# Hepatitis B virus, alcohol, and liver cancer

**Authors:** Anup S. Pathania, Natalia A. Osna

PMC · DOI: 10.3389/fonc.2026.1751474 · Frontiers in Oncology · 2026-02-18

## TL;DR

This paper reviews how alcohol consumption worsens liver disease and increases cancer risk in people infected with hepatitis B virus.

## Contribution

The paper provides a mechanistic review of alcohol's role as a comorbid factor in HBV-related liver disease progression.

## Key findings

- Alcohol consumption accelerates disease progression in HBV-infected individuals.
- Heavy alcohol use significantly increases hepatocellular carcinoma risk in HBV-related cirrhosis.
- Alcohol interacts with other factors to worsen HBV outcomes.

## Abstract

Viral hepatitis is an infection caused by hepatotropic viruses that leads to liver inflammation and may progress from a prolonged asymptomatic phase to decompensated liver disease. Among the main types, hepatitis A (HAV), B (HBV), and C(HCV) are most common, with HBV being the most widespread worldwide. Both HBV and HCV contribute substantially to global morbidity and mortality. However, HBV accounts for the most significant burden of chronic infections and associated complications, including cirrhosis and hepatocellular carcinoma (HCC). HBV infection is one of the leading causes of HCC globally. The chronically infected individuals face a lifetime risk of up to 25% of developing liver cancer, which progresses from cirrhosis and is affected by many comorbidities. Clinical and epidemiological studies, including research from our group, have shown that alcohol consumption in HBV-infected people speeds up disease progression, increases viral replication, and worsens liver damage. Heavy alcohol use is a major cofactor that significantly raises the risk of HCC in patients with HBV-related cirrhosis. Despite this well-established link, the safe level of alcohol consumption for HBV-infected patients remains unclear. Additionally, other cofactors such as viral co-infections, metabolic disorders, genetic predisposition, demographic factors, and environmental exposures interact with alcohol to influence HBV-related disease outcomes. Understanding the systemic effects of alcohol and its underlying mechanisms in HBV development is essential to defining its role as a comorbid factor in liver disease progression. This brief review highlights current knowledge and mechanistic insights into how alcohol influences HBV infection, contributes to HCC development, and acts as a comorbid factor that worsens disease severity.

## Linked entities

- **Diseases:** cirrhosis (MONDO:0005155), hepatocellular carcinoma (MONDO:0007256), liver cancer (MONDO:0002691)

## Full-text entities

- **Genes:** Psmb9 (proteasome (prosome, macropain) subunit, beta type 9 (large multifunctional peptidase 2)) [NCBI Gene 16912] {aka Lmp-2, Lmp2, Ring12}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, ADH1B (alcohol dehydrogenase 1B (class I), beta polypeptide) [NCBI Gene 125] {aka ADH2, HEL-S-117}, CD19 (CD19 molecule) [NCBI Gene 397669], Havcr2 (hepatitis A virus cellular receptor 2) [NCBI Gene 363578] {aka tim3}, Gpt (glutamic pyruvic transaminase, soluble) [NCBI Gene 76282] {aka 1300007J06Rik, 2310022B03Rik, ALT, ALT1, Gpt-1, Gpt1}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic subunit 3G) [NCBI Gene 60489] {aka A3G, ARCD, ARP-9, ARP9, CEM-15, CEM15}, GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944] {aka GST1, GSTM1-1, GSTM1a-1a, GSTM1b-1b, GTH4, GTM1}, CD40LG (CD40 ligand) [NCBI Gene 959] {aka CD154, CD40L, HIGM1, IGM, IMD3, T-BAM}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, OAS1 (2'-5'-oligoadenylate synthetase 1) [NCBI Gene 4938] {aka E18/E16, IFI-4, IMD100, OIAS, OIASI}, Psmb8 (proteasome (prosome, macropain) subunit, beta type 8 (large multifunctional peptidase 7)) [NCBI Gene 16913] {aka Lmp-7, Lmp7}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Fah (fumarylacetoacetate hydrolase) [NCBI Gene 14085] {aka swst}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Tnfsf10 (TNF superfamily member 10) [NCBI Gene 246775] {aka Tnlg6a, Trail}, ADH1C (alcohol dehydrogenase 1C (class I), gamma polypeptide) [NCBI Gene 126] {aka ADH3}, KLRD1 (killer cell lectin like receptor D1) [NCBI Gene 3824] {aka CD94}, Aldh2 (aldehyde dehydrogenase 2, mitochondrial) [NCBI Gene 11669] {aka AHD-M1, ALDH-E2, ALDHI, Ahd-5, Ahd5}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, CGAS (cyclic GMP-AMP synthase) [NCBI Gene 115004] {aka C6orf150, D4, MB21D1, h-cGAS}, CYP2E1 (cytochrome P450 family 2 subfamily E member 1) [NCBI Gene 1571] {aka CPE1, CYP2E, P450-J, P450C2E}, CAT (catalase) [NCBI Gene 847], PRMT1 (protein arginine methyltransferase 1) [NCBI Gene 3276] {aka ANM1, HCP1, HRMT1L2, IR1B4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CPQ (carboxypeptidase Q) [NCBI Gene 10404] {aka LDP, PGCP}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Ctla4 (cytotoxic T-lymphocyte-associated protein 4) [NCBI Gene 63835] {aka CTLA-4, Cd152, sCTLA4}, IFNA8 (interferon alpha 8) [NCBI Gene 3445] {aka IFN-alphaB}, Tapbp (TAP binding protein) [NCBI Gene 21356] {aka D17Wsu91e, TPN}, Pla2g15 (phospholipase A2, group XV) [NCBI Gene 192654] {aka ACS, LLPL, Lpla2, Lypla3}, Cd80 (CD80 antigen) [NCBI Gene 12519] {aka B71, Cd28l, Ly-53, Ly53, MIC17, TSA1}, Tafazzin (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 66826] {aka 5031411C02Rik, 9130012G04Rik, G4.5, Taz}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, MIR187 (microRNA 187) [NCBI Gene 406963] {aka MIRN187, miR-187, miRNA187}, IL21 (interleukin 21) [NCBI Gene 403123], GSTT1 (glutathione S-transferase theta 1) [NCBI Gene 2952], Tap1 (transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)) [NCBI Gene 21354] {aka ABC17, APT1, Abcb2, Ham-1, Ham1, MTP1}, IL10 (Interleukin 10 level) [NCBI Gene 103158318], STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, SOD2 (superoxide dismutase 2) [NCBI Gene 6648] {aka GC1, GClnc1, IPO-B, IPOB, MNSOD, MVCD6}, AKR1A1 (aldo-keto reductase family 1 member A1) [NCBI Gene 10327] {aka ALDR1, ALR, ARM, DD3, HEL-S-6}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, Mlkl (mixed lineage kinase domain-like) [NCBI Gene 74568] {aka 9130019I15Rik}, CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}, ADH1A (alcohol dehydrogenase 1A (class I), alpha polypeptide) [NCBI Gene 124] {aka ADH1}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, MIR3188 (microRNA 3188) [NCBI Gene 100422833] {aka mir-3188}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, Faslg (Fas ligand) [NCBI Gene 25385] {aka Apt1Lg1, CD95-L, Fasl, Tnfsf6, Tnlg1a}, LAMP2 (lysosome associated membrane protein 2) [NCBI Gene 3920] {aka CD107b, DND, LAMP-2, LAMPB, LGP-96, LGP110}, ATF6 (activating transcription factor 6) [NCBI Gene 22926] {aka ACHM7, ATF6A, ATP6alpha}
- **Diseases:** liver failure (MESH:D017093), hepatic injury (MESH:D056486), CHB (MESH:D019694), inflammatory cytokines (MESH:D000080424), ALD (MESH:D008108), liver tumor (MESH:D008113), tissue injury (MESH:D017695), necrosis (MESH:D009336), Immune dysregulation (OMIM:614878), HCC (MESH:D006528), biliary cirrhosis (MESH:D008105), Viral hepatitis (MESH:D014777), ALC (MESH:D008104), hypertension (MESH:D006973), tumorigenic (MESH:D002471), blood disorders (MESH:D006402), carcinogenic (MESH:D011230), HCV (MESH:D006526), end-stage liver disease (MESH:D058625), alcohol flush (MESH:D005483), anemia (MESH:D000740), ascites (MESH:D001201), portal hypertension (MESH:D006975), co-infection (MESH:D060085), advanced (MESH:D020178), insulin resistance (MESH:D007333), Macrophage dysfunction (MESH:D055501), infected (MESH:D007239), cardiovascular (MESH:D002318), overweight (MESH:D050177), oncogenic (MESH:D000074723), carcinogenesis (MESH:D063646), function (MESH:D003291), obesity (MESH:D009765), hepatic steatosis (MESH:D005234), AIDS (MESH:D000163), -cell impairment (MESH:D000077428), metabolic disorders (MESH:D008659), cirrhotic (MESH:D000094724), AUD (MESH:D000437), mitochondrial dysfunction (MESH:D028361), immune impairment (MESH:D020274), dyslipidemia (MESH:D050171), Cirrhosis (MESH:D005355), Metabolic syndrome (MESH:D024821), hepatocyte injury (MESH:D014947), MASLD (MESH:D008107), chronic liver inflammation (MESH:D007249), HBV (MESH:D006509), chronic kidney disease (MESH:D051436), pancreatitis (MESH:D010195), liver fibrosis (MESH:D008103), ALDH2 deficiency (MESH:D016111), diabetes (MESH:D003920), HIV/AIDS Cancer (MESH:D009369), NAFLD (MESH:D065626)
- **Chemicals:** LPS (MESH:D008070), lipid (MESH:D008055), glutathione (MESH:D005978), carbon dioxide (MESH:D002245), ATP (MESH:D000255), calcium (MESH:D002118), ROS (MESH:D017382), Alcohol (MESH:D000438), Acetaldehyde (MESH:D000079), acetate (MESH:D000085), DEN (MESH:D004052), NAD+ (MESH:D009243), disulfide (MESH:D004220), HBsAg (-), malondialdehyde (MESH:D008315), fatty acid (MESH:D005227), homocysteine (MESH:D006710), aflatoxin (MESH:D000348), arachidonic acid (MESH:D016718), water (MESH:D014867), aldehydes (MESH:D000447), BMP (MESH:C012786), ethanol (MESH:D000431)
- **Species:** Hepatitis E virus [taxon 12461], Homo sapiens (human, species) [taxon 9606], Nicotiana tabacum (American tobacco, species) [taxon 4097], Human immunodeficiency virus 1 (no rank) [taxon 11676], Hepatitis B virus (no rank) [taxon 10407], Mus musculus (house mouse, species) [taxon 10090], Hepatitis delta virus (no rank) [taxon 12475]
- **Mutations:** V131I, K130M

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12956680/full.md

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12956680/full.md

## References

106 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956680/full.md

---
Source: https://tomesphere.com/paper/PMC12956680