Imbalance of Lymphocytes and Neutrophils May Indicate HCC Risk in HCV Infection

An imbalance between lymphocytes and neutrophils may be present in patients infected with HCV that develop hepatocellular carcinoma.

During treatment with direct-acting antivirals (DAAs), a significant imbalance between lymphocytes and neutrophils may be particularly evident in patients developing hepatocellular carcinoma (HCC), according to a study published in Gastroenterology.1

A previously published study found that serum levels of inflammatory cytokines before treatment, and their modification with DAAs, were associated with the occurrence or recurrence of HCC in patients with hepatitis C-related cirrhosis.2

Researchers in Italy hypothesized that this may also be a result of a dysregulation of the antitumor response after the sharp decrease in the hepatitis C virus (HCV) viral load induced by DAA therapy, thereby promoting tumor development.1

To test this, they used retrospective laboratory data obtained at baseline and at the end of treatment in 308 patients with HCV-related cirrhosis but without previous HCC to determine whether changes in neutrophil and lymphocyte counts during DAA treatment can be associated with the development of HCC.

They found that HCC was detected and confirmed in 7.24% (23/308) of patients after a median follow-up of 10.5 months. In patients with HCC development, a significant increase in neutrophils (2.35×109/L±1.02 vs 3.11×109/L±1.26; P =.033) and a decrease in lymphocytes (1.78×109/L±1.07 vs 0.99×109/L±0.53; P =.003) was observed during treatment, whereas in patients without HCC development (n=285), there was a similar trend, but it was not statistically significant (neutrophils: 3.00×109/L±1.26 vs 3.23×109/L±1.41 [P =.08]; lymphocytes: 1.66×109/L±0.86 vs 1.54×109/L±0.85 [P =.14]).

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The authors concluded that, “evaluation of changes in neutrophil and lymphocyte counts during treatment with DAAs adds a simple and easily to obtain information about the patient’s inflammatory state and their possible risk of developing HCC after DAA treatment.”1


  1. Gardini AC, Conti F, Brillanti S, Andreone P, and the members of Bologna DAA group. Imbalance of neutrophils and lymphocyte counts can be predictive of hepatocellular carcinoma occurrence in hepatitis C-related cirrhosis treated with direct-acting antivirals. Gastroenterology. 2018;154(8):2281-2282.
  2. Debes JD, van Tilborg M, Groothuismink ZMA, et al. Levels of cytokines in serum associate with development of hepatocellular carcinoma in patients with HCV infection treated with direct-acting antivirals. Gastroenterology. 2018;154(3):515-517.