Lorenzo A Orci1, Marco Sanduzzi-Zamparelli2, Berta Caballol3, Victor Sapena3, Nicola Colucci4, Ferran Torres5, Jordi Bruix3, María Reig6, Christian Toso7. 1. Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; Hepato-pancreato-biliary Centre, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. 2. BCLC Group, Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain; Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples Federico II, Naples, Italy. 3. BCLC Group, Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain. 4. Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy. 5. Medical Statistics Core Facility, Hospital Clinic Barcelona, IDIBAPS, Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain. 6. BCLC Group, Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain. Electronic address: mreig1@clinic.cat. 7. Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; Hepato-pancreato-biliary Centre, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. Electronic address: christian.toso@hcuge.ch.
Abstract
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) may be a risk factor for hepatocellular carcinoma (HCC), but the extent of this association still needs to be addressed. Pooled incidence rates of HCC across the disease spectrum of NAFLD have never been estimated by meta-analysis. METHODS: In this systematic review, we searched Web of Science, Embase, PubMed, and the Cochrane Library from January 1, 1950 through July 30, 2020. We included studies reporting on HCC incidence in patients with NAFLD. The main outcomes were pooled HCC incidences in patients with NAFLD at distinct severity stages. Summary estimates were calculated with random-effects models. Sensitivity analyses and meta-regression analyses were carried out to address heterogeneity. RESULTS: We included 18 studies involving 470,404 patients. In patients with NAFLD at a stage earlier than cirrhosis, the incidence rate of HCC was 0.03 per 100 person-years (95% confidence interval [CI], 0.01-0.07; I2 = 98%). In patients with cirrhosis, the incidence rate was 3.78 per 100 person-years (95% CI, 2.47-5.78; I2 = 93%). Patients with cirrhosis undergoing regular screening for HCC had an incidence rate of 4.62 per 100 person-years (95% CI, 2.77-7.72; I2 = 77%). CONCLUSIONS: Patients with NAFLD-related cirrhosis have a risk of developing HCC similar to that reported for patients with cirrhosis from other etiologies. Evidence documenting the risk in patients with nonalcoholic steatohepatitis or simple steatosis is limited, but the incidence of HCC in these populations may lie below thresholds used to recommend a screening. Well-designed prospective studies in these subpopulations are needed. The protocol for this systematic review is registered in the Prospero database (registration number CRD42018092861).
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) may be a risk factor for hepatocellular carcinoma (HCC), but the extent of this association still needs to be addressed. Pooled incidence rates of HCC across the disease spectrum of NAFLD have never been estimated by meta-analysis. METHODS: In this systematic review, we searched Web of Science, Embase, PubMed, and the Cochrane Library from January 1, 1950 through July 30, 2020. We included studies reporting on HCC incidence in patients with NAFLD. The main outcomes were pooled HCC incidences in patients with NAFLD at distinct severity stages. Summary estimates were calculated with random-effects models. Sensitivity analyses and meta-regression analyses were carried out to address heterogeneity. RESULTS: We included 18 studies involving 470,404 patients. In patients with NAFLD at a stage earlier than cirrhosis, the incidence rate of HCC was 0.03 per 100 person-years (95% confidence interval [CI], 0.01-0.07; I2 = 98%). In patients with cirrhosis, the incidence rate was 3.78 per 100 person-years (95% CI, 2.47-5.78; I2 = 93%). Patients with cirrhosis undergoing regular screening for HCC had an incidence rate of 4.62 per 100 person-years (95% CI, 2.77-7.72; I2 = 77%). CONCLUSIONS: Patients with NAFLD-related cirrhosis have a risk of developing HCC similar to that reported for patients with cirrhosis from other etiologies. Evidence documenting the risk in patients with nonalcoholic steatohepatitis or simple steatosis is limited, but the incidence of HCC in these populations may lie below thresholds used to recommend a screening. Well-designed prospective studies in these subpopulations are needed. The protocol for this systematic review is registered in the Prospero database (registration number CRD42018092861).
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