Elevated serum levels of Wisteria floribunda agglutinin-positive human Mac-2 binding protein predict the development of hepatocellular carcinoma in hepatitis C patients.

UNLABELLED: The Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) was recently shown to be a liver fibrosis glycobiomarker with a unique fibrosis-related glycoalteration. We evaluated the ability of WFA+-M2BP to predict the development of hepatocellular carcinoma (HCC) in patients who were infected with the hepatitis C virus (HCV). A total of 707 patients who had been admitted to our hospital with chronic HCV infection without other potential risk factors were evaluated to determine the ability of WFA+-M2BP to predict the development of HCC; factors evaluated included age, sex, viral load, genotypes, fibrosis stage, aspartate and alanine aminotransferase levels, bilirubin, albumin, platelet count, alpha-fetoprotein (AFP), WFA+-M2BP, and the response to interferon (IFN) therapy. Serum WFA+-M2BP levels were significantly increased according to the progression of liver fibrosis stage (P<0.001). In each distinctive stage of fibrosis (F0-F1, F2, F3, and F4), the risk of development of HCC was increased according to the elevation of WFA+-M2BP. Multivariate analysis identified age>57 years, F4, AFP>20 ng/mL, WFA+-M2BP ≥4, and WFA+-M2BP 1-4 as well as the response to IFN (no therapy vs. sustained virological response) as independent risk factors for the development of HCC. The time-dependent areas under the receiver operating characteristic curve demonstrated that the WFA+-M2BP assay predicted the development of HCC with higher diagnostic accuracy than AFP. CONCLUSION: WFA+-M2BP can be applied as a useful surrogate marker for the risk of HCC development, in addition to liver biopsy.

Combined Transhepatic and Transsplenic Recanalization of Chronic Portal Vein Occlusion to Treat Jejunal Varices: A Report of Two Cases.

We report two cases of chronic portal vein occlusion with jejunal varices successfully treated using percutaneous intervention with a combined transhepatic and transsplenic approach. Case 1 was a 60-year-old man with uncontrolled jejunal variceal bleeding, and case 2 was a 79-year-old man with anastomotic jejunal variceal bleeding and cholangitis. Single access via the transhepatic or transsplenic route failed to allow catheter advancement through the occlusion. After introducing pull-through access via the transhepatic and transsplenic routes, a metallic stent was could be used to dilate the occluded portal vein. Anastomotic jejunal varices functioning as hepatopetal collaterals were embolized after the establishment of antegrade portal flow. No symptom relapse was observed during the follow-up period (31 months for case 1 and 34 months for case 2).

Extracellular vesicles from senescent hepatic stellate cells promote cell viability of hepatoma cells through increasing EGF secretion from differentiated THP-1 cells.

Since the discovery of the senescence-associated secretory phenotype, the role of senescent hepatic stellate cells (HSCs) in hepatocellular carcinoma (HCC) development has gained increasing attention. Similar to cytokines, extracellular vesicles (EVs) are essential for intercellular communication. However, the function of EVs derived from senescent HSCs in HCC progression has not been extensively studied. The aims of the present study were to characterize the EVs derived from senescent HSCs and determine their role in the tumor microenvironment. Cellular senescence was induced in human hepatic stellate cells (HHSteCs) with various concentrations of etoposide. Induction was confirmed using EdU staining and 53BP1 and p21 immunostaining. EVs were isolated by ultracentrifugation and analyzed by nanoparticle tracking analysis. Multiplex immunoassays were used to compare the levels of growth factors secreted from hepatoma cell lines and macrophage cells pretreated with EVs derived from senescent HHSteCs (senescent EVs) with those pretreated with EVs derived from normal cultured HHSteCs (normal EVs). Treatment with 25 µM etoposide for 3 days was the most effective at inducing senescence in HHSteCs. This finding was confirmed by induction of irreversible cell-cycle arrest, upregulation of 53BP1 and p21 expression, and increased SA-ß-gal staining. Senescent HHSteCs released increased quantities of EV particles compared with normally cultured HHSteCs. Multiplex analysis revealed that there was no difference between hepatoma cell lines treated with normal EVs and those treated with senescent EVs in growth factor secretion. In contrast, the secretion of epidermal growth factor (EGF) was increased by macrophage cells treated with senescent EVs compared with those treated with normal EVs. Furthermore, senescent EVs did not affect the viability of hepatoma cells but increased the viability of hepatoma cells co-cultured with macrophage cells. In conclusion, the release of EVs from senescent HSCs was higher compared with normal HSCs. Furthermore, senescent EVs promoted HCC development by upregulating EGF secretion from macrophages.

Ketone bodies as a predictor of prognosis of hepatocellular carcinoma after transcatheter arterial chemoembolization.

OBJECTIVE: Arterial ketone bodies, which reflect liver function, have been investigated. However, the relationship between venous ketone bodies and hepatocellular carcinoma (HCC) is unclear. We investigated whether prognosis of patients with HCC after transcatheter arterial chemoembolization (TACE) was associated with venous blood ketone bodies. METHODS: Sixty-eight patients with HCC who underwent TACE were recruited for this study. The venous blood ketone body levels were measured 1 d before (pretreatment) and 7 d after TACE (posttreatment). Skeletal muscle quality was evaluated using the intramuscular adipose tissue content (IMAC). RESULTS: Of the 68 patients, 43 (63.2%) were male, with median age of 73.0 y, and the IMAC was -0.274 (range -0.82 to 0.24). The median ketone body levels pre- and posttreatment were 63.0 µmol/L (13-310) and 48.0 µmol/L (8-896), respectively. The cumulative survival rate of patients with total ketone body ratio ([TKBR]: posttreatment/pretreatment total ketone bodies) <1 was 86.6%. The rate with TKBR ≥1 was 59.0% at 300 d (P < 0.05). Cox regression analysis identified the TKBR (≥1, hazard ratio: 2.954, 95% confidence interval [CI]: 1.040-8.390, P = 0.030) that independently and significantly predicted the patients' prognoses. Logistic regression analysis revealed the IMAC (>-0.2745, odds ratio: 3.958, 95% CI: 1.137-13.779, P = 0.031) that predicted TKBR. TKBR and IMAC were positively correlated (rS = 0.358, P = 0.003). CONCLUSIONS: The changes in the venous ketone body were associated with the muscle status and predicted the prognosis of patients with HCC who underwent TACE. The venous ketone bodies could be a new predictor of the prognosis of HCC patients after TACE.