Clinical Significance of Annexin A4 as a Biomarker in the Early Diagnosis of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent cancer worldwide. Early detection of HCC is crucial to improve prognosis and survival. Nearly 30 % of HCC patients present with normal serum alpha fetoprotein (AFP), which highlights the need for new biomarkers for HCC. Annexin A4 (ANXA4) is one of the annexin family with high expressions found in gastric, liver, lung, colorectal and ovarian cancers. AIM: to evaluate the clinical significance of ANXA4 in the early diagnosis of HCC. METHODS: Thirty patients with hepatitis C virus (HCV) related HCC were enrolled in this study. They were stage A according to Barcelona Clinic Liver Cancer (BCLC) staging and they were grade A or B according to Child Pugh Classification. Twenty patients with HCV-related liver cirrhosis and 20 healthy persons seronegative for both HCV and HBV served as control group. ANXA4 and AFP were measured in serum of all cases. RESULTS: Serum ANXA4 level was significantly higher in HCC patients compared to patients with liver cirrhosis and healthy controls (188, IQR 42-428 and 23, IQR 24-33 and and 21, IQR 22-24 ng Ì· ml, respectively). By using the ROC curve, the area under the curve of ANXA4 was 0.972 and the best cut-off value was115 ng/ml, with sensitivity 95% and specificity 80%. CONCLUSION: The serum level of ANXA4 might be a good biomarker for the early detection of HCC.
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Clinical significances and diagnostic utilities of both miR-215 and squamous cell carcinoma antigen-IgM versus alpha-fetoprotein in Egyptian patients with hepatitis C virus-induced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It has been widely established that the early detection of HCC enables more treatment options with improvements in prognosis and survival. OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of both circulating miR-215 and squamous cell carcinoma antigen-IgM (SCCA-IgM) as serum biomarkers for HCC by examining their diagnostic sensitivity, specificity, accuracy, and predictive values in hepatitis C virus (HCV)-induced HCC patients. SUBJECTS AND METHODS: This study included 60 patients with HCV-related HCC. In addition, 60 patients with HCV-related liver cirrhosis (LC) and 60 apparently healthy subjects were involved, and served as diseased and healthy control groups, respectively. The relative expression levels of miR-215 were detected using quantitative real-time PCR. SCCA-IgM levels in serum were measured by enzyme immunoassay. We used receiver operating characteristic (ROC) curve to calculate the diagnostic accuracy against alpha-fetoprotein (AFP). RESULTS: Relative miR-215 expression levels increased the most in HCC patients compared to that in healthy or diseased controls (P<0.001). Serum concentration of SCCA-IgM was significantly higher in HCC group than that in the two control groups. We performed multivariate analysis using AFP level, focal lesion size, and portal vein thrombosis as independent variables. ROC curves showed that the optimum diagnostic miR-215 cutoff value for identifying HCC patients from cirrhotic ones was 417 (sensitivity, 97%; specificity, 91%) and for SCCA-IgM was 95 AU/mL (sensitivity, 92%; specificity, 98%). Moreover, the superiority of both miR-215 and SCCA-IgM to AFP is obvious in our study and this superiority is more evident in distinguishing HCC with AFP levels <200 ng/mL and HCC patients with small-sized focal lesions from cirrhotic patients. CONCLUSION: Cell-free miR-215 and serum SCCA-IgM could be used for early diagnosis of HCC either each one as a single marker or with AFP complement measurement.

Cystatin C: a predictor of hepatorenal syndrome in patients with liver cirrhosis.

BACKGROUND: Recent studies suggest that serum cystatin C (CysC) is a more sensitive marker of renal functions than serum creatinine (Cr). AIM: Evaluation of the clinical significance of cystatin C as a predictor of hepatorenal syndrome (HRS) in patients with liver cirrhosis, ascites, and normal serum Cr level. METHODS: Eighty patients with cirrhotic ascites were enrolled in this study (53 men and 27 women; age: 59.5 ± 7.5 years). All patients were subjected to full clinical assessment and laboratory investigations focussing on renal functions, glomerular filtration rate, and measurement of serum cystatin level. RESULTS: The Serum Cr and CysC levels were 1.04 ± 0.1 and 1.8 ± 0.8 mg/L, respectively. HRS developed in 18 patients during the follow-up period (6 months). Type 1 HRS was found in 5 patients and type 2 HRS was found in 13 patients with no significant difference between both types regarding baseline characteristics. Age (p < 0.001), albumin (p < 0.001), sodium (p < 0.005), cystatin C (p < 0.001), and e-GFRMDRD (estimated glomerular filtration rate-modification of the diet in renal disease) (p < 0.007) were significant dependent predictive factors for the development of HRS. The CysC level was the most independent predictive factor for HRS (OR, 2.1; 95% CI, 0.75-0.97; p < 0.002). Eighteen patients died during the follow-up period. Age (p < 0.001), INR (p < 0.001), e-GFRMDRD (p < 0.03), sodium (p < 0.01), MELD score (p < 0.05), albumin (p < 0.001), and CysC (p < 0.001) levels were significant dependent factors for predicting mortality. CysC (OR, 5.3; p < 0.006) level and INR (OR, 1.01; p < 0.006) were the most independent factors for predicting mortality. CONCLUSION: Serum CysC level may be considered a predictor of HRS and mortality in patients with liver cirrhosis and ascites.