Effect of antiviral therapy in patients with low HBV DNA level on transarterial chemoembolization for hepatocellular carcinoma.

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low-level viremia HBV-HCC receiving non-curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low-level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV-HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non-antiviral group). The definition of low-level viremia was an HBV DNA level <2000 IU/ml. Kaplan-Meier curves, log-rank tests and Cox regression analysis were used for statistical analyses. The median follow-up duration was 39 months (1-174 months). Overall survival (OS) did not differ between groups (P = .227). Barcelona Clinic Liver Cancer stage (BCLC), Child-Pugh (CP) class and α-fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P = .022) was a prognostic factor for 2-year survival. On subgroup analysis, antiviral therapy improved short-term survival in patients with BCLC stage 0 and A (P = .037) and CP class A (P = .04). In patients with low-level viremia, antiviral therapy yielded short-term survival benefits, particularly in patients with early-stage HCC.

Selected nasogastric lavage in patients with nonvariceal upper gastrointestinal bleeding.

BACKGROUND: Risk stratification before endoscopy is crucial for proper management of patients suspected as having upper gastrointestinal bleeding (UGIB). There is no consensus regarding the role of nasogastric lavage for risk stratification. In this study, we investigated the usefulness of nasogastric lavage to identify patients with UGIB requiring endoscopic examination. METHODS: From January 2017 to December 2018, patients who visited the emergency department with a clinical suspicion of UGIB and who underwent nasogastric lavage before endoscopy were eligible. Patients with esophagogastric variceal bleeding were excluded. The added predictive ability of nasogastric lavage to the Glasgow-Blatchford score (GBS) was estimated using category-free net reclassification improvement and integrated discrimination improvement. RESULTS: Data for 487 patients with nonvariceal UGIB were analyzed. The nasogastric aspirate was bloody in 67 patients (13.8 %), coffee-ground in 227 patients (46.6 %), and clear in 193 patients (39.6 %). The gross appearance of the nasogastric aspirate was associated with the presence of UGIB. Model comparisons showed that addition of nasogastric lavage findings to the GBS improved the performance of the model to predict the presence of UGIB. Subgroup analysis showed that nasogastric lavage improved the performance of the prediction model in patients with the GBS ≤ 11, whereas no additive value was found when the GBS was greater than 11. CONCLUSIONS: Nasogastric lavage is useful for predicting the presence of UGIB in a subgroup of patients, while its clinical utility is limited in high-risk patients with a GBS of 12 or more.

Clinical outcomes of endoscopic removal of foreign bodies from the upper gastrointestinal tract.

BACKGROUND: Ingested foreign objects frequently require emergency removal. This study aimed to investigate the clinical outcomes of endoscopic removal of foreign bodies from the upper gastrointestinal tract and the risk factors for adverse events. METHODS: Adults (> 18 years) who underwent endoscopic management of ingested foreign bodies at two centers, one inland and one on the coast, between January 2008 and December 2017 were eligible. Clinical characteristics and procedure-related outcomes were retrospectively reviewed. Patients were divided into two groups, based on whether the foreign bodies were sharp or blunt in shape. RESULTS: A total of 853 patients aged 19-96 years were analyzed. Ingestion of fish bones was more common in the coastal area, whereas ingestion of food boluses was more common in the inland area. The duration of impaction ranged from 1 h to over 1 month and was significantly longer in patients who ingested blunt than sharp foreign bodies (15 vs. 5 h, p < 0.001). Most (98.9%) foreign bodies were successfully removed. Adverse events occurred in 31.2 % of patients, including ulcers (4.0%) and perforations (3.3 %). Multivariate analysis showed that age (odds ratio [OR] 1.015, p = 0.012), sharp foreign bodies (OR 5.133, p < 0.001), location in the esophagus (OR 2.723, p = 0.018), and duration of impaction (OR 1.431, p < 0.001) were factors associated with adverse events. CONCLUSIONS: Early recognition and timely endoscopic removal of ingested foreign bodies, particularly in elderly patients and those with sharp foreign bodies, may improve clinical outcomes.

Optimal Timing of Feeding After Endoscopic Hemostasis in Patients With Peptic Ulcer Bleeding: A Randomized, Noninferiority Trial (CRIS KCT0001019).

OBJECTIVES: The optimal duration of fasting after endoscopic hemostasis in patients with peptic ulcer bleeding has not yet been determined. We investigated the appropriate timing of feeding after endoscopic hemostasis in patients with high-risk peptic ulcer bleeding. METHODS: This study was a randomized, single center, noninferiority trial. Between February 2014 and March 2019, consecutive patients with peptic ulcer bleeding were randomized to resume feeding either 24 or 48 hours after successful endoscopic hemostasis. A total of 209 eligible patients were included in the intention-to-treat analysis and 200 in the per-protocol (PP) analysis. The primary outcome measure was recurrent bleeding within 7 days of hemostasis. Noninferiority testing was performed in the PP population, and the noninferiority margin was set at 10%. Secondary outcomes included 30-day rebleeding and mortality, transfusion requirements, and length of hospital stay. RESULTS: Recurrent bleeding rates at 7 days were 7.9% in the 24-hour group and 4.0% in the 48-hour group in the PP analysis; tests for noninferiority did not reach statistical significance (difference: 3.9%, 95% confidence interval [CI]: -2.7 to 10.5, P value for noninferiority = 0.034). The recurrent bleeding rates within 30 days were 10.9% and 4.0% in the 24- and 48-hour groups (difference: 6.9%, 95% CI: -0.5 to 14.2), and the 30-day mortality rates were 5.9% and 14.1%, respectively (difference: -8.2%, 95% CI: -16.5 to 0.1) in the PP analysis. The transfusion requirement and the length of hospital stay were similar between the 2 groups. DISCUSSION: Early refeeding at 24 hours after endoscopic hemostasis is not noninferior to later refeeding at 48 hours for rebleeding in patients with high-risk peptic ulcer bleeding. Our results do not allow a recommendation of refeeding at 24 hours, rather than later refeeding in this population.

Prevalence, incidence and risk factors of tamoxifen-related non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: Tamoxifen is associated with an increased risk of developing fatty liver. The aim of this systematic review and meta-analysis was to evaluate the prevalence and incidence of fatty liver developed after tamoxifen treatment in breast cancer patients. METHODS: A systematic search of PubMed (Medline), EMBASE, OVID Medline, the Cochrane Library and other databases was performed for this review. The abstracts obtained from the search were reviewed by two investigators who chose manuscripts for full-text review. The event rates were calculated with a random-effects model and quality-effects model. RESULTS: The search yielded 165 references. Of these, 24 were included in the quantitative summary. We analysed the data of a total of 6,962 patients treated with tamoxifen and 975 patients not treated with tamoxifen. The prevalence of fatty liver among patients with breast cancer taking tamoxifen was 40.25 per 100 patients and the incidence rate was 12.37 per 100 person-years. The incidence of fatty liver was much higher in the tamoxifen group than in the control group [incidence rate ratio: 3.12, 95% CI (confidence interval): 2.05-4.75, I2  = 61%], regardless of region. The main risk factors were body mass index (BMI) [hazard ratio (HR): 1.15, 95% CI: 1.09-1.22] and hypercholesterolaemia (HR: 1.01, 95% CI: 1.00-1.02). CONCLUSION: The use of tamoxifen was associated with increased risks in the incidence and prevalence of fatty liver, especially in patients with high BMI and hypercholesterolaemia.

Clinical significance of regional lymph node enlargement in patients with EGC within the expanded criteria for ESD.

BACKGROUND: Lymph node (LN) metastasis is negligible in early gastric cancer (EGC) within expanded criteria for endoscopic submucosal dissection (ESD). However, regional lymph nodes in abdominal CT scans are sometimes enlarged in patients with EGC within the expanded criteria for endoscopic submucosal dissection (ESD). In this study, we investigated the clinical significance of regional lymph node enlargement on abdominal CT scan in patients with EGC within the expanded criteria for ESD. METHODS: From December 2010 to April 2015, among 301 patients with EGC within the ESD expanded criteria, 47 patients with regional lymph node enlargement shown by abdominal CT scan were prospectively enrolled. We performed surgical resection or periodic follow-up with abdominal CT scans and upper endoscopy every 6 months to evaluate whether the enlarged lymph nodes are due to metastasis or a reactive change. RESULTS: The mean age of the 47 patients (38 males, 9 female) was 64.8 years. The enlarged lymph nodes were usually single (26/47, 44.6%) and sized as follows: 11 nodes were ≤ 5 mm, 19 were 6-10 mm, and 17 were ≥ 10 mm. Four of the 47 patients initially underwent surgical resection, and 8 patients underwent surgical resection after ESD. However, there was no lymph node metastasis in surgical specimens. Thirty-five patients received ESD and periodically followed up at a median duration of 56 months (IQR: 44-59 month). The enlarged lymph node disappeared in 12 of 35 patients, decreased in 9 patients and remained the same size in 13 patients, and increased in 1 patient. CONCLUSION: Regional lymph node enlargement on abdominal CT scan in patients within expanded criteria for ESD of ECG may be not due to metastasis but a reactive change.

Improved detection of hepatocellular carcinoma by dynamic computed tomography in cirrhotic patients with chronic hepatitis B: A multicenter study.

BACKGROUND AND AIMS: Current guidelines for chronic hepatitis B (CHB) patients are to undergo surveillance for hepatocellular carcinoma (HCC) with 6-monthly ultrasonography (US). However, sensitivities of US to detect early-stage HCC in cirrhotic patients are suboptimal. We aimed to compare overall survival and detection rates of very-early-stage HCC in two groups: group A, undergoing 6-monthly US versus group B, undergoing 6-monthly US alternating with dynamic computed tomography (CT). METHODS: This retrospective multicenter study assessed 1235 cirrhotic patients with CHB under entecavir/tenofovir therapy from 2007 to 2016. The primary endpoint was overall survival rates between the two groups. The Cox proportional hazards model and propensity score matching analyses were used to assess the effect of surveillance modalities on overall survival and detection of Barcelona Clinic Liver Cancer stage 0 HCC after balancing. RESULTS: During a median follow-up of 4.5 years, 10-year cumulative HCC incidence rates of 16.3% were significantly higher in group B (n = 576) than 13.7% in group A (n = 659; P < 0.001). However, in patients with HCC, 10-year overall survival rates of 85.1% were significantly higher in group B than 65.6% in group A (P = 0.001 by log-rank test). CT exam alternating with US was independently associated with reduced overall mortality (hazard ratio 0.47, P = 0.02). Cumulative incidence of Barcelona Clinic Liver Cancer stage 0 HCC was significantly higher in group B than in group A (hazard ratio 2.82, P < 0.001). CONCLUSION: In cirrhotic patients with CHB, dynamic CT exam alternating with US led to higher detection rates of very-early-stage HCC and benefit of overall survival than did US exams.

Estimation of renal function in patients with liver cirrhosis: Impact of muscle mass and sex.

BACKGROUND & AIMS: Accurate evaluation of renal function in patients with liver cirrhosis is critical for clinical management. However, there are still discrepancies between the measured glomerular filtration rate (mGFR) and creatinine-based estimated GFR (eGFR). In this study, we compared the performance of 2 common eGFR measurements with mGFR and evaluated the impact of low muscle mass on overestimation of renal function in patients with cirrhosis. METHODS: This study included 779 consecutive cirrhotic patients who underwent 51Cr-ethylenediamine tetra acetic acid (EDTA) (as a mGFR) and abdominal computed tomography (CT). The eGFR was calculated using creatinine or cystatin C. Muscle mass was assessed in terms of the total skeletal muscle at L3 level using CT. RESULTS: Modification of diet in renal disease (MDRD)-eGFR was overestimated in 47% of patients. A multivariate analysis showed that female sex (adjusted odds ratio [aOR] 4.91), Child B and C vs. A (aOR 1.69 and 1.84) and skeletal muscle mass (aOR 0.89) were independent risk factors associated with overestimation. Interestingly, the effect of skeletal muscle mass on overestimation varied based on sex. Decreased muscle mass significantly enhanced the risk of overestimation of MDRD-eGFR in male patients, but not in female patients. Cystatin C-based eGFR showed a better correlation with mGFR than MDRD-eGFR; it was also better at predicting overall survival and the incidence of acute kidney injury than MDRD-eGFR. CONCLUSIONS: The risk factors associated with overestimation included female sex, impaired liver function, and decreased muscle mass in males. In particular, eGFR in male patients with sarcopenia should be carefully interpreted. Creatinine-based eGFR was overestimated more often than cystatin C-based eGFR, with overestimation of eGFR closely related to poor prognostic performance. LAY SUMMARY: Overestimation of renal function frequently occurs in patients with liver cirrhosis when using serum creatinine. Decreased muscle mass has a great impact on overestimation of kidney function especially in male patients with cirrhosis. Compared with creatinine, cystatin C was more closely correlated with measured glomerular filtration rate and had a higher predictive ability for renal complications and survival than creatinine.

Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy.

BACKGROUND & AIMS: Recently, the PAGE-B score and Toronto HCC risk index (THRI) have been developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB). We aimed to validate PAGE-B scores and THRI in Asian patients with CHB and suggested modified PAGE-B scores to improve the predictive performance. METHODS: From 2007 to 2017, we examined 3,001 Asian patients with CHB receiving entecavir/tenofovir therapy. We assessed the performances of PAGE-B, THRI, CU-HCC, GAG-HCC, and REACH-B for HCC development. A modified PAGE-B score (mPAGE-B) was developed (derivation set, n = 2,001) based on multivariable Cox models. Bootstrap for internal validation and external validation (validation set, n = 1,000) were performed. RESULTS: The five-year cumulative HCC incidence rates were 6.6% and 7.2% in the derivation and validation datasets after entecavir/tenofovir onset. In the derivation dataset, age, gender, serum albumin levels, and platelet counts were independently associated with HCC. The mPAGE-B score was developed based on age, gender, platelet counts, and serum albumin levels (time-dependent area under receiver operating characteristic curves [AUROC] = 0.82). In the validation set, the PAGE-B and THRI showed similar AUROCs to CU-HCC, GAG-HCC, and REACH-B at five years (0.72 and 0.73 vs. 0.70, 0.71, and 0.61 respectively; all p >0.05 except REACH-B), whereas the AUROC of mPAGE-B at five years was 0.82, significantly higher than the five other models (all p <0.01). HCC incidence rates after initiation of entecavir/tenofovir therapy in patients with CHB were significantly decreased in all risk groups in long-term follow-up periods. CONCLUSION: Although PAGE-B and THRI are applicable in Asian patients with CHB receiving entecavir/tenofovir therapy, mPAGE-B scores including additional serum albumin levels showed better predictive performance than the PAGE-B score. LAY SUMMARY: PAGE-B scores and Toronto HCC risk index were developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with CHB under potent antiviral therapy. This study validated these two scores in Asian patients with CHB and suggested that modified PAGE-B scores could improve the predictive performance. A modified PAGE-B score, which is based only on a patient's age, gender, baseline platelet counts, and serum albumin levels at treatment initiation, represents a reliable and easily available risk score to predict HCC development during the first five years of antiviral treatment in Asian patients with CHB. With a scoring range from 0 to 21 points, a modified PAGE-B score differentiates the HCC risk. A modified PAGE-B score significantly differentiates the five-year HCC risk: low ≤8 points and high ≥13 points.

Follow-up Creatinine Level Is an Important Predictive Factor of In-hospital Mortality in Cirrhotic Patients with Spontaneous Bacterial Peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is one of the severe complications of liver cirrhosis. Early detection of high-risk patients is essential for prognostic improvement. The aim of this study is to investigate the predictive factors related to in-hospital mortality in patients with SBP. METHODS: This was a retrospective study of 233 SBP patients (181 males, 52 females) who were admitted to four tertiary referral hospitals between August 2002 and February 2013. The patients' laboratory and radiologic data were obtained from medical records. The Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease sodium model (MELD-Na) scores were calculated using the laboratory data recorded at the time of the SBP episode. RESULTS: The causes of liver cirrhosis were hepatitis B (44.6%), alcohol (43.8%), hepatitis C (6.0%), and cryptogenic cirrhosis (5.6%). The mean MELD-Na and CTP scores were 27.1 and 10.7, respectively. Thirty-one of the patients (13.3%) died from SBP in hospital. Multivariate analysis revealed that maximum creatinine level during treatment was a statistically significant factor for in-hospital mortality (P = 0.005). The prognostic accuracy of the maximum creatinine level during treatment was 78.0% (P < 0.001). The optimal cutoff point for the maximum serum creatinine was 2 mg/dL (P < 0.001). CONCLUSION: The follow-up creatinine level during treatment is an important predictive factor of in-hospital mortality in cirrhotic patients with SBP. Patients with SBP and a serum creatinine level during treatment of ≥ 2.0 mg/dL might have a high risk of in-hospital mortality.

Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study.

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m2 (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m2 along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m2. CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m2 and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.

Efficacy and safety of human placental extract for alcoholic and nonalcoholic steatohepatitis: an open-label, randomized, comparative study.

Human placental extract (HPE) is a traditional medicine that has been used for the symptomatic treatment of liver disease without any verifying clinical evidence. This study aimed to evaluate the efficacy and safety of HPE in patients with alcoholic or nonalcoholic steatohepatitis (ASH or NASH). We designed this clinical trial as a multicenter, open-label, randomized, comparative noninferiority study to improve the reliability of analyses. The enrollment criteria were limited to ASH or NASH patients with serum alanine aminotransferase (ALT) 1.5-fold higher than the normal level. Patients in the control group were treated with a commercially available mixture of liver extract and flavin adenine dinucleotide (LE­FAD). Intention-to-treat (ITT) analysis was applied to 194 patients, and per-protocol (PP) analysis was available for 154 patients. The rate of primary goal achievement of treatment efficacy was arbitrarily defined as 20% or greater improvement in ALT level compared with the pretreatment level and did not differ significantly between the HPE and control groups [62.9% (44/70) vs. 48.8% (41/84); p=0.0772]. ITT and modified ITT analysis showed results similar to those of PP analysis. Adverse drug reactions (ADRs) of minimal to moderate degree occurred in 3.1% of patients. The ADR and treatment compliance rates were similar in both groups. In conclusion, the clinical value of HPE in the treatment of ASH and NASH is equivalent to that of LE­FAD.

Enhancing liver cirrhosis varices and CSPH risk prediction with spleen stiffness measurement using 100-Hz probe.

Managing complications of liver cirrhosis such as varices needing treatment (VNT) and clinically significant portal hypertension (CSPH) demands precise and non-invasive diagnostic methods. This study assesses the efficacy of spleen stiffness measurement (SSM) using a 100-Hz probe for predicting VNT and CSPH, aiming to refine diagnostic thresholds. A retrospective analysis was conducted on 257 cirrhotic patients, comparing the diagnostic performance of SSM against traditional criteria, including Baveno VII, for predicting VNT and CSPH. The DeLong test was used for statistical comparisons among predictive models. The success rate of SSM@100 Hz was 94.60%, and factors related to SSM failure were high body mass index and small spleen volume or length. In our cohort, the identified SSM cut-off of 38.9 kPa, which achieved a sensitivity of 92% and a negative predictive value (NPV) of 98% for detecting VNT, is clinically nearly identical to the established Baveno threshold of 40 kPa. The predictive capability of the SSM-based model for VNT was superior to the LSM ± PLT model (p = 0.017). For CSPH prediction, the SSM model notably outperformed existing non-invasive tests (NITs), with an AUC improvement and significant correlations with HVPG measurements (obtained from 49 patients), highlighting a correlation coefficient of 0.486 (p < 0.001) between SSM and HVPG. Therefore, incorporating SSM into clinical practice significantly enhances the prediction accuracy for both VNT and CSPH in cirrhosis patients, mainly due to the high correlation between SSM and HVPG. SSM@100 Hz can offer valuable clinical assistance in avoiding unnecessary endoscopy in these patients.

Evaluation of the Efficacy and Safety of DW1903 in Patients with Gastritis: A Randomized, Double-Blind, Noninferiority, Multicenter, Phase 3 study.

Background/Aims: H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA. However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis. Methods: A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared. Results: According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different. Conclusions: DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).

Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells.

Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (P<0.0001) and lymph node metastasis (P<0.0001), higher pathological T and tumor node metastasis stages (P=0.047 and P=0.001), and more frequent SOX2 (P=0.038) and NOTCH3 expressions (P=0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%, P<0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (P<0.0001) and multivariate (P=0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma.

Hepatogenous diabetes in cirrhosis is related to portal pressure and variceal hemorrhage.

BACKGROUND AND AIM: The clinical impact and complications of hepatogenous diabetes (HD) on cirrhosis have not been elucidated. This study aimed to evaluate the relationship of HD with portal hypertension (PHT) and variceal hemorrhage and to assess the prevalence of HD. METHODS: From July 2007 to December 2009, 75-g oral glucose tolerance test and insulin resistance (IR) were evaluated for 195 consecutive cirrhotic liver patients (M:F = 164:1, 53.0 ± 10.2 years) who had no history of diabetes mellitus. IR was calculated using the homeostasis model of assessment-insulin resistance (HOMA-IR) formula. Endoscopy for varices, hepatic venous pressure gradient (HVPG), and serologic tests were also conducted. RESULTS: HD was observed in 55.4 % (108/194) of the patients. Among them, 62.0 % required OGTT for diagnosis because they did not show an abnormal fasting plasma glucose level. The presence of HD showed a significant correlation with high Child-Pugh's score, variceal hemorrhage, and HVPG (p = 0.004, 0.002, and 0.019, respectively). In multivariate analysis, Child-Pugh's score (OR 1.43, 95 % CI 1.005-2.038) and HVPG (OR 1.15, 95 % CI 1.003-2.547) had significant relationships with HD. Patients with recent variceal hemorrhages (within 6 months) exhibited significantly higher glucose levels at 120 min in OGTT compared to patients without hemorrhages (p = 0.042). However, there was no difference in fasting glucose levels. The 120-min glucose level and HOMA-IR score were significantly and linearly correlated with HVPG (r (2) = 0.189, p < 0.001 and r (2) = 0.033, p = 0.011, respectively). CONCLUSION: HD and IR have significant relationships with PHT and variceal hemorrhage. Postprandial hyperglycemia in particular had a significant relationship with variceal hemorrhage.

Risk factors for acute hepatitis A infection in Korea in 2007 and 2009: a case-control study.

This study aimed to identify the risk factors associated with acute hepatitis A virus (HAV) infection in the Korean population. Participants were recruited from five referral hospitals across the country in 2007 and from 11 hospitals in 2009. Patients with positive anti-HAV IgM antibody tests became the case group, while patients treated for non-contagious diseases at the same hospitals were recruited as controls. A total of 222 and 548 case-control pairs were studied in the 2007 and 2009 surveys, respectively. Data from the surveys were analyzed jointly. In a multivariate analysis, sharing the household with HAV-infected family members (OR, 6.32; 95% CI, 1.4-29.6), contact with other HAV-infected individuals (OR, 4.73; 95% CI, 2.4-9.4), overseas travel in 2007 (OR, 19.93; 95% CI, 2.3-174.4), consumption of raw shellfish (OR, 2.51; 95% CI, 1.8-3.5), drinking bottled water (OR, 1.64; 95% CI, 1.3-8.4), and occupation that involve handling food (OR, 3.30; 95% CI, 1.3-8.4) increased the risk of HAV infection. Avoiding contact with HAV-infected individuals and avoiding raw foods eating could help minimize the risk of hepatitis A infection. Immunization must be beneficial to individuals who handle food ingredients occupationally or travel overseas to HAV-endemic areas.

Randomised clinical trial: comparison of tegoprazan and lansoprazole as maintenance therapy for healed mild erosive oesophagitis.

BACKGROUND: Tegoprazan is a novel potassium-competitive acid blocker used to treat acid-related disorders. AIM: To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in healed erosive oesophagitis (EE) METHODS: In this phase 3, double-blind, multi-centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels. RESULTS: We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan-treated than lansoprazole-treated patients. CONCLUSIONS: Tegoprazan 25 mg was non-inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.

The Clinical Courses and Prognosis of Cirrhotic Patients after First Acute Decompensation: Prospective Cohort Study.

BACKGROUND: The European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium suggested that the clinical courses after acute decompensation (AD) stratify the long-term prognosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre acute-on-chronic liver failure (pre ACLF), and ACLF. However, previous studies included patients with a history of previous AD and had limitations associated with identifying the clinical factors related to prognosis after the first AD. METHOD: The prospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort included cirrhotic patients who were hospitalised with first AD between July 2015 and August 2018. We analysed the factors associated with readmission after the first AD and compared the characteristics and prognosis among each subgroup to evaluate the risk factors for the occurrence of pre ACLF after AD. RESULT: A total of 746 cirrhotic patients who were hospitalised with first AD were enrolled. The subgroups consisted of SDC (n = 565), UDC (n = 29), pre ACLF (n = 28), and ACLF (n = 124). Of note, pre ACLF showed a poorer prognosis than ACLF. The risk factors associated with readmission within 3 months of first AD were non-variceal gastrointestinal (GI) bleeding, hepatic encephalopathy (HE), and high MELD score. Viral aetiology was associated with the occurrence of pre ACLF compared with alcohol aetiology regardless of baseline liver function status. CONCLUSION: Cirrhotic patients with first AD who present as non-variceal GI bleeding and HE can easily relapse. Interestingly, the occurrence of AD with organ failure within 3 months of first AD (pre ACLF) has worse prognosis compared with the occurrence of organ failure at first AD (ACLF). In particular, cirrhotic patients with viral hepatitis with/without alcohol consumption showed poor prognosis compared to other aetiologies. Therefore, patients with ACLF after AD within 3 months should be treated more carefully and definitive treatment through LT should be considered.