Diagnostic Performance of a Fecal Calprotectin Assay as a Biomarker for Mayo Endoscopic Subscore in Ulcerative Colitis: Result From a Tertiary Referral Center.

BACKGROUND: Fecal calprotectin (FC) is a promising biomarker for assessing ulcerative colitis (UC) endoscopic activity. However, the optimal FC cutoff to identify each Mayo endoscopic subscore (MES) remains inconclusive. METHODS: The electronic medical records of 177 adult UC patients evaluated at Mayo Clinic Rochester from January 2017 to March 2023 were retrospectively reviewed, obtaining clinical data and US-based Werfen Diagnostics FC levels collected within 30 days before colonoscopy or flexible sigmoidoscopy. Three independent inflammatory bowel disease specialist endoscopists blindly reviewed the most severe endoscopic images for grading MES. RESULTS: The median interval between FC collection and endoscopy was 2 days. Fecal calprotectin showed strong positive correlations with MES (Spearman's r = 0.709; P < .01) and other clinical parameters. Fecal calprotectin cutoff of 60 mcg/g effectively distinguished MES 0 from MES 1-3 (sensitivity, 0.78; specificity, 0.97; area under the receiver operating characteristic curve [AUC], 0.901) and predicted clinical remission (Total Mayo Score ≤2 and no subscore >1; sensitivity, 0.83; specificity, 0.98; AUC, 0.921). Fecal calprotectin cutoff of 110 mcg/g effectively differentiated MES 0-1 from MES 2-3 (sensitivity, 0.86; specificity, 0.87; AUC, 0.915), while a cutoff of 310 mcg/g distinguished MES 0-2 from MES 3 (sensitivity, 0.80; specificity, 0.76; AUC, 0.820). CONCLUSIONS: This study supports the reliability and applicability of FC as a valuable marker of endoscopic inflammation, particularly in distinguishing MES 0 from MES 1-3 using the FC cutoff of 60 mcg/g. Sensitivity analysis demonstrated robust results.

This study from a tertiary referral center evaluated 177 patients with ulcerative colitis and found that a fecal calprotectin cutoff of 60 mcg/g effectively distinguished between a Mayo endoscopic subscore (MES) 0 and MES 1-3, as well as clinical remission, with high specificity, supporting its reliability as a valuable biomarker.

Characteristics, Clinical Outcomes, and Prognosis of Anal and Pouch-related Carcinoma in Patients With Crohn's Disease.

BACKGROUND: This study described the clinical characteristics, outcomes, and prognosis of Crohn's disease (CD) patients with anal cancer in a tertiary referral center. METHODS: The electronic medical records of 35 adult CD patients, including CD of the pouch, with anal carcinoma evaluated at Mayo Clinic Rochester, Florida, or Arizona between January 1989 and August 2022 were retrospectively reviewed. RESULTS: Before cancer diagnosis, patients with pouch-related carcinoma had a shorter median duration of inflammatory bowel disease than those with anal carcinoma (10 vs 26 years). Twenty-six patients (74%) had perianal diseases or rectovaginal fistula, and 35% had a history of human papillomavirus infection. Twenty-one patients (60%) were diagnosed with cancer by anal examination under anesthesia (EUA). More than half of adenocarcinomas were mucinous. Sixteen patients (47%) were American Joint Committee on Cancer (AJCC) Tumor Nodes Metastasis (TNM) stage 3, and 83% were treated by surgery. At last follow-up, 57% of patients were alive without cancer. The 1-, 3- and 5-year overall survival rates were 93.8% (95% confidence interval [CI], 85.7%-100%), 71.5% (95% CI, 56.4%-90.7%), and 67.7% (95% CI, 51.2%-87.7%), respectively. Advanced AJCC TNM stage (hazard ratio, 3.20 per stage; 95% CI, 1.05-9.72; P = .040) was significantly associated with increased risk of death, whereas the period of cancer diagnosis in 2011-2022 (HR, relative to 1989-2000, 0.16; 95% CI, 0.04-0.72; P = .017) was significantly related to decreased risk of death. CONCLUSIONS: Anal and pouch-related carcinomas were rare complications of CD, and long-standing perianal diseases were an important risk factor. Anal EUA improved the diagnostic yield. Newer cancer treatment strategies and surgery were associated with excellent survival outcome.

This study described the uncommon Crohn's disease (CD) complications of squamous cell carcinoma and adenocarcinoma of the anus and was characterized pouch-related carcinoma in patients with CD of the ileal pouch-anal anastomosis (IPAA). The 5-year overall survival rate was 68%.

Incidence and Predictors of an Abnormal Liver Function Test Among 674 Systemic Sclerosis Patients: A Cohort Study.

Background: Abnormal liver function tests (LFTs) can indicate cirrhosis or liver cancer leading to mortality among systemic sclerosis (SSc) patients. No recent studies have investigated the clinical predictors of an abnormal LFT in SSc. We aimed to determine the incidence of abnormal LFT (including from hepatitis and cholestasis) and to identify its clinical predictors in SSc patients. Methods: An historical cohort was conducted on 674 adult SSc patients who attended the Scleroderma Clinic, Khon Kaen University, between January 2012 and November 2019 and who underwent routine screening for LFT. A Cox regression was used to analyze the clinical predictors of abnormal LFT. Results: Four hundred and thirty cases, representing 4190 person-years, had abnormal LFTs (viz, from hepatitis, cholestasis, and cholestatic hepatitis) for an incidence rate of 10.2 per 100 person-years. The respective incidence of hepatitis, cholestasis, and cholestatic hepatitis was 20.5, 12.9, and 20.4 per 100 person-years. The respective median first-time detection of hepatitis, cholestasis, and cholestatic hepatitis was 3.0, 5.9, and 2.8 years, and none had signs or symptoms suggestive of liver disease. According to the Cox regression analysis, the predictors of an abnormal LFT in SSc were elderly onset of SSc (hazard ratio (HR) 1.02), alcoholic drinking (HR 1.74), high modified Rodnan Skin Score (mRSS) (HR 1.03), edematous skin (HR 2.94), Raynaud's phenomenon (HR 1.39), hyperCKaemia (HR 1.88), and methotrexate use (HR 1.55). In contrast, current sildenafil treatment (HR 0.63) and high serum albumin (HR 0.70) were protective factors. Conclusion: Occult hepatitis, cholestasis, and cholestatic hepatitis can be detected in SSc patients using LFT screening, especially in cases of early disease onset. The long-term outcome is uncertain, and more longitudinal research is required.

PIVKA-II or AFP has better diagnostic properties for hepatocellular carcinoma diagnosis in high-risk patients.

Background: Hepatocellular carcinoma (HCC) is a lethal cancer. Two biomarkers were used for HCC diagnosis including alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II or antagonist (PIVKA-II). However, data on biomarkers and HCC diagnosis are not consistent. This study aimed to evaluate if PIVKA-II, AFP, or a combination of both biomarkers had the best diagnostic properties for HCC. Methods: This was a prospective study and enrolled patients 18 years or over with a high risk for HCC. AFP and PIVKA-II levels were calculated for HCC diagnosis. Diagnostic properties of both biomarkers were reported with sensitivity, specificity, and a receiver operating characteristic (ROC) curve. Results: There were 260 patients with high risk for HCC in this cohort. Of those, 219 patients were diagnosed with HCC: confirmed by biopsy in 7 patients (2.69%) and by imaging in the others. Median values of AFP and PIVKA-II were 56 ng/mL and 348 mAU/mL, respectively. PIVKA-II level of 40 mAU/mL had sensitivity of 80.80%, while AFP of 10 ng/mL had sensitivity of 75.80%. A combination of PIVKA-II at 100 mAU/mL or over and AFP of 11 ng/mL gave sensitivity of 60.30%. The ROC curve of PIVKA-II plus AFP was significantly higher than the AFP alone (0.855 vs. 0.796; p = 0.027), but not significantly different from the PIVKA-II alone (0.855 vs. 0.832; p = 0.130). Conclusion: PIVKA-II may have more diagnostic yield for HCC compared with AFP. It can be used alone without a combination with AFP.

Validation of prognostic scores predicting mortality in acute liver decompensation or acute-on-chronic liver failure: A Thailand multicenter study.

BACKGROUND & OBJECTIVES: Cirrhosis patients with worsening of the liver function are defined as acute decompensation (AD) and those who develop extrahepatic organ failure are defined as acute-on-chronic liver failure (ACLF). Both AD and ACLF have an extremely poor prognosis. However, information regarding prognostic predictors is still lacking in Asian populations. We aimed to identify prognostic factors for 30-day and 90-day mortality in cirrhosis patients who develop AD with or without ACLF. METHODS: We included 9 tertiary hospitals from Thailand in a retrospective observational study enrolling hospitalized cirrhosis patients with AD. ACLF was diagnosed according to the EASL-CLIF criteria, which defined as AD patients who have kidney failure or a combination of at least two non-kidney organ failure. Outcomes were clinical parameters and prognostic scores associated with mortality evaluated at 30 days and 90 days. RESULTS: Between 2015 and 2020, 602 patients (301 for each group) were included. The 30-day and 90-day mortality rates of ACLF vs. AD were 57.48% vs. 25.50% (p<0.001) and 67.44% vs. 32.78% (p<0.001), respectively. For ACLF patients, logistic regression analysis adjusted for demographic data, and clinical information showed that increasing creatinine was a predictor for 30-day mortality (p = 0.038), while the CLIF-C OF score predicted both 30-day (p = 0.018) and 90-day (p = 0.037) mortalities, achieving the best discriminatory power with AUROCs of 0.705 and 0.709, respectively. For AD patients, none of the parameters was found to be significantly associated with 30-day mortality, while bacterial infection, CLIF-AD score and Child-Turcotte-Pugh score were independent parameters associated with 90-day mortality, with p values of 0.041, 0.024 and 0.024. However, their predictive performance became nonsignificant after adjustment by multivariate regression analysis. CONCLUSIONS: Regarding Thai patients, the CLIF-C OF score was the best predictor for 30-day and 90-day mortalities in ACLF patients, while appropriate prognostic factors for AD patients remained inconclusive.

A surveillance for hepatitis C virus infection in northeastern, Thailand: a 10-year cohort.

Introduction: Hepatitis C virus (HCV) infection is an infection that may lead to cirrhosis and hepatocellular carcinoma. Most patients with HCV infection are asymptomatic. The previous study conducted in age group of 30-64 years and in two provinces. Additionally, most surveillance studies conducted in a point period; not longitudinally. This study aimed to evaluate HCV infection rate in all age groups in the northeastern, Thailand in a longitudinal fashion. Methods: This was a surveillance study conducted in 20 provinces of northeastern, Thailand. The study period was between July 2010 and November 2019. During the surveillance, demographic data of participants were collected. HCV screening test was performed in each participant by using a rapid point-of-care assay. Rates of HCV infection in each province and in overall were calculated. Results: During the surveillance period, there were 31,855 subjects who participated the project. Of those, 1,285 subjects (4.037%) were tested positive for HCV infection (Tab. I). The HCV infection rate was highest in 2011 (8.98%): ranges 1.28 to 9.59%. The age group of over 50 years had 690 subjects with HCV infection (5.45%) out of 12,660 subjected tested in this age group. There was significant different among age groups (p < 0.001) and difference of age over 30 years and sex (p 0.043). Conclusions: This longitudinal surveillance showed that HCV infection rates in northeastern, Thailand were varied across the provinces with the highest rate of 9.59%. The HCV infection should be aware in male with age over 30 years.

Application of Mac-2 binding protein glycosylation isomer as a non-invasive biomarker for probing liver disease.

Liver disease remains a major critical challenge in Thailand due to viral hepatitis. Clinical management requires close monitoring of liver fibrosis severity. Non-invasive testing is an attractive method for probing of disease progression. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum marker for fibrosis staging. The current study evaluates the marker among healthy donors and hepatitis C (HCV) patients. 100 HCV subjects were evaluated by liver biopsy. These patients had varying fibrosis severity based on METAVIR scores. Healthy donors were confirmed based on normal liver functions tests. Comparisons of M2BPGi levels among different study groups were performed and the effectiveness was evaluated using receiver operating characteristics (ROC) curves. Using liver biopsy as the reference standard, median M2BPGi levels in HCV cases were 0.74, 1.38 and 2.88 COI for F0-1, F2 and > F3 cases respectively. In healthy donors, the baseline values ranged 0.1-0.24 COI and statistically lower than liver disease cases profiled using M2BPGi. ROC analysis demonstrated superior results for M2BPGi levels among diseased populations and healthy controls. AUROC was determined at 0.983. Comparing with other non-invasive tests, M2BPGi showed a positive linear trend that indicated a strong match to existing methodologies. M2BPGi addresses a critical need in the management of liver disease by providing straightforward means to probe fibrosis severity. In this study, we found significant differences between hepatitis C and healthy subjects and established the background level in healthy donors.

Clinical versus radiographical factors associated with hepatocellular carcinoma diagnosis in high-risk patients: sizes matter.

Aim: This study aimed to evaluate if clinical or radiographic findings can be used for hepatocellular carcinoma (HCC) diagnosis particularly in high-risk patients. Methods: This was a prospective study and evaluated factors associated with HCC. Results: There were 260 patients met the study criteria: 219 patients (84.23%) were HCC. Two factors significantly associated with HCC: portal vein invasion and the largest mass size. The cutoff point for the largest mass size of 2 cm or over gave sensitivity and specificity for HCC of 83.56 and 87.80%, respectively. Conclusion: Portal vein invasion and the largest liver mass of 2 cm or over may be diagnostic factors for HCC in high-risk patients, while clinical factors were not suggestive for HCC.

Acute-on-chronic liver failure: Epidemiology, prognosis, and outcome of a multicenter study in Thai population.

Background and Aim: Acute-on-chronic liver failure (ACLF) leads to multi-organ failure related to high mortality rates. This study aimed to gather epidemiological data and validate a scoring system to predict mortality in ACLF. Methods: This retrospective cohort study collected data from multicenter tertiary care hospitals in Thailand. A total of 638 hospitalized patients (acute decompensated liver disease [ADLD], 292 patients; ACLF, 346 patients) from January 2019 to June 2020 were enrolled in this study. We compared the mortality rate at days 30 and 90 between patients with ADLD and ACLF. Areas under the receiver operating characteristic (AUROC) curves of chronic liver failure-sequential organ failure assessment (CLIF-SOFA) and other existing scoring systems were compared among patients with ACLF. Results: The incidence of patients with ACLF was 54%. The main cause of chronic liver disease was alcohol (38%), with sepsis (50%) as the most common precipitating factor. ACLF with coagulopathy (AUROC 0.58, 95% confidence interval [CI]: 0.52-0.64), metabolic acidosis (AUROC 0.58, 95% CI: 0.52-0.64), and high aspartate aminotransferase (AST) (AUROC 0.59, 95% CI: 0.53-0.66) were associated with high 30-day mortality. The 30-day mortality rate of patients with acute decompensation and patients with ACLF was 46 and 58%, respectively. Respiratory system (P = 0.001) failure was the major end result in ACLF and constituted a significant factor to predict mortality. The AUROC of CLIF-SOFA score was superior to that of the other predicted score (AUROC 0.64, 95% CI: 0.585-0.704). Conclusion: Patients with ACLF with more organ failure and high CLIF-SOFA score were associated with high short-term mortality. Future studies should include an ACLF prospective registry to confirm these finding.

Surveillance for hepatitis B virus seroprevalence nearly 30 years after the implementation of a national vaccination program.

INTRODUCTION: Hepatitis B virus (HBV) infection is associated with cirrhosis and hepatocellular carcinoma. Vaccination is one aspect of public health policy aimed at eliminating HBV infection. After the implementation of an HBV vaccination program for newborns in Thailand, the estimated residual infection rate was 3.5%. However, that study was conducted in only 5,964 participants in seven provinces and only 22 years after the start of the campaign. This study aimed to evaluate the HBV seroprevalence rate in Thailand in larger sample size and a longer duration after program implementation using HBV surveillance. METHODS: This was a surveillance study conducted in 20 provinces in northeast Thailand. The study period was between July 2010 and November 2019. Rates of HBV seroprevalence in each province and overall were calculated. Participants were divided into two groups: those vaccinated under the national campaign and those who were not. Participants aged 0-20 years were used as references, while other age groups (intervals of 10 years) were comparators. Residual HBV seroprevalence after the vaccination program was calculated with odds ratio for HBV seroprevalence in each age group. RESULTS: There were 31,855 subjects who participated in the project. Of those, 1,805 (5.7%) had HBV. The HBV seroprevalence rate in the national HBV vaccination group was significantly lower than that in those not vaccinated under the national program (1.0% vs 5.9%; p<0.001). Seroprevalence was 1.0% in participants ≤20 years of age. Participants 31-40 years of age had the highest odds ratio (10.41), followed those 21-30 years of age (7.42). CONCLUSIONS: This real-world surveillance study showed that residual HBV infection was 1.0% after nearly 30 years of nationwide HBV vaccination.

Prognostic factors for remission, relapse, and treatment complications in type 1 autoimmune hepatitis.

BACKGROUND AND AIM: Autoimmune hepatitis (AIH) is a rare chronic form of hepatitis, the prognosis for which has not been definitively established. The current study aimed to define the prognostic factors for remission and compare the median time to remission, complications, and relapse rate between type 1 AIH patients treated with prednisolone monotherapy and those treated using prednisolone in combination with azathioprine. MATERIALS AND METHODS: The data of 86 patients diagnosed with type 1 AIH between January 1998 and January 2018 were retrospectively reviewed. Clinical, serological, and histological parameters were obtained. Cox-proportional hazard and logistic regression analyses were applied to the data. RESULTS: The prognostic factors related to complete remission were absence of liver cirrhosis, hypertension, and azathioprine exposure. The median time to complete remission of the prednisolone group (92 days; 95%CI; 65-264 days) was significantly shorter (P = 0.01) than that of the combination group (336 days; 95%CI; 161-562 days); however, the prednisolone group had higher rates of treatment complications-including skin and soft tissue infections (P = 0.010) and cushingoid appearance (P = 0.011)-than the combination group. The prednisolone group also had a higher relapse rate (odds ratio 6.13, 95% CI 1.72-21.80, P = 0.005). CONCLUSIONS: The absence of liver cirrhosis and hypertension at the time of diagnosis and no azathioprine exposure during the treatment period were favorable prognostic factors for complete remission. The prednisolone group had a significantly shorter median time to complete remission but higher rates of treatment complications and a higher relapse rate than the combination group.

Prevalence and associated factors of small intestinal bacterial overgrowth among systemic sclerosis patients.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) results in nutrient malabsorption and malnutrition, thereby increasing the morbidity and mortality in systemic sclerosis (SSc) patients. OBJECTIVES: To evaluate the prevalence and associated factors of SIBO in SSc patients. METHOD: A cross-sectional study was conducted between July 2015 and January 2016 in SSc patients over 18, using the glucose H2 /CH4 breath test to evaluate SIBO. RESULTS: Eighty-nine SSc patients (30 male and 59 female) underwent the glucose H2 /CH4 breath test. The mean age was 54.4. Twelve participants were positive for the glucose H2 /CH4 breath test, yielding a SIBO prevalence of 13.5% (95% CI 7.2-22.4) among SSc patients. A multivariate analysis revealed that duration of disease >5 years was significantly associated with SIBO (adjusted odds ratio 9.38; 95% CI 1.09-80.47). CONCLUSION: The prevalence of SIBO, using the glucose H2 /CH4 breath test, is not common among Thai SSc patients. However, a positive result was associated with longer duration of disease.

Outcomes of a Randomized Controlled Trial Comparing Modified High Dose Omeprazole and Amoxicillin Triple Therapy with Standard Triple Therapy for Helicobacter Pylori Eradication

Background: Helicobacter pylori (H. pylori) infection is related to peptic ulcer diseases and gastric cancer and eradication of H. pylori should be expected to decrease the risk of their development. Factors affecting H. pylori eradication are antibiotic resistance, CYP2C19 genotypes, drug regimen and patient compliance. Increment of omeprazole and amoxicillin dosage in clarithromycin-containing triple therapy regimen may overcome these problems and may be a better choice than the conventional clarithromycin-containing triple therapy regimen. Objective: To compare the eradication rates with modified triple therapy (MTT) and standard triple therapy (STT) as first-line treatment. Materials and Methods: The study was an open label, multicenter, randomized controlled trial. A total of 170 patients infected with H. pylori diagnosed by rapid urease test were randomly assigned into 2 groups. The first was treated with a 14-day MTT (20 mg omeprazole t.i.d., 500 mg amoxicillin t.i.d., and 500 mg clarithromycin b.i.d.) and the second with a 14-day STT (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 500 mg clarithromycin b.i.d.). H. pylori eradication was evaluated by 14C-urea breath test. CYP2C19 genotypes, clarithromycin resistance, side effects and patient compliance were also recorded. Results: There were 85 patients in each group. The H. pylori eradication rate in the MTT group was 84.7% by ITT analysis and 91.1% by PP analysis, compared to the STT group values of 76.5% and 87.8% (p = 0.18 and 0.51), respectively. CYP2C19 genotypes and patient compliance were similar in both groups. Prevalence of clarithromycin resistance was 7.0%. Side effects were all mild with no significant differences between the twogroups. Conclusions: MTT is not superior to STT. From this study, MTT may not be recommended as the first-line treatment for H. pylori infection in Thailand because eradication rates proved to be less than 90% by ITT analysis.