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Page 10 of 18 Alqahtani et al. Hepatoma Res 2020;6:58 I http://dx.doi.org/10.20517/2394-5079.2020.49

Figure 1. Reduction in HCC incidence and all-cause mortality in patients with advanced hepatitis C who achieve an SVR to DAA. Data
from the Veteran Health Administration cohort [133] . HCC: Hepatocellular carcinoma; SVR: sustained virologic response; DAA: direct-
acting antiviral

carcinogenic damage of hepatocellular DNA fueled by unrested HCV replication [139] . The latter usually takes
place 1 to 2 years after the cure of a primary HCC (late recurrence), at variance with earlier recurrence that
is caused by the proliferation of pre-existing cancer cells surviving the removal of the primary tumor, for
which no effective adjuvant therapy exists. The early recurrence depends on tumor size and cell grading,
reflecting the cancer cells that invade the tumor vessels and/or to tumor satellites emerging far from

parental HCC [140] ,theevidence is mounting that early recurrence of HCC in DAA-treated patients is often
bound to pre-existing liver nodules with undefined vascular patterns at MRI [138] .

In a final note on anti-HCV therapy, it is important to underscore that achieving an SVR to antiviral
therapy does not tell the whole story. In fact, data from Lens et al. [141] reported in 2017 indicate that
obtaining an SVR to all-oral anti-HCV therapy in patients with HCV-associated cirrhosis indeed leads to
decrease in a hepatic venous pressure gradient, but that clinically significant hypertension did persist in
78% of patients. These patients have a continued risk for liver decompensation, and subsequently, maintain
a higher risk of HCC [141] .

A recent study based on Swedish nationwide registries has demonstrated a significant reduction of HCC
risk in a population including more than 50,000 HCV infected and 10,000 HBV infected adults. The
latter had been chronically exposed to low doses of aspirin (HR = 0.69, 95%CI: 0.62-0.76). After adjusting
for relevant confounding morbidities, chemoprevention of liver cancer was confirmed and found to be
associated with a similar risk reduction of liver-related mortality [142] . These findings align with studies done
in HBV patients showing chemoprevention of HBV-related liver cancer following long-term exposure to
aspirin.

HEPATITIS D
HDV is a small replication-defective RNA virus that relies on HBV to replicate and propagate. Due to
a lack of dedicated studies assessing the prevalence of HDV, the global disease burden of HDV is likely
underestimated [143] . In a recently published systematic review and meta-analysis, 650-700 million people