸着剂试金(ELISA ) 测量。结果：有 26 男性(55.32%) 和 21 女性(44.68%) ，他们的年龄从 33 ～ 85 年(意味着年龄 64.49 +/- 13.83 年) 。普通演讲是重量损失(41.2%) ，消化不良(39.2%) ，并且上面的胃肠的流血 15.7%) 。35.3% 胃的癌症病人的一个总数并且 6.3% 胃溃疡病人是吸烟者(P = 0.029 ) 。而且， 32.4% 胃的癌症病人和 6.3% 胃溃疡病人是含酒精的喝酒者(P = 0.044 ) 。损害地点在 39.4% 是幽门窦的，在 39.4% 的胃的身体，在 12.2% 的上面的胃和在 6.1% 病人的全部胃。H pylori 感染在 44.4% 被检测。糟糕区分的腺癌是最普通的病理学的发现(60.7%) 。外科疗法在 44.1% 病人被执行(在 5.9% 的全胃切除术，在 32.4% 的大部胃切除术和 palliative 在 5.9% 绕过外科) 。全身的化疗在 8.8% 病人作为辅助治疗被给。癌病 peritoneii 在 18.8% 病人被发现。吝啬的生存时间是 13.03 +/- 9.75 瞬间。在胃的癌症病人组的 IL-18 水平(58.54 +/- 43.96 pg/mL ) 在胃溃疡病人组比那显著地高(30.84 +/- 11.18 pg/mL )(P = 0.0001 )(95% CI 是 42.20， 13.19 ) 。为胃的癌症的诊断的 IL-18 的伤口点是 40 pg/mL，积极预兆的价值是 92.31% 。在有远转移的胃的癌症病人的 IL-6 水平(20.21 +/- 9.37 pg/mL ) 在没有转移的那些比那显著地高(10.13 +/- 7.83 pg/mL )(P = 0.037 )(95% CI 是 19.51， 0.65 ) 。在胃的癌症病人的 IL-10 和 IL-12 层次的角色是没有有效差量提供数据。结论：这些调查结果表明那浆液 IL-6 和 IL-18，然而并非 IL-10 和 IL-12 层次可以在有胃的癌症的病人是临床的关联和预示的因素的有用生物标记。而且， IL-18 能与高积极的预兆的价值为胃的癌症用作一个诊断标记。

Gender difference in clinicopathologic features and survival of patients with hepatocellular carcinoma

AIM: To determine the influence of gender on the clinicopathologic characteristics and survival of patients with hepatocellular carcinoma (HCC). METHODS: A retrospective analysis of medical records was performed in 299 patients with HCC and their clinicopathologic features and survival were compared in relation to gender. RESULTS: There were 260 male (87%) and 39 female patients (13%), with a male-to-female ratio of 6.7:1. Female patients had lower mean serum bilirubin levels (P=O.03), lower proportion of alcohol abuse (P=O.O02), smaller mean tumor size (P=O.02), more frequent nodular type but less frequent massive and diffuse types of HCC (P=O.01), wereless advanced in Okuda's staging (P=O.04), and less frequently associated with venous invasion (P=O.03). The median survivals in females (14 mo) were significantly longer than that of male patients (4 mo) (P=O.O04, log-rank test). Multivariate analysis demonstrated that high serum alphafetoprotein levels, venous invasion, extrahepatic metastasis and lack of therapy were independent factors related to unfavorable prognosis. However, gender did not constitute a predictive variable associated with patient survival. CONCLUSION: Female patients tend to have higher survival rates than males. These differences were probably due to more favorable pathologic features of HCC at initial diagnosis and greater likelihood to undergo curative therapy in female patients.

Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundicestatus. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children.

Virological course of hepatitis A virus as determined by real time RT-PCR: Correlation with biochemical, immunological and genotypic profiles

瞄准：承担肝炎 A 的分析，并且相关病毒的负担，丙氨酸 aminotransferase (中高音) ，和有病毒血的持续时间的病毒的遗传型有控制调停房间的免疫的 CD4 (+)/ CD8 (+) 淋巴细胞人口的这些参数。方法：房间计数用用荧光在乙二胺四乙酸小瓶收集的新鲜全血被执行激活的房间 sorter。肝炎 A 病毒(HAV ) RNA 从血浆液被提取，抄录进 cDNA 并且由实时聚合酶链反应确定了并且是 genotyped 的颠倒。结果：在 11 个病人之中， 10 能完全被分析。这些， 3 有严重尖锐肝炎(s -- 啊) 并且剩余物有自我限制尖锐肝炎 A (啊哈) ，在第 4 d 上与有暴发性的疾病(脑病等级 IV ) 的一个病人一起死。中高音水平在啊哈两个都是显著地更高的(1070.9 +/- 894.3；P = 0.0014 ) 并且 s -- 啊(1713.9 +/- 886.3；P = 0.001 ) 与正常控制相比(23.6 +/- 7.2 ) 。在 s 的前凝血酶时间 -- 啊病人(21.0 +/- 2.0；P = 0.02 ) 比在啊哈显著地高(14.3 +/- 1.1；P = 0.44 ) 。在啊哈病人的 CD4 (+)/CD8 (+) 比率(1.17 +/- 0.11；P = 0.22 ) 并且 s -- 啊(0.83 +/- 0.12；P = 0.0002 ) 比在正常健康控制(1.52 ) 看低。有的自我限制盒子达到顶点在分析的开始的病毒的负担当时在 s -- 啊病人这发生在第 15 或第 30 d。在敏锐、严格的组，一耐心的各个属于遗传型 IA，与仍然是 8 个盒子属于遗传型 IIIA。唯一的暴发性的肝的失败大小写属于遗传型 IA。在自我限制感染的全部功课期间收集的 HAV 病毒的负担和中高音价值直接为 s 被相关，但是这不是事实 -- 啊病人。结论：基于小规模的研究， s 的固执地更高的病毒的负担 -- 啊可能由于减少的细胞免疫和溶血。病毒血的持续时间依赖于主人，当病毒的遗传型没在 AVH 和 s 的临床的结果有明显的角色 -- 啊盒子。

High prevalence of hepatitis B-antibody loss and a case report of de novo hepatitis B virus infection in a child after living-donor liver transplantation

AIM To assess the seroprevalence of hepatitis B virus(HBV) immunity among previously vaccinated pediatric liver transplant recipients and present a case report of de novo hepatitis B infection after liver transplantation.METHODS This study focused on children with chronic liver diseases who received primary hepatitis B immunization and had a complete dataset of anti-HBs before and after liver transplantation between May 2001 and June 2017. Medical records were retrospectively reviewed for potential factors relating to HBV immunity loss. RESULTS In total, 50 children were recruited. The mean time from liver transplantation to anti-HBs testing was 2.53 ± 2.11 years. The mean anti-HBs levels before and after liver transplantation were 584.41 ± 415.45 and 58.56 ± 6.40 IU/L, respectively. The rate of nonimmunity(anti-HBs < 10 IU/L) in the participants was 46%(n = 26) at one year, 57%(n = 7) at two years and 82%(n = 17) at > three years following liver transplantation. The potential factors relating to HBV immunity loss after liver transplantation were identified as anti-HBs(P = 0.002), serum albumin(P = 0.04), total bilirubin(P = 0.001) and direct bilirubin(P = 0.003) before liver transplantation. A five-year-old boy with biliary cirrhosis received 4 doses of HBV vaccine with an anti-HBs titer of > 1000 IU/L and underwent liver transplantation; his anti-HBc-negative father was the donor. After liver transplantation, the boy had stenosis of the hepatic artery up to the inferior vena cava anastomosis and underwent venoplasty three times. He also received subcutaneous injections of enoxaparin for 5 mo and 20 transfusions of blood components. Three years and ten months after the liver transplantation, transaminitis was detected with positive tests for HBs Ag, HBe Ag, and anti-HBc(2169.61, 1706 and 8.45, respectively; cutoff value: < 1.00) and an HBV viral load of 33212320 IU/mL.CONCLUSION The present study showed that loss of hepatitis B immunity after liver transplantation is unexpectedly common. In our case report, despite high levels of antiHBs prior to transplantation, infection occurred at a time when, unfortunately, the child had lost immunity to hepatitis B after liver transplantation.

Adiponectin as a novel biomarker for liver fibrosis

Adiponectin is known to play primary roles in the regulation of systemic glucose homeostasis and lipid metabolism. Interestingly, emerging evidence indicates beneficial effects of adiponectin on liver fibrosis; however, the exact mechanisms of this action remain unclear. Herein, we aimed to summarize the recent findings regarding the role of adiponectin in liver fibrogenesis and update the current comprehensive knowledge regarding usefulness of adiponectin-based treatments in liver fibrosis. Adiponectin has been demonstrated to have an anti-fibrotic action in the liver by blocking the activation of hepatic stellate cellmediated adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptoralpha pathways, which in turn diminish the expression of pro-fibrotic genes. In addition, hyperadiponectinemia was noted in patients with various chronic liver diseases(CLDs)-related liver fibrosis. An increase in circulating adiponectin levels was also found to be associated with the development of liver fibrosis, indicating a role of adiponectin as a non-invasive biomarker for predicting the progression of liver fibrosis. It is therefore reasonable to speculate that adiponectin may be developed as a new therapeutic candidate for the treatment of liver fibrosis. Nonetheless, future observations are still necessary to fully elucidate the extent of the effects of adiponectin onliver fibrotic outcomes, in order to modify adiponectin as an anti-fibrotic therapy that would speed up fibrosis reversal in patients with CLD.

Hepatitis C virus genotype 6:Virology,epidemiology,genetic variation and clinical implication

Hepatitis C virus(HCV)is a serious public health problem affecting 170 million carriers worldwide.It is a leading cause of chronic hepatitis,cirrhosis,and liver cancer and is the primary cause for liver transplantation worldwide.HCV genotype 6(HCV-6)is restricted to South China,South-East Asia,and it is also occasionally found in migrant patients from endemic countries.HCV-6 has considerable genetic diversity with23 subtypes(a to w).Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping,there are also now rapid genotyping tests available such as the reverse hybridization line probe assay(INNO-LiPAⅡ;Innogenetics,Zwijnaarde,Belgium).HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes.Based on current evidence,the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk,although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response.In addition,the development of direct-acting antiviral agents is ongoing,and they give high response rate when combined with standard therapy.Herein,we review the epidemiology,classification,diagnosis and treatment as it pertain to HCV-6.

Multiplex real-time RT-PCR for detecting chikungunya virus and dengue virus

Objective:To develop diagnostic test for detection chikungunya virus(CHIKV and Dengue virus (DENV) infection.Methods:We have performed a rapid,accurate laboratory confirmative method to simultaneously detect,quantify and differentiate CHIKV and DENV infection by single-step multiplex real-time RT-PCR.Results:The assay’s sensitivity was 97.65%,specificity was 92.59% and accuracy was 95.82%when compared to conventional RT-PCR.Additionally,there was no cross-reaction between CHIKV,DENV,Japanese encephalitis virus,hepatitis C,hepatitis A or hepatitis E virus.Conclusions:This rapid and reliable assay provides a means for simultaneous early diagnosis of CHIKV and DENV in a single-step reaction.

There is no association between K469E ICAM-1 gene polymorphism and biliary atresia

AIM: To determine whether there was an association between inter-cellular adhesion molecule-1 (ICAM-1) gene polymorphism and biliary atresia (BA), and to investigate the relationship between serum soluble ICAM-1 (sICAM-1)and clinical outcome in BA patients after surgical treatment.METHODS: Eighty-three BA patients and 115 normal controls were genotyped. K469EICAM-1 polymorphism was analyzed using PCR assay. Serum sICAM-1 was determined using ELISA method from 72 BA patients. In order to evaluate the association between these variables and their clinical outcome, the patients were categorized into two groups:patients without jaundice and those with persistent jaundice.RESULTS: There were no significant differences between BA patients and controls in terms of gender, K469E ICAM-1genotypes, and alleles. The proportion of patients having serum sICAM-1 ≥3 500 ng/mL in persistent jaundice group was significantly higher than that in the other group. In addition, there was no association between K469EICAM-1polymorphism and the status of jaundice in BA patients after Kasai operation.CONCLUSION: ICAM-1 possibly plays an important and active role in the disease progression. However, the process is not associated with genetic variation of K469EICAM-1 polymorphism.

Unusual manifestations of gastric inflammatory fibroid polyp in a child

AIM:Inflammatory fibroid polyp (IFP) is a rare benign lesion that may occur throughout the digestive tract. IFP is more commonly found in the antrum of the stomach in particular.It mostly affects adults at the average age of 60 years. These polyps are able to cause abdominal pain, gastrointestinal bleeding, intestinal obstruction or intussusception. In bhis paper we report a case of gastric IFP with unusual presenting features.

Role of serum total sialic acid in differentiating cholangiocarcinoma from hepatocellular carcinoma

AIM:This study was designed to evaluate the clinical application of serum total sialic acid (TSA) in the diagnosis of cholangiocarcinoma (CCA).METHODS: Serum TSA was determined by periodateresorcinol microassay in 69 patients with CCA, 59 patients with hepatocellular carcinoma (HCC), 37 patients with cirrhosis, 61 patients with chronic hepatitis and 50 healthy blood donors.RESULTS: The mean serum TSA concentration in CCA (2.41±0.70 mmol/L) was significantly higher than those of HCC, cirrhosis, chronic hepatitis and healthy blood donors (1.41±0.37 mmol/L, 1.13±0.31 mmol/L, 1.16±0.26 mmol/L, and 1.10±0.14 mmol/L, respectively; P＜0.001). Based on ROC curve analysis, a cut-off point of 1.75 mmol/L discriminated between CCA and HCC with a sensitivity,specificity and accuracy of 82.6%, 83.1%, and 82.8%,respectively.CONCLUSION: Based on our results, serum TSA would be a useful marker for the differential diagnosis of CCA from HCC.

Hepatitis E virus infection: Epidemiology and treatment implications

Hepatitis E virus(HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylatedinterferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable.

Immunization status and hospitalization for vaccine-preventable and non-vaccine-preventable infections in liver-transplanted children

BACKGROUND Infections and associated morbidity and mortality may be more frequent in children who have undergone liver transplant than in healthy children.Immunization strategies to prevent vaccine-preventable infections(VPIs)can effectively minimize this infection burden.However,data on age-appropriate immunization and VPIs in children after liver transplant in Asia are limited.AIM To evaluate the immunization status,VPIs and non-VPIs requiring hospitalization in children who have undergone a liver transplant.METHODS The medical records of children who had a liver transplant between 2004 and 2018 at King Chulalongkorn Memorial Hospital(Bangkok,Thailand)were retrospectively reviewed.Immunization status was evaluated via their vaccination books.Hospitalization for infections that occurred up to 5 years after liver transplantation were evaluated,and divided into VPIs and non-VPIs.Hospitalizations for cytomegalovirus and Epstein-Barr virus were excluded.Severity of infection,length of hospital stay,ventilator support,intensive care unit requirement,and mortality were assessed.RESULTS Seventy-seven children with a mean age of 3.29±4.17 years were included in the study,of whom 41(53.2%)were female.The mean follow-up duration was 3.68±1.45 years.Fortyeight children(62.3%)had vaccination records.There was a significant difference in the proportion of children with incomplete vaccination according to Thailand’s Expanded Program on Immunization(52.0%)and accelerated vaccine from Infectious Diseases Society of America(89.5%)(P<0.001).Post-liver transplant,47.9%of the children did not catch up with ageappropriate immunizations.There were 237 infections requiring hospitalization during the 5 years of follow-up.There were no significant differences in hospitalization for VPIs or non-VPIs in children with complete and incomplete immunizations.The risk of serious infection was high in the first year after receiving a liver transplant,and two children died.Respiratory and gastrointestinal systems were common sites of infection.The most common pathogens that caused VPIs were rotavirus,influenza virus,and varicella-zoster virus.CONCLUSION Incomplete immunization was common pre-and post-transplant,and nearly all children required hospitalization for non-VPIs or VPIs within 5 years posttransplant.Infection severity was high in the first year post-transplant.

Retinoic acid receptor beta promoter methylation and risk of cervical cancer

Cervical cancer is one of the leading causes of death in women worldwide, particularly in developing countries. Human papillomavirus has been reported as one of the key etiologic factors in cervical carcinoma. Likewise, epigenetic aberrations have ability to regulate cancer pathogenesis and progression. Recent research suggested that methylation has been detected already at precancerous stages, which methylation markers may have significant value in cervical cancer screening. The retinoic acid receptor beta (RARβ) gene, a potential tumor suppressor gene, is usually expressed in normal epithelial tissue. Methylation of CpG islands in the promoter region of the RARβ gene has been found to be associated with the development of cervical cancer. To investigate whether RARβ methylation is a potential biomarker that predicts the progression of invasive cancer, we reviewed 14 previously published articles related to RARβ methylation. The majority of them demonstrated that the frequency of RARβ promoter methylation was significantly correlated with the severity of cervical epithelium abnormalities. However, methylation of a single gene may not represent the best approach for predicting disease prognosis. Analyzing combinations of aberrant methylation of multiple genes may increase the sensitivity, and thus this approach may serve as a better tool for predicting disease prognosis.

Elevation of serum urokinase plasminogen activator receptor and liver stiffness in postoperative biliary atresia

AIM To investigate serum urokinase-type plasminogen activator receptor(u PAR) and liver stiffness in biliary atresia(BA) and examine the correlation of circulating u PAR, liver stiffness, and clinical outcomes in postoperative BA children.METHODS Eighty-five post Kasai BA children and 24 control subjects were registered. Circulating u PAR was measured using enzyme-linked immunosorbent essay. Liver stiffness was analyzed using transient elastography.RESULTS BA children had significantly greater circulating u PAR andliver stiffness scores than control subjects(P < 0.001). Circulating u PAR and liver stiffness were substantially higher in jaundiced BA children than non-jaundiced BA children(P < 0.001). In addition, circulating u PAR was positively associated with serum aspartate aminotransferase(r = 0.507, P < 0.001), alanine aminotransferase(r = 0.364, P < 0.001), total bilirubin(r = 0.559, P < 0.001), alkaline phosphatase(r = 0.325, P < 0.001), and liver stiffness scores(r = 0.508, P < 0.001).CONCLUSION Circulating u PAR and liver stiffness values were greater in BA children than healthy controls. The increased circulating u PAR was associated with liver dysfunction in BA. As a consequence, serum u PAR and liver stiffness may be used as noninvasive biomarkers indicating the progression of liver fibrosis in post Kasai BA.

Liver tumors in children with chronic liver diseases

Liver tumors are rare in children,but the incidence may increase in some circumstances and particularly in chronic liver diseases.Most liver tumors consequent to chronic liver diseases are malignant hepatocellular carcinoma.Other liver tumors include hepatoblastoma,focal nodular hyperplasia,adenoma,pseudotumor,and nodular regenerative hyperplasia.Screening of suspected cases is beneficial.Imaging and surrogate markers of alpha-fetoprotein are used initially as noninvasive tools for surveillance.However,liver biopsy for histopathology evaluation might be necessary for patients with inconclusive findings.Once the malignant liver tumor is detected in children with cirrhosis,liver transplantation is currently considered the preferred option and achieves favorable outcomes.Based on the current evidence,this review focuses on liver tumors with underlying chronic liver disease,their epidemiology,pathogenesis,early recognition,and effective management.

Low bone mineral density and the severity of cholestasis in biliary atresia

AIM To investigate the prevalence of osteopenia and osteoporosis in postoperative biliary atresia(BA) children and the association of bone mineral density(BMD) and biochemical parameters in post Kasai BA subjects. METHODS A total of 70 patients with post Kasai BA were enrolled in this prospective study. The patients were classified into two groups according to their jaundice status. BMD of the lumbar spine was analyzed using dual energyX-ray absorptiometry.RESULTS The prevalence of low bone mass(osteopenia and osteoporosis) in BA patients were 51.4%(36 out of 70). Ten patients(35.7%) in the jaundice group and 8 patients(19.0%) in the non-jaundice group had osteopenia. Sixteen patients(57.1%) in the jaundice group and 2 patients(4.8%) in the no jaundice group had osteoporosis. In addition, lumbar spine BMD Z-score was substantially lower in the jaundice BA patients compared with non-jaundice patients. BA subjects with persistent jaundice had significantly lower serum 25-hydroxyvitamin D than those without jaundice. Further analysis revealed that lumbar spine BMD was correlated with age(r = 0.774, P < 0.001), serum albumin(r = 0.333, P = 0.005), total bilirubin(r =-0.476, P < 0.001), aspartate aminotransferase(r =-0.583, P < 0.001), alanine aminotransferase(r =-0.428, P < 0.001), and alkaline phosphatase(r =-0.456, P < 0.001).CONCLUSION Low BMD was associated with biochemical parameters reflecting the severity of cholestasis in post Kasai BA patients.