Serum AFP Level Research Articles

Risk factors and prognosis of patients with recurrent hepatocellular carcinoma who undergo liver re-resections

BackgroundManagement of recurrent hepatocellular cancer (HCC) after liver resection is challenging, with unsatisfactory long-term patient outcomes. Liver re-resection, in theory, is a good treatment option. We therefore studied prognosis and risk factors of patients who undergo re-hepatectomy. MethodsWe retrospectively analyzed 103 patients who underwent re-hepatectomy. ResultsThe re-resection postoperative complication rate was 31.1% (32/103). Patients with gross vascular invasion (GVI), cirrhosis, or hepatitis B (HBV) infections not treated with antiviral therapy had higher morbidity than patients without these diseases (per chi-square tests). In bivariate regression analysis, cirrhosis (odds ratio [OR]: 10.308, P = 0.031) and HBV not treated with antiviral therapy (OR: 3.982, P = 0.011) were associated with immediate postoperative morbidity. Median overall survival (OS) after re-resection was 65.0 months (range: 2.1–119.3 months); cumulative OS rates were 1-year: 92.1%, 2-year: 78.2%, and 5-year: 54.4%. Independent risk factors for worse survival were serum AFP level > 20 ng/mL at first resection, portal hypertension (PH) and GVI at recurrence. In the non-PH group, microvascular invasion (micro-VI), GVI and pTNM III–IV disease were associated with poor prognosis; patients with pTNM I–II disease had significantly less micro-VI and GVI than did patients with advanced disease. ConclusionRepeat hepatectomy has favorable long-term outcomes. Cirrhosis and HBV not treated with antiviral therapy were associated with immediate postoperative morbidity. Serum AFP > 20 ng/mL at first resection, PH, and GVI at recurrence are independent prognostic factors. For patients without PH, TNM staging can predict prognosis.

MicroRNA-200c expression is decreased in hepatocellular carcinoma and associated with poor prognosis

Accumulating evidences have shown that microRNA-200c (miR-200c) expression is associated with the prognosis of many types of human cancer. However, the prognostic value of miR-200c in hepatocellular carcinoma (HCC) is still unknown. In the present study, the expression of miR-200c in paired HCC and adjacent non-tumor tissues from 148 patients was determined by quantitative real-time PCR (qRT-PCR), and we analyzed its association with clinicopathological characteristics and prognosis of HCC patients. Our results showed that the expression of miR-200c was significantly decreased in HCC tissues compared with adjacent non-tumor tissues (P < 0.0001). Correlation analysis showed that miR-200c expression was significantly associated with tumor size (P = 0.021), serum AFP level (P = 0.016), TNM stage (P = 0.019) and vein invasion (P = 0.026). Patients with lower miR-200c expression had significantly worse overall survival (OS, P = 0.023) and recurrence-free survival (RFS, P = 0.002). The multivariate Cox regression analysis revealed that miR-200c expression was an independent prognostic factor for OS (hazard ratio (HR) [95% CI] = 2.226 [1.235-4.012], P = 0.008) and RFS (HR [95% CI] = 2.662 [1.618-4.38], P < 0.001). In conclusion, our results suggest that the miR-200c expression was significantly down-regulated and associated with poor prognosis in HCC.

Overexpression of PARPBP Correlates with Tumor Progression and Poor Prognosis in Hepatocellular Carcinoma.

PARP1-binding protein (PARPBP/PARI/C12orf48), a negative regulator of homologous recombination (HR), has been suggested to function as an oncogene in cervical, lung, and pancreatic cancer. To investigate the expression profile of PARPBP and its role in hepatocellular carcinoma (HCC). Using data from the Cancer Genome Atlas and Human Protein Atlas databases, PARPBP expression level and its clinical implication in HCC were identified by t test and Chi-square test. The prognostic value of PARPBP in HCC was evaluated by Kaplan-Meier method, Cox regression analysis, and nomogram. Gene set enrichment analysis (GSEA) was used to screen biological pathways correlated with PARPBP expression in HCC. PARPBP was significantly upregulated in HCC tissues compared with normal liver tissues (P < 0.05). High PARPBP expression was significantly associated with elevated serum AFP level, vascular invasion, poor tumor differentiation, and advanced TNM stage (all P < 0.05). Kaplan-Meier analyses suggested that upregulation of PARPBP was correlated with worse overall survival (OS) and recurrence-free survival (RFS) in HCC. Multivariate analyses further confirmed that PARPBP upregulation was an independent indicator of poor OS and RFS (all P < 0.05). The prognostic nomograms based on PARPBP mRNA expression and TNM stage were superior to those based on the TNM staging system alone (all P < 0.05). Besides, PARPBP DNA copy gain and miR-139-5p downregulation were associated with PARPBP upregulation in HCC. GSEA revealed that "cell cycle," "HR," "DNA replication," and "p53 signaling" pathways were enriched in high PARPBP expression group. PARPBP may be a promising prognostic biomarker and candidate therapeutic target in HCC.

Retraction: The Human Homolog of Drosophila Headcase Acts as a Tumor Suppressor through Its Blocking Effect on the Cell Cycle in Hepatocellular Carcinoma.

The molecular pathogenesis of hepatocellular carcinoma (HCC) is heterogeneous and extremely complex. Thus, for individual molecular targeted therapy, novel molecular markers are needed. The abnormal expression of the human homolog of Drosophila headcase (HECA homo) has been found in pancreatic, colorectal, and oral squamous cell carcinoma. Studies of oral squamous cell carcinoma have also demonstrated that the HECA homo protein can be negatively controlled by the Wnt-pathway and transcription factor 4 (TCF4) and can slow cell division by interacting with cyclins and CDKs. However, the role of HECA in HCC has not been reported elsewhere. Here, immunohistochemical analysis revealed that the downregulation of HECA homo protein occurred in 71.0% (66/93) of HCC cases and was positively correlated with a poorly differentiated grade, high serum AFP level, liver cirrhosis and large tumor size. The expression of HECA homo was detected in five live cell lines. In vitro, the overexpression of HECA homo in HepG2, Huh-7 and MHCC-97H cells could inhibit cell proliferation and colony formation and induce G1 phase arrest. In contrast, the downregulation of HECA homo could promote cell proliferation, colony formation and the cell cycle process. However, neither the overexpression nor downregulation of HECA homo in the three cell lines could affect cell migration or invasion. Collectively, HECA homo is regularly expressed in normal live cells, and the HECA homo protein level is heterogeneously altered in HCC, but the downregulation of HECA homo is more common and positively correlated with several malignant phenotypes. The HECA homo protein can slow cell proliferation to some extent primarily through its blocking effect on the cell cycle. Hence, the HECA homo protein may act as a tumor suppressor in HCC and might be a potential molecular marker for diagnostic classification and targeted therapy in HCC.

Involvement of PI3K/Akt pathway in the protective effect of hesperidin against a chemically induced liver cancer in rats.

Hesperidin is a flavanone glycoside that is found in the Citrus species and showed antioxidant, hepatoprotective as well as anticancer activity. This study investigated the effect of hesperidin on the PI3K/Akt pathway as a possible mechanism for its protective effect against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Adult Wistar rats were divided into Control group (received drug vehicle); DEN group (received 100 mg/L of DEN solution for 8 weeks), and hesperidin + DEN group (received 200 mg/kg body weight of hesperidin/day orally for 16 weeks + DEN solution as DEN group). Our findings showed that the administration of hesperidin significantly decreased the elevation in liver function enzymes, serum AFP level, and oxidative stress markers. Moreover, hesperidin administration suppressed DEN-induced upregulation of PI3K, Akt, CDK-2 protein expression, and preserved the integrity of the liver tissues from HCC formation. In conclusion, the hepatoprotective activity of hesperidin is mediated via its antioxidation and downregulation of the PI3K/Akt pathway.

Activated Wnt signaling promotes growth and progression of AFP-producing gastric cancer in preclinical models.

BackgroundCharacterized by elevated AFP levels in serum, AFP-producing gastric cancer (APGC) is a very special type of gastric cancer (GC) that is difficult to treat and has poor prognosis. However, little is known about the role of AFP in GC, which was investigated in this study with in vitro and in vivo experiments.MethodsAPGC cells were established with lentivirus infection and validated by PCR assay and ELISA in HCG27 and AGS cells. Cell growth, migration, and invasion were determined by CCK8, transwell assays, and animal experiments. RNA sequencing, Western blot, dual-luciferase-reporter assays, and RNA interference were employed to understand mechanisms underlying AFP activity, followed by therapeutic investigations for APGC.ResultsAPGC cells featured significantly increased AFP levels in cellular supernatants. AFP potentiated growth and aggression in GC cell lines and their derived xenografts. Wnt-signaling activation was responsible for AFP function, indicated by decreased Axin 1 and pGSK3β, followed by cascade activation of β-catenin, downstream transcription factors TCF1/TCF7, and the target gene – c-Myc. Wnt-signaling blockade by Axin 1 rescue or pathway inhibitor XAV939 reversed AFP function, suggesting the potential therapeutic value of APGC.ConclusionAFP played a critical role in APGC through activating Wnt signaling, and targeting Wnt pathways might be a promising strategy against APGC.

Transient increases in serum α fetoprotein and protein induced by vitamin K antagonist II levels following proton therapy does not necessarily indicate progression of hepatocellular carcinoma.

Transient increases in α-fetoprotein (AFP) and protein induced by vitamin K antagonist II (PIVKA-II), so-called flares, are frequently observed after treatment of hepatocellular carcinoma (HCC). In the present study, changes in AFP and PIVKA-II levels after proton therapy (PT), and the relationship between the flare phenomenon and clinical response were investigated. In 82 patients with stage I/II HCC (59 with no recurrence and 23 with out-of-field recurrence within 1 year), serum AFP and PIVKA-II levels were measured at 1, 3, 6, 9 and 12 months post-PT. AFP and PIVKA-II flares were defined as a >20% increase from the preceding serum level above 20 ng/ml (AFP) or 40 mAU/ml (PIVKA-II), followed by a >20% drop. Among the 59 patients with no recurrence, 3 (5.1%) had an AFP flare, while 23 (39%) had a PIVKA-II flare. The median time to AFP and PIVKA-II flare peaks was 1 and 6 months, respectively. In 4 patients, PIVKA-II flares were observed twice during follow-up. In 1 patient, AFP and PIVKA-II flares were observed simultaneously at 1 month post-PT. The PIVKA-II level pre-PT was significantly higher in the PIVKA-II flare-positive group compared with that in the flare-negative group (P=0.015, odds ratio 4.3, 95% confidence interval, 1.3-14.0). In the 23 patients with out-of-field recurrence, the median increase rate of PIVKA-II (203%) was higher than that in the PIVKA-II-flare-positive group (111%, P=0.035) and the time to recurrence (median, 9 months) was longer than the time to peak AFP level (1 month) in the AFP-flare-positive group (P=0.033). There was no significant association between flares and clinical response. Increases in AFP and PIVKA-II levels following PT should be assessed with caution to avoid misinterpretation of therapeutic outcome.

The safety of alpha fetoprotein in diagnosis of hepatocellular carcinoma in patients with type 2 diabetes mellitus

Aim: Diabetes mellitus is closely associated with many types of cancer including hepatocellular carcinoma (HCC). Alpha feto protein is still used as a biomarker for HCC worldwide but relation between type 2 diabetes mellitus (T2DM) and AFP is unclear. We aimed to investigate relations between AFP, T2DM and metabolic markers in this study.Material and Methods: 208 HCC patients were enrolled to study. 50 patients had T2DM (T2DM+HCC) and 158 patients were non-diabetic (NDM+HCC). 50 healthy people enrolled to the study as control group. Serum AFP levels were compared between healthy control group, T2DM+HCC group and NDM+HCC group. Serum AFP levels were compared with age, BMI, HgbA1c, fasting plasma glucose level (FPG), serum insulin level and insulin resistance (HOMA-IR).Results: AFP levels were higher in T2DM + HCC group patients according to healthy control group (p0,01). Mean AFP level was 201.97 ± 1093,89 in NDM + HCC group and 43.73 ± 85.67 in T2DM + HCC group. AFP levels were significantly higher in NDM + HCC group according to T2DM + HCC group (p0.05). Serum AFP levels were negatively correlated with increasing age and FPG (p0.05). Conclusion: HCC is an aggressive tumour that usually develops on cirrhotic liver and AFP levels are important for the diagnosis of HCC. Our study showed AFP levels could be significantly lower in the presence of T2DM. This study showed AFP could not be a reliable marker in cirrhosis for screening or diagnosis of the HCC in patients with T2DM.

Detection of Serum Biomarkers In Hepatocellular Carcinoma Patients

Scientific background: HCC has increased significantly in the last decade, as the major risk factors are chronic infections withhepatitis B and C viruses (HBV &amp; HCV), other risk factors involve aflatoxin B1 exposure, pesticides, alcohol consumption, andgenetic defects. New serum tumor markers are required for the diagnosis of HCC instead of alpha-fetoprotein (the most widelyused marker) as it's diagnostic accuracy is poor. Aim: To assess the diagnostic accuracy of serum AFP, AFP-L3, soluble Fas (sFas) and soluble Fas Ligand (sFasL) levels as biomarkers for the diagnosis of HCC. Subjects and Methods: 100 adult patients were selected for this study. Fifty (50) healthysubjects, age and sex-matched, were considered as controls. Routine tests for liver cirrhosis &amp; HCC were done. Serum sFas andsFasL levels were measured using enzyme-linked immunosorbent assay. Results: Serum AFP, AFPL3, sFas, and sFasL levels were significantly elevated in HCC group when compared with other 2 groups. At a cut off level AFP ≥ 20 pg/ml, the sensitivity and specificity were 70 and 77 respectively. Serum sFas had sensitivity and specificity much better than AFPL3 in the diagnosis of HCC. Regarding serum sFasL level for diagnosis of HCC, it had 87% sensitivity, 84% specificity at a cut off level ≥ 17.5pg/ml.Conclusions: The results of this present study clearly demonstrate that serum sFas and sFasL had a better sensitivity and specificity than AFP in differentiating patients with HCC from those with cirrhosis. s FasL could be used as the best reliable biomarkers in HCC resulting from chronic hepatitis C.

Impact of ss18l1 polymorphism in predicting prognosis of hepatocellular carcinoma

Introduction: Synovial sarcoma translocation gene on chromosome 18-like 1(SS18L1) has been found to be associated with hepatocellular carcinoma (HCC) development and progression by chromatic structure. However, the relationships between SS18L1 polymorphism and HCC have not been studied, yet. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of SS18L1 gene are associated with HCC in a Korean population. Method: We genotyped four SNPs (rs6142970, rs6061450, rs6142969 and rs2295207) using direct sequencing in 189 HCC patients and 194 controls. Clinicians were fulfilled detailed clinical features such as cancer size, stage of cancer and radiologic morphology. To analyze the genetic data, SNPAnalyzer, and SNPStats were used. Multiple logistic regression models (codominant, dominant, recessive and log-additive) were performed for odds ratio, 95% confidence interval, and p value. Age and gender as covariates were adjusted to obtain statistical significance. Result: No SNPs of the SS18L1 gene were found to be associated with the risk of HCC development. Next, the relationships between SS18L1 SNPs and the clinical characteristics of HCC were investigated. rs6142970 was associated with tumor size, significantly (p= 0.034) Also, rs6061450 and rs6142969 were associated with HCC stage and tumor size. rs2295207 was associated with serum AFP level, significantly (p=0.042) Conclusion: In conclusion, we found that SS18L1 may have a significant role in predicting the prognosis of HCC. This is the first study to demonstrate that SS18L1 polymorphisms may be associated with susceptibility to HCC in the Korean population.

Pattern of hepatocellular carcinoma recurrence following living donor liver transplantation

Background: The aim of the present study was to identify the pattern of HCC recurrence after LDLT for early detection and management Methods: From April 2003 to October 2014, the record of 60 patients who underwent LDLT for HCC at the National Liver Institute, Menoufia University, Egypt, were retrospectively reviewed. Results: Seven patients (11.7 per cent) had HCC recurrence after LDLT. Pretransplant α-fetoprotein (AFP) > 1000 ng/mL, tumour grade and microvascular invasion were the incriminated risk factors for recurrence. Three patients (42.8 per cent) had intrahepatic and extrahepatic recurrence (lung and bone), two patients (28.6 per cent) had only extrahepatic recurrence in bones and two patients (28.6 per cent) had only intrahepatic recurrence. Management was as follows: two patients (28.6 per cent) had surgical excision of intrahepatic recurrence and extrahepatic metastasis, two patients (28.6 per cent) underwent radiotherapy for bone metastasis, one patient (14.2 per cent) underwent intraoperative radiofrequency ablation for liver recurrence and two patients (28.6 per cent) received sorafenib as medical treatment. The mean time of recurrence was 19.7 months, and mean survival was 29 months. Conclusion: The majority of HCC recurrences after LDLT are extrahepatic and occur mainly in the first 2 years; strict follow up is required during this period. A high level of pretransplant serum AFP and microvascular invasion are risk factors for tumour recurrence and should be taken into account when selecting candidates for LDLT.

Effect of Punica granatum peel and Vitis vinifera seeds on Biochemical Indices in DEN induced Hepatocellular Carcinoma in Rats

Plants have been the source of traditional medicines for many diseases known to mankind. Many materials which are considered as waste products from plants are reservoir of phytochemicals possessing important biological activities. In the current study the hepatoprotective potential of Punica granatum peel and Vitis vinifera seeds were evaluated in rats against diethylnitrosamine (DEN) induced hepatocellular carcinoma. Rats were divided into four groups. The first group served as normal control group, the second group received DEN at a dose of 200 mg/kg body weight by Single intraperitoneal administration. The third one received DEN as in DEN-treated group and co-treated with 400 mg/kg Punica granatum peel extract (EPGP). The final group also received DEN and co-treated with 400 mg/kg Vitis vinifera seeds extract (EVVS). DEN administration to rats resulted in significantly elevated levels of serum AFP, bilirubin, triglycerides, cholesterol and urea. The levels of plasma total protein, albumin and blood glucose were significantly decreased in DEN treated rats. No significant changes were noted in creatinine levels of DEN induced rats. Co-treatment with the Punica granatum peel and Vitis vinifera seed extracts orally for 12 weeks significantly reversed the DEN induced alterations of above mentioned parameters in the serum. The present study indicates that both the selected extracts exhibits good hepatoprotectivity against diethylnitrosamine induced hepatocellular damage in rats.

The evaluation of tumor markers and their impact on prognosis in gallbladder, bile duct, and cholangiocellular carcinomas – a pilot study

Background: The behavior of tumor markers in biliary tract malignancies is not well-known and studied enough. This study analyzed the preoperative serum levels of AFP, CEA, CA 19-9, CA 72-4, TPA, TPS, CYFRA 21.1 in patients with gallbladder carcinoma, bile duct carcinoma (Klatskin) and cholangiocellular carcinoma in relation to the patient prognosis. Methods: The study included 43 patients, who underwent either radical surgical procedure (n = 21) or explorative laparotomy (n = 22) for gallbladder carcinoma, bile duct carcinoma and cholangiocellular carcinoma (24, 8 and 11 patients) between 2003 and 2010 at the Department of Surgery, University Hospital and Faculty of Medicine in Pilsen, Charles University. Overall survival (OS) and disease-free interval (DFI) were computed by Kaplan-Meier method and statistically evaluated using LogRank test. Results: The statistical analysis proved TK as a poor prognostic factor for shorter DFI (p < 0.05) and also OS (p < 0.05) in patients with gallbladder carcinoma treated with radical surgery. TPS was demonstrated as a poor prognostic factor for OS in patients with gallbladder carcinoma (p < 0.05). CEA was proved as a factor of poor OS in patients after explorative laparotomy for all cumulated studied diagnoses (p < 0.05). Conclusion: The results of this study suggested the importance of tumor markers for assessment of prognosis. This work was supported by the National Sustainability Program I (NPU I) Nr.LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic.

Impact of Elevated Second Trimester Maternal Serum Alpha-Fetoprotein on Pregnancy Outcome-A Prospective Observational Study

Introduction: The major goal behind prenatal screening is to identify and intervene in high risk pregnancy. Measurement of second trimester maternal serum alpha-fetoprotein (MSAFP) has been shown to be useful in screening both for Aneuploidies and neural tube defects7-9. Additionally in Pregnancies with normal fetus, high levels of MSAFP is associated with increased risk of adverse pregnancy and fetal outcome. Aim: To determine the association between the second trimester MSAFP and adverse pregnancy outcome. Method: This Prospective observational study was conducted in 200 antenatal women of gestational age between 14-24 weeks, with singleton pregnancy. Determination of maternal serum AFP levels was carried out and were followed till delivery. Fetal outcome was reported in terms of live birth, still birth, neonatal death. Results: The mean age of study subjects with MSAFP?2MoM was slightly higher compared to those with MSAFP>2 MoM and the difference was not statistically significant (P>0.05).The frequency of pregnancy outcomes were as following; 10(5%) Pre-eclampsia, 20(10%)Preterm labour, 7(3.5%)PROM ,18(9%) Oligohydraminos, 2(1%)Still birth.There were significant correlation between Preterm labour, Pre-eclampsia, Oligohydramnios and higher MSAFP levels and was statistically significant. But corelation between PROM, Still birth and MSAFP levels were not significant. Conclusion: Unexplained elevated second trimester MSAFP is associated with adverse pregnancy outcomes such as preeclampsia, oligohydramnios and preterm labour. So it would be worthwhile for screening pregnant women in second trimester for MSAFP, as it would help to identify high risk pregnancies

Expression of TBX3 in Hepatocellular Carcinoma and Its Clinical Implication.

BackgroundHepatocellular carcinoma (HCC) is the fifth most common malignancy in China, and China’s annual number of new cases accounts for about 45% of the world total. This research was aimed to study the expression of TBX3 protein in HCC and exploring its clinical significance.Material/MethodsWe collected tumor tissues and adjacent non-tumoral tissues of 174 patients with HCC undergoing surgical resection. The expression of TBX3 protein in different tissues and cell lines in vitro (LO2, HHL-5, MHC97-L, MHC97-H) was detected by immunohistochemistry or Western blotting, and the relationship between TBX3 expression and clinical data of patients with HCC was analyzed.ResultsThe expression of TBX3 protein in HCC was significantly correlated with histological grade, tumor size, cancer cell metastasis, hepatitis B surface antigen, and the expression of Ki-67 in tumor tissues (P<0.05), and it was positively correlated with serum AFP level (r=0.766, P<0.05). The expression of TBX3 increased with increased histological grade in HCC (P<0.05). Cox regression analysis showed that the expression of TBX3 protein in HCC was an independent risk factor for prognosis (OR=0.524, 95% CI=0.283–0.964). The 5-year survival rate of patients with HCC that highly expressed TBX3 protein was 20.83%, which was significantly lower than the 40.20% rate in patients with low expression (P<0.05).ConclusionsThe expression of TBX3 in HCC patients undergoing surgical resection is high, and its expression increases with the degree of tumor differentiation. It is related to the metastasis of tumor cells and is positively correlated with the serum level of AFP and may affect the survival time of HCC patients undergoing surgical resection.

The expression of CD74 and macrophage migration inhibitory factor protein is upregulated in hepatitis B virus-related hepatocellular carcinoma

Background: Pro-inflammatory cytokine production, such as CD74 and macrophage migration inhibitory factor (MIF) could play an important role in liver cancer following chronic hepatitis B virus (HBV) infection. Methods: The level of CD74 was evaluated by using a capture enzyme-linked immunosorbent assay (ELISA) kit. The level of MIF protein was determined using Human Magnetic Luminex ® Assays on 60 HBV-related hepatocellular carcinoma (HCC) patients. The level of HBV copies was determined by using real-time polymerase chain reaction (RT-PCR). Furthermore, α-fetoprotein (AFP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined by the cobas 6000 analyzer. Results: The mean concentration of CD74 was elevated significantly in the tumor tissues (10.24 ng/mg) when it was compared with non-tumor tissues (3.86 ng/mg). Meanwhile, the level of MIF was 63.49 ng/mg in the tumor tissues, and 45.47 ng/mg in non-tumor samples. We found that elevated CD74 protein expression was associated with an elevated serum AFP level and the AST/ALT ratio; however, an elevated MIF protein level was associated with a lymph node metastasis, serum AFP level and AST/ALT ratio. Only a high level of MIF protein was associated with a short-term survival rate of just months in the HBV-related HCC patients. The elevated expression of MIF protein was associated with HBV ≥10 5 (copies/mL) in liver cancer. The elevated level of MIF protein was associated with the elevated level of CD74 protein in HBV-associated HCC progression. Conclusions: These results suggest that the elevated level of CD74 and MIF cytokines could play a significant role in HBV-related HCC.

Analysis of cognition for regular laboratory monitoring of HBeAg negative with chronic HBV infection

Objective To investigate the cognition influencing factors of regular laboratory monitoring of HBeAg negative in chronic HBV infection, and analyze the related factors of HBeAg conversion. Methods From January 2015 to March 2017, a total of 302 chronic HBV infected patients in Jinin Infectious Disease Hospital were investigated with a questionnaire about disease related cognition.Single factor and multiple factors Logistic regression analysis was used to analyze the influencing factors of regular monitoring behavior and HBeAg conversion.At the same time, 163 cases of HBeAg negative HBV infection were divided into the two groups: regular and irregular monitoring, and disease related laboratory tests and the outcomes were analyzed. Results Psychological pressure(OR=4.339, 95%CI: 1.322-14.243), antiviral treatment(OR=5.149, 95%CI: 1.628-16.283), knowledge of hepatitis B(OR=3.306, 95%CI: 1.108-9.867) and the stability of disease(OR=3.229, 95%CI: 1.094-9.528) were the regular monitoring promoting factors(all P<0.05). Antiviral therapy(OR=0.298, 95%CI: 0.108-0.822), virus gene mutation(OR=0.202, 95%CI: 0.048-0.856), and duration of disease(OR=0.340, 95%CI: 0.122-0.949) were related factors of HBeAg conversion(all P<0.05). The serum levels of ALT, ALB, AFP and HBV-DNA in the HBeAg negative regular monitoring group were (68±34)IU/L, (40±12)g/L, (23.0±5.9)μg/L, (2.0±1.3)copies/mL, respectively, which in the non-regular monitoring group were (126±56)IU/L, (35±10)g/L, (78.0±12.8)μg/L, (3.9±1.7)copies/mL, respectively, the differences were statistically significant (t=2.323, 2.097, 2.109, 2.234, all P<0.05). Conclusion HBeAg negative patients is a key group to monitor and control disease progression.Regular laboratory monitoring is better.Medical staff should enhance patients' cognition education and improve disease control rate. Key words: Hepatitis B virus; Hepatitis B surface antigens; Biosurveillance; Cognition

Overexpression of RALY promotes migration and predicts poor prognosis in hepatocellular carcinoma.

IntroductionRALY plays a critical role in promoting invasiveness and is associated with poor prognosis in different types of cancers. However, the prognostic value of RALY and its precise role in hepatocellular carcinoma (HCC) remain unknown.Materials and methodsWe detected the expression of RALY in 127 clinical HCC tissue samples and seven HCC cell lines by immunohistochemical staining and Western blotting. The prognostic value of RALY expression was assessed using the Kaplan–Meier method. The expression and prognostic value of RALY were also studied by bioinformatics analysis of data from the Gene Expression Omnibus and The Cancer Genome Atlas. The biological influence of RALY on HCC cell lines was studied using proliferation, transwell migration, and invasion assays in vitro.ResultsThe expression of RALY in HCC tissues was significantly higher than that in adjacent normal liver tissues. Abnormally high expression of RALY was associated with tumor size (P=0.031), TNM stage (P=0.026), presurgical serum AFP levels (P=0.025), and vascular invasion (P=0.001). Kaplan–Meier analysis demonstrated that higher expression of RALY correlated with poorer overall survival and disease-free survival in HCC patients. High RALY expression was an independent adverse prognostic factor for overall survival (HR =2.559, 95% CI: 1.710–3.827, P<0.001) and disease-free survival (HR =2.053, 95% CI: 1.384–3.047, P<0.001) in HCC. Moreover, knockdown of RALY expression using a specific shRNA suppressed the proliferation, migration, and invasion capabilities of HCC cells in vitro. Knockdown of RALY expression in HCC cell lines resulted in upregulation of E-cadherin and downregulation of N-cadherin, vimentin, and snail.ConclusionTaken together, our results indicate that RALY represents a biomarker for the prognosis of patients with HCC and highlight the importance of RALY as an oncogene in HCC.

Hepatocellular Carcinoma Presenting as Hemobilia: A Case Report

Introduction Hemobilia from hepatocellular carcinoma (HCC) is rare and is usually noted in established cases of HCC after an invasive procedure. We describe an unusual case of hemobilia causing obstructive jaundice, cholangitis and pancreatitis with subsequent work up revealing HCC. Case report A 61 yr old Hispanic M presented with one day of abdominal pain, N/V, subjective fevers. His PMH was significant for recent right portal vein thrombosis (PVT) and E coli sepsis for which he was on anticoagulation and oral antibiotics. His vitals were stable. Labs were significant for WBC 15 k/μL, Total bilirubin 15.2 mg/dL (direct bilirubin 12 mg/dl), ALP 704 U/L, lipase 3463 U/L, INR 2.7 and Hgb 11.8 g/dL. CT revealed persistence of right PVT, peripancreatic edema and fluid, and intra and extrahepatic biliary dilation with CBD measuring 17mm with hyperdense material within it suspicious for blood (Fig. 1). ERCP with biliary sphincterotomy was performed due to obstructive jaundice and suspected cholangitis. A large and long organized clot was swept from the CBD confirming hemobilia. A 10 mm x 8 cm covered metal stent was placed in the CBD for tamponade effect and to relieve obstruction. A CT angiogram showed a focus of hypervascularity measuring 19 mm on arterial phase within hepatic segment 5 suspicious for a pseudoaneurysm. A subsequent arteriogram showed the right hepatic lesion to be a hypervascular lesion concerning for HCC with no apparent pseudoaneurysm or active extravasation (Fig. 2). Serum AFP level was elevated at 653 ng/ml. Patient was diagnosed with HCC, which likely was the cause of his right PVT and subsequent hemobilia in the setting of anticoagulation. Patient's hospital course was otherwise unremarkable. During subsequent follow up, he has continued to do well. He has declined liver transplant evaluation and is being evaluated for either transarterial chemoembolization or radiofrequency ablation.2271_A Figure 1. Computerized tomography showing hyperdense material within dilated CBD2271_B Figure 2. A hypervascular lesion right hepatic lobe on arteriogramDiscussion HCC related hemobilia is rare and is usually reported in established HCC patients undergoing hepatobiliary procedures. In our case, patient presented with complication related to hemobilia with subsequent diagnosis of HCC. Bleeding usually stops with supportive therapy alone but in persistent or severe bleeding arterial embolization may be needed. ERCP is warranted when biliary obstruction and its complications are evident. Fully covered metal stents can be effective in achieving hemostasis and relieving obstruction.

Impact of DAA-Based Therapy on Alfa-Fetoprotein Level in Chronic Hepatitis C Patients

Introduction: Backgrounds: Chronic hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. High AFP level has been identified as a risk factor for the development of HCC in chronic hepatitis C patients. The aim of this study is to investigate the impact of DAA-based triple therapy on serum AFP levels of patients with chronic hepatitis C. Methods: We reviewed records of 132 consecutive patients with chronic hepatitis C who received DAAbased therapy over past 16 months. Inclusion criteria: patients who completed treatment, had baseline AFP within 3 months of treatment, and AFP within 6 months post-treatment. 54 patients were excluded (52: no AFP level, and 2 patient were lost to follow). Results: 78 patients completed the treatment: age: 24-78 year, 45 males, 33 females. Of these patients: 46 genotype 1, 22 genotype 2, 10 genotypes 3 and 4. All had viral loads, and fibrosis score. 76 patients achieved SVR at 3 months and 6 months pots-treatment. 2 patients relapsed. Conclusion: Discussion: AFP is commonly used for surveillance for HCC. In this review, there was universal and lasting ( beyond 6 months posttreatment) reduction in AFP below 50% of baseline level in all patients s who received treatment even in those who relapsed, and across all genotypes, most pronounced in patients with markedly high pretreatment level and those with documented HCC. This phenomenon supports the evidence that DAA therapy may prevent HCC in hepatitis C patients. Conclusion: DAA therapy of hepatitis C-infected patient effectively reduce the level of AFP and so potentially may prevent HCC in this group of patients2851_A Figure 1. AFP: Pre- and posttreatment