Hepatocellular carcinoma is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis have been identified as emergent risk factors for this primary liver cancer. Incidence of NAFLD is increasing as a consequence of the epidemic spread of metabolic syndrome, which can result in progressive liver disease, leading to cirrhosis and its complications. Most data about the prevalence and incidence of hepatocellular carcinoma in patients with NAFLD are from a few population and cohort studies; its incidence is increasing and it is likely to become a leading indication for liver transplantation, especially in industrialised countries. In patients with NAFLD, hepatocellular carcinoma can arise in the context of non-cirrhotic liver, suggesting a specific carcinogenic pathway. Pathology studies have also described steatohepatitic hepatocellular carcinoma as a specific histological variant. NAFLD is underdiagnosed as causative liver disease, and patients are often diagnosed with hepatocellular carcinoma in the advanced stage because of the absence of efficient surveillance policies in this patient population. Management of hepatocellular carcinoma in patients with NAFLD is also complicated by comorbidities, mainly cardiac disease and diabetes, which negatively affect eligibility for radical treatments, including hepatic resection and, especially, liver transplantation. Finally, the effect of hepatocellular carcinoma treatments on postoperative morbidity, mortality, and disease-free survival remains to be precisely defined.

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ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.ResultsRecurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1).ConclusionEffects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.