Change in the Recurrence Pattern and Predictors over Time after Complete Cure of Hepatocellular Carcinoma

Background/Aims@#We investigated changes in recurrence rates and significant recurrence predictors over time after complete cure of hepatocellular carcinoma (HCC). @*Methods@#A total of 1,491 patients with first-time diagnosis of Barcelona Clinic Liver Cancer stage A HCC, completely cured by treatment between 2007 and 2016, were recruited from two Korean tertiary institutes. @*Results@#The mean age of the population (1,144 men and 347 women) was 58.6 years. Of the total population, 914 patients (61.3%) had liver cirrhosis. Nine-hundred and forty-one (63.1%) and 550 (36.9%) patients were treated with surgical resection and radiofrequency ablation (RFA), respectively. One-year cumulative incidences of HCC recurrence were 14.3%, 9.9%, and 5.1% from the time of treatment, 3 years after treatment, and 5 years after treatment, respectively. Upon multivariate analysis, multiple tumors, maximal tumor size ≥3 cm, and high Model for End-Stage Liver Disease scores were independently associated with increased HCC recurrence risk from the time of treatment and 1 and 2 years after curative treatment (all p<0.05, except for maxi-mal tumor size ≥3 cm for recurrence 2 years after treatment). Meanwhile, liver cirrhosis and RFA were independently associated with the increased HCC recurrence risk for almost all time points (liver cirrhosis: all p<0.05; RFA: all p<0.005 except for recurrence from 5 years after treatment). @*Conclusions@#The recurrence rate of HCC after curative treatment gradually decreased over time. Two years after treatment, when tumor-related factors lose their prognostic implications, may be used as a cutoff to define the boundary between early and late recurrence of HCC.

Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome

Background/Aims@#Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome. @*Methods@#Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline. @*Results@#A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P<0.001). MFG-E8 level was significantly correlated with all metabolic syndrome components and pulse wave velocity (all P<0.05). Subjects were categorized into two groups according to the best MFG-E8 cut-off value as follows: group 1, MFG-E8 level <4,745.1 pg/mL (n=401, 72.1%); and group 2, MFG-E8 level ≥4,745.1 (n=155, 27.9%). At baseline, metabolic syndrome in group 2 was significantly more prevalent than in group 1 (63.9% vs. 34.2%, P<0.001). During median follow-up of 17 months, metabolic syndrome developed in 122 (38.1%) subjects among 320 subjects without it at baseline. The incidence of metabolic syndrome in group 2 was significantly higher than that in group 1 (55.4% vs. 34.5%, P=0.003). On multivariate analysis, MFG-E8 level ≥4,745.1 pg/mL was an independent predictor for diagnosis and development of metabolic syndrome after adjusting other factors (all P<0.05). @*Conclusions@#Serum MFG-E8 level is a potent biomarker for the screening and prediction of metabolic syndrome.

Change in the Recurrence Pattern and Predictors over Time after Complete Cure of Hepatocellular Carcinoma

Background/Aims@#We investigated changes in recurrence rates and significant recurrence predictors over time after complete cure of hepatocellular carcinoma (HCC). @*Methods@#A total of 1,491 patients with first-time diagnosis of Barcelona Clinic Liver Cancer stage A HCC, completely cured by treatment between 2007 and 2016, were recruited from two Korean tertiary institutes. @*Results@#The mean age of the population (1,144 men and 347 women) was 58.6 years. Of the total population, 914 patients (61.3%) had liver cirrhosis. Nine-hundred and forty-one (63.1%) and 550 (36.9%) patients were treated with surgical resection and radiofrequency ablation (RFA), respectively. One-year cumulative incidences of HCC recurrence were 14.3%, 9.9%, and 5.1% from the time of treatment, 3 years after treatment, and 5 years after treatment, respectively. Upon multivariate analysis, multiple tumors, maximal tumor size ≥3 cm, and high Model for End-Stage Liver Disease scores were independently associated with increased HCC recurrence risk from the time of treatment and 1 and 2 years after curative treatment (all p<0.05, except for maxi-mal tumor size ≥3 cm for recurrence 2 years after treatment). Meanwhile, liver cirrhosis and RFA were independently associated with the increased HCC recurrence risk for almost all time points (liver cirrhosis: all p<0.05; RFA: all p<0.005 except for recurrence from 5 years after treatment). @*Conclusions@#The recurrence rate of HCC after curative treatment gradually decreased over time. Two years after treatment, when tumor-related factors lose their prognostic implications, may be used as a cutoff to define the boundary between early and late recurrence of HCC.

Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome

Background/Aims@#Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome. @*Methods@#Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline. @*Results@#A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P<0.001). MFG-E8 level was significantly correlated with all metabolic syndrome components and pulse wave velocity (all P<0.05). Subjects were categorized into two groups according to the best MFG-E8 cut-off value as follows: group 1, MFG-E8 level <4,745.1 pg/mL (n=401, 72.1%); and group 2, MFG-E8 level ≥4,745.1 (n=155, 27.9%). At baseline, metabolic syndrome in group 2 was significantly more prevalent than in group 1 (63.9% vs. 34.2%, P<0.001). During median follow-up of 17 months, metabolic syndrome developed in 122 (38.1%) subjects among 320 subjects without it at baseline. The incidence of metabolic syndrome in group 2 was significantly higher than that in group 1 (55.4% vs. 34.5%, P=0.003). On multivariate analysis, MFG-E8 level ≥4,745.1 pg/mL was an independent predictor for diagnosis and development of metabolic syndrome after adjusting other factors (all P<0.05). @*Conclusions@#Serum MFG-E8 level is a potent biomarker for the screening and prediction of metabolic syndrome.

Evaluation of Treatment Response after Endoscopic Variceal Obturation with Abdominal Computed Tomography

Background@#s/Aims: Rebleeding of gastric varices (GVs) after endoscopic variceal obturation (EVO) can be fatal. This study was performed to evaluate the usefulness of computed tomography (CT) for the prediction of rebleeding after EVO GV bleeding. @*Methods@#Patients who were treated with EVO for GV bleeding and underwent CT before and after EVO were included. CT images of the portal phase showing pretreatment GVs and feeding vessels, and nonenhanced images showing posttreatment cyanoacrylate impaction were reviewed. @*Results@#Fifty-three patients were included. Their mean age was 60.6±11.6 years, and 40 patients (75.5%) were men. Alcoholic liver disease was the most frequent underlying liver disease (45.3%). Complete impaction of cyanoacrylate in GVs and feeding vessels were achieved in 40 (75.5%) and 24 (45.3%) of patients, respectively. During the follow-up, GV rebleeding occurred in nine patients, and the cumulative incidences of GV rebleeding at 3, 6, and 12 months were 11.8%, 18.9%, and 18.9%, respectively. The GV rebleeding rate did not differ significantly according to the complete cyanoacrylate impaction in the GV, while it differed significantly according to complete cyanoacrylate impaction in the feeding vessels. The cumulative incidences of GV rebleeding at 3, 6, and 12 months were 22.3%, 35.2%, and 35.2%, respectively, in patients with incomplete impaction in feeding vessels, and there was no rebleeding during the follow-up period in patients with complete impaction in the feeding vessels (p=0.002). @*Conclusions@#Abdominal CT is useful in the evaluation of the treatment response after EVO for GV bleeding. Incomplete cyanoacrylate impaction in feeding vessels is a risk factor for GV rebleeding.

Clinical usefulness of psoas muscle thickness for the diagnosis of sarcopenia in patients with liver cirrhosis

BACKGROUND/AIMS: The most widely used method for diagnosing sarcopenia is the skeletal muscle index (SMI). Several studies have suggested that psoas muscle thickness per height (PMTH) is also effective for detecting sarcopenia and predicting prognosis in patients with cirrhosis. The aim of this study was to evaluate the optimal cutoff values of PMTH for detecting sarcopenia in cirrhotic patients. METHODS: All cirrhotic patients who underwent abdominal computed tomography (CT) scan including L3 and umbilical levels for measuring SMI and transverse psoas muscle thickness, respectively, were included. Two definitions of sarcopenia were used: (1) sex-specific cutoffs of SMI (≤52.4 cm² /m² in men and ≤38.5 cm² /m² in women) for SMI-sarcopenia and (2) cutoff of PMTH ( < 16.8 mm/m) for PMTH-sarcopenia. RESULTS: Six hundred fifty-three patients were included. The average age was 53.6 ± 10.2 years, and 499 patients (76.4%) were men. PMTH correlated well with SMI in both men and women (P < 0.001). Two hundred forty-one (36.9%) patients met the criteria for SMI-sarcopenia. The best PMTH cutoff values for predicting SMI-sarcopenia were 17.3 mm/m in men and 10.4 mm/m in women, and these were defined as sex-specific cutoffs of PMTH (SsPMTH). The previously published cutoff of PMTH was defined as sex-nonspecific cutoff of PMTH (SnPMTH). Two hundred thirty (35.2%) patients were diagnosed with SsPMTH-sarcopenia, and 280 (44.4%) patients were diagnosed with SnPMTH-sarcopenia. On a multivariate Cox regression analysis, SsPMTH-sarcopenia (hazard ratio [HR], 1.944; 95% confidence interval [CI], 1.144–3.304; P=0.014) was significantly associated with mortality, while SnPMTH-sarcopenia was not (HR, 1.446; 95% CI, 0.861–2.431; P=0.164). CONCLUSIONS: PMTH was well correlated with SMI in cirrhotic patients. SsPMTH-sarcopenia was an independent predictor of mortality in these patients and more accurately predicted mortality compared to SnPMTH-sarcopenia.

Cyanoacrylate injection versus band ligation for bleeding from cardiac varices along the lesser curvature of the stomach

BACKGROUND/AIMS: Practice guidelines recommend endoscopic band ligation (EBL) and endoscopic variceal obturation (EVO) for bleeding from esophageal varices and fundal varices, respectively. However, the optimal treatment for bleeding from cardiac varices along the lesser curvature of the stomach (GOV1) remains undefined. This retrospective study compared the efficacy between EBL and EVO for bleeding from GOV1. METHODS: Patients treated by EBL or EVO via cyanoacrylate injection for bleeding from GOV1 were enrolled. Patients diagnosed with hepatocellular carcinoma or treated with endoscopic injection sclerotherapy were excluded. RESULTS: The study included 91 patients treated for bleeding from GOV1. The mean age was 56.3±10.9 years (mean±SD), and 78 of them (85.7%) were men. Overall, 51 and 40 patients were treated with EBL and EVO, respectively. A trend for a higher hemostasis rate was noted in the EVO group (100%) than in the EBL group (82.6%, P=0.078). Varices rebled in 15 patients during follow-up. The rebleeding rate was significantly higher in the EBL group than in the EVO group (P=0.004). During follow-up, 13 patients died (11 in the EBL group and 2 in the EVO group); the survival rate was marginally significant between two groups (P=0.050). The rebleeding-free survival rate was significantly higher in the EVO group than in the EBL group (P=0.001). CONCLUSIONS: Compared to EBL, EVO offered significantly lower rebleeding rates, significantly higher rebleeding-free survival rates, and a trend for higher hemostasis and survival rates. EVO appears to be the better therapeutic option for bleeding from GOV1.

Hepatitis B surface antigen titer is a good indicator of durable viral response after entecavir off-treatment for chronic hepatitis B

BACKGROUND/AIMS: Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response. METHODS: This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg) at baseline, 56.8%; HBV DNA level, 6.8±1.3 log₁₀ IU/mL) treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal. RESULTS: After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076–4.706; P=0.031). When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log10 IU/mL (n=5), while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log₁₀ IU/mL (n=11) and >3 log₁₀ IU/mL (n=28), respectively. CONCLUSION: The off-treatment HBsAg level is closely related to clinical relapse after treatment cessation. A serum HBsAg level of <2 log₁₀ IU/mL is an excellent predictor of a sustained off-treatment response in CHB patients who have received ETV for a sufficient duration.