Efficacy of Tegoprazan in Patients With Functional Dyspepsia: A Prospective, Multicenter, Single-arm Study.

Background/Aims: Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD. Methods: FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean (NDI-K), and gastroesophageal reflux disease-health-related quality of life (GERD-HRQL). The main outcome was satisfactory symptom relief rates at 8 weeks. Results: In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study. Conclusion: Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.

Clinical Trial: Efficacy of Mosapride Controlled-release and Nortriptyline in Patients With Functional Dyspepsia: A Multicenter, Double-placebo, Double-blinded, Randomized Controlled, Parallel Clinical Study.

Background/Aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Conclusion: Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Constipation in Patients With Chronic Kidney Disease.

Constipation is a frequent symptom in patients with chronic kidney disease (CKD). This review outlines the mechanisms and management of constipation in patients with CKD from a physician's perspective. Common causes of constipation in patients with CKD include concomitant medications, low dietary fiber intake, water-restricted diet, lack of physical activity, altered gut microbiota, and reduced gastrointestinal motility. Constipation has a negative impact on overall health, and, in particular, the presence of constipation has been associated with worsening kidney function and increased risk of developing advanced stages of CKD. Although lifestyle and dietary modifications may not always be practical for patients with CKD, they are recommended because they are beneficial as they lower mortality in patients with CKD. The use of laxatives containing magnesium salts, bulking agents, and osmotic laxatives may have insufficient efficacy and may be associated with adverse effects. In contrast, lactulose and lubiprostone have been shown to exhibit reno-protective effects. Linaclotide and plecanatide have very limited systemic absorption and appear safe in patients with CKD. Tenapanor reduces paracellular intestinal phosphate absorption in addition to blocking sodium uptake by enterocytes, and provides additional benefit in patients patients with CKD who have hyperphosphatemia and constipation. Prucalopride leads to improvements in bowel function and constipation-related symptoms in cases in which response to conventional laxatives are inadequate. However, the dose of prucalopride should be reduced to 1 mg once daily for patients with CKD. In conclusion, there are important advances on the impact and treatment of constipation in patients with CKD.

Two Cases of Severe Complications Due to an Esophageal Fish Bone Foreign Body.

Cases of foreign body ingestion are encountered relatively often in clinical settings; however, serious complications are rare. In such cases, mediastinal abscess due to esophageal perforation can become a life-threatening complication. We encountered two cases of severe complications due to an esophageal fish bone foreign body. The first case was a 40-year-old male with an intramural esophageal abscess due to a fish bone after eating fish five days before visiting the hospital. The patient underwent surgical treatment, but the esophageal abscess did not improve; so, the abscess was drained through endoscopic mucosal dissection, and the abscess improved. In the second case, a 64-year-old male, who had eaten fish three days before visiting the hospital, had esophageal perforation by a fish bone, and abscess formation in the mediastinum and the lesser sac in the abdominal cavity were observed. Although surgical treatment was performed, the intra-abdominal abscess formation was not controlled; so, percutaneous drainage (PCD) was inserted, and the abscess improved. Both patients were discharged without any complications. Here, we report two cases that were improved through surgical treatments and additional treatments such as endoscopic dissection and PCD.

2022 Seoul Consensus on Clinical Practice Guidelines for Functional Constipation.

Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.

Case report of laryngeal infection by Clinostomum complanatum 24 days after ingestion of raw fish.

RATIONALE: Clinostomum complanatum is a laryngeal fluke whose hosts include birds and mammals.[1] In humans, infection occurs accidentally during the consumption of raw freshwater fish.[1,2]. PATIENT CONCERNS: A 59-year-old female presented to our hospital with throat pain and globus sensation. The patient had been prescribed Proton Pump Inibitor for 3 weeks at another hospital. The patient continued the medication, but the discomfort persisted, and she was admitted to our hospital for further examination. The patient had eaten raw fish 24 days before, and the symptoms occurred after eating the raw fish. Endoscopy under sedation showed a fluke, with an approximate length of 8.0 mm and width of 3.2 mm, on the interaryepiglottic fold, with active motility on the mucosa. DIAGNOSIS INTERVENTIONS: It was extracted from the larynx using biopsy forceps and identified as C complanatum. OUTCOMES: After the fluke was removed, symptoms improved, and the patient was discharged. The globus symptoms completely resolved at the last follow-up visit. LESSONS: To the best of our knowledge, this is an endoscopically diagnosed and treated case of human infection by C complanatum in Korea after the longest period of infection. This suggests that C complanatum can survive for up to 3 weeks or more in the gastrointestinal tract. Endoscopy is a useful tool for the diagnosis and treatment of patients with atypical extraesophageal symptoms who do not respond to Proton Pump Inibitors.

Association of the etiology and peak level of markedly elevated aminotransferases with mortality: a multicenter study.

BACKGROUND: Markedly elevated aminotransferase levels are commonly encountered among hospitalized patients. However, data regarding the trajectory of enzyme elevation and disease-specific prognosis are limited. METHODS: This study included 3237 patients with at least one episode of aspartate aminotransferase or alanine aminotransferase level being higher than 400 U/L between January 2010 and December 2019 at 2 centers. Patients were classified into 5 groups comprising 13 diseases according to etiology. Factors associated with 30-day mortality were evaluated using a logistic regression analysis. RESULTS: The most common disease leading to markedly elevated aminotransferase level was ischemic hepatitis (33.7%), followed by pancreatobiliary disease (19.9%), DILI (12.0%), malignancy (10.8%), and viral hepatitis (7.0%). The 30-day all-cause mortality rate was 21.6%. The mortality rate for patients from the pancreatobiliary, hepatocellular, extrahepatic, malignancy, and ischemic hepatitis groups was 1.7%, 3.2%, 13.8%, 39.9%, and 44.2%, respectively. Age, etiology, and peak aminotransferase levels were independently associated with 30-day mortality. CONCLUSIONS: In patients with markedly elevated liver enzymes, the etiology and peak AST level are significantly associated with mortality.

Clinical Features of Hepatitis C Virus-related Acute-on-chronic Liver Failure in a Korean Population.

Background/Aims: Acute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failure and high short-term mortality. On the other hand, few studies reflecting the various etiologies of cirrhosis are available. This study examined the clinical features of patients with hepatitis C virus (HCV)-related ACLF. Methods: Between January 2005 and December 2018, 109 HCV-related cirrhosis patients hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and bacterial infection) were enrolled for ACLF defined by the European Association for the Study of the Liver (EASL). Results: ACLF developed in 35 patients (32.1%) on admission. Eight, eight, and 19 patients had ACLF grades 1, 2, and 3, respectively. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%). Compared with all other prognostic scores, the Chronic liver failure Consortium Organ Failure score predicted the 90-day mortality most accurately, with an area under the receiver operator characteristic of 0.921. Conclusions: HCV-related ACLF has unique clinical characteristics distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful for predicting the short-term mortality in HCV-related cirrhosis.

Self-reported Non-celiac Gluten Sensitivity in the Korean Population: Demographic and Clinical Characteristics.

Background/Aims: Non-celiac gluten sensitivity is characterized by intestinal and extra intestinal symptoms associated with the consumption of gluten-containing food. Since biomarkers for non-celiac gluten sensitivity are lacking, its prevalence is estimated based on self-reported symptoms. However, no data exist on self-reported non-celiac gluten sensitivity in the Korean population. Thus, we aim to investigate the prevalence of self-reported non-celiac gluten sensitivity in the Korean population and to determine its demographic and clinical characteristics. Methods: This study surveyed Korean participants aged 18-80 years who visited gastroenterology outpatient clinics at 9 tertiary hospitals in South Korea from January 2016 to February 2017. They were questioned regarding symptoms related to gluten ingestion: degree of discomfort (visual analog scale score), frequency, time of symptom onset, and duration. Abdominal discomfort caused by 11 different kinds of gluten-containing Korean food items was investigated. Results: More non-celiac gluten sensitivity self-reporters were identified among those with irritable bowel syndrome (33.6%) than among controls (5.8%). Major gastrointestinal symptoms included bloating (75.0%), abdominal discomfort (71.3%), and belching (45.0%). Common extra-intestinal symptoms included fatigue (20.0%) and headache (13.7%). More than half of those who self-reported non-celiac gluten sensitivity (66.3%) developed symptoms within 1 hour of food ingestion, and symptoms were localized in the upper abdomen (37.5%) and entire abdomen (30.0%). Conclusion: Our findings suggest that if there are gluten-related symptoms in irritable bowel syndrome, the possibility of accompanying non-celiac gluten sensitivity should be considered.

Clinical characteristics and outcome of iatrogenic colonic perforation related to diagnostic vs. therapeutic colonoscopy.

AIM: Iatrogenic colonic perforation (ICP) is a rare serious complication of colonoscopy, where standard treatment is controversial. This study aimed to characterize diagnostic ICP (DICP) compared to therapeutic ICP (TICP) and determine the possible indication of endoscopic repair. METHODS: We studied patients with ICP over 7 years starting in 2011. Their demographics and data regarding perforation, treatment, and outcome were investigated by retrospective review of medical records, and the diagnostic and therapeutic groups were compared. RESULTS: Among 29,882 patients who underwent colonoscopy, ICP was identified in 28 (0.09%: diagnostic, 15/24,758, 0.06%; therapeutic, 13/5124, 0.25%). A total of 56 patients (33 DICP and 23 TICP) including 28 referred cases were analyzed. Mean age was 62.3 ± 11.4 years, and 24 were men. Perforations occurred mostly in the rectosigmoid region and half were detected during or immediately after colonoscopy. Endoscopic treatment was successful in 22 cases and 34 required surgery. Mortality occurred in 4 (7.1%). Compared to TICP, DICP was more prevalent in females and rectosigmoid region and more frequently detected immediately (all p < 0.05); DICP tended to occur in older patients, be larger and have better chance of endoscopic repair. Regardless of type of ICP, female predominance, smaller perforation, more frequent immediate detection, and shorter hospital stay (all p = 0.01) were found in the endoscopic repair group. CONCLUSION: DICP was more frequent in the rectosigmoid area in older women and could be detected immediately. Immediate detection and small perforation size could be important factors for endoscopic repair. Careful attention and gentle manipulation should be required.

Acute hepatitis E virus superinfection increases mortality in patients with cirrhosis.

BACKGROUND: Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD). METHODS: This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed. RESULTS: Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. CONCLUSIONS: Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

Markedly Elevated Aspartate Aminotransferase from Non-Hepatic Causes.

There have been no reports on mortality in patients with markedly elevated aspartate aminotransferase (AST) levels from non-hepatic causes to date. This study aimed to determine the etiologies of markedly elevated AST levels > 400 U/L due to non-hepatic causes and to investigate the factors associated with mortality in these cases. This retrospective study included 430 patients with AST levels > 400 U/L unrelated to liver disease at two centers between January 2010 and December 2021. Patients were classified into three groups according to etiology: skeletal muscle damage, cardiac muscle damage, and hematologic disorder. Binary logistic regression analysis was performed to evaluate the factors associated with 30-day mortality. The most common etiology for markedly elevated AST levels was skeletal muscle damage (54.2%), followed by cardiac muscle damage (39.1%) and hematologic disorder (6.7%). The 30-day mortality rates for the skeletal muscle damage, cardiac muscle damage, and hematologic disorder groups were 14.2%, 19.5%, and 65.5%, respectively. The magnitude of the peak AST level significantly correlated with 30-day mortality, with rates of 12.8%, 26.7%, and 50.0% for peak AST levels < 1000 U/L, <3000 U/L, and ≥3000 U/L, respectively. In the multivariate analysis, cardiac muscle damage (odds ratio [OR] = 2.76, 95% confidence interval [CI] = 1.31−5.80), hematologic disorder (OR = 9.47, 95% CI = 2.95−30.39), peak AST < 3000 U/L (OR = 2.94, 95% CI = 1.36−6.35), and peak AST ≥ 3000 U/L (OR = 9.61, 95% CI = 3.54−26.08) were associated with increased 30-day mortality. Our study revealed three etiologies of markedly elevated AST unrelated to liver disease and showed that etiology and peak AST level significantly affected the survival rate.

Clinical Features and Prognosis of Patients with Primary Intestinal B-cell Lymphoma Treated with Chemotherapy with or without Surgery.

Background/Aims: This multicenter study reviewed the clinical features and prognosis according to the primary site of involvement and the treatment modality in patients with B-cell primary intestinal lymphoma (PIL). Methods: Among 125 consecutive patients diagnosed with PIL, 100 patients were analyzed. Results: The median age was 59 years, and the male to female ratio was 1.86:1. Diffuse large B-cell lymphoma (66/100, 66.0%) was the most common histological subtype. The estimated 5-year survival rate (5-YSR) was 48.5%. The 5-YSR was similar regardless of the type of primary treatment (chemotherapy alone vs. surgery/chemotherapy, 50.7 vs. 45.3%, p=0.582). A comparison of the survival according to the primary site of involvement revealed a 5-YSR of 32.5% (p=0.027), 64.3% (reference), 46.5% (p=0.113), and 49.8% (p=0.024) for the small intestine, ileocecal region, large intestine, and multiple sites, respectively. Multivariate analysis, however, revealed a low hemoglobin level, advanced Ann Arbor stage, and aggressive histological type to be independent prognostic factors for shorter survival but not ileocecal region involvement. Conclusions: The Ann Arbor stage, hemoglobin level, and histological type were independent prognostic factors for survival, while the primary site of involvement and treatment modality did not affect the prognosis in patients with B-cell PIL.

Impact of non-hepatic hyperammonemia on mortality in intensive care unit patients: a retrospective cohort study.

BACKGROUND/AIMS: The effect of hyperammonemia on the mortality in patients with liver cirrhosis is well documented. However, little is known about the impact of hyperammonemia on mortality among intensive care unit patients without hepatic disease. We aimed to investigate factors associated with non-hepatic hyperammonemia among intensive care unit patients and to evaluate the factors related to the 7- and 90-day mortality. METHODS: Between February 2016 and February 2020, 948 patients without hepatic disease who had 972 episodes of admission to the intensive care unit were retrospectively enrolled and classified as hyperammonemia grades 0 (≤ 80 µg/dL; 585 [60.2%]), 1 (≤ 160 µg/dL; 291 [29.9%]), 2 (≤ 240 µg/dL; 55 [5.7%]), and 3 (> 240 µg/dL; 41 [4.2%]). Factors associated with hyperammonemia and the 7- and 90-day mortality were evaluated by multivariate logistic regression analysis and Cox regression analysis, respectively. Kaplan-Meier survival curves for the 7- and 90-day mortality were constructed. RESULTS: The independent risk factors for hyperammonemia were male sex (odds ratio, 1.517), age (0.984/year), acute brain failure (2.467), acute kidney injury (1.437), prothrombin time-international normalized ratio (2.272/unit), and albumin (0.694/g/dL). The 90-day mortality rate in the entire cohort was 24.3% and gradually increased with increasing hyperammonemia grade at admission (17.9%, 28.2%, 43.6%, and 61.0% in patients with grades 0, 1, 2, and 3, respectively). Additionally, non-hepatic hyperammonemia was an independent predictor of the 90- day mortality in intensive care unit patients. CONCLUSION: Non-hepatic hyperammonemia is common (39.8%) and associated with the 90-day mortality among intensive care unit patients.

Impact of acute kidney injury on mortality in patients with acute variceal bleeding.

BACKGROUND: The effect of acute kidney injury (AKI) on patients with acute variceal bleeding (AVB) using the recently proposed International Club of Ascites (ICA) criteria is unclear. This study aimed to evaluate the incidence of AKI using the ICA criteria and factors associated with the outcomes in cirrhotic patients with AVB. METHODS: This retrospective cohort study included data of cirrhotic patients with AVB from two centers in Korea. The association of the ICA criteria for AKI with 6-week mortality was analyzed through univariate and multivariate analyses using the Cox proportional hazard model. RESULTS: In total, there were 546 episodes of AVB in 390 patients, of which 425 and 121 episodes were due to esophageal and gastric variceal bleeding, respectively. Moreover, 153 patients fulfilled the ICA criteria for AKI, and 64, 30, 39, and 20 patients were diagnosed with stages 1a, 1b, 2, and 3, respectively. Conversely, 97 patients developed AKI within 42 days as per the conventional criteria. The 6-week mortality rate was significantly higher in patients with ICA-AKI than in patients without ICA-AKI; the occurrence of ICA-AKI was an independent factor for predicting the 6-week mortality. CONCLUSION: The ICA criteria could help diagnose renal dysfunction earlier, and presence of AKI is a predictor of mortality in patients with cirrhosis and AVB.

Impact of acute kidney injury on survival in patients with chronic hepatitis C: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is expected to occur commonly in patients with chronic hepatitis C. In addition, AKI may affect the survival of patients with chronic hepatitis C. However, few studies are available on this topic. We aimed to evaluate the incidence of AKI in patients with chronic hepatitis C and investigate the factors related to overall mortality. METHODS: Between January 2005 and December 2018, 1252 patients with chronic hepatitis C virus (HCV) infection, defined as persistent HCV RNA for at least 6 months, were retrospectively enrolled at two centers. Of them, 1008, 123, and 121 patients had chronic hepatitis (CH), compensated cirrhosis (Com-LC), and decompensated cirrhosis (Decom-LC) or hepatocellular carcinoma (HCC) at entry, respectively. Factors associated with AKI and overall mortality were evaluated using the Cox proportional regression model. The Kaplan-Meier survival curves for the development of AKI and overall mortality were generated. RESULTS: Over a mean follow-up period of 5.2 years, 285 patients developed AKI, with an incidence rate of 4.35 per 100 person-years. The incidence of AKI increased gradually with progression of chronic hepatitis C: CH (3.32 per 100 person-years), Com-LC (5.86 per 100 person-years), and Decom-LC or HCC (17.28 per 100 person-years). The patients without AKI showed better survival rates at 14 years than the patients with AKI (94.2% vs. 26.3%, P < 0.001). In multivariate Cox regression analysis, AKI (hazard ratio, 6.66; 95% confidence interval, 4.26-10.41) remained an independent risk factor for overall mortality. CONCLUSION: AKI is common in patients with chronic HCV infection and is associated with significant overall mortality. Therefore, clinicians should carefully monitor the occurrence of AKI, which is an important predictor of mortality in patients with chronic hepatitis C.

[Non-celiac Gluten Sensitivity].

Non-celiac gluten sensitivity (NCGS) is a term that is used to describe individuals who are not affected by celiac disease or wheat allergy, yet they have intestinal and/or extra-intestinal symptoms related to gluten ingestion with improvement of their symptoms upon withdrawing gluten from their diet. Gluten-related disorder groups are manifested by symptoms of gastrointestinal tract disorders, as well as hematological dermatological endocrinological, gynecological, rheumatological and nervous system symptoms. It is believed that NCGS represents heterogeneous groups with different subgroups characterized by different etiologies, clinical histories and clinical courses. There also appears to be an overlap between NCGS and irritable bowel syndrome (IBS). There is a need for establishing strict criteria for diagnosing NCGS. The absence of validated biomarkers remains a significant limitation for research studies on NCGS. New evidence shows that a gluten-free diet may be beneficial for some patients with gastrointestinal symptoms, such as those symptoms commonly found in patients with IBS. Further studies about NCGS are needed.

Clinical significance of endothelial progenitor cells in patients with liver cirrhosis with or without hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: The role of endothelial progenitor cells in patients with cirrhosis has seldom been investigated. This study was conducted to assess the clinical significance of circulating endothelial progenitor cells in patients with liver cirrhosis with or without hepatocellular carcinoma. METHODS: A blood sample was collected once from patients with cirrhosis alone (n = 34) or cirrhosis and hepatocellular carcinoma (n = 46) and healthy controls (n = 27) for assessing levels of endothelial progenitor cells and vascular endothelial growth factor. Blood cells staining positive for CD34/CD133/KDR using flow cytometry were characterized as endothelial progenitor cells. Plasma vascular endothelial growth factor was quantified by ELISA. RESULTS: The levels of CD34/KDR-positive endothelial progenitor cells, CD133/KDR-positive endothelial progenitor cells, and vascular endothelial growth factor were higher in patients with cirrhosis ± hepatocellular carcinoma than in healthy controls (P = 0.017, P < 0.001 and P < 0.001, respectively). The levels of endothelial progenitor cells and vascular endothelial growth factor did not show statistical difference according to Child-Turcotte-Pugh class. There was a moderately significant correlation between vascular endothelial growth factor levels and hepatocellular carcinoma stage (ρ = 0.464, P = 0.001). Smoking, ascites, and portal vein thrombosis were independently related to lower levels of circulating CD34/KDR-positive endothelial progenitor cells, higher levels of CD133/KDR-positive endothelial progenitor cells, and higher levels of vascular endothelial growth factor, respectively (P = 0.041, P = 0.023, and P < 0.001, respectively). CONCLUSION: Circulating endothelial progenitor cells and plasma vascular endothelial growth factor levels were higher in patients with liver cirrhosis ± hepatocellular carcinoma compared to healthy controls. The increase in endothelial progenitor cells and vascular endothelial growth factor may have a possible role in the development of complications, especially ascites and portal vein thrombosis, or in progression of hepatocellular carcinoma.

Hepatitis C virus genotype affects survival in patients with hepatocellular carcinoma.

BACKGROUND: There is currently no evidence that hepatitis C virus (HCV) genotype affects survival in patients with hepatocellular carcinoma (HCC). This study aimed to investigate whether the HCV genotype affected the survival rate of patients with HCV-related HCC. METHODS: We performed a retrospective cohort study using the data of patients with HCV-related HCC evaluated at two centers in Korea between January 2005 and December 2016. Propensity score matching between genotype 2 patients and non-genotype 2 patients was performed to reduce bias. RESULTS: A total of 180 patients were enrolled. Of these, 86, 78, and 16 had genotype 1, genotype 2, and genotype 3 HCV-related HCC, respectively. The median age was 66.0 years, and the median overall survival was 28.6 months. In the entire cohort, patients with genotype 2 had a longer median overall survival (31.7 months) than patients with genotype 1 (28.7 months; P = 0.004) or genotype 3 (15.0 months; P = 0.003). In the propensity score-matched cohort, genotype 2 patients also showed a better survival rate than non-genotype 2 patients (P = 0.007). Genotype 2 patients also had a longer median decompensation-free survival than non-genotype 2 patients (P = 0.001). However, there was no significant difference in recurrence-free survival between genotype 2 and non-genotype 2 patients who underwent curative treatment (P = 0.077). In multivariate Cox regression analysis, non-genotype 2 (hazard ratio, 2.19; 95% confidence interval, 1.29-3.71) remained an independent risk factor for death. CONCLUSION: Among patients with HCV-related HCC, those with genotype 2 have better survival.