Hepatocellular carcinoma (HCC) has one of the worst prognoses amongst all malignancies. It commonly arises in patients with established liver disease and the diagnosis often occurs at an advanced stage. Genetic variations, such as single nucleotide polymorphisms (SNPs), may alter disease risk and thus may have use as predictive markers of disease outcome. The aims of this study were (i) to assess the association of two SNPs, rs430397 in GRP78 and rs738409 in PNPLA3 with the risk of developing HCC in a Sicilian association cohort and, (ii) to use a machine learning technique to establish a predictive combinatorial phenotypic model for HCC including rs430397 and rs738409 genotypes and clinical and laboratory attributes. The controls comprised of 304 healthy subjects while the cases comprised of 170 HCC patients the majority of whom had hepatitis C (HCV)–related cirrhosis. Significant associations were identified between the risk of developing HCC and both rs430397 (p=0.0095) and rs738409 (p=0.0063). The association between rs738409 and HCC was significantly stronger in the HCV positive cases. In the best prediction model, represented graphically by a decision tree with an acceptable misclassification rate of 17.0%, the A/A and G/A genotypes of the rs430397 variant were fixed and combined with the three rs738409 genotypes; the attributes were age, sex and alcohol. These results demonstrate significant associations between both rs430397 and rs738409 and HCC development in a Sicilian cohort. The combinatorial predictive model developed to include these genetic variants may, if validated in independent cohorts, allow for earlier diagnosis of HCC.

There are currently no biomarkers that predict hepatocellular carcinoma (HCC) risk in patients with hepatitis C virus (HCV)-related cirrhosis. We investigated the relationships among major histocompatibility complex (MHC) class I chain-related gene A (MICA) polymorphisms, plasma levels of soluble MICA (sMICA), and HCC risk in patients with HCV-related HCC. One hundred fifty-four HCV-related HCC patients, 93 HCV-related liver cirrhosis (LC) cases, and 244 healthy controls, all sampled from the native Sicilian population, were genotyped using the KASP single-nucleotide polymorphism genotyping method. The MICA rs2596542 polymorphism showed that the G/G genotype was significantly more frequent in HCC than control subjects and LC patients (p < 0.005). For MICA rs2596538 polymorphism, the C allele and C/C genotype were significantly more frequent in HCC than in controls and LC cases (p < 0.005), after controlling for potential confounders. These results demonstrate that MICA rs2596542G/G, and particularly the rs2596538C/C polymorphism, are associated with the risk of developing HCV-related HCC in a Sicilian population sample. Importantly, using a machine learning classifier, we found that "age" and either rs2596542 or rs2596538 were important discriminating factors for patients with LC and HCC. Finally, sMICA levels significantly increased during HCV-related liver disease progression, while a significant relationship between both rs2596542 and rs2596538 genotypes and sMICA plasma levels was identified in patients with LC and HCC. In summary, the MICA rs2596538 and rs2596542 variants warrant further research for their clinical validity and utility in relationship to the risk of developing HCV-related HCC in independent populations.

Patients with chronic cryptogenic hypertransaminasemia are at high risk of developing celiac disease (CD). In fact, among the various serological disorders, CD patients at onset frequently present hypertransaminasemia. In this study, we evaluated usefulness and reliability of the new test for antitissue transglutaminase (tTG) in screening for CD as well as in estimating the prevalence of CD in a population of blood donors presenting unexplained hypertransaminasemia at donation. Controls were 180 consecutive healthy donors without hypertransaminasemia and 20 CD patients with known antiendomysial antibody (EmA) positivity. Out of 22,204 blood donors over a period of 2 years, we found 258 subjects (1.2%) with cryptogenic hypertransaminasemia. Four of these subjects (1.5%) were positive for anti-tTG, but only 3 of them were positive for EmA. EmA were negative in all the remaining hypertransaminasemia subjects. In the control groups, anti-tTG antibodies were negative in all the 180 healthy donors without hypertransaminasemia, but positive in all the CD patients known to be EmA positive. 3 of the 4 subjects positive for anti-tTG, including 2 who were also EmA positive, underwent biopsy of the distal duodenal mucosa which showed a picture compatible with CD only in the 2 patients with concomitant EmA positivity. After 3 months of gluten-free diet, the serum transaminase values normalized in these 2 patients. In conclusion, the prevalence of CD in our blood bank population was lower than that reported in other similar studies, but the new test for anti-tTG showed a good sensitivity and reliability, and, therefore, it can be proposed as a first-level test in screening for CD in selected populations such as subjects with hypertransaminasemia.

The administration of cryopreserved platelets (PLTs) may overcome the limits of platelet shortage and availability, especially during some seasons or in specific contexts like rural areas. After in vitro validation studies, ad hoc prepared buffy coat-derived pooled platelet concentrates (BC-PLTs), treated with dimethyl sulphoxide (DMSO) and cryopreserved (CRY BC-PLTs) at-80°C with a modified Valeri method, were transfused in patients with severe thrombocytopenia secondary to chemotherapy for acute leukaemia (AL). Five inpatients were enrolled in the pivotal clinical trial NCT02032134: 4 males and 1 female with a mean age of 71 years (range: 65-80). Four patients were diagnosed with acute myeloid leukaemia and 1 had acute lymphoblastic leukaemia.Transfusion of one Unit of CRY BC-PLTs resulted effective in active bleeding control in two patients without any adverse reaction or concomitant antihaemorrhagic therapies. CRY BC-PLTs met the currently accepted criteria for cryopreserved PLTs, their transfusion in patients with AL was safe. (Clinical trial: NCT02032134).

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