Anna Pecorelli

Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study.

Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD‐related HCC (NAFLD‐HCC) and to compare them to those of hepatitis C virus (HCV)‐related HCC. A total of 756 patients with either NAFLD (145) or HCV‐related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead‐time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD‐HCC patients, in contrast to the near totality of HCV‐HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD‐HCC, 25.5 months (95% confidence interval 21.9‐29.1), than in those with HCV‐HCC, 33.7 months (95% confidence interval 31.9‐35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD‐HCC and HCV‐HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) Conclusions: NAFLD‐HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. (Hepatology 2016;63:827–838)

Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma

BACKGROUND & AIMS Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. METHODS One-thousand three-hundred and eighty Child-Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. RESULTS The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p<0.001). In a 10-year follow-up perspective, the median lead-time calculated for all surveilled patients was 6.5 months (7.2 for semiannual and 4.1 for annual surveillance). Lead-time bias accounted for most of the surveillance benefit until the third year of follow-up after HCC diagnosis. However, even after lead-time adjustment, semiannual surveillance maintained a survival benefit over symptomatic diagnosis (number of patients needed to screen = 13), as did annual surveillance (18 patients). CONCLUSIONS Lead-time bias is the main determinant of the short-term benefit provided by surveillance for HCC, but this benefit becomes factual in a long-term perspective, confirming the clinical utility of an anticipated diagnosis of HCC.

Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma.

The aim of this review is to present the similarities and differences between the latest guidelines for noninvasive diagnosis of hepatocelullar carcinoma (HCC) of American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), Asian Pacific Association for the Study of the Liver (APASL), and Japanese Society of Hepatology. All the four guidelines defined a typical HCC vascular pattern as the homogeneous hyperenhancement (wash-in) in the arterial phase followed by wash-out in the venous or late phase. The AASLD and EASL guidelines accept only four-phase computed tomography and dynamic contrast magnetic resonance imaging (MRI) for HCC diagnosis, whereas the APASL and Japanese guidelines also accept contrast-enhanced ultrasound (CEUS). Regarding CEUS, the APASL guidelines accept the use of Levovist or Sonazoid as contrast agents, whereas the Japanese guidelines accept only the use of Sonazoid. The AASLD and EASL guidelines recommend using only extracellular contrast agents such as gadolinium for MRI, whereas the APASL guidelines also included the use of super paramagnetic iron oxid-MRI, and the Japanese guidelines recommended the use of gadolinium-ethoxybenzyl-diethylentriamine pentaacetic acid-MRI. The AASLD and EASL guidelines propos a diagnostic algorithm starting from the tumor size, whereas the APASL and Japanese guidelines recommend an algorithm starting from arterial tumor vascularity (hyper- or hypovascular in the arterial phase). In conclusion, important differences exist among the Western and Eastern guidelines for noninvasive HCC diagnosis.

Determinants of alpha‐fetoprotein levels in patients with hepatocellular carcinoma: Implications for its clinical use

α‐Fetoprotein (AFP) is a biomarker commonly used in the management of patients with hepatocellular carcinoma (HCC), although the possible determinants of its serum levels in these patients have not been adequately explored. For this study, the authors evaluated the relevance of demographic, clinical, and oncologic factors to the presence of elevated AFP levels in large cohort of patients with HCC.

Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma

The Barcelona Clinic Liver Cancer intermediate stage (BCLC‐B) of hepatocellular carcinoma (HCC) includes extremely heterogeneous patients in terms of tumour burden and liver function. Transarterial‐chemoembolization (TACE) is the first‐line treatment for these patients although it may be risky/useless for someone, while others could undergo curative treatments. This study assesses the treatment type performed in a large cohort of BCLC‐B patients and its outcome.

The evolutionary scenario of hepatocellular carcinoma in Italy: an update

Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of aetiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years.

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.

Contrast-enhanced ultrasonography to diagnose complicated acute cholecystitis

Gangrenous cholecystitis and perforation are severe complications of acute cholecystitis, which have a challenging preoperative diagnosis. Early identification allows better surgical management. Contrast-enhanced computed tomography (ceCT) is the current diagnostic gold standard. Contrast-enhanced ultrasonography (CEUS) is a promising tool for the diagnosis of gallbladder perforation, but data from the literature concerning efficacy are sparse. The aim of the study was to evaluate CEUS findings in pathologically proven complicated cholecystitis (gangrenous, perforated gallbladder, pericholecystic abscess). A total of 8 patients submitted to preoperative CEUS, and with subsequent proven acute complicated cholecystitis at surgical inspection and pathological analysis, were retrospectively identified. The final diagnosis was gangrenous/phlegmonous cholecystitis (n. 2), phlegmonous/ulcerative changes plus pericholecystic abscess (n. 2), perforated plus pericholecystic abscess (n. 3), or perforated plus pericholecystic biliary collection (n. 1). Conventional US findings revealed irregularly thickened gallbladder walls in all 8 patients, with vaguely defined walls in 7 patients, four of whom also had striated wall thickening. CEUS revealed irregular enhancing gallbladder walls in all patients. A distinct wall defect was seen in six patients, confirmed as gangrenous/phlegmonous cholecystitis at pathology in all six, and in four as perforation at macroscopic surgical inspection. CEUS is a non-invasive easily repeatable technique that can be performed at the bedside, and is able to accurately diagnose complicated/perforated cholecystitis. Despite the limited sample size in the present case series, CEUS appears as a promising tool for the management of patients with the clinical possibility of having an acute complicated cholecystitis.

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.