Phytoextraction efficiency of Pteris vittata grown on a naturally As-rich soil and characterization of As-resistant rhizosphere bacteria.

This study evaluated the phytoextraction capacity of the fern Pteris vittata grown on a natural arsenic-rich soil of volcanic-origin from the Viterbo area in central Italy. This calcareous soil is characterized by an average arsenic concentration of 750 mg kg-1, of which 28% is bioavailable. By means of micro-energy dispersive X-ray fluorescence spectrometry (µ-XRF) we detected As in P. vittata fronds after just 10 days of growth, while a high As concentrations in fronds (5,000 mg kg-1), determined by Inductively coupled plasma-optical emission spectrometry (ICP-OES), was reached after 5.5 months. Sixteen arsenate-tolerant bacterial strains were isolated from the P. vittata rhizosphere, a majority of which belong to the Bacillus genus, and of this majority only two have been previously associated with As. Six bacterial isolates were highly As-resistant (> 100 mM) two of which, homologous to Paenarthrobacter ureafaciens and Beijerinckia fluminensis, produced a high amount of IAA and siderophores and have never been isolated from P. vittata roots. Furthermore, five isolates contained the arsenate reductase gene (arsC). We conclude that P. vittata can efficiently phytoextract As when grown on this natural As-rich soil and a consortium of bacteria, largely different from that usually found in As-polluted soils, has been found in P. vittata rhizosphere.

Comparative analysis of 2 commercial molecular tests for the detection of gastroenteric viruses on stool samples.

OBJECTIVE: Our purpose was to compare the performance of 2 recently introduced molecular tests for the identification of gastrointestinal viral infections. METHODS: One hundred fecal samples from pediatric patients were analyzed using 2 workflows, each including nucleic acids extraction and multiplex Real-Time PCR: Allplex™ GI-Virus Assay and FTD Viral gastroenteritis. The agreement was evaluated calculating Cohen's kappa and applying McNemar's test. RESULTS AND CONCLUSION: Allplex and FTD assays showed 100% overall agreement for Norovirus GI/GII and Sapovirus (κ: 1.00), and 99% for Astrovirus (κ: 0.66). A lower agreement was detected for Adenovirus (89%; κ: 0.72) and Rotavirus (91%, k: 0.53), owing to samples resulted positive only with FTD test. The discrepancies were attributed to a different efficiency of extraction/amplification and to the different Adenovirus serotype specificity of the tests since Allplex detects only AdVF40 and AdVF41. FTD test should be used when non enteric adenovirus could have a clinical significance.

A Phase 2 Study of Galunisertib (TGF-ß1 Receptor Type I Inhibitor) and Sorafenib in Patients With Advanced Hepatocellular Carcinoma.

INTRODUCTION: Inhibition of tumor growth factor-ß (TGF-ß) receptor type I potentiated the activity of sorafenib in preclinical models of hepatocellular carcinoma (HCC). Galunisertib is a small-molecule selective inhibitor of TGF-ß1 receptor type I, which demonstrated activity in a phase 2 trial as second-line HCC treatment. METHODS: The combination of galunisertib and sorafenib (400 mg BID) was tested in patients with advanced HCC and Child-Pugh A liver function without prior systemic therapy. Galunisertib dose was administered 80 or 150 mg b.i.d. orally for 14 days every 28 days in safety lead-in cohorts; in the expansion cohort, all patients received galunisertib 150 mg b.i.d. Objectives included time-to-tumor progression, changes in circulating alpha fetoprotein and TGF-ß1, safety, overall survival (OS), response rate, and pharmacokinetics (PK). RESULTS: Patients (n = 47) were enrolled from 5 non-Asian countries; 3 and 44 patients received the 80 mg and 150 mg b.i.d. doses of galunisertib, respectively. The pharmacokinetics and safety profiles were consistent with monotherapy of each drug. For the 150 mg b.i.d. galunisertib cohort, the median time-to-tumor progression was 4.1 months; the median OS was 18.8 months. A partial response was seen in 2 patients, stable disease in 21, and progressive disease in 13. TGF-ß1 responders (decrease of >20% from baseline) vs nonresponders had longer OS (22.8 vs 12.0 months, P = 0.038). DISCUSSION: The combination of galunisertib and sorafenib showed acceptable safety and a prolonged OS outcome.

Double intestinal duplication and incidental neuroendocrine tumor of appendix, a rare case of acute abdomen.

INTRODUCTION: Intestinal duplication is rarely reported in adulthood and often remains undiagnosed until onset of complications. We describe the case of a 39 year old woman who came to our observation for acute abdomen due to a combination of double intestinal duplication (colon and ileum) and an incidental neuroendocrine tumor of the appendix. MATERIALS AND METHODS: A 39 year old woman who was admitted at with upper abdominal pain. Multisliced spiral CT scan showed a cystic lesion suggestive of an inflammed Meckel's diverticulum.The patient was underwent an urgent explorative laparoscopy. The intraoperative findings revealed a cystic lesion of the anti-mesenteric side of transverse colon, apparently dissectable from the bowel and a second lesion with a strongly adherent and unresectable from the anti-mesenteric aspect of the small bowel. A combined appendectomy was also performed. The histological diagnosis was consistent with a typical intestinal duplication for both intestinal lesionsand an incidental 2mm carcinoid tumor was also found in the appendix. The postoperative course was uneventful and the patient was discharged on p.o. day 5. At the presenttime she is well and following a regular oncologic follow-up. DISCUSSION: The rarity of this case is due to the concomitant presence of an incidental, sincronous, appendiceal NET. The elective treatment is surgical resection. CONCLUSION: Intestinal duplication in the adulthood is extremely rare and may either have an acute presentation as acute abdomen or represents an incidental finding of mass. We suggest that, once the diagnosis is suspected patient must undergo surgery.

SCCA-IC serum levels are predictive of clinical response in HCV chronic hepatitis to antiviral therapy: a multicentric prospective study.

The combination of pegylated interferon (Peg-IFN) and ribavirin is currently the gold standard therapy in patients with HCV chronic infection. The duration of therapy, as well as the therapeutic dosage, depend on the genotype. Identification of the genotype and rapid virological response (RVR) are widely accepted as the most important predictors of clinical outcome during antiviral therapy but to optimize cost-benefits and to reduce possible side effects, further prognostic factors are needed. Squamous cell carcinoma antigens immunocomplex (SCCA-IC) has been reported to be increased in the serum of patients with liver cancer. In this multicentric prospective study, we investigated the serum levels of SCCA-IC in 103 patients with HCV chronic infection. Serum HCV-RNA was detected before the beginning of treatment, after 4, 12, 24 or 48 weeks, and at week 24 during follow-up. RVR, early virological response and sustained virological response (SVR) were assessed following the international guidelines. SCCA-IC levels were higher in responders (238 AU, interquartile difference 130-556 AU) and decreased significantly to 125 AU (70-290 AU). The mean baseline value in nonresponders was 149 AU (86.5-306.5 AU), but after 4 weeks of treatment the serum levels decreased to 115 AU (80-280 AU): the profile of reduction was different between patients with or without a positive SVR. Logistic regression with SVR as dependent variable identified as significant independent variables: the reduction in SCCA-IC after 1 month (OR = 4.82; 95% CI 1.39-16.67; P = 0.131) and a genotype other than 1 (OR = 0.094; 95% CI 0.21-0.42; P = 0.002); sex and age were also significant factors influencing SVR. SCCA-IC seems to be a reliable independent prognostic marker of therapeutic effectiveness in anti-HCV positive patients undergoing antiviral therapy.

Interleukin-28B (IL-28B) single-nucleotide polymorphisms and interferon plus ribavirin treatment outcome in Italian chronically HCV-infected patients.

To determine the single or combined effect of both rs12979860 and rs8099917 SNPs on HCV treatment response, these variants were genotyped in samples from a cohort of 170 patients infected with different HCV genotypes (HCVGT). The favourable rs12979860 CC genotype was found only in patients with sustained or rapid virological responses (SVR/RVR) and at significantly high proportions in HCVGT1/4 SVR patients. A significant association was also found between the rs8099917 TT genotype and SVR in both HCVGT1/4 and HCVGT2/3 groups of patients. In contrast, we found that there was significantly more of the rs8099917 GG genotype in nonresponders (NR) than in SVR patients which suggests a good association of the minor homozygote GG with the lack of treatment response. The combination of rs12979860/rs8099917 CC/TT favourable genotypes was found only in SVR patients and matched the frequency observed for their rs12979860 CC genotypes alone. By contrast, the inverse unfavourable correlate rs12979860/rs8099917 TT/GG genotype was seen more in NR than in SVR patients as observed for the single GG genotype. This study confirms the impact of both rs12979860 and/or rs8099917 IL-28B SNPs on treatment-induced clearance of HCV-RNA and demonstrates that the rs12979860 CC genotype is stronger than rs8099917 TT genotype in predicting a positive treatment response in HCVGT1/4 patients. The unfavourable rs8099917 GG genotype seems to be more important in predicting the failure of treatment response independently from HCV genotype.

Development and specificities of anti-interferon neutralizing antibodies in patients with chronic hepatitis C treated with pegylated interferon-α.

Only limited data are available on the development of neutralizing antibodies (NAB) in patients with chronic hepatitis C (CHC) treated with pegylated interferon-α (PEG-IFN-α). The aim of this study was to evaluate the immunogenicity of PEG-IFN-α when administered to CHC patients who had or had not previously received standard IFN-α therapy. In addition, the specificities of NAB, together with the ability of leucocyte (LE) -IFN-α to re-establish therapeutic responsiveness in NAB-positive patients, were evaluated. NAB were assessed using a quantitative, standardized, virus-induced cytopathic effect assay. The seroconversion rate to PEG-IFN-α was higher in patients who had received previous standard IFN-α treatment than in those treated exclusively with PEG-IFN-α. Also, NAB produced during PEG-IFN-α therapy were unable to neutralize LE-IFN-α entirely, even though they can neutralize several IFN-α subtypes. In addition, the results indicate that a change to LE-IFN-α therapy can be associated with restoration of clinical responses in NAB-positive patients who had become resistant after showing an initial response to PEG-IFN-α treatment. This study emphasizes the importance of evaluating NAB development in CHC patients who become resistant to PEG-IFN-α treatment, and suggests management alternatives for patients who develop NAB.

Relation of C. pneumoniae antibodies to inflammation and atherosclerosclerosis in dialysis patients.

AIM: the aim of this study was to investigate the association between the presence of antibodies to C. pneumoniae, some markers of inflammation and the presence of preclinical atherosclerotic lesions in hemodyalisis (HD) patients treated with different dialytic membranes. METHODS: C. pneumoniae antibodies were measured by microimmunofluorescence in blood samples of 68 chronic HD patients and in 120 healthy blood donors. Intima-media thickness (IMT) of carotid and of femoral arteries, eco-color doppler of sovraortic trunk and lower limb vessels were evaluated. Plasma levels of C-reactive protein (CRP) and terminal complement (C) complex, C5b-9, were measured. RESULTS: HD patients treated by cellulosic membranes have significantly higher plasma levels of C5b-9 and of CRP compared to those treated by synthetic membranes. A significantly higher prevalence of IgG antibodies to C. pneumoniae and also at higher titre was observed in HD patients in comparison to the controls (66% vs. 28%). The carotid artery mean wall thickness was significantly lower in C. pneumoniae seronegative patients than C. pneumoniae seropositive patients. Similar results were obtained for limb arteries. The use of cellulosic membranes, but not synthetic membranes, was associated with higher carotid IMT and this was independent of the C. pneumoniae serology status. CONCLUSION: in addition to known risk factors, the type of dialytic membrane used may contribute to the progression of atherosclerosis lesions in HD patients. Our data strengthen the evidences that C. pneumoniae infection under high inflammatory status might be a further risk factor for progression of atherosclerosis in HD patients, particularly in those treated with cellulosic membranes.

Expression of metalloproteinases MMP-2 and MMP-9 in sentinel lymph node and serum of patients with metastatic and non-metastatic breast cancer.

The objective of this study was to evaluate the expression of MMP-2 and MMP-9 in sentinel lymph node and serum of breast cancer patients in order to evaluate their clinical significance and usefulness as diagnostic tumour markers. Expression of MMP-2 and MMP-9 was performed on sentinel lymph node by immunohistochemistry while gelatine zymography was used to determinate the serum expression. The association of gelatinases with clinicopathological features, were analysed. Metastatic and non-metastatic breast cancer patients and 34 healthy women were involved. Gelatinases expression were significantly higher in metastatic breast cancer in comparison to non-metastatic cancer and the control group both in the sentinel lymph node and serum. Results showed a statistically significant correlation between MMP-2 or MMP-9 and cancer familiality, MMP-9 and CA 15.3 levels, and MMP-9 and grading. This study suggests a clinical utility of these proteolytic markers in malignant tumour, growth, invasion and metastasis in breast cancer.

Immune complexed (IC) hepatitis C virus (HCV) in chronically and acutely HCV-infected patients.

In infected individuals, hepatitis C virus (HCV) exists in various forms of circulating particles which role in virus persistence and in HCV resistance to IFN therapy is still debated. Here, the proportion of HCV bound to immunoglobulin was determined in plasma of 107 chronically infected patients harbouring different HCV genotypes and, for comparison, of six patients with acute HCV infection. The results showed that, in spite of wide individual variability, chronically HCV-infected patients exhibited an extremely high proportion of immune complexed (IC) virus regardless of plasma HCV load and infecting genotype. Moreover, no significant association was found between baseline proportion of IC HCV and response to IFN treatment. Plasma samples collected within 2 weeks of treatment from 20 patients revealed a significant decline of mean IC HCV values relative to baseline that clearly paralleled the decay of total HCV load. In acutely infected patients, circulating HCV was not IC or IC at very low levels only in patients developing chronic HCV infection. Collectively, these findings strengthen the possibility that IC virus could play a critical role in the pathogenesis of HCV infection.

The use of different Peg-interferon alpha-2b regimens plus ribavirin in HCV-1b-infected patients after rapid virological response does not affect the achievement of sustained virological response.

In patients with chronic hepatitis C, rapid virological response (RVR) at week 4 of treatment seems to be strongly associated with a high probability of achieving a sustained virological response (SVR). The aim of this study was to investigate the outcome of different pegylated interferon-alpha2b (Peg-IFN-alpha2b) dosages plus ribavirin (RBV) in patients with RVR. Forty-five naïve patients chronically infected with hepatitis C virus (HCV)-1b started Peg-IFN-alpha2b (1.5 microg/kg/week) in combination with weight-based RBV doses (800-1200 mg/day). Thirty-one patients (68.9%) attained RVR at week 4 of therapy, while four further patients showed negative HCV-RNA values for the first time at week 12 and were considered early virological responders (EVR). The 31 RVR patients were randomized to receive either RBV plus 1.5 microg/kg/week (17 pts) or 1.0 microg/kg/week (14 pts) of Peg-IFN-alpha2b for the remaining 44 weeks. The two groups were matched for age, sex, baseline alanine aminotransferase levels, viral load and fibrosis score. After 6 months of post-treatment follow-up, the prevalence of SVR was 94.1% (16/17) among RVR patients treated with 1.5 microg/kg/week and 92.8% (13/14) in RVR patients treated with 1.0 microg/kg/week (P = not significant). A high-baseline viral load (P = 0.01) and bridging fibrosis/cirrhosis (P = 0.02) negatively influenced the likelihood of achieving RVR. On the contrary, the ability of RVR patients to achieve SVR did not correlate with these baseline characteristics in either of the treatment group. Finally, the SVR rate among EVR patients who responded after more than 4 weeks of treatment was significantly lower than among RVR patients (1/4 = 25%vs 29/31 = 93.5%; P = 0.0058), because of a high prevalence of post-treatment relapse among patients with EVR.

MMP-2, MMP-9, VEGF and CA 15.3 in breast cancer.

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of extracellular matrix degrading proteinases. Owing to their matrix-degrading abilities and high expression in advanced tumours, MMPs were originally implicated in cancer progression, invasion and metastasis. PATIENTS AND METHODS: In this study, the correlation was determined between the expression of gelatinases (MMP-2 and MMP-9) in the sera of breast cancer patients from zymographic analysis and serum concentrations of VEGF and CA 15.3, before surgery and after 1 and 6 months; the association of both markers with clinicopathological features including histological type, stage of disease and estrogen (ER) and progesterone (PgR) receptors status were also analysed. In all, 88 breast cancer patients and 20 healthy women were involved in this study. RESULTS: No statistically significant correlation between pro MMP-2, pro MMP-9, VEGF and CA 15.3 serum levels was found (p>0.05). In breast cancer patients, a significant decrease of the pro MMP-2 serum expression 1 month after surgery with respect to serum levels before surgery (p=0.0008) was evident, as well as of CA 15.3 serum levels at baseline and after 1 month (p=0.017). Moreover a strong decrease of pro MMP-9 serum levels was found in 88 breast cancer patients after 1 month (p=0.028) and after 6 months (p =0.009) from surgery. On the other hand, no significant differences in the serum levels of VEGF, CA 15.3, pro MMP-2 or pro MMP-9 between 88 breast cancer patients preoperatively and 20 healthy women as controls were found. Our findings did indicate a significant positive association between higher preoperative levels of CA 15.3 and progression of disease (p=0.03), as well as a longer disease-free survival in patients who exhibited a decrease of serum pro MMP-9 expression compared to other biomarkers. No relationship between these four markers and the main clinical and pathological parameters was found. CONCLUSION: The present study failed to demonstrate any association between serum levels of MMPs, VEGF and CA 15.3 and well-known clinicopathological characteristics of breast carcinoma, while demonstrating the prognostic value of CA 15.3 and pro MMP-9 in the follow-up of breast cancer patients.

Rationale for new drugs targeting the tissue microenvironment in patients with HCC.

A better knowledge of the mechanisms underlying hepatocellular carcinoma (HCC) growth and spread is essential to improve the available treatment options. So far, the only therapies available for HCC are mainly based on tumor-destructive approaches, whereas no therapies are available to consolidate these invasive therapies or to cure the tumor. The fact that HCC develops on cirrhotic liver strongly limits the use of common anti-cancer drugs, but the need to find new therapies is strongly felt by clinicians. A large body of evidence suggests that the tissue microenvironment represents a potential target for therapies. Consistently, biological therapies such as inhibitors of the epithelial growth factor receptor (EGFR), are currently under investigation. Unfortunately, there is a discrepancy between the very promising experimental data and the results obtained in patients, although limited sample sizes and advanced stage of the disease could be important factors hampering a reliable judgment of the efficacy of such drugs. Nevertheless, a better identification of the molecular pathways involved in drug effectiveness as well as in HCC tumor progression indicates that the tissue microenvironment likely harbors the solution to the problem. In this review the role and the rationale of using biological drugs to target the microenvironment is discussed, taking into consideration new experimental advances in the field.

Tyrosine kinase inhibitors: a potential approach to the treatment of hepatocellular carcinoma.

The increasing number of patients with hepatocellular carcinoma (HCC) and the highly unfavourable prognosis of the disease are two important reasons why more effort needs to be devoted to investigating other therapies able to block or reduce tumor progression and cancer metastasis. The underlying cirrhosis on which HCC develops limits the use of common chemotherapies, mainly because of their toxicity. Recently, great attention has been paid to a family of molecules that inhibits the tyrosine kinase (TK) receptors, because of their relevant role in activating intracellular pathways responsible for several biological activities of the HCC cells. In particular, proliferation, invasion, survival, apoptosis, are regulated by Erk1/2 and Akt pathways, that can be considered for this reason as potential therapeutic targets. Therefore, the idea is to fight HCC by blocking the molecular mechanisms exploited by the cancer to develop and to metastasize. The epithelial growth factor and the vascular endothelial growth factor receptors (EGFR and VEGFR, respectively) have been identified as the major targets for these new therapies. In this review the biological role of both growth factors in HCC will be discussed, together with the use of anti-EGFR and anti-VEGFR. The preliminary results obtained in vitro or in "in vivo" experimental models have been very promising, whereas the few studies conducted in patients have been not comparably satisfactory. This could be because of the limited number of patients and of their advanced stage of HCC, nevertheless the possibilities of using this family of drugs should be further explored, together with aspects contributing to a better understanding of the molecular mechanisms driving HCC progression.

Endometriosis is characterized by an impaired localization of laminin-5 and alpha3beta1 integrin receptor.

Endometriosis is an estrogen-correlated benign disease characterized by a marked ability of endometrial-like cells to invade and proliferate outside uterine cavity, resembling for some invasive aspect the cancer growth. The molecular mechanisms regulating endometrial cell invasiveness are mostly unknown, although interactions between extracellular matrix (ECM) proteins and their transmembrane receptors, integrins, are likely to play a central role. In particular, laminin (Ln)-5 could be closely involved, as it is in cancer. We have investigated the expression of Ln-1, Ln-5, and collagen IV (Coll IV) ECM proteins and their receptors, alpha3beta1 and alpha6beta4 integrins, in atrophic, proliferative, and secretive endometrium and in endometriosis. The results show that Ln-5, but not Ln-I and Coll IV, is altered in secretive endometrium as well as in endometriosis tissues. No alterations are observed in atrophic or proliferative endometrium. Consistently, the polarization of both integrin subunits alpha3 and beta1, but not alpha6 and beta4, is altered in secretive endometrium and endometriosis tissues, but not in atrophic and proliferative endometrium. These results seem to suggest that Ln-5 and alpha3beta1 could be involved in the invasive mechanism of endometriosis. The altered expression of Ln-5, by upregulating matrix metalloproteases activity, suggest an invading process similar to that of many cancer processes.

Single hepatocellular carcinoma ranging from 3 to 5 cm: radiofrequency ablation or resection?

BACKGROUND: The optimal therapy for hepatocellular carcinoma (HCC) is transplantation. For all those patients not eligible for transplantation (or on the waiting list) among the treatments of choice used more frequently in recent years are resection (RES) and radiofrequency ablation (RFA). RFA is less efficacious for HCC ranging over 3 cm. The aim of this study was to compare RFA to RES in a restricted cohort of patients with a single naive HCC ranging from 3 to 5 cm in size and without end-stage liver disease. PATIENTS AND METHODS. A total of 102 patients who had never been treated before were enrolled. Those patients whose HCC position would have required too much parenchymal loss at RES (central or close to main vascular structures) were treated with RFA (n=60), and the others underwent RES (n=42). The two groups were similar for HCC size and liver disease status. The outcome was considered in terms of overall survival (OS) and disease-free survival (DFS) calculated by the Kaplan-Meier method. Differences among groups were validated by log-rank test. RESULTS: The RES group seemed to present a better long-term OS (91%, 57%, and 43% vs 96%, 53%, and 32% at 1, 3, and 5 years, respectively) and DFS (74%, 35%, and 14% vs 68%, 18%, and 0%, respectively) but there was no statistical significance. Age, gender, virus etiology, HCC size and alpha-fetoprotein levels did not correlate with survival. Patients with recurrence within the first 12 months after treatment showed a worse long-term survival (p=0.011). Patients in Child-Pugh class B had poor prognoses compared with those in class A (p=0.047). CONCLUSION: Even if RES seemed to promise better long-term results, in the medium term this difference had no statistical significance. Survival in this series was more closely related to the stage of the underlying liver disease than to treatment (RES/RFA).

Clinical outcomes of bosentan in pulmonary arterial hypertension do not correlate with levels of TIMPs.

BACKGROUND: Matrix metalloproteinases (MMP) and their inhibitors, tissue inhibitors of metalloproteinases (TIMP), are involved in tissue inflammation and fibrotic processes. Treatment with bosentan has been shown to improve the clinical outcome of patients with pulmonary arterial hypertension (PAH) with and without association with systemic sclerosis (SSc), and also to modulate the serum levels of matrix metalloproteases-9. We measured TIMP-1 and TIMP-2 in the serum of patients with SSc with and without PAH treated with long-term bosentan compared with healthy donors (HD). MATERIALS AND METHODS: Serum samples from HD (n = 16) and patients with SSc (n = 35), including patients with SSc without PAH (n = 23) and patients with PAH (n = 12), were analyzed using enzyme-linked immunosorbent assays (ELISAs) for total TIMP-1 and TIMP-2. RESULTS: Both mean TIMP-1 and TIMP-2 levels were significantly increased in patients with SSc compared with HD, but no differences were observed between patients with SSc with and without PAH. In the eight bosentan-treated patients, TIMP-1 and TIMP-2 levels did not change during 1 year of treatment, while bosentan increased the 6-min walking distance by 136 meters after 1 year, as well as clinical outcomes. CONCLUSIONS: Increased levels of TIMP-1 and TIMP-2 in patients with SSc compared with HD suggest that the inhibition of proteolysis allows the accumulation of ECM proteins. As bosentan does not stimulate TIMPs, it appears to favour proteolytic imbalance and to increase the turnover of ECM proteins.

New frontiers in biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma represents the fifth most frequent cancer in the world; it commonly occurs on cirrhotic liver. Prognosis and survival are still poor, mainly because of diagnosis at a late stage and/or recurrence of the disease. For this reason, surveillance strategies are widely used to screen for early occurrence of cancer in populations at risk. Alpha-foetoprotein is so far the only serological marker available, but its diagnostic accuracy is unsatisfactory because of low sensitivity despite reliable specificity. For this reason, new biomarkers for the diagnosis of hepatocellular carcinoma are in strong demand by clinicians. In this review, we will focus on new biomarkers currently under investigation, but also on still newer, very promising biomarkers that seem to significantly improve diagnosis.