Research Article Details
| Article ID: | A22830 |
| PMID: | 24275855 |
| Source: | Curr Opin Oncol |
| Title: | Contributions of metabolic dysregulation and inflammation to nonalcoholic steatohepatitis, hepatic fibrosis, and cancer. |
| Abstract: | PURPOSE OF REVIEW: We review accumulating evidence that nonalcoholic steatohepatitis (NASH), a more advanced form of nonalcoholic fatty liver disease (NAFLD), predisposes patients to the risk of developing hepatocellular carcinoma (HCC), and we summarize recent advances in the elucidation of cancer-promoting pathways in NASH. We highlight the potential role of progenitor cells and hepatic stellate cells (HSCs) in promoting the early events that could culminate in cancer, as well as the emerging contribution of the gut-liver axis in promoting inflammation, senescence, and tumor growth in NASH and HCC. Finally, we review the role of bile acid receptors, vitamin D, and protective cellular pathways such as autophagy. RECENT FINDINGS: Studies have recently uncovered roles for gut microbiota, bile acid receptors and vitamin D in regulating the progression from NAFLD to HCC. Intriguing findings linking senescence and autophagy in hepatic stellate cells to HCC have also been discovered, as well as a link between dysregulated progenitor cell regulation and HCC. SUMMARY: NAFLD is the most common cause of chronic liver disease in the United States and Western Europe. The lack of definitive mechanisms underlying development of NASH among patients with NAFLD and its progression to HCC limit diagnosis and management, but new findings are paving the way for better biomarkers and therapies. |
| DOI: | 10.1097/CCO.0000000000000042 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S06 | Regulating intestinal flora | intestine gut microbiota; gut microbiota | farnesoid X receptor (FXR); fibroblast growth factor-19 (FGF19) | Probiotics; Prebiotics; Rifaximin; Yaq-001; Cilofexor; EDP-305; EYP001a; INT-767 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T17 | Farnesoid X-activated receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D387 | Vitamin D | Supplement | DB11094 | -- | Vitamin source drug | Under clinical trials | Details |
| D054 | Calcitriol | Supplement | DB00136 | -- | -- | Under clinical trials | Details |