Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

Giant hepatic extra-gastrointestinal stromal tumor treated with cytoreductive surgery and adjuvant systemic therapy:A case report and review of literature

BACKGROUND Primary extra-gastrointestinal stromal tumors(E-GIST)of the liver are rare.The clinical presentation may range from asymptomatic to bleeding or manifestations of mass effect.Oncologic surgery followed by adjuvant therapy with imatinib is the standard of care.However,under specific circumstances,a cytoreductive approach may represent a therapeutic option.We describe herein the case of an 84-year-old woman who presented with a tender,protruding epigastric mass.Abdominal computed tomography scan revealed a large,heterogeneous mass located across segments III,IV,V,and VIII of the liver.The initial approach was transarterial embolization of the tumor,which elicited no appreciable response.Considering the large size and central location of the tumor and the advanced age of the patient,non-anatomic complete resection was indicated.Due to substantial intraoperative bleeding and hemodynamic instability,only a near-complete resection could be achieved.Histopathology and immunohistochemical staining confirmed the diagnosis of primary E-GIST of the liver.Considering the risk/benefit ratio for therapeutic options,debulking surgery may represent a strategy to control pain and prolong survival.CASE SUMMARY Here,we present a case report of a patient diagnosed with E-GIST primary of the liver,which was indicated a cytoreductive surgery and adjuvant therapy with imatinib.CONCLUSION E-GIST primary of the liver is a rare conditional,the treatment is with systemic therapy and total resection surgery.However,a cytoreductive surgery will be necessary when a complete resection is no possible.