Table III.

Function of lactate in liver diseases.

Liver diseases	Function	(Refs.)
Liver fibrosis	Increases in lactate levels could promote HSC activation and liver fibrosis. Lactate could promote HSC activation through lactylation. HK2 deficiency could lead to a reduction of H3K181a inhibiting lactylation and HSC activation. HK2/H3K18la axis is a potential target for the treatment of liver fibrosis	(55,74,75)
NAFLD	Lactate levels in the blood and liver gradually increase with lesion aggravation. PCAF-dependent K82 acetylation reduces LDHB activity and inhibits lactate clearance, and upregulation of LDHB-K82Q increases histone acetylation and promotes NAFLD	(23)
ALF	Increased lactate levels, which could be used as a predictor even though they have low specificity, could inform decision process of the transplant team that may benefit the prognosis of the patient. Markedly elevated serum LDH levels, but of low diagnostic value	(84-103)
HCC	Increased lactate levels. Accumulation of lactate in the TME could lead to acidification of the extracellular environment, which can inhibit the function of T cells and NK cells, and enhance the immunosuppressive function of TAMs, MDSCs and regulatory T cells thereby promoting tumor progression. Increased lactate levels along with increased drug resistance in HCC. Knockdown of LDHA in mice markedly inhibited the growth of HCC; however, it is ineffective in vivo when LDHA is used as a target for drug development. Targeted delivery of D-lactate to macrophages could inhibit the growth of HCC. LDH levels could be used as a prognostic indicator for HCC. Lactylation of adenylate kinase 2 promotes the progression of HCC. SIRT3 induces delactylation of CCNE2 to inhibit the development of HCC. H3 histones lactylation could promote the progression of HCC. Knockdown of HK2 suppressed the incidence of HCC in mice	(9,56,57,76,108,117-123,128,129,133-142)

HK2, hexokinase 2; HSCs, hepatic stellate cells; NAFLD, non-alcoholic fatty liver disease; PCAF, P300/cyclic AMP response element-binding protein-associated factor; LDH, lactate dehydrogenase; ALF, acute liver failure; HCC, hepatocellular carcinoma; TME, tumor microenvironment; TAMs, tumor-associated macrophages; MDSCs, myeloid-derived suppressor cells; SIRT3, sirtuin 3; CCNE2, cyclin E2; NK, natural killer.