Paisarn Vejchapipat

Association between serum hepatocyte growth factor and survival in untreated hepatocellular carcinoma.

BackgroundHepatocellular carcinoma (HCC) is a common hepatic malignancy worldwide. Its nature of rapid growth results in a grave prognosis. Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, responsible for their proliferation. The aim of the present study was to investigate the prognostic roles of serum HGF in untreated HCC patients.MethodsFifty-five patients with inoperable HCC were studied. The diagnosis of HCC was based on either liver histopathology or imaging evidence of a liver mass, together with elevated serum alpha-fetoprotein. Serum HGF levels of the patients, at the time of diagnosis, were compared to those of 28 healthy controls. All patients received only palliative treatments and were followed up until they died. Comparison of survival curves between patients with a serum HGF level of 1.0 ng/ml or more and those with lower serum HGF was performed, using the log-rank test. Data values are expressed as means and SD.ResultsFifty-one men and four women with inoperable HCC were recruited. The mean age was 54.15 ± 15.34 years. The serum HGF levels in the inoperable HCC patients were significantly higher than those in the controls (0.58 ± 0.43 vs 0.14 ± 0.04 ng/ml; P < 0.001). The patients’ mean survival time was 5.28 ± 6.73 months (range, 0.1–33 months). Serum HGF levels exhibited a negative correlation with the survival time (P = 0.032). In addition, HCC patients with serum HGF levels of 1.0 ng/ml or more had a shorter survival time than the other HCC patients (P = 0.0025).ConclusionsPatients with inoperable HCC had higher levels of serum HGF than the healthy controls, and serum HGF was negatively correlated with the survival time. Serum HGF levels of 1.0 ng/ml or more in HCC patients are suggestive of a grave prognosis, indicating that HGF plays important and active roles in the disease progression. The detailed mechanisms need to be further investigated.

Association of X‐prolyl aminopeptidase 1 rs17095355 polymorphism with biliary atresia in Thai children

Aim:  To investigate XPNPEP1 rs17095355 polymorphism in biliary atresia (BA) patients and to determine whether there is an association between XPNPEP1 gene polymorphism and susceptibility to BA in a Thai population.

Serum adiponectin and transient elastography as non-invasive markers for postoperative biliary atresia

BackgroundBiliary atresia (BA) is a progressive inflammatory disorder of the extrahepatic bile ducts leading to the obliteration of bile flow. The purpose of this study was to determine serum adiponectin in BA patients and to investigate the relationship of adiponectin with clinical parameters and liver stiffness scores.MethodsSixty BA patients post Kasai operation and 20 controls were enrolled. The mean age of BA patients and controls was 9.6 ± 0.7 and 10.1 ± 0.7 years, respectively. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (non-jaundice, TB < 2 mg/dl vs. jaundice, TB ≥ 2 mg/dl) and liver stiffness (insignificant fibrosis, liver stiffness < 7 kPa vs. significant fibrosis, liver stiffness ≥ 7 kPa). Serum adiponectin levels were analyzed by enzyme-linked immunosorbent assay. Liver stiffness scores were examined by transient elastography (FibroScan).ResultsBA patients had markedly higher serum adiponectin levels (15.5 ± 1.1 vs. 11.1 ± 1.1 μg/ml, P = 0.03) and liver stiffness than controls (30.1 ± 3.0 vs. 5.1 ± 0.5 kPa, P < 0.001). Serum adiponectin levels were significantly elevated in BA patients with jaundice compared with those without jaundice (24.4 ± 1.4 vs. 11.0 ± 0.7 μg/ml, P < 0.001). In addition, BA patients with significant liver fibrosis had remarkably greater serum adiponectin than insignificant fibrosis counterparts (17.7 ± 1.2 vs. 9.4 ± 1.1 μg/ml, P < 0.001). Subsequent analysis revealed that serum adiponectin was positively correlated with total bilirubin, hyaluronic acid, and liver stiffness (r = 0.58, r = 0.46, and r = 0.60, P < 0.001, respectively).ConclusionsSerum adiponectin and liver stiffness values were higher in BA patients compared with normal participants. The elevated serum adiponectin levels also positively correlated with the degree of hepatic dysfunction and liver fibrosis. Accordingly, serum adiponectin and transient elastography could serve as the useful non-invasive biomarkers for monitoring the severity and progression in postoperative BA.

Overexpression of survivin and caspase 3 in oral carcinogenesis.

Survivin is an inhibitor of apoptosis protein that inhibits caspase 3 function. While cytoplasmic survivin suppresses apoptosis, nuclear survivin regulates cell division. Little is known about the subcellular localization of survivin in oral carcinogenesis. This study examined the subcellular distribution of these 2 proteins in oral squamous cell carcinoma (OSCC) and premalignant lesions including oral leukoplakia (OL) with and without dysplasia. Expression of survivin and caspase 3 were immunohistochemically analyzed in 114 samples including OSCC, OL with and without dysplasia, and normal oral mucosa (NM). Cytoplasmic and nuclear positive cells were counted separately. The results were presented as the frequency of positive cases. The positive expression rates of cytoplasmic and nuclear survivin in OSCC were significantly higher than in NM, OL with and without dysplasia. NM showed a low rate of cytoplasmic survivin expression compared to OL with and without dysplasia. The numbers of cytoplasmic and nuclear expression of caspase 3 in OSCC were significantly higher than that of NM, OL with and without dysplasia. In conclusion, the overexpression of cytoplasmic survivin in OSCC and premalignant lesions suggest that suppression of apoptosis by survivin occurs at early and late stages of oral carcinogenesis. The elevated expression of nuclear survivin and caspase 3 in OSCC indicate that at the late stage survivin increases cell proliferation whereas caspase 3 promotes apoptosis.

Elevated Serum Bone Morphogenetic Protein 7 Levels and Clinical Outcome in Children with Biliary Atresia

BACKGROUND AND AIM Biliary atresia (BA) is one of the most serious liver disorders in children. The purposes of the present study were to investigate serum levels of bone morphogenetic protein 7 (BMP7) in BA children compared with healthy controls and to evaluate the association between serum BMP7 and the clinical outcome of BA patients post Kasai operation. METHODS Sixty-two BA patients post Kasai operation and 14 healthy controls were enrolled. The patients were divided into two groups according to their serum total bilirubin levels (TB<2, no jaundice vs. TB> or =2 mg/dL, persistent jaundice) and alanine aminotransferase levels (ALT<45, normal ALT vs. ALT> or =45 IU/L, elevated ALT). Serum BMP7 levels were determined by commercial enzyme-linked immunoabsorbent assay. RESULTS The mean serum BMP7 was higher in BA patients compared with that of healthy controls (35.4+/-3.6 vs. 20.6+/-2.7 pg/mL, p=0.002). The BA patients with persistent jaundice had more elevated serum BMP7 levels than those without jaundice (59.5+/-6.5 vs. 20.3+/-1.6 pg/mL, p=0.001). There was also a correlation between serum total bilirubin and serum BMP7 levels (r=0.57, p<0.001). Moreover, the levels of serum BMP7 in BA patients with elevated ALT were significantly higher than those with normal ALT (41.6+/-4.7 vs. 22.4+/-4.2 pg/mL, p=0.003). Additionally, BA patients with portal hypertension had higher increased serum BMP7 levels compared to those without portal hypertension (45.3+/-4.9 vs. 18.7+/-2.8 pg/mL, p<0.001). CONCLUSION The significant increment of serum BMP7 was associated with a deterioration of hepatic function and the progression of liver fibrosis. Serum BMP7 could be used as a prognostic marker to reflect disease severity and monitor disease progression in BA patients post Kasai operation.

+276 G/T single nucleotide polymorphism of the adiponectin gene is associated with the susceptibility to biliary atresia

BackgroundBiliary atresia (BA) is an intractable neonatal inflammatory and obliterative cholangiopathy, leading to progressive fibrosis and cirrhosis. Adiponectin, an anti-inflammatory adipokine, is known to play a possible role in liver diseases. The objective of our study was to determine the relationship between adiponectin gene polymorphisms and BA susceptibility.MethodsA total of 106 BA patients and 107 healthy controls were included in this study. Two single nucleotide polymorphisms (SNPs) of the adiponectin gene, +45T/G (rs2241766) and +276G/T (rs1501299), were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis.ResultsGenotype distributions of +45 T/G and +276 G/T SNPs were seen in the Hardy-Weinberg equilibrium for both BA patients and controls. The frequency of the G/G genotype at +276G/T was significantly higher in BA patients than in the controls (P=0.009). Regarding +45T/ G in BA patients, the frequency of the T/T genotype tended to be lower than in the controls, but the difference was not significant. Moreover, the G allele at +276G/T in BA patients was more common than in the controls (P=0.0043). In contrast, the frequency of the T allele at +45T/G was not significantly different between BA patients and the controls. None of the haplotypes studied was found to significantly influence the risk of BA.Conclusions+276G/T SNP is strongly associated with BA, particularly with the G allele. We postulate that the +276G/T adiponectin gene polymorphism confers increased susceptibility to BA.

Short-term Results of Kasai Operation for Biliary Atresia: Experience from One Institution

BACKGROUND The purpose of this study is to review the short-term outcome of patients with biliary atresia (BA) treated by the Kasai operation at our institution. METHODS Ninety-two BA patients treated by the Kasai operation between January 1996 and December 2002 were reviewed. The diagnosis of BA was confirmed by intraoperative cholangiography. The outcome of treatment was categorized into two groups: jaundice-free (total bilirubin < 2 mg%) and persistent jaundice (>or= 2 mg%). The outcome of Kasai operation was evaluated 1 year after surgery. Data are expressed as mean +/- SD. RESULTS Average age at the time of surgery was 90.26 +/- 36.44 days. Only 22.8% (21/92) of patients had Kasai operation before 60 days of age. Histologically, 49 patients (54.4%) had liver fibrosis at the time of surgery. Of 92 patients, 17 were not included in outcome evaluation as they were less than 1-year postsurgery. Therefore, 75 patients could be evaluated for the outcome. Thirty-eight patients (50.67%) were jaundice-free 1 year after surgery. Liver histology and age at the time of the Kasai operation did not influence early outcome. The most common complication was ascending cholangitis. CONCLUSION Half of our BA patients who underwent Kasai operation were jaundice-free 1 year after surgery. The lack of impact of age and liver pathology on outcome is presumably due to the briefness of the follow-up. In general, our patients underwent Kasai procedure too late. It is therefore important for us to conduct a campaign to highlight the plight of these patients and the urgency of referral for neonates with jaundice.

Serum autotaxin levels correlate with hepatic dysfunction and severity in postoperative biliary atresia

Abstract Objective: To investigate correlation of serum autotaxin and disease severity in biliary atresia (BA). Methods: Eighty postoperative BA patients and 15 controls were recruited. Serum autotaxin levels were determined by enzyme-linked immunosorbent assay. Results: BA patients had greater serum autotaxin and liver stiffness than controls. Serum autotaxin and liver stiffness were markedly elevated in BA patients with jaundice compared to those without jaundice. Furthermore, serum autotaxin was correlated with liver stiffness and biochemical parameters in BA. Conclusions: Elevated serum autotaxin was correlated with hepatic dysfunction in BA. Accordingly, serum autotaxin is a promising biomarker reflecting the severity in BA.

Elevated serum periostin is associated with liver stiffness and clinical outcome in biliary atresia.

Abstract Objective: To analyze serum periostin and liver stiffness in postoperative biliary atresia (BA). Methods: A total of 60 BA patients and 14 controls were enrolled. Serum periostin levels were analyzed by ELISA. Liver stiffness measurement was determined by transient elastography. Results: Biliary atresia patients had significantly higher periostin and liver stiffness values than controls. Serum periostin levels were remarkably increased in BA patients with jaundice compared to those without jaundice. Moreover, serum periostin was correlated with liver stiffness. Conclusions: Serum periostin was associated with liver stiffness in BA. Thus, serum periostin has potential as a parameter reflecting the severity in BA.

Circulating leptin levels and bone mineral density in children with biliary atresia

Aim: To investigate circulating leptin levels in biliary atresia (BA) patients and the association of leptin with bone mineral density (BMD) and the severity of BA.