Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study

Abstract

Background We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. Methods The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. Results NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P = 0.008), hypertension (48.5–57.4%: P = 0.047), and hyperlipidemia (39.2–53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61: P = 0.026) and the median platelet count increased (15.1–17.9 × 104/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC. Conclusions The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

Metabolic Risks Are Increasing in Non-B Non-C Early-Stage Hepatocellular Carcinoma: A 10-Year Follow-Up Study

“…Moreover, when we further investigated the assessment criteria for MAFLD, the patients with NBNC-HCC in the second five-year period were significantly older, and had a higher frequency of T2DM, hypertension, and higher BMI compared to the patients with HBV-HCC. This result is similar, but not exactly the same, as recently published Japanese study ( 41 ). Nagaoki et al.…”

MAFLD enhances clinical practice for liver disease in the Asia-Pacific region

“…Non-B non-C HCC is now becoming the leading cause of HCC in many countries of the Asia-Pacific region following the control and treatment of viral hepatitis [ 30 , 53 , 93 - 96 ]. Eighty-five percent of patients with non-B non-C HCC have at least one risk factor for MAFLD, suggesting that it is the dominant etiology for non-B non-C HCC [ 97 ].…”

Prevalence of fatty liver and advanced fibrosis by ultrasonography and FibroScan in a general population random sample

“…However, the incidence of HCC in patients who are negative for HCVAb and HBsAg (NBNC-HCC) has gradually increased from 19% in 2009 to 35% in 2018. 3 Tateishi et al reported that the incidence of NBNC-HCC has increased from 10% in 1991 to 32.5% in 2015. 4,5 Therefore, increasing numbers of patients with NBNC-HCC related to NAFLD have recently become a serious problem in Japan.…”

“…The incidence of HCV‐related HCC has gradually decreased. However, the incidence of HCC in patients who are negative for HCVAb and HBsAg (NBNC‐HCC) has gradually increased from 19% in 2009 to 35% in 2018 3 . Tateishi et al.…”