Comparative study of MAFLD as a predictor of metabolic disease treatment for NAFLD.

A novel concept of Metabolic Associated Fatty Liver Disease (MAFLD) was proposed, incorporating metabolic abnormalities such as obesity and diabetes, which are risk factors that affect the prognosis. Non-Alcoholic Fatty Liver Disease (NAFLD), entails fat accumulation in the liver without alcohol consumption and is often linked to obesity, insulin resistance, and metabolic syndrome. However, the broad nature of the disease concept has hindered prognosis accuracy. In this study, we assess the contribution of the impact of diagnostic criteria for MAFLD on metabolic disease progression compared to conventional diagnostic criteria for NAFLD. A total of 7159 patient who were presented to the health screening center in Tokai University Hospital both in 2015 and 2020 were included in the study. Fatty liver was diagnosed using abdominal ultrasonography. The diagnostic criteria for NAFLD were consistent with the global guidelines based on alcohol consumption. The diagnostic criteria for MAFLD were based on the International Consensus Panel. Medications (anti-hypertensive, diabetic, and dyslipidemia medications) were evaluated by self-administration in the submitted medical questionnaire. A total of 2500 (34.9%) participants were diagnosed with fatty liver (FL +), 1811 (72.4%) fit both NAFLD and MAFLD diagnostic criteria (overlap), 230 (9.2%) fit only the NAFLD diagnostic criteria (NAFLD group) and 404 (16.1%) fit the MAFLD diagnostic criteria (MAFLD group) at 2015. Over the next 5 years, medication rates increased in the NAFLD group for anti-hypertensive, + 17 (7.4%); diabetes, + 3 (1.3%); and dyslipidemia, + 32 (13.9%). In contrast, the only-MAFLD group showed a more significant increase with + 49 (12.1%), + 21 (5.2%), and + 49 (12.1%), for the respective medications, indicating a substantial rise in patients starting new medications. Our analysis of repeated health check-ups on participants revealed that the diagnostic criteria for MAFLD are more predictive of future treatment for metabolic disease than conventional diagnostic criteria for NAFLD.

Macrophage-depleted young mice are beneficial in vivo models to assess the translocation of Klebsiella pneumonia from the gastrointestinal tract to the liver in the elderly.

Pathobionts are commensal intestinal microbiota capable of causing systemic infections under specific conditions, such as environmental changes or aging. However, it is unclear how pathobionts are recognized by the intestinal mucosal immune system under physiological conditions. This study demonstrates that the gut pathobiont Klebsiella pneumoniae causes injury to the epithelium and translocates to the liver in specific pathogen-free mice treated with clodronate-liposomes that depleted macrophages. In the clodronate-liposome-treated mice, indigenous classical K. pneumoniae (cKp) with non-K1/K2 capsular serotypes were isolated from the liver, indicating that gut commensal cKp translocated from the gastrointestinal tract to the liver due to the depletion of intestinal macrophages. Oral inoculation of isolated cKp to clodronate-liposome-treated mice significantly reduced the survival rates compared to that of non-treated mice. Our findings demonstrate that intestinal mucosal macrophages play a pivotal role in sensing commensal cKp and suppressing their translocation to the liver. This study demonstrates that clodronate-liposome-treated mouse models are effective for screening and evaluating drugs that prevent the translocation of cKp to the liver, providing new insights into the development of preventive protocols against K. pneumoniae infection.

Prognostic Factors in Prostate Cancer Associated with Ulcerative Colitis.

Ulcerative colitis (UC) has been associated with increased prostate cancer (PCa) risk. However, the mechanisms underlying UC and increased PCa risk remain unclear, and research on this topic is scarce in Japan. We have investigated whether UC is associated with PCa risk in the Japanese population and the risk factors related to PCa among older UC patients. This retrospective single-center cohort study was conducted between January 2010 and April 2022. A total of 68 cases were analyzed, and 9 cases of PCa were observed (13.2%). PCa occurred more frequently in the adult-onset group (8/40, 20.0%) than in the older-onset group with UC (1/28; 3.57%). No significant differences were observed between immunosuppressive therapies and PCa in patients, excluding those with pancolitis-type UC. PCa occurred more frequently in the pancolitis type, and the biologics group had no PCa cases, but the difference was not statistically significant (p = 0.07). This study suggests that pancolitis type and UC onset in middle-aged patients may be risk factors and found that biologics potentially suppress PCa development.

Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments.

BACKGROUND: Adherent-invasive Escherichia coli (AIEC) is isolated from patients with Crohn's disease (CD). AIEC can invade the intestinal epithelium, suggesting that it is involved in the development and pathogenesis of CD. However, the mechanism by which AIEC acquired the invasive phenotype remains unknown. RESULTS: This study was designed to examine the mechanisms of AIEC invasiveness. We found that the flagellin (fliC) expression in AIEC was two-fold higher than that in non-AIEC strains, and this overexpression induced the formation of long-filament flagellin. Deletion of fliC in the AIEC LF82 strain resulted in the disappearance of flagellar filaments and attenuated the motility and invasive ability of the bacterium, suggesting that the formation of long filament flagellin induced by increased fliC expression is required by AIEC to invade the intestinal epithelium. In AIEC and non-AIEC K12 strains cultured in the presence of cyclic-di-AMP (c-di-AMP), the expression of fliC was enhanced, and flagellar filaments were elongated. Stimulation with c-di-AMP enhanced the bacterial motility and ability to invade epithelial cells, even in the non-AIEC K12 strain. CONCLUSIONS: Our findings show that c-di-AMP confers an AIEC-like phenotype on non-AIEC strains by enhancing the expression of fliC. The results should be useful for understanding the pathogenesis of CD.

Prediction and Validation of Metabolic Dysfunction-Associated Fatty Liver Disease Using Insulin Resistance-Related Indices in the Japanese Population.

Background: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD), which is based on evidence of hepatic steatosis and any of the following three conditions: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation, has been proposed. It is uncertain how indices that predict insulin resistance (IR) are associated with MAFLD. Methods: Among subjects who had undergone health examinations at our hospital, 1,257 (787 men and 474 women) who underwent fatty liver evaluation, were included in this cross-sectional study. The discriminatory ability of each index for MAFLD was tested using a receiver operating characteristic curve analysis. The associations between the homeostasis model assessment-IR (HOMA-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride-glucose (TyG) index, and MAFLD were investigated using multiple logistic regression analysis. Results: The mean age and body mass index of MAFLD subjects were 58.1 years and 26.0 kg/m2 in men and 63.0 years and 26.1 kg/m2 in women, respectively. The cutoff values of HOMA-IR, TG/HDL-C ratio, and TyG index in men and women were 1.40 (area under the curve [AUC]: 0.81) and 1.90 (AUC: 0.88); 1.56 (AUC: 0.75) and 1.06 (AUC: 0.78); and 8.62 (AUC: 0.75) and 8.45 (AUC: 0.80), respectively. All indices were significantly higher in both men and women with MAFLD. In the multivariate models, the odds of MAFLD were higher among both men and women in the highest tertile than those in the lowest tertile. When subjects were divided by sex, presence of MAFLD, and alanine aminotransferase (ALT) values, all indices were significantly higher in both men and women with high ALT levels who were diagnosed with MAFLD. Conclusion: IR strongly correlated with MAFLD, particularly in subjects with high ALT levels.

Adherent-invasive E. coli - induced specific IgA limits pathobiont localization to the epithelial niche in the gut.

Background and aim: Adherent-invasive E. coli (AIEC) has been identified as a pathobiont associated with Crohn's disease (CD), that prefers to grow in inflammatory conditions. Although the colonization by AIEC is implicated in the progression of the disease and exacerbates inflammation in murine colitis models, the recognition and response of host immunity to AIEC remains elusive. Methods: Antibiotic treated female C57BL/6 mice were inoculated by commensal E. coli and LF82 AIEC strains. Luminal-IgA fractions were prepared from feces and their binding to AIEC and other strains was assessed to confirm specificity. IgA binding to isogenic mutant strains was performed to identify the functional molecules that are recognized by AIEC specific IgA. The effect of IgA on epithelial invasion of LF82 strain was confirmed using in vitro invasion assay and in vivo colonization of the colonic epithelium. Results: Persistent colonization by AIEC LF82 induced secretion of luminal IgA, while commensal E. coli strain did not. Induced anti-LF82 IgA showed specific binding to other AIEC strains but not to the commensal, non-AIEC E. coli strains. Induced IgA showed decreased binding to LF82 strains with mutated adhesin and outer membrane proteins which are involved in AIEC - epithelial cell interaction. Consistently, LF82-specific IgA limited the adhesion and invasion of LF82 in cultured epithelial cells, which seems to be required for the elimination in the colonic epithelium in mice. Conclusion: These results demonstrate that host immunity selectively recognizes pathobiont E. coli, such as AIEC, and develop specific IgA. The induced IgA specific to pathobiont E. coli, in turn, contributes to preventing the pathobionts from accessing the epithelium.

A case of breast cancer with extensive colon metastasis.

Breast cancer is one of the most common malignancies in women worldwide. Although most breast cancers are curable, in cases of metastasis, many are often found in the lungs, bones, liver, and central nervous system; however, metastasis to the gastrointestinal tract is rare. Invasive lobular carcinoma, which represents only 5%-10% of breast cancers, has a higher risk of metastasis to the gastrointestinal tract than invasive ductal carcinoma. Here, we report a rare case of gastrointestinal metastasis of invasive lobular carcinoma that spread extensively to the colonic mucosa. Given the improved survival rates of breast cancer patients with current treatments, many rarer metastatic diseases, including gastrointestinal metastases, are likely to be increased in the future.

Mucolytic bacteria license pathobionts to acquire host-derived nutrients during dietary nutrient restriction.

Pathobionts employ unique metabolic adaptation mechanisms to maximize their growth in disease conditions. Adherent-invasive Escherichia coli (AIEC), a pathobiont enriched in the gut mucosa of patients with inflammatory bowel disease (IBD), utilizes diet-derived L-serine to adapt to the inflamed gut. Therefore, the restriction of dietary L-serine starves AIEC and limits its fitness advantage. Here, we find that AIEC can overcome this nutrient limitation by switching the nutrient source from the diet to the host cells in the presence of mucolytic bacteria. During diet-derived L-serine restriction, the mucolytic symbiont Akkermansia muciniphila promotes the encroachment of AIEC to the epithelial niche by degrading the mucus layer. In the epithelial niche, AIEC acquires L-serine from the colonic epithelium and thus proliferates. Our work suggests that the indirect metabolic network between pathobionts and commensal symbionts enables pathobionts to overcome nutritional restriction and thrive in the gut.

Dll1 Can Function as a Ligand of Notch1 and Notch2 in the Thymic Epithelium.

T-cell development in the thymus is dependent on Notch signaling induced by the interaction of Notch1, present on immigrant cells, with a Notch ligand, delta-like (Dll) 4, on the thymic epithelial cells. Phylogenetic analysis characterizing the properties of the Dll4 molecule suggests that Dll4 emerged from the common ancestor of lobe- and ray-finned fishes and diverged into bony fishes and terrestrial organisms, including mammals. The thymus evolved in cartilaginous fishes before Dll4, suggesting that T-cell development in cartilaginous fishes is dependent on Dll1 instead of Dll4. In this study, we compared the function of both Dll molecules in the thymic epithelium using Foxn1-cre and Dll4-floxed mice with conditional transgenic alleles in which the Dll1 or Dll4 gene is transcribed after the cre-mediated excision of the stop codon. The expression of Dll1 in the thymic epithelium completely restored the defect in the Dll4-deficient condition, suggesting that Dll1 can trigger Notch signaling that is indispensable for T-cell development in the thymus. Moreover, using bone marrow chimeras with Notch1- or Notch2-deficient hematopoietic cells, we showed that Dll1 is able to activate Notch signaling, which is sufficient to induce T-cell development, with both the receptors, in contrast to Dll4, which works only with Notch1, in the thymic environment. These results strongly support the hypothesis that Dll1 regulates T-cell development via Notch1 and/or Notch2 in the thymus of cartilaginous fishes and that Dll4 has replaced Dll1 in inducing thymic Notch signaling via Notch1 during evolution.

Primary Sclerosing Cholangitis Complicated with Aphthoid Colitis Difficult to Diagnose from IgG4-Related Sclerosing Cholangitis.

A 19-year-old man visited our hospital because of diarrhea and blood and liver dysfunction. Magnetic and endoscopic retrograde cholangiography revealed diffuse narrowing of the common biliary tract and intrahepatic biliary tract. A biopsy specimen from the narrowed area of the common biliary tract revealed IgG4-related sclerosing cholangitis (IgG4-SC). Colonoscopy showed multiple aphthoid colitis. He was treated with corticosteroids, and the levels of hepatobiliary enzymes, IgG, and IgG4 gradually decreased. This is an extremely rare case of colitis in which the patient had a phenotype of sclerosing cholangitis similar to IgG4-SC, which was finally diagnosed as primary sclerosing cholangitis.

A potential pathogenic association between periodontal disease and Crohn's disease.

Oral conditions are relatively common in patients with inflammatory bowel disease (IBD). However, the contribution of oral maladies to gut inflammation remains unexplored. Here, we investigated the effect of periodontitis on disease phenotypes of patients with IBD. In all, 60 patients with IBD (42 with ulcerative colitis [UC] and 18 with Crohn's disease [CD]) and 45 healthy controls (HCs) without IBD were recruited for this clinical investigation. The effects of incipient periodontitis on the oral and gut microbiome as well as IBD characteristics were examined. In addition, patients were prospectively monitored for up to 12 months after enrollment. We found that, in both patients with UC and those with CD, the gut microbiome was significantly more similar to the oral microbiome than in HCs, suggesting that ectopic gut colonization by oral bacteria is increased in patients with IBD. Incipient periodontitis did not further enhance gut colonization by oral bacteria. The presence of incipient periodontitis did not significantly affect the clinical outcomes of patients with UC and CD. However, the short CD activity index increased in patients with CD with incipient periodontitis but declined or was unchanged during the study period in patients without periodontitis. Thus, early periodontitis may associate with worse clinically symptoms in some patients with CD.

Notch signaling supports the appearance of follicular helper T cells in the Peyer's patches concomitantly with the reduction of regulatory T cells.

The intracellular fragment of Notch1, a mediator of Notch signaling that is frequently detected in thymic immigrants, is critical for specifying T-cell fate in the thymus, where Delta-like 4 (Dll4) functions as a Notch ligand on the epithelium. However, as such Notch signaling has not been detected in mature T cells, how Notch signaling contributes to their response in secondary lymphoid organs has not yet been fully defined. Here, we detected the marked expression of Dll4 on the stromal cells and the active fragment of Notch1 (Notch1 intracellular domain, N1ICD) in CD4+ T cells in the follicles of Peyer's patches (PPs). In addition, N1ICD-bearing T cells were found in the T-cell zone of PPs, especially in the transcription factor Foxp3+ regulatory T (Treg) cells, with slight expression of Dll4 on the stromal cells. These fragments disappeared in Dll4-deficient conditions. It was also found that Notch1- and Notch2-deficient T cells preferentially differentiated into Treg cells in PPs, but not CXCR5+PD-1+ follicular helper T (Tfh) cells. Moreover, these phenotypes were also observed in chimeric mice reconstituted with the control and T-cell-specific Notch1/2-deficient bone marrow or Treg cells. These results demonstrated that Dll4-mediated Notch signaling in PPs is required for the efficient appearance of Tfh cells in a Treg cell-prone environment, which is common among the gut-associated lymphoid tissues, and is critical for the generation of Tfh-mediated germinal center B cells.

The pathogenic oral-gut-liver axis: new understandings and clinical implications.

INTRODUCTION: Oral health is closely related to extra-oral disease status, as may be represented by the manifestations of gastrointestinal and liver diseases. AREAS COVERED: This review focuses on the roles that the oral-gut or the oral-gut-liver axis play in the pathogenesis of inflammatory bowel disease, colorectal cancer, metabolic fatty liver disease, and nonalcoholic steatohepatitis. The discussion will begin with clinical data, including data from preclinical animal models, to elucidate mechanisms. We will also discuss ways to target oral dysbiosis and oral inflammation to treat gastrointestinal and liver diseases. EXPERT OPINION: Several studies have demonstrated that oral pathobionts can translocate to the gastrointestinal tract where they contribute to inflammation and tumorigenesis. Furthermore, oral bacteria that migrate to the gastrointestinal tract can disseminate to the liver and cause hepatic disease. Thus, oral bacteria that ectopically colonize the intestine may serve as biomarkers for gastrointestinal and liver diseases. Also, understanding the characteristics of the oral-gut and oral-gut-liver microbial and immune axes will provide new insights into the pathogenesis of these diseases.

The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis.

The precise mechanism by which oral infection contributes to the pathogenesis of extra-oral diseases remains unclear. Here, we report that periodontal inflammation exacerbates gut inflammation in vivo. Periodontitis leads to expansion of oral pathobionts, including Klebsiella and Enterobacter species, in the oral cavity. Amassed oral pathobionts are ingested and translocate to the gut, where they activate the inflammasome in colonic mononuclear phagocytes, triggering inflammation. In parallel, periodontitis results in generation of oral pathobiont-reactive Th17 cells in the oral cavity. Oral pathobiont-reactive Th17 cells are imprinted with gut tropism and migrate to the inflamed gut. When in the gut, Th17 cells of oral origin can be activated by translocated oral pathobionts and cause development of colitis, but they are not activated by gut-resident microbes. Thus, oral inflammation, such as periodontitis, exacerbates gut inflammation by supplying the gut with both colitogenic pathobionts and pathogenic T cells.

Inhibition of plasminogen activator inhibitor-1 attenuates against intestinal fibrosis in mice.

BACKGROUND/AIMS: Intestinal fibrosis is a major complication of Crohn's disease (CD). The profibrotic protein transforming growth factor-ß (TGF-ß) has been considered to be critical for the induction of the fibrotic program. TGF-ß has the ability to induce not only the expression of extracellular matrix (ECM) including collagen, but also the production of plasminogen activator inhibitor-1 (PAI-1) that prevents enzymatic degradation of the ECM during the onset of fibrotic diseases. However, the significance of PAI-1 in the developing intestinal fibrosis has not been fully understood. In the present study, we examined the actual expression of PAI-1 in fibrotic legion of intestinal inflammation and its correlation with the abnormal ECM deposition. METHODS: Chronic intestinal inflammation was induced in BALB/c mice using 8 repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). TM5275, a PAI-1 inhibitor, was orally administered as a carboxymethyl cellulose suspension each day for 2 weeks after the sixth TNBS injection. RESULTS: Using a publicly available dataset (accession number, GSE75214) and TNBS-treated mice, we observed increases in PAI-1 transcripts at active fibrotic lesions in both patients with CD and mice with chronic intestinal inflammation. Oral administration of TM5275 immediately after the onset of intestinal fibrosis upregulated MMP-9 (matrix metalloproteinase 9) and decreased collagen accumulation, resulting in attenuation of the fibrogenesis in TNBS-treated mice. CONCLUSIONS: PAI-1-mediated fibrinolytic system facilitates collagen degradation suppression. Hence, PAI-1 inhibitor could be applied as an anti-fibrotic drug in CD treatment.

Prediction of steroid demand in the treatment of patients with ulcerative colitis by immunohistochemical analysis of the mucosal microenvironment and immune checkpoint: role of macrophages and regulatory markers in disease severity.

We aimed to characterize the mucosal immune microenvironment and immune checkpoint of Ulcerative colitis (UC) by immunohistochemistry with correlation to prognosis: requirement of second-line steroid-therapy within the 2-years after diagnosis (SR). A series of 72 cases included 56 UC, 43 non-SR (with first-line treatment 5-ASA) and 13 SR, 11 infectious colitis and 5 normal colonic biopsies. Normal mucosa was characterized by low infiltrates but high BTLA and TNFRSF14. Compared to normal, UC had increased pan-immune-markers of CD3, CD8, FOXP3, PD-1, CD68, CD16, CD163, PTX3 and CD11C but had decreased BTLA (P < 0.05); by GSEA analysis comparable results were found in an independent UC gene-expression-data set (GSE38713). Compared to infectious, UC had higher CD4, CD8, PTX3 and CD11C but lower BTLA (P < 0.05). Compared to non-SR, SR had lower FOXP3 + Tregs (Odds-Ratio = 0.114, P = 0.002), PD-1 (OR = 0.176, P = 0.002) and CD163/CD68 M2-ratio (OR, 0.019, P = 0.019) but higher CD68 + pan-macrophages (OR = 6.034, P = 0.002). Higher Baron endoscopic and Geboes histologic disease activity scores also correlated with SR. In summary, UC was characterized by increased pan-immune-markers, normal TNFRSF14 and low BTLA. SR had increased CD68 + pan-macrophages but lower immune inhibitors of FOXP3 + Tregs, PD-1 and CD163/CD68 M2-macrophage ratio. In conclusion, alterations of the immune homeostasis mechanisms are relevant in the UC pathogenesis and steroid-requiring situation.

Flagellin-mediated activation of IL-33-ST2 signaling by a pathobiont promotes intestinal fibrosis.

Intestinal fibrosis is a severe complication in patients with Crohn's disease (CD). Unfortunately, the trigger leading to the development of intestinal fibrosis in the context of CD remains elusive. Here, we show that colonization by a CD-associated pathobiont adherent-invasive Escherichia coli (AIEC) promotes the development of intestinal fibrosis. Exogenously inoculated AIEC strain LF82 and commensal E. coli HS were gradually eradicated from the intestine in healthy mice. In Salmonella- or dextran sodium sulfate-induced colitis models, AIEC exploited inflammation and stably colonize the gut. Consequently, persistent colonization by AIEC LF82 led to substantial fibrosis. In contrast, commensal E. coli HS was unable to derive a growth advantage from inflammation, thereby failing to colonize the inflamed intestine or promote intestinal fibrosis. AIEC colonization potentiated the expression of the IL-33 receptor ST2 in the intestinal epithelium, which is crucial for the development of intestinal fibrosis. The induction of ST2 by AIEC LF82 was mediated by flagellin, as the ΔfliC mutant failed to induce ST2. These observations provide novel insights into pathobiont-driven intestinal fibrosis and can lead to the development of novel therapeutic approaches for the treatment of intestinal fibrosis in the context of CD that target AIEC and/or its downstream IL-33-ST2 signaling.

Treatment of a Case of Ulcerative Colitis with Sacroiliitis Using Granulocyte and Monocyte Adsorption Apheresis.

In Japan, sacroiliitis is a very rare extraintestinal manifestation in patients with ulcerative colitis (UC), and it typically presents with intestinal symptoms. Radiography is used for diagnosis, and reveals erosions, sclerosis, and ankylosis, but magnetic resonance imaging is more useful for early detection. The treatment of spondyloarthropathy such as sacroiliitis and spondylitis includes physiotherapy, nonsteroidal anti-inflammatory drugs, sulfasalazine, and immunomodulators. In patients intolerant or cases refractory to these treatments, anti-tumor necrosis factor agents are recommended. Granulocyte and monocyte adsorption (GMA) apheresis was developed in Japan in the 1980s, and is currently used widely in clinical practice for UC patients. Unlike conventional medication, GMA apheresis has no serious adverse effects. We present the first report of a UC patient with sacroiliitis, who responded well to GMA therapy. GMA apheresis may be considered a new treatment option for UC-associated spondyloarthropathy that is refractory or tolerant to conventional treatment.

Feasibility and Safety of Repeated Transarterial Chemoembolization Using Miriplatin-Lipiodol Suspension for Hepatocellular Carcinoma.

AIM: To retrospectively evaluate the feasibility and safety of repeated transarterial chemoembolization (TACE) three or more times using miriplatin-lipiodol (M-LPD) suspension (repeated M-LPD TACE) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Sixteen patients who underwent repeated M-LPD TACE were examined. Total dose of miriplatin, lipiodol and porous gelatin sponge particles and adverse events of the first and last M-LPD TACE were evaluated. RESULTS: The mean±standard deviation (SD) of the total number of M-LPD TACE per patient was 3.7±1.1. The mean±SD dose of total miriplatin, lipiodol and porous gelatin sponge particles per patient was 303±103 mg, 21±7.3 ml and 84±57 mg, respectively. There were no significant differences in any adverse events between the first and last M-LPD TACE. CONCLUSION: Repeated M-LPD TACE for HCC is feasible and safe in selected patients.