Veronica Vanin

Diagnostic and prognostic role of SCCA-IgM serum levels in hepatocellular carcinoma (HCC).

The serpin squamous cell carcinoma antigen complexed with IgM (SCCA‐IgM) has been reported as a promising serological marker for hepatocellular carcinoma (HCC). We aimed to further evaluate SCCA‐IgM diagnostic accuracy and to determine its prognostic role.

BCLC stage B hepatocellular carcinoma and transcatheter arterial chemoembolization: a 20-year survey by the Italian Liver Cancer group

Significant proportion of Hepatocellular Carcinoma (HCC) cases are diagnosed in stage B of Barcelona Clinic Liver Cancer (BCLC) algorithm, in which the standard of care is Transcatheter Arterial ChemoEmbolization (TACE). We aimed to ascertain adherence to current guidelines, survival and prognostic factors in BCLC stage B patients.

Liver transplantation for hepatocellular carcinoma in clinical practice: the lesson from a 20-year multicentre experience in Italy.

Introduction Hepatocellular carcinoma (HCC) is an established indication for liver transplantation (LT), but the selection criteria and priority are still debated. Aims To ascertain the number and features of patients with HCC who undergo transplantation in a Western country, the number of patients eligible for LT according to the American Association for the Study of Liver Diseases (AASLD) guidelines, the number of patients who actually undergo transplantation and whether adherence affects survival. Methods This is a retrospective analysis from a multicentre Italian database of 2042 cases of HCC, recruited prospectively and consecutively. Kaplan–Meier (log rank) and Cox multivariate analysis estimated survival. Results Patients who had undergone transplantation (50, 2.5%, with no change over time) had a median survival of 133 months, significantly influenced by the number of lesions and alpha-fetoprotein levels, which were found to be independent predictors of survival on multivariate analysis. Milan criteria were fulfilled in 68%, impacting on survival, whereas 48% fulfilled AASLD guidelines, without such an impact. Two hundred and twenty-eight (11%) patients were eligible for LT according to AASLD; in this group, alpha-fetoprotein levels and Child–Pugh class were independent predictors of survival. Conclusion Among patients with HCC, those undergoing LT represent a small minority; even fewer (1%) are those who undergo transplantation according to AASLD guidelines, adherence to which only marginally affects survival. Overall, LT impact on HCC patients’ treatment is very limited.

TACE treatment in hepatocellular carcinoma: What should we do now?

To the Editor: We read with much interest the comment by Forner et al. [1] on the recently published Cochrane review on Transcatheter Arterial (Chemo) Embolization (TACE/TAE) treatment in hepatocellular carcinoma by Oliveri et al. [2]. The debate on the effectiveness of TACE in patients with intermediate stage hepatocellular carcinoma (HCC) is still open, indeed. On the one hand, as summarized in the updated American Association for the Study of Liver Diseases (AASLD) guidelines, there is no doubt that the level of evidence on the efficacy of TACE in the treatment of intermediate stage HCC is strong (IA, according to the standard evaluation [3], with a consequently strong grade of recommendation [Grade A]). On the other hand, there is also no doubt that this strength lies basically on the results of two randomized prospective studies [4,5] that deeply condition the two meta-analyses published on the topic [6,7]. Nevertheless, TACE is also supported by the fact that it is used in the everyday clinical practice of every center involved in the management of HCC, a very low level (IV), but still important, evidence. Dr. Forner correctly underlines that one of the papers quoted in Olivieri’s meta-analysis, the Doffoel’s randomized prospective trial of TACE vs. tamoxifen [8], presents many biases and includes patients that may have been ‘‘sub-optimally staged, selected and/ or treated’’. In several French studies, indeed (see also the two Pelletier’s articles [9,10]), the survival after TACE is so short that being affected by an intermediate stage HCC in France at the end of the last century would have suggested to move to other countries for treatment. Indeed, the reported 1-year survival (ranging from 25% to 50%) was not considered acceptable elsewhere and in past years those two studies heavily conditioned the clinical evaluation of TACE as a treatment for patients with multinodular HCC. The Cochrane review in any case casts new doubts on the topic, doubts that induce to wonder what to do in patients with intermediate stage HCC, if one accepts the conclusions of the review. In our experience, based on the data (prospectively collected over 20 years) of the ITA.LI.CA database, patients with intermediate stage HCC treated by TACE present a median survival of 35 months (42 months in those treated in the last decade), with 1and 5-year survivals of 80% and 18%, respectively. Having said this, it is worth noting that only a fraction of patients with an intermediate stage HCC were treated by TACE, while in the other cases, the treatment options vary from surgery or percutaneous treatments to best supportive care, depending on a number of factors not considered in the Barcelona Clinic Liver Cancer (BCLC) algorithm, such as age, co-morbidities, patient’s decision, and local expertise, particularly, as far as the availability of highly experienced surgical teams is concerned. Interestingly enough, patients with intermediate stage HCC who can be treated more aggressively tend to survive longer than those treated by

Role of antiviral therapy in the natural history of hepatitis B virus-related chronic liver disease.

Hepatitis B virus (HBV) infection is a dynamic state of interactions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B (CHB) infection have shown an association between active viral replication and adverse clinical outcomes such as cirrhosis and hepatocellular carcinoma. The goal of therapy for CHB is to improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensation, end-stage liver disease, hepatocellular carcinoma (HCC) and death. This goal can be achieved if HBV replication is suppressed in a sustained manner. The accompanying reduction in histological activity of CHB lessens the risk of cirrhosis and of HCC, particularly in non-cirrhotic patients. However, CHB infection cannot be completely eradicated, due to the persistence of covalently closed circular DNA in the nucleus of infected hepatocytes, which may explain HBV reactivation. Moreover, the integration of the HBV genome into the host genome may favour oncogenesis, development of HCC and may also contribute to HBV reactivation.

Application of the Intermediate-Stage Subclassification to Patients With Untreated Hepatocellular Carcinoma.

OBJECTIVES:The Barcelona Clinic Liver Cancer (BCLC) intermediate stage (BCLC B) includes a heterogeneous population of patients with hepatocellular carcinoma (HCC). Recently, in order to facilitate treatment decisions, a panel of experts proposed to subclassify BCLC B patients. In this study, we aimed to assess the prognostic capability of the BCLC B stage reclassification in a large cohort of patients with untreated HCC managed by the Italian Liver Cancer Group.METHODS:We assessed the prognosis of 269 untreated HCC patients observed in the period 1987–2012 who were reclassified according to the proposed subclassification of the BCLC B stage from stage B1 to stage B4. We evaluated and compared the survival of the various substages.RESULTS:Median survival progressively decreased from stage B1 (n=65, 24.2%: 25 months) through stages B2 (n=105, 39.0%: 16 months) and B3 (n=22, 8.2%: 9 months), to stage B4 (n=77, 28.6%: 5 months; P<0.0001). Moreover, we observed a significantly different survival between contiguous stages (B1 vs. B2, P=0.0002; B2 vs. B3, P<0.0001; B3 vs. B4, P=0.0219). In multivariate analysis, the BCLC B subclassification (P<0.0001), MELD score (P=0.0013), and platelet count (P=0.0252) were independent predictors of survival.CONCLUSIONS:The subclassification of the intermediate-stage HCC predicts the prognosis of patients with untreated HCC. The prognostic figures identified in this study may be used as a benchmark to assess the efficacy of therapeutic intervention in the various BCLC B substages, whereas it remains to be established whether incorporation of the MELD score might improve the prognosis of treated patients.

Years of life that could be saved from prevention of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved.

Megestrol and embryonic extracts in the treatment of advanced hepatocellular carcinoma : A prospective randomized trial in the pre-sorafenib era

Background:  Patients with advanced hepatocellular carcinoma (HCC) achieved significant results by the new treatment with sorafenib (a multi‐tyrosine kinase inhibitor), but, because it has been tested mainly in Child A cirrhosis, patients with impaired liver function are not eligible for the treatment.

Rise and fall of HCV‐related hepatocellular carcinoma in Italy: a long‐term survey from the ITA.LI.CA centres

Hepatitis C virus (HCV) is the leading aetiological factor of HCC in the western world where, overall, its incidence is increasing, despite data suggesting an initial drop in some areas. The aim of this study was to evaluate epidemiology, clinical features and survival of HCV‐related HCC (HCV‐HCC) in a wide time range in Italy.

Molecular Targeted Therapy in Hepatocellular Carcinoma: Present Achievements and Future Challenges

Therapeutic options in advanced stage hepatocellular carcinoma have been very poor until the discovery of new therapeutic agents that target the molecular pathways involved in hepatocarcinogenesis. In this paper we try to review the most important molecular agents in development, with a specific focus on sorafenib’s role and safety profile, especially in the treatment of patients with suboptimal liver function.