Reduced hepatic steatosis is associated with higher risk of hepatocellular carcinoma in chronic hepatitis B infection

Abstract

BackgroundConcomitant chronic hepatitis B infection (CHB) and non-alcoholic fatty liver disease (NAFLD) is common, but the implications of NAFLD on clinical outcomes of CHB, including hepatocellular carcinoma (HCC), are not well-investigated. MethodsCHB patients were recruited for transient elastography assessment for liver stiffness (LS), and controlled attenuation parameter (CAP), a non-invasive quanti cation of hepatic steatosis, and were prospectively followed up for development of HCC. Steatosis and severe steatosis were diagnosed by CAP ≥248 dB/m and ≥280 dB/m respectively, and advanced brosis/ cirrhosis was diagnosed by LS ≥9 kPa. The independent effect of hepatic steatosis on HCC was examined via propensity score matching (PSM) of LS and other signi cant clinical variables. ResultsForty-eight patients developed HCC among 2403 CHB patients (55.6% male, median age 55.6 years, 57.1% antiviral-treated, median ALT 26 U/L) during a median follow-up of 46.4 months. Multivariate Cox regression analysis showed age (HR 1.063), male (HR 2.032), Albumin-Bilirubin score (HR 2.393) and CAP (HR 0.993) were associated with HCC development. The cumulative probability of HCC was 2.88%, 1.56% and 0.71%, respectively for patients with no steatosis, mild-to-moderate steatosis, and severe steatosis, respectively (p=0.01). The risk of HCC increased from 1.56% to 8.89% in patients without severe steatosis if advanced brosis/cirrhosis were present (p<0.001). PSM yielded 957 pairs of CHB patients and hepatic steatosis was independently associated with HCC (HR 0.41). ConclusionReduced hepatic steatosis was signi cantly associated with a higher risk of incident HCC in CHB infection. Routine CAP and LS measurements are important for risk strati cation.

Impact of NAFLD on the outcome of patients with chronic hepatitis B in Asia

“…61 A prospective cohort study from Hong Kong showed that CAP diagnosed steatosis was found in 1156 (48.1%) patients of 2403 CHB patients without significant alcohol intake at baseline and 12 (25.0%) of 48 incident HCC patients at a median follow-up of 21.7 months. 68 The cumulative probability of HCC increased with the decrease of hepatic steatosis (no steatosis vs. mild to moderate steatosis vs. severe steatosis = 2.88% vs. 1.56% vs. 0.71%, p = 0.01).…”

“…The authors speculated that the negative association between hepatic steatosis and HCC development was as a result of: (1) suppression of HBsAg and HBV DNA or any upstream steps of viral lifecycle by steatosis, (2) "burnt-out NASH" usually with low CAP value but more severe fibrosis even cirrhosis. 68 Similarly, a retrospective cohort study from South Korea also demonstrated that among 1823 CHB patients with HBV replication suppressed by antiviral therapy, a low CAP value predicted a higher risk for HCC among patients with LS above 10 kPa (aHR 0.47, p = 0.003). 69 The impact of NAFLD on the recurrence of CHB-related HCC has also been explored.…”

“…The aforementioned prospective study from Taiwan including 2903 male CHB patients showed ultrasonographically diagnosed concurrent fatty liver was associated with a lower risk of HCC development (aHR = 0.24, 95% CI: 0.14–0.42) 61 . A prospective cohort study from Hong Kong showed that CAP diagnosed steatosis was found in 1156 (48.1%) patients of 2403 CHB patients without significant alcohol intake at baseline and 12 (25.0%) of 48 incident HCC patients at a median follow‐up of 21.7 months 68 . The cumulative probability of HCC increased with the decrease of hepatic steatosis (no steatosis vs. mild to moderate steatosis vs. severe steatosis = 2.88% vs. 1.56% vs. 0.71%, p = 0.01).…”

“…CAP value was negatively associated with HCC development in multivariate Cox regression analysis (HR = 0.993, 95% CI: 0.987–0.999) and hepatic steatosis was negatively associated with HCC development in propensity score matching analysis (HR = 0.41, 95% CI: 0.21–0.83). The authors speculated that the negative association between hepatic steatosis and HCC development was as a result of: (1) suppression of HBsAg and HBV DNA or any upstream steps of viral lifecycle by steatosis, (2) “burnt‐out NASH” usually with low CAP value but more severe fibrosis even cirrhosis 68 . Similarly, a retrospective cohort study from South Korea also demonstrated that among 1823 CHB patients with HBV replication suppressed by antiviral therapy, a low CAP value predicted a higher risk for HCC among patients with LS above 10 kPa (aHR 0.47, p = 0.003) 69 …”

Magnetic resonance imaging metrics and the predictability of adverse outcomes in on‐treatment Asian chronic hepatitis B

“…[9][10][11] Multiparametric MR liver has been validated against histology in NAFLD and mixed chronic liver disease cohorts [9][10][11][12][13][14] and can predict liver-related adverse outcomes. 15 While VCTE has been studied extensively on assessing treatment response and predicting complications in on-treatment CHB, 16,17 the use of multiparametric MR in this aspect has yet to be explored. Multiparametric MR of the pancreas has been studied in pancreatitis and pancreatic cancer.…”