RESULTS
1. All Patients
1.1. Presentation at a multidisciplinary consultation meeting on the last 10 years 1.2. Caracteristics
1.2.1. Malignant tumors’s caracteristics
1.2.2. Hepatocellular carcinoma’s caracteristics
2. Hepatocellular carcinoma in the patients with NAFLD 2.1. Presence or absence of cirrhosis
2.2. Diagnosis mode, discovery circumstance, treatment
2.3. Treatments proposed within BCLC stage in NAFLD patients 2.3.1. In cirrhotic patients
Evolution of hepatocellular carcinoma in NAFLD: retrospective analysis of data from the multidisciplinary consultation meeting on liver tumors in Maine and Loire from 2007 to 2018
Hélène Julien 1 ; Frédéric Oberti 1,2, MD ; Isabelle Fouchard 1,2, MD ; Adrien Lannes1,2, MD ; Floraine Zuberbulher 1,2, MD ; Paul Calès 1,2, MD PhD ; Jérôme Boursier 1,2, MD PhD.
1 CHU Angers, Service d’Hépato-gastro-entérologie, Angers, France.
2 HIFIH Laboratory, UPRES 3859, SFR 4208, Bretagne Loire University, Angers, France
ABSTRACT
Background and Aims : HCC commonly complicates chronic liver disease. NAFLD and
NASH are very common, more and more patients develop HCC despite the absence of cirrhosis.
Objectives : Using our multidisciplinary consultation meeting in Angers, we established
the epidemiology of HCC in Maine et Loire, then specifically analyzed patients with HCC on NAFLD. Then, we checked if the therapeutic management of patients was in compliance with the EASL 2018 guidelines.
Methods : Following our consultation meeting, we characterized the demographics of
HCC patients referred in the Maine et Loire between 2007 and 2018. All patients over 18 years of age who were presented at a liver tumour consultation meeting in our centre were included. Among the 2119 included patients, those with HCC on NAFLD were selected was extensively examined.
Results : 1440 patients (68%) had a malignant tumor, 30.5% of the tumors were benign and 1.5% unknown. 1203 patients were a diagnosis confirmed HCC. The majority of HCC occurred in patients with either underlying alcohol-induced cirrhosis (n=812;
cirrhotic patients (p<0.001). 69 patients NAFLD were offered curative treatment (43.7%), 39.5% in cirrhotic patients versus 54.0% in non-cirrhotic patients (p=0.097).
In both cirrhotic and non-cirrhotic patients, two thirds of patients were offered treatment in accordance with the guidelines (98/158).
Conclusion : HCC on NAFLD represents nearly 13.1% of all HCC cases. Non-cirrhotic HCC-NAFLD is increasing in this population.
INTRODUCTION
Hepatocellular carcinoma (HCC) is nowadays the second leading cause of cancer death worldwide (1). It is a major public health concern with one of the highest overall mortality compared to other cancers (2). It is also the most common primary hepatic malignancy in the world (3), with an increasing worldwide prevalence, with over 782,000 cases estimated to have occurred in 2012 according to the International Agency for Research on Cancer (IARC) (1,4). Therefore, there has been a significant increase in incidence over the last 20 years due to the increased incidence of viral cirrhosis C, probably of metabolic liver disease, and improving diagnostic possibilities. In France, the annual incidence of HCC was 12.1/100000 in men and 2.4/100000 in women in 2012 (5).
It occurs in the vast majority of cases on a liver that is already damaged by chronic liver disease, developed in 80% of cases on cirrhosis. However, more and more HCC are diagnosed on normal liver. In the Nzeoko’s study, 42.6% of HCC appeared on non-cirrhotic liver, and patients without cirrhosis survived longer than patients with cirrhosis.
The pathology, natural history, and prognosis of this tumor are significantly influenced by the presence or absence of cirrhosis in the non-neoplasic liver, and the presence of cirrhosis portends a poorer prognosis (6).
Nonalcoholic fatty liver disease (NAFLD) is a large spectrum of features that encompasses a spectrum of histological liver changes ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with/without fibrosis, occurring in a dysmetabolic milieu (7),
by 9% per year from 2004 to 2009 in the United States (10). More studies describe HCC in the setting of obesity and diabetes, two major risk factors for NAFLD (10–14). The increasing incidence of these conditions and the emerging evidence of HCC in non-cirrhotic NAFLD shows us the interest of diagnosing and managing them as soon as possible.
Unfortunately, it is a cancer with limited treatment options, aggressive nature and very low overall survival (8–10,12). In contrast to all other solid tumors, the therapeutic decision for HCC is not based on a prognostic classification. The TNM classification (tumor, node, metastasis) is not suitable because it does not take into account the severity of the underlying liver disease. Many other classifications have been proposed. The Barcelona Clinic Liver Cancer (BCLC) algorithm is the most widely used staging system(15). In practice, the therapeutic decision must be made in a multidisciplinary meeting according to three criteria: non-tumoral liver assessment, tumor extension assessment and general condition assessment. In theory, liver transplantation is the ideal treatment for cancer and cirrhosis simultaneously.
In the Dyson’s study, in 2000, less than 10% of Newcastle upon Tyne’s regional patients were referred to specialist services, increasing to over 85% by 2010 (16). It is important to involve all key professional groups in making clinical decisions for individual patients.
In the Taylor’s study, at least 90% of respondents agreed that effective team work results in improved clinical decision making, more coordinated patient care, improvement to overall quality of care, more evidence based treatment decisions, and improved treatment (17). Hence, importance of multidisciplinary consultation meetings that bring expertise.
In our University Hospital, in Angers, our pluridisciplinary meeting established since
2007, allowed us to establish a database of patients with a probable HCC. This hospital served a stable population of about 800 000 people, and its weekly meeting was assisted by a clinical database that was retrospectively collected. The presence of associated liver disease was determined based on history, clinical, laboratory, radiological, histological and noninvasive screening tests. However, none has yet analyzed the prevalence outcome, the incidence of HCC as well as the evolution of our practices at Angers.
In the present work, we analyze the clinical presentation and histological diagnosis of all patients presented at a multidisciplinary meeting of liver tumors. Our first objective was to study the epidemiology of HCC in Maine and Loire.
In a second step, we specifically analyze patients with HCC on liver NAFLD and we compare them according to the therapeutic choices. Our second objective was to study the epidemiology of HCC on NALFD and to verify if the management is in accordance with the EASL 2018 guidelines.
PATIENTS AND METHODS
1. Study population and design
In this retrospective observational study, we include all patients over the age of 18 who were presented at a multidisciplinary liver tumor meeting between January 1st, 2007 and April 1st, 2018 in the hepatogastroenterology department of the University Hospital Angers, France.
2. Data collection
First, we classified patients based on the data in the paper from the consultation meeting.
The data collected were as follows: tumor type (malignant / benign / undetermined), then malignant tumor type, and finally the etiology of chronic liver disease.
Patients were considered NAFLD when they met all the following criteria: no excessive alcohol consumption (20g / day in women, 30g / day in men) or other cause of chronic liver disease, overweight (BMI ≥ 25 kg/m2) and at least one of the following metabolic complication: diabetes, dyslipidemia, hypertension.
Secondly, for each patient with HCC on NAFLD, epidemiological and clinical data were recorded. The recorded data include: age, sex, etiology of chronic liver disease, circumstance of discovered HCC and non-invasive test.
The following radiological data were extracted from medical records: imaging type, size, location, presence of vascular invasion or metastases.
The following anathomopathological data were retained: histology in tumoral liver and in healthy liver.
We collected treatments proposed. We then calculated the BCLC for each patient based on the available data.
3. BCLC staging Classification and treatment schedule
BCLC algorithm is the most widely used staging system (5–9). It includes prognostic variables related to tumour status, liver function and health performance status (Figure 1).
We focused our analysis on HCC on NAFLD group and we first analysed their BCLC stage.
We split our sections in 4 parts: Agreement with the Guidelines EASL 2018, “More aggressive” treatment compared to EASL Guidelines, “Less aggressive” treatment compared to EASL Guidelines, no treatment decision.
In addition, we split the BCLC A in 3 subgroups for more precision: BCLC A, 1 tumor <
5cm, BCLC A, 1 tumor > 5cm, BCLC A, 2 or 3 tumor < 3cm each one.