Elevated lactate impairs the efficacy of antiviral treatment on post-hepatectomy survival for advanced stage hepatitis B virus - related hepatocellular carcinoma

Clin Res Hepatol Gastroenterol. 2019 Feb;43(1):67-76. doi: 10.1016/j.clinre.2018.08.008. Epub 2018 Sep 13.

Abstract

Background: Nucleoside and nucleotide analogues (NAs) have a risk of mitochondrial toxicity and then inducing the increase of lactate. We aim to evaluate the impact of lactate on the effects of NAs therapy in hepatitis B virus-related hepatocellular carcinoma (HCC) patients after curative liver resection.

Materials and methods: Five hundred and fifty-seven HBV-related HCC patients were divided into the treatment and control group according to whether they received NAs therapy or not. Perioperative and prognosis data were retrospectively reviewed.

Results: The treatment group had a better overall survival rate (OS) than the control group (P = 0.017). The recurrence-free survival rate (RFS) did not significantly differ between the two groups (P = 0.174). NAs could improve the OS of early stage HCC patients (P = 0.028), as well as the OS of advanced stage HCC patients with low level of lactate in subgroup analysis stratified against the level of lactate (P = 0.037). Advanced stage HCC patients in the treatment group had a higher value of lactate than those in the control group (P = 0.024). Besides, advanced stage HCC patients had a higher value of lactate than early stage HCC patients in the treatment group (P < 0.001), as well as in the control group (P < 0.001).

Conclusions: NAs could improve the long-term outcomes of HBV-related HCC patients after curative liver resection. However, the improvement effect of NAs therapy is counteracted by the adverse effect of elevated lactate in advanced stage HBV-related HCC patients.

Keywords: Hepatitis B virus; Hepatocellular carcinoma; Lactate; Nucleotide and nucleotide analogues.

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / surgery*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Hepatectomy*
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lactates / blood*
  • Liver Neoplasms / blood*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / surgery*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Nucleosides / analogs & derivatives
  • Nucleosides / therapeutic use
  • Nucleotides / therapeutic use
  • Retrospective Studies
  • Severity of Illness Index
  • Survival Rate
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Lactates
  • Nucleosides
  • Nucleotides