https://www.medigraphic.com/pdfs/hepato/ah-2014/ah146c.pdf

Role of SERPINB3 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) surveillance lacks a reliable biomarker. Alpha-fetoprotein (AFP) is the most widely used. However, not all HCCs secrete AFP. AFP may be elevated with cirrhosis in the absence of HCC. Serum alpha-L-fucosidase (AFU) and squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IgM) were found to be useful markers in diagnosing HCC. SCCA-IgM and AFU were assessed by ELISA technique; AFP was measured by enzyme chemiluminescence in serum of 40 patients with HCC, 30 patients with liver cirrhosis, and 20 healthy control participants to compare their accuracy in early diagnosis of HCC. Serum SCCA-IgM and AFU levels were significantly elevated in HCC group compared to cirrhotic group (P value<0.001 and <0.001, respectively). Receiver operating characteristic curve showed the optimal cutoff value for SCCA-IgM was 233 AU/ml with sensitivity 87.5% and specificity 66% and for AFU was 25 U/L with sensitivity 87.5% and specificity 98%. AFP cutoff value was 48 ng/mL with sensitivity of 70% and specificity of 53.3%. The simultaneous determination of AFP and SCCA-IgM activity increased the sensitivity to 92.5% and specificity to 62.1%. There were positive significant correlations between SCCA-IgM and each of AFU (r=0.296, P=0.005) and AFP (r=0.284, P=0.007) and no correlation between AFP and AFU. All markers did not correlate with the tumor size or affected by the Child score. The significant difference between SCCA-IgM and AFU levels among HCC and cirrhotic patients suggests their use as potential diagnostic tools and allows identifying a new group of HCC patients even in the absence of elevated AFP.

Evaluation of squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM) and alpha-L-fucosidase (AFU) as novel diagnostic biomarkers for hepatocellular carcinoma.

Background & aims Squamous cell carcinoma antigen (SCCA) and its immune complex (SCCA-IgM) have been proposed for use in the screening of hepatocellular carcinoma (HCC). We conducted a meta-analysis to evaluate the diagnostic performance of SCCA and SCCA-IgM and of both combined with alpha-foetoprotein. Methods After a systematic review of the relevant studies, the sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio (DOR) and area under curve (AUC) for the diagnosis of HCC were pooled using bivariate meta-analysis. Hierarchic summary receiver operating characteristic curves were used to summarize the overall test performance. Bivariate boxplots were used to confirm whether the threshold effect existed. A Fagan nomogram was used to assess the clinical utility. Heterogeneity was explored by sensitivity analysis, univariable meta-regression and subgroup analysis. Results Eleven studies that had HCC diagnosis as their purpose were ultimately included in the quantitative analysis. The summary estimates were as follows: SCCA (AUC: 0.80 [95% CI: 0.76-0.83]) and SCCA-IgM (AUC: 0.77 [95% CI: 0.74-0.83]) demonstrated similar diagnostic performance, while a combination of AFP and SCCA-IgM had an AUC of 0.90 (95% CI: 0.87-0.92) and a DOR of 22.87 (95% CI: 8.38-62.40). Meta-regression showed that patient selection, cut-off values, reference standards and tumour biopsy as the diagnostic method significantly influenced the heterogeneity of the included studies. Conclusions Both SCCA and SCCA-IgM showed a moderate diagnostic accuracy for HCC screening; the combination of SCCA-IgM and AFP is the best diagnostic option.

Diagnostic accuracy of SCCA and SCCA‐IgM for hepatocellular carcinoma: A meta‐analysis

Squamous cell carcinoma antigen-IgM is associated with hepatocellular carcinoma in patients with cirrhosis: A prospective study

Introduction: Hepatocellular carcinoma (HCC) develops in about 3–4% of cirrhotic patients every year. The squamous cell carcinoma antigen (SCCA) has been found elevated in liver cancer specimens by...

Circulating SCCA-IgM complex is a useful biomarker to predict the outcome of therapy in hepatocellular carcinoma patients

Aberrant Squamous Cell Carcinoma Antigen (SCCA) expression is an early hepatocarcinogenetic event and circulating SCCA-IgM complexes are elevated in most HCC patients. We evaluated whether serum SCCA-IgM levels can identify HCV +ve cirrhotic patients at low HCC risk. In this retrospective study we enrolled 29 cirrhotic patients in whom serum SCCA-IgM was measured 8 - 69 months (median 31) before HCC diagnosis, and 28 cirrhotic patients who remained HCC- free, with SCCA-IgM measured 15 - 68 months (median 48) before the study end. The best discriminating value of SCCA-IgM was calculated and tested in predicting HCC diagnosis within 12, 24 and 36 months. Sensitivity analysis, considering different HCC incidence, was conducted to identify the patient subgroup with an annual cancer risk below the threshold of a cost-effective semiannual surveillance with ultrasound. Cumulative HCC incidence at 12, 24 and 36 months was 7.0%, 15.7% and 26.3%, respectively. SCCA-IgM levels were higher in HCC than in cirrhotic patients [median: 381 (95% C.I.: 50 - 5289) vs. 100 (70 - 493) AU/mL, P = 0.005]. The SCCA-IgM value ≤ 200 AU/mL accurately identified patients at low risk of HCC development in the subsequent year (sensitivity 75%, specificity 62%, positive predictive value 13% and negative predictive value 97%). Considering an annual HCC incidence ≤ 3%, patients with SCCA-IgM ≤ 200 AU/mL (60% of the whole patients) had an HCC risk below the accepted threshold of a cost-effective surveillance (1.5%). In conclusion, provided that our provocative results are confirmed in larger 
studies, SCCA-IgM serum measurement could permit implementation of a two step (with different costs) surveillance: an initial serological surveillance, based on the annual monitoring of this biomarker, and the conventional surveillance by semiannual US when SCCA-IgM becomes >200 AU/mL. This could improve the cost/effectiveness of surveillance of HCV infected patients at risk of HCC.

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Serum SCCA-IgM as a Predictor of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Epizootic haemorrhagic disease virus (EHDV) is a member of the Orbivirus genus in the Reoviridae family, and it is the etiological agent of an arthropod-transmitted disease that affects domestic and wild ruminants. Due to its significant economic impact, many attempts have been done in order to develop diagnostic immunoassays mainly based on the use of the viral protein 7 (VP7), that is, the immunodominant serogroup-specific antigen. In this work, a recombinant VP7 (recVP7) of EHDV serotype 2 was produced in a baculovirus system, and after purification using ion metal affinity chromatography, we obtained a high yield of recombinant protein characterized by a high degree of purity. We used the purified recVP7 as reagent to develop a competitive enzyme-linked immunoassay (c-ELISA), and we tested the presence of EHDV antibodies in 185 dromedary camel serum samples. The c-ELISA showed good performance parameters in recognising positive sera of naturally EHDV-infected dromedary camels; in particular, our developed test reached 85.7% of sensitivity, 98.1% of specificity, 93% of accuracy, and a high agreement value with results obtained by the commercial ELISA kit (Cohen's kappa value of 0.85) that we adopted as the reference method. This c-ELISA could be a useful screening test to monitor the virus spread in camels that are sentinel animals for endemic areas of disease.

Development of a Competitive Enzyme-Linked Immunosorbent Assay Based on Purified Recombinant Viral Protein 7 for Serological Diagnosis of Epizootic Haemorrhagic Disease in Camels

Immunogenicity and safety studies of an inactivated vaccine against Rift Valley fever.

Bluetongue virus (BTV) is the etiologic agent of bluetongue (BT), a viral WOAH-listed disease affecting wild and domestic ruminants, primarily sheep. The outermost capsid protein VP2, encoded by S2, is the virion’s most variable protein, and the ability of reference sera to neutralize an isolate has so far dictated the differentiation of 24 classical BTV serotypes. Since 2008, additional novel BTV serotypes, often referred to as “atypical” BTVs, have been documented and, currently, the full list includes 36 putative serotypes. In March 2015, a novel atypical BTV strain was detected in the blood of asymptomatic goats in Sardinia (Italy) and named BTV-X ITL2015. The strain re-emerged in the same region in 2021 (BTV-X ITL2021). In this study, we investigated the pathogenicity and kinetics of infection of BTV-X ITL2021 following subcutaneous and intravenous infection of small ruminants. We demonstrated that, in our experimental settings, BTV-X ITL2021 induced a long-lasting viraemia only when administered by the intravenous route in goats, though the animals remained healthy and, apparently, did not develop a neutralizing immune response. Sheep were shown to be refractory to the infection by either route. Our findings suggest a restricted host tropism of BTV-X and point out goats as reservoirs for this virus in the field.

/pdf/intravenous-infection-of-small-ruminants-suggests-a-goat-34q82mm0.pdf

Intravenous Infection of Small Ruminants Suggests a Goat-Restricted Host Tropism and Weak Humoral Immune Response for an Atypical Bluetongue Virus Isolate

Lilia Testa

Papers

Serum SCCA-IgM as a Predictor of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Development of a Competitive Enzyme-Linked Immunosorbent Assay Based on Purified Recombinant Viral Protein 7 for Serological Diagnosis of Epizootic Haemorrhagic Disease in Camels

Immunogenicity and safety studies of an inactivated vaccine against Rift Valley fever.

Intravenous Infection of Small Ruminants Suggests a Goat-Restricted Host Tropism and Weak Humoral Immune Response for an Atypical Bluetongue Virus Isolate