Predictors for the Progression of Hepatic Cirrhosis to Hepatocellular Carcinoma

hep c
Hepatitis C virus (close to the Flavivirid family). HCV causes blood-borne hepatitis, cirrhosis occurs in 25% of cases, 10 to 20 years after the onset of infection, with a risk of hepatic carcinoma. Image made from transmission electron microscopy. Approximate viral diameter: 50 to 60 nm. (Photo by: BSIP/Universal Images Group via Getty Images)
Liver stiffness measurement value and the serum vitamin K absence or antagonist-II level may be significant predictors of HCC occurrence among patient with HBV-related cirrhosis.

Patients with hepatitis B virus (HBV)-related cirrhosis have the potential to progress to hepatocellular carcinoma (HCC) even under long-term nucleos(t)ide analog therapy; however, liver stiffness measurement value and the serum vitamin K absence or antagonist-II (PIVKA‑II) level may be significant predictors of HCC occurrence, according to results of a retrospective study published in the European Journal of Gastroenterology & Hepatology.1

HCC is the third leading cause of cancer-related deaths worldwide and therefore is a global health crisis.2-4 Nucleos(t)ide analog therapy is recommended first-line for patients infected with hepatitis C virus and significantly lowers the incidence of HCC.1 However, this incidence is still higher compared with patients with liver fibrosis and cirrhosis, and the effects of nucleos(t)ide analog therapy on the progression of hepatic cirrhosis to HCC are largely unknown.

Therefore, researchers enrolled 898 patients diagnosed with HBV-related hepatic cirrhosis who received nucleos(t)ide analog therapy between January 2012 and January 2015 and found that the overall 2- and 3-year cumulative incidence of HCC was 6.8% and 15.15%, respectively. They also found that liver stiffness values were higher in patients who had progressed to HCC and that HCC occurrence was significantly associated with the baseline liver stiffness measurements. At the end of the study, patients with higher liver stiffness measurements had a higher mortality rate than patients with lower liver stiffness measurements (67.88% vs 39.90%, respectively). In addition, serum PIVKA-II levels were more efficient than the serum alpha-fetoprotein (AFP) levels for the diagnosis of early HCC.  

“In conclusion, the patients with HBV-related cirrhosis have the potential for progression to HCC even under long-term [nucleos(t)ide analog] therapy,” stated the study authors.1 They added, “Therefore, in addition to receiving [nucleos(t)ide analog] treatment, [chronic hepatitis B] patients with severe hepatic cirrhosis should have their [liver stiffness measurement] values and serum PIVKA-II levels monitored over long periods of time.”

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  1. Li Z, Hu Y, Wang H, et al. Predictors for the progression of hepatic cirrhosis to hepatocellular carcinoma under long-term antiviral therapy. Eur J Gastroenterol Hepatol. 2020;32:447-453.
  2. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245-1255.
  3. Lin S, Zhang YJ. Interference of apoptosis by hepatitis B virus. Viruses. 2017;9:230.
  4. Tepper CG, Dang JHT, Stewart SL, et al. High frequency of the PNPLA3 rs738409 [G] single-nucleotide polymorphism in among individuals as a potential basis for a predisposition to chronic liver disease. Cancer. 2018;124(suppl 7):1583-1589.