Adherence to Barcelona Clinic Liver Cancer guidelines in field practice: Results of Progetto Epatocarcinoma Campania.

BACKGROUND AND AIM: The Barcelona Clinic Liver Cancer (BCLC) algorithm is the standard system for clinical management of hepatocellular carcinoma (HCC). Data on adherence to this therapeutic paradigm are scarce. This field practice study aimed to provide a description of HCC cirrhotic patients in Southern Italy, to evaluate the adherence to BCLC guidelines and its impact on patients' survival. METHODS: We analyzed the region-wide Italian database of Progetto Epatocarcinoma Campania, which includes data of HCC cirrhotic patients, prospectively collected from January 2013 to December 2015 in 16 regional centers. RESULTS: Overall, 1008 HCC patients were enrolled: 70.6% patients received therapies recommended by BCLC algorithm, while 29.4% underwent different treatments. Among patients who were treated in adherence to guidelines, a higher rate of diagnosis on surveillance programs, better liver function, lower rate of alpha-fetoprotein > 200 ng/mL, more early-stage and monofocal HCC, lower frequency of nodules > 5 cm, portal vein thrombosis and metastases were observed. The overall survival was evaluated according to HCC stage and no differences between groups and patients managed differently were found. The multivariate analysis showed that non-adherence to treatment guidelines was independently associated to the BCLC stage B, Child-Pugh classes B and C, and the presence of neoplastic thrombosis and metastases. CONCLUSION: Adherence to BCLC algorithm in field practice was high in early and end-stage HCC patients, but it was poor in intermediate and advanced patients.

Radiofrequency ablation versus laser ablation for the treatment of small hepatocellular carcinoma in cirrhosis: a randomized trial.

BACKGROUND AND AIM: In patients with cirrhosis and small hepatocellular carcinoma (HCC), thermal ablation is currently recognized as an effective local treatment. Among thermal procedures, radiofrequency ablation (RFA) is the most diffusely used and is the standard against which any new treatment should be compared. In retrospective studies, laser ablation (LA) resulted as safe and effective as RFA. Therefore, we performed a non-inferiority randomized trial comparing RFA with LA in patients with cirrhosis and HCC within Milan criteria. METHODS: Overall, 140 patients with 157 HCC nodules were randomly assigned to receive RFA or LA. The primary end-point was the proportion of complete tumor ablation (CTA). Secondary end-points were time to local progression (TTLP) and overall survival (OS). RESULTS: Per patient CTA rates after RFA and LA were 97.4% (95% CI, 91.0-99.3) and 95.7% (88.1-98.5), respectively (difference = 1.4%, 95% CI from -6.0% to + 9.0%). Per nodule CTA rates for RFA and LA were 97.4% (91.0-99.3) and 96.3% (89.6-98.7), respectively (difference = 1.1%, from -5.7% to + 8.1%). The mean TTLP was comparable between RFA group (42.0 months; 95% CI, 36.83-47.3) and LA group (46.7 months; 95% CI, 41.5-51.9) (P = .591). The mean OS was 42 months in both groups and survival probability at 1 and 3 years was 94% and 89% in RFA group, and 94% and 80% in LA group. CONCLUSION: LA resulted not inferior to RFA in inducing the CTA of HCC nodules and therefore it should be considered as an evaluable alternative for thermal ablation of small HCC in cirrhotic patients.

Sorafenib off-target effects predict outcomes in patients treated for hepatocellular carcinoma.

AIM: Sorafenib is the standard of care in advanced hepatocellular carcinoma. This study was aimed to identify clinical parameters that may predict survival in these patients. MATERIALS & METHODS: In this observational study, a training (226 patients) and validation cohorts (54 patients) were analyzed for evaluating pretreatment and on-treatment parameters. RESULTS: At multivariate analysis, only on-treatment variables (skin toxicity, diarrhea and arterial hypertension - sorafenib off-target effects), alphafetoprotein and radiological responses predicted survival. Using the occurrence of off-target effects, a prognostic index able to distinguish three groups of patients with different survival was constructed and externally validated. CONCLUSION: In hepatocellular carcinoma patients, on-treatment variables are the best predictors of survival. Among these, sorafenib off-target effects may be the most useful indicators for prognostication in field practice.

Refining sorafenib therapy: lessons from clinical practice.

Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symptomatic progression should also be considered. If second-line therapies or trials are unavailable, continuing sorafenib beyond radiologic progression may provide a clinical benefit. Our recommendations enable the maximization of treatment duration, and hence clinical benefit, for patients.

Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B.

OBJECTIVE: Treatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population. METHODS: 128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 µg PegIFN for 48 weeks (group A, n=51), 180 µg PegIFN for 48 weeks followed by 135 µg weekly for an additional 48 weeks (group B, n=52) or 180 µg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 µg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (primary), HBV DNA <2000 IU/ml and HBsAg clearance at 48 weeks after treatment. RESULTS: Forty-eight weeks after treatment, six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (11.8% vs 25.0%, p=0.08), 6 vs 15 patients had HBV DNA <2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg <10 IU/ml (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, the combination with lamivudine did not improve responses. Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81) and were mostly due to PegIFN-related adverse events. CONCLUSIONS: In HBeAg-negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment. TRIAL REGISTRATION NUMBER: http://ClinicalTrials.gov registration number: NCT01095835.

Prediction of cardiovascular risk in patients with hepatocellular carcinoma receiving anti-angiogenic drugs: lessons from sorafenib.

Antiangiogenics are associated with an increased risk of major adverse cardiac and cerebrovascular events (MACE). The identification of at-risk subjects is relevant in the case of hepatocellular carcinoma (HCC), for which anti-angiogenic TKIs and bevacizumab are used in first and subsequent lines of therapy, to select alternative drugs for patients with excessive risk. We verified the ability to predict MACE in sorafenib-treated patients of the 2022 European Society of Cardiology (ESC-2022) score for anti-angiogenics and the recently proposed CARDIOSOR score. A retrospective analysis was conducted of prospectively collected data of the ARPES and ITA.LI.CA databases. All patients received sorafenib for unresectable HCC from 2008 to 2018. Baseline information to calculate the ESC-2022 and CARDIOSOR scores and registration of evolutive events (including MACE) were available for all patients. The predictive ability of both scores was verified using competing risk regressions and tests for goodness of fit. This study included 843 patients (median follow-up 11.3 months). Thirty-four (4.0%) patients presented a MACE. The four-tier ESC-2022 classification showed a progressive risk increase for every class (cumulative risk 1.7%, 2.7%, 4.3%, and 15.0% in the low, medium, high, and high-risk tiers, respectively). The dichotomous CARDIOSOR scale identified a high-risk group with a fourfold increased risk of MACE (sHR 4.66, p = 0.010; cumulative risk 3.8% and 16.4%). ESC-2022 showed a better goodness of fit compared to the CARDIOSOR score [C-index 0.671 (0.583-0.758) vs 0.562 (0.501-0.634), p = 0.021], but this gap was eliminated using the linear version of CARDIOSOR. Both the ESC-2022 and CARDIOSOR scores discriminated patients at increased risk for MACE. The use of these scores in clinical practice should be encouraged, since therapeutic measures can mitigate the cardiovascular risk.

A novel needle guide system to perform percutaneous laser ablation of liver tumors using the multifiber technique.

BACKGROUND: Previous studies have shown that laser ablation with the multifiber technique is effective in the treatment of liver tumors. However, the correct positioning of multiple needles may be challenging. PURPOSE: To investigate the use of a novel needle guide system that was developed to perform percutaneous laser ablation of liver tumors with the multifiber technique under ultrasonographic guidance. MATERIAL AND METHODS: Between February 2009 and June 2011, 116 patients (104 hepatocellular carcinomas and 12 metastases) with 127 liver nodules (median diameter, 3.0 cm; range, 1.5-6.0) were treated. Nineteen nodules were in high-risk locations. A needle guide with separate channels to insert two needles in a parallel position and at a prefixed distance was used. RESULTS: Needles were positioned inside the target nodule easily and quickly, and correct spacing (1.5-1.8 cm) between light sources was immediately achieved. Complete tumor ablation was achieved in a single session in 112 (88.2%) lesions. In nodules ≤3.0 cm and >3.0 cm in size, ablation was complete in 93.6% and 79.6% of cases, respectively. Of note, complete ablation was achieved in 91.7% of nodules up to 5.0 cm. CONCLUSION: With the new guidance system, needles could be inserted in parallel fashion, which facilitated positioning the needles in geometrical configurations to maximize the ablative effect. Worthy of note, the complete ablation rate in nodules >3.0 cm using the new guide system was higher than what has been reported in the literature so far.

Outcomes of Sorafenib for Recurrent Hepatocellular Carcinoma After Liver Transplantation in the Era of Combined and Sequential Treatments.

BACKGROUND: Sorafenib and other tyrosine kinase inhibitors are the current standard of care for hepatocellular carcinoma (HCC) recurring after liver transplantation (LT). Sorafenib is sometimes regarded as a scarcely effective treatment in this setting because of some studies showing a short overall survival (OS) indirectly compared with historical series of nontransplanted patients. Additional data from multicenter prospective studies are needed before drawing definite conclusions. METHODS: Retrospective analyses of a large prospective multicenter dataset of sorafenib-treated HCC patients to report the characteristics and outcomes of LT recipients (n = 81). RESULTS: At the baseline, LT patients had key prognostic features (high prevalence of metastatic disease, and low prevalence of macrovascular invasion, α-fetoprotein >400 ng/mL, ALBI grade >1, performance status >0) that differentiated them from the typical populations of non-LT patient reported in clinical trials and observational studies. Moreover, a relevant proportion of LT patients received concurrent locoregional (12.3%) and postprogression systemic treatments (34.2%), resulting in a median OS of 18.7 mo. CONCLUSIONS: Multimodal and sequential treatments are relatively frequent in post-LT HCC patients and contribute to a remarkable OS, together with favorable baseline characteristics. Despite the impossibility of matching with non-LT patients, our results indirectly suggest that the metastatic nature of post-LT recurrence and concurrent antirejection regimens should not discourage systemic treatments.

Development of a risk score to predict portal vein tumor thrombosis in patients with hepatocellular carcinoma.

BACKGROUND: Portal vein tumor thrombosis (PVTT) is a common complication of hepatocellular carcinoma and is one of the most negative prognostic factors. The management of patients with PVTT is challenging. The aim of the study was to develop a score predictive of tumor thrombosis. METHODS: Data from a large cohort of 2243 hepatocellular carcinoma patients (all stages) recorded in the Progetto Epatocarcinoma Campania (January 2013-April 2021) database were analyzed. To construct the score, univariate generalized estimated equation models, the bootstrap approach for internal validation, and a regression coefficient-based scoring system were used. RESULTS: PVTT (any location) was found in 14.4% of cases and was related to shorter survival. Males, younger patients, and symptomatic cases were more prevalent among the PVTT group. At multivariate analysis, size ≥5 cm, massive or infiltrative hepatocellular carcinoma growth, and alpha-fetoprotein ≥400 ng/mL were significantly associated with PVTT. A risk prediction score of PVTT based on eight variables was developed. Using a continuous score, the risk was associated with an odds ratio (OR) of 1.30 (1.27-1.34; P  < 0.001). Considering a dichotomous score >8 versus a score ≤8 the OR for PVTT was 11.33 (8.55-15.00; P  < 0.001). CONCLUSION: The risk score for PVTT might be useful for clinicians to optimize hepatocellular carcinoma management by picking out patients with more aggressive cancers and higher mortality rates. Prospective validation of the score is needed before its application in daily clinical practice.

Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis.

Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed. Actuarial survival estimates were computed using the Kaplan−Meier method and compared with the log-rank test. We performed an event-based counterfactual mediation analysis to estimate direct (chronic inflammation and immunosuppression), indirect (tobacco smoking, alcohol use, illicit drug abuse with injections), and the total effect of viral etiology on OS. Results were expressed as hazard ratio (HR) and 95% CI. Results: Median OS was 21 months (95% CI: 20−23) in the group with other etiologies and 15 months (14−16) in the group with viral etiology (p < 0.0001). The total effect of viral etiology was associated with OS (HR 2.76, 1.32−5.21), and it was mainly explained by the pure direct effect of viral etiology (HR 2.74, 1.15−4.45). By contrast, its total indirect effect was not associated with poorer survival (HR 1.05, 0.82−2.13). These results were confirmed when considering tobacco, alcohol consumption, or injection drug abuse as potential mediators. Median progression-free survival was 9 months (8−10) in patients with other etiologies and 6 months (5−7) in patients with viral etiology (p < 0.0001). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Patients affected by HCC with nonviral etiology treated with lenvatinib exhibit longer survival than those with viral etiology. This finding may have relevance in the treatment decision-making process.

Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection.

BACKGROUND & AIMS: Patients with chronic hepatitis C virus (HCV) infection are frequently treated with a combination of pegylated interferon (peginterferon) and ribavirin. This study compared the efficacy and safety of peginterferon alfa-2a and peginterferon alfa-2b, each in combination with ribavirin. METHODS: A total of 320 consecutive, treatment-naive, HCV RNA-positive patients with chronic hepatitis were randomly assigned to once-weekly peginterferon alfa-2a (180 microg, group A) or peginterferon alfa-2b (1.5 microg/kg, group B) plus ribavirin 1000 mg/day (body weight <75 kg) or 1200 mg/day (body weight >or=75 kg) for 48 weeks (genotype 1 or 4) or 24 weeks (genotype 2 or 3). The primary end point was sustained virological response (SVR) by intention-to-treat. RESULTS: More patients in group A than group B achieved an SVR (110/160 [68.8%] vs 87/160 [54.4%]; P = .008). Higher SVR rates were obtained in group A than group B among patients with genotype 1/4 (51/93 [54.8%] vs 37/93 [39.8%]; P = .04), with genotype 2/3 (59/67 [88.1%] vs 50/67 [74.6%]; P = .046), without cirrhosis (96/127 [75.6%] vs 75/134 [55.9%]; P = .005), and with baseline levels HCV RNA >500,000 IU/mL (58/84 [69%] vs 43/93 [46.2%]; P = .002). SVR rates in groups A and B were not statistically different among patients with baseline HCV RNA

Adipopenia Is the Rapid Screening Tool that Best Predicts Mortality in Patients with Decompensated Cirrhosis: Results of a Prospective Study.

BACKGROUND AND AIMS: Patients with liver cirrhosis (LC) often have malnutrition (MN), which can be associated with decompensation, infection, and death. The aims were to determine: the prevalence of MN in patients with LC and ascites, its impact on mortality, and the relationship between MN and spontaneous bacterial peritonitis (SBP). METHODS: Nutritional status (NS) was analysed in cirrhotic patients, experiencing their first episode of ascites, who were consecutively admitted at two clinical liver centres between November 2014 and October 2016. The participants underwent diagnostic paracentesis and were followed up to assess their outcomes. RESULTS: 110 participants underwent NS assessment in addition to routine clinical procedures. The prevalence of MN was 30.9% according to corrected body mass index, 67.3% according to upper mid-arm muscle area (UMA) and 40% according to upper mid-arm fat area (UFA). The percentages of the participants remaining alive were 68.1% at 3 months, 59.3% at 6 months, 45.1% at 12 months and 24.2% at the end of the study. Univariate analysis showed that SBP, model for end-stage liver disease (MELD), UFA, UMA and age were significantly associated with mortality. Multivariate analysis showed that only SBP, MELD and UFA (hazard ratio 2.2) were independently associated with mortality. There was a correlation between adipopenia, but not sarcopenia, and SBP. CONCLUSIONS: Adipopenia, as assessed by UFA, was present in 40% of the cirrhotic patients, and it was independently associated with mortality.

Comparison of Prognostic Scores in Patients With Hepatocellular Carcinoma Treated With Sorafenib.

INTRODUCTION: Prognostic classifications for patients treated with sorafenib for hepatocellular carcinoma (HCC) facilitate stratification in trials and inform clinical decision making. Recently, 3 different prognostic models (hepatoma arterial-embolization prognosis [HAP] score, sorafenib advanced HCC prognosis [SAP] score, and Prediction Of Survival in Advanced Sorafenib-treated HCC [PROSASH]-II) have been proposed specifically for patients treated with sorafenib. This study aimed to compare the prognostic performance of different scores. METHODS: We analyzed a large prospective database gathering data of 552 patients treated with sorafenib from 7 Italian centers. The performance of the HAP, SAP, and PROSASH-II models were compared with those of generic HCC prognostic models (including the Barcelona Clinic for Liver Cancer and Italian Liver Cancer staging systems, albumin-bilirubin grade, and Child-Pugh score) to verify whether they could provide additional information. RESULTS: The PROSASH-II model improved discrimination (C-index 0.62) compared with existing prognostic scores (C-index ≤0.59). Its stratification significantly discriminated patients, with a median overall survival of 21.5, 15.3, 9.3, and 6.0 months for risk group 1, 2, 3, and 4, respectively. The HAP and SAP score were also validated but with a poorer performance compared with the PROSASH-II. DISCUSSION: Although suboptimal, PROSASH-II is the most effective prognostic classification model among other available scores in a large Italian population of patients treated with sorafenib.

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

Prognostic value of neutrophil-to-lymphocyte ratio and its correlation with fluorine-18-fluorodeoxyglucose metabolic parameters in intrahepatic cholangiocarcinoma submitted to 90Y-radioembolization.

OBJECTIVE: The aim of this study was to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and its relationship with several metabolic parameters obtained through PET in intrahepatic cholangiocarcinoma (ICC) submitted to radioembolization with Y-microspheres (Y-radioembolization). METHODS: Records of 20 subjects affected by ICC and submitted to Y-radioembolization were retrospectively evaluated. In all cases, pretreatment NLR was carried out and fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT was acquired with the calculation of the following metabolic parameters: maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic total volume and total lesion glycolysis. After Y-radioembolization, all patients underwent regular imaging and laboratory follow-up. RESULTS: All patients presented F-FDG-avid hepatic tumors at pretreatment PET/CT examination. NLR significantly correlated with SUVmax (r = 0.64; P = 0.002) and SUVmean (r = 0.67; P = 0.001). After treatment with Y-microspheres, the mean OS resulted 12.5 ± 1.5 months. When the average pretreatment NLR value (i.e. 2.7) was used as a cutoff for patients' stratification, subjects with low NLR (<2.7) had a significantly longer OS than those with high NLR (>2.7). At Cox regression analysis including bilirubin, age, the presence of extrahepatic disease, hepatitis C virus/hepatitis B virus status and PET-derived parameters, only NLR resulted to be a significant predictor of OS (P = 0.01; hazard ratio = 13.1, 95% confidence interval = 1.6-102.7). CONCLUSION: NLR is correlated with SUVmax-mean values in ICC and resulted to be an easy available predictor of survival in patients submitted to treatment with Y-microspheres.

Repeated Treatment with 90Y-Microspheres in Intrahepatic Cholangiocarcinoma Relapsed After the First Radioembolization.

Background: The aim of this study was to evaluate the safety and efficacy of repeated administration of 90Y-microspheres in intrahepatic cholangiocarcinoma (ICC) relapsed after the first radioembolization (RE). Methods: Nine patients with ICC relapsed after the first 90Y-RE were enrolled. Six patients presented recurrence in the right hepatic lobe, 3 in the left lobe. All subjects underwent a second administration of 90Y-resin microspheres. Toxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE, version 4.02). After the repeated treatment, all patients were submitted to follow-up with laboratory, imaging, and clinical examinations. Results: The mean cumulative activity administered considering both treatments was 2.7 ± 0.5 GBq. After the second treatment, 3 patients presented complete metabolic response (33.3%) and 6 had partial response (66.6%). The following adverse events were registered: transient increased levels of liver enzymes (grade 1 = 4; grade 2 = 2), hyperbilirubinemia (grade 1 = 2), ascites (grade 2 = 1), and duodenal ulcer (grade 2 = 1). Two patients developed a significant shrinking of the targeted hepatic lobe, as for radiation lobectomy. No case of RE-induced liver disease was registered. Median overall survival was 16.5 ± 1.4 months after the first RE. Conclusions: The authors' results suggest that repeated administration of 90Y-microspheres may be considered in patients affected by ICC relapsed after the first 90Y-RE.

Effect of alcohol, cigarette smoking, and diabetes on occurrence of hepatocellular carcinoma in patients with transfusion-acquired hepatitis C virus infection who develop cirrhosis.

AIM: Alcohol drinking, cigarette smoking, and diabetes have been claimed as risk factors for hepatocellular carcinoma in case-control studies. The aim of this study was to define the impact of these risk factors on the development of hepatocellular carcinoma in hepatitis C virus-related liver cirrhosis. METHODS: A historical cohort of 138 patients with posttransfusion hepatitis C virus-related cirrhosis was selected by reviewing all files of patients referred to our liver unit. Sixty-three of them (46%) developed hepatocellular carcinoma. RESULTS: At univariate analysis, risk factors for hepatocellular carcinoma were observed in patients aged above 59 years [P=0.004; relative risk (RR): 2.08, 95% confidence interval (CI): 1.19-3.68], male sex (P<0.001; RR: 2.48, 95% CI: 1.59-3.87), habit of alcohol drinking (P=0.001; RR: 1.89, 95% CI: 1.24-2.88), and duration of alcohol consumption of more than 30 years (P=0.02; RR: 2.08, 95% CI: 0.98-4.40). At Cox regression analysis, only male sex was an independent predictive factor (beta=0.86; P=0.002; hazard ratio=2.4, 95% CI: 1.3-4.1). CONCLUSION: Diabetes, smoking, and alcohol drinking were not independently related to the risk of developing hepatocellular carcinoma in hepatitis C virus-related cirrhosis.

Circulating Cell-Free DNA in Hepatocellular Carcinoma: Current Insights and Outlook.

Over the past decade, the advancements in massively parallel sequencing have provided a new paradigm in biomedical research to uncover the genetic basis of human diseases. Integration of 'omics information has begun transforming clinical management of cancer patients in terms of diagnostics and treatment options, giving rise to the era of precision medicine. Currently, nucleic acids for molecular profiling for patients diagnosed with hepatocellular carcinoma (HCC) are typically obtained from resected tumor materials or transplanted neoplastic liver and occasionally from biopsies. Given the intrinsic risks associated with such invasive procedures, circulating cell-free DNA (cfDNA) has been proposed as an alternative source for tumor DNA. Circulating cfDNA is a type of cell-free nucleic acid that derives from apoptotic, necrotic, as well as living eukaryotic cells. Importantly, the detection of abnormal forms of circulating cfDNA that originate from cancer cells provides a new tool for cancer detection, disease monitoring, and molecular profiling. Currently, cfDNA is beginning to be adopted into clinical practice as a non-invasive tool to monitor disease by tracking the evolution of disease-specific genetic alterations in several major cancer types. Moreover, cfDNA is demonstrating potential clinical value as a surrogate to assess the molecular makeup of tumors and to overcome the sampling biases inherent to intra-tumor genetic heterogeneity, especially in the metastatic setting. With the improvements in 'omics and molecular biology techniques, coupled with the increasing understanding in the molecular pathogenesis of cancer, it can be anticipated that the detection and analysis of cfDNA will become more specific and sensitive and thus enable cfDNA analysis to be used as a diagnostic aid in patients with early-stage disease and perhaps even in a screening setting. In this review, we provide an overview of the latest findings on the role and potential utility of cfDNA analysis in the diagnosis, management, and screening of HCC.

Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: a pilot case-control study.

BACKGROUND: Limited therapies are available for large (≥40 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. METHODS: Eighty-two patients with a single HCC nodule ≥40 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. RESULTS: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively (p < 0.001). Subsequently we stratified the HCCs in 3 categories according to the nodule size: 40-50 mm, 51-60 mm, and >60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively (p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. CONCLUSIONS: LA is a more effective therapeutic option than TACE in patients with solitary large HCC.