Update on the second-line treatment of Helicobacter pylori infection: a narrative review.

A standard bismuth quadruple therapy, a fluoroquinolone-containing triple (or quadruple) therapy or a proton pump inhibitor (PPI)-amoxicillin high-dose dual therapy has been recommended as a second-line treatment for Helicobacter pylori infection by the Maastricht VI/Florence Consensus Report. The major shortcoming of levofloxacin-amoxicillin triple therapy is low cure rate for eradicating levofloxacin-resistant strains. With the rising prevalence of levofloxacin-resistant strains, levofloxacin-amoxicillin triple therapy cannot reliably achieve a high eradication rate for second-line treatment of H. pylori infection in most countries now. The present article aims to review current second-line eradication regimens with a per-protocol eradication rate exceeding 85% in most geographic areas. Recently, a novel tetracycline-levofloxacin quadruple therapy consisting of a PPI, bismuth, tetracycline, and levofloxacin for rescue treatment of H. pylori infection has been developed. The new therapy achieved a higher per-protocol eradication rate than levofloxacin-amoxicillin triple treatment in a randomized controlled trial (98% versus 69%). Additionally, the tetracycline-levofloxacin quadruple therapy also exhibits a higher eradication rate than amoxicillin-levofloxacin quadruple therapy. High-dose dual PPI-amoxicillin therapy is another novel second-line treatment for H. pylori infection. The new therapy can achieve an eradication rate of 89% by per-protocol analysis for the second-line treatment in Taiwan. Recently, levofloxacin-based sequential quadruple therapy and potassium-competitive acid blocker have also been applied in the second-line treatment of H. pylori infection. A meta-analysis revealed that a vonoprazan-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. In conclusion, the eradication rate of levofloxacin-amoxicillin triple therapy is suboptimal in the second-line treatment of H. pylori infection now. Currently, a standard bismuth quadruple therapy (tetracycline-metronidazole quadruple therapy), a tetracycline-levofloxacin quadruple therapy, an amoxicillin-levofloxacin quadruple therapy, a levofloxacin-based sequential quadruple therapy or a high-dose PPI-amoxicillin dual therapy is recommended for the second-line treatment of H. pylori infection.

Application of artificial intelligence in endoscopic image analysis for the diagnosis of a gastric cancer pathogen-Helicobacter pylori infection.

Helicobacter pylori (H. pylori) infection is the principal cause of chronic gastritis, gastric ulcers, duodenal ulcers, and gastric cancer. In clinical practice, diagnosis of H. pylori infection by a gastroenterologists' impression of endoscopic images is inaccurate and cannot be used for the management of gastrointestinal diseases. The aim of this study was to develop an artificial intelligence classification system for the diagnosis of H. pylori infection by pre-processing endoscopic images and machine learning methods. Endoscopic images of the gastric body and antrum from 302 patients receiving endoscopy with confirmation of H. pylori status by a rapid urease test at An Nan Hospital were obtained for the derivation and validation of an artificial intelligence classification system. The H. pylori status was interpreted as positive or negative by Convolutional Neural Network (CNN) and Concurrent Spatial and Channel Squeeze and Excitation (scSE) network, combined with different classification models for deep learning of gastric images. The comprehensive assessment for H. pylori status by scSE-CatBoost classification models for both body and antrum images from same patients achieved an accuracy of 0.90, sensitivity of 1.00, specificity of 0.81, positive predictive value of 0.82, negative predicted value of 1.00, and area under the curve of 0.88. The data suggest that an artificial intelligence classification model using scSE-CatBoost deep learning for gastric endoscopic images can distinguish H. pylori status with good performance and is useful for the survey or diagnosis of H. pylori infection in clinical practice.

Update on the first-line treatment of Helicobacter pylori infection in areas with high and low clarithromycin resistances.

Current international consensuses on Helicobacter pylori eradication therapy recommend that only regimens that reliably produce eradication rates of ⩾90% should be used for empirical treatment. The Real-world Practice & Expectation of Asia-Pacific Physicians and Patients in Helicobacter Pylori Eradication Survey also showed that the accepted minimal eradication rate in H. pylori-infected patients was 91%. According to efficacy prediction model, the per-protocol eradication rates of 7-day and 14-day standard triple therapies fall below 90% when clarithromycin resistance rate ⩾5%. Several strategies including bismuth-containing, non-bismuth-containing quadruple therapies (including sequential, concomitant, hybrid and reverse hybrid therapies), high-dose dual therapy and vonoprazan-based triple therapy have been proposed to increase the eradication rate of H. pylori infection. According to efficacy prediction model, the eradication rate of 14-day concomitant therapy, 14-day hybrid therapy and 7-day vonoprazan-based triple therapy is less than 90% if the frequency of clarithromycin-resistant strains is higher than 90%, 58% and 23%, respectively. To meet the recommendation of the consensus report and patients' expectation, local surveillance networks for resistance of H. pylori to clarithromycin are required to select appropriate eradication regimens in each geographic region. In areas with low (<5%) clarithromycin resistance (e.g. Sweden, Philippine, Myanmar and Bhutan), 7-day and 14-day standard triple therapies can be adopted for the first-line treatment of H. pylori infection with eradication rates of ⩾90%. In areas with high (⩾5%) clarithromycin resistance (most other countries worldwide) or unknown clarithromycin resistance, 14-day hybrid, 14-day reverse hybrid, 14-day concomitant and 10- to 14-day bismuth quadruple therapy can be used to treat H. pylori infection.

REAP-HP survey 2020: Comparing the real-world practice and expectation in Helicobacter pylori eradication of the Taiwanese gastroenterologists in 2015 and 2020.

BACKGROUND: REAP-HP study (Real-world practice and Expectation of Asia-Pacific physicians and patients in Helicobacter Pylori eradication) was the pioneer study investigating the expectation and preference of physicians across Asia-Pacific in H. pylori eradication in 2015. This study is the first follow-up study of REAP-HP in Taiwan. AIMS: (1) To investigate the preference in regimens for the first-line anti-H. pylori therapy of Taiwanese gastroenterologist in 2020, (2) To survey the factor that cause the most concern when prescribing anti-H. pylori regimens in clinical practice, and (3) to compare REAP-HP survey data in 2020 and those surveyed in 2015 regarding the abovementioned end-points. METHODS: A questionnaire for H. pylori eradication survey of physicians was distributed to the gastroenterologists who attended the Taiwan Digestive Disease Week 2020. Data of most commonly used first-line anti-H. pylori regimens and concerned factors when prescribing anti-H. pylori regimens between 2015 and 2020 were compared. RESULTS: A total of 258 physicians from different districts of Taiwan participated in the REAP-HP Survey in 2020. The top three most commonly used anti-H. pylori regimens in Taiwan in 2020 were 14-day standard triple therapy (36.8%; 95% confidence interval [CI]: 30.9%-42.7%), 7-day standard triple therapy (17.8%; 95% CI: 13.1%-22.5%) and 14-day reverse hybrid therapy (14.7%; 95% CI: 10.4%-19.0%) respectively. The top two factors that cause the most concern during prescribing anti-H. pylori therapy were eradication rate (82.3%; 95% CI: 77.6%-87.0%) and side effect (10.4%; 95% CI: 6.7%-15.1%). In 2015, the top three most commonly used regimens in Taiwan were 7-day standard triple therapy (62%; 95% CI: 56.2%-67.8%), 14-day standard triple therapy (21%; 95% CI: 16.1%-25.9%) and 10-day sequential therapy (7%; 95% CI: 4%-10%). A remarkable difference of the most commonly used anti-H. pylori regimens between 2015 and 2020 existed (p < .001). The top two factors that cause the most concern during prescribing anti-H. pylori therapy in 2015 were eradication rate (84.1%) and side effect (7.0%). There were no differences in the factors that cause the most concern during prescribing anti-H. pylori regimens between 2015 and 2020. CONCLUSION: 14-day standard triple therapy has replaced 7-day standard triple therapy as the most commonly used first-line anti-H. pylori therapy among Taiwanese gastroenterologists in 2020. 14-day reverse hybrid therapy is on rise to the third place as the most commonly used anti-H. pylori regimen in Taiwan.

Comparison of the Efficacies of Direct-Acting Antiviral Treatment for HCV Infection in People Who Inject Drugs and Non-Drug Users.

Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users.

Prevention of hepatitis B reactivation in patients requiring chemotherapy and immunosuppressive therapy.

Hepatitis B virus (HBV) reactivation can lead to severe acute hepatic failure and death in patients with HBV infection. HBV reactivation (HBVr) most commonly develops in patients undergoing cancer chemotherapy, especially B cell-depleting agent therapy such as rituximab and ofatumumab for hematological or solid organ malignancies and that receiving hematopoietic stem cell transplantation without antiviral prophylaxis. In addition, the potential consequences of HBVr is particularly a concern when patients are exposed to either immunosuppressive or biologic therapies for the management of rheumatologic diseases, inflammatory bowel disease and dermatologic diseases. Thus, screening with HBV serological markers and prophylactic or pre-emptive antiviral treatment with nucleos(t)ide analogues should be considered in these patients to diminish the risk of HBVr. This review discusses the clinical manifestation, prognosis and management of HBVr, risk stratifications of cancer chemotherapy and immunosuppressive therapy and international guideline recommendations for the prevention of HBVr in patients with HBV infection and resolved hepatitis B.

Gallbladder function predicts subsequent biliary complications in patients with common bile duct stones after endoscopic treatment?

BACKGROUND: In patients with common bile duct stones (CBDS) and intact gallbladder, further management for the gallbladder after the CBDS clearance is still controversial. The relationship between gallbladder motility and the biliary complications were seldom discussed. Our study is to predict the subsequent biliary complications by gallbladder function test using fatty meal sonography (FMS) in patients with CBDS who had been treated by endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients with an intact gallbladder and CBDS after endoscopic clearance of bile duct were enrolled. Patients received a fatty meal sonography after liver function returned to normal. The fasting volume, residual volume, and gallbladder ejection fraction (GBEF) in FMS were measured. Relationships of patients' characteristics, gallbladder function and recurrent biliary complication were analyzed. RESULTS: From 2011 to 2014, 118 patients were enrolled; 86 patients had calculus gallbladders, and 32 patients had acalculous gallbladders. After a mean follow- up of 33 months, 23 patients had recurrent biliary complications. Among 86 patients with calculus gallbladder, 15 patients had spontaneous clearance of gallbladder stones; 14 patients received cholecystectomy due to acute cholecystitis or recurrent colic pain with smooth postoperative courses. In the follow up period, six patients died of non-biliary causes. The GBEF is significant reduced in most patients with a calculus gallbladder in spite of stone color. Calculus gallbladder, alcohol drinking and more than one sessions of initial endoscopic treatment were found to be the risk factors of recurrent biliary complication. CONCLUSIONS: Gallbladder motility function was poorer in patients with a calculus gallbladder, but it cannot predict the recurrent biliary complication. Since spontaneous clearance of gallbladder stone may occur, wait and see policy of gallbladder management after endoscopic treatment of CBDS is appropriate, but regular follow- up in those patients with risk factors for recurrence is necessary.

Risk of Severe Acute Exacerbation of Chronic HBV Infection Cancer Patients Who Underwent Chemotherapy and Did Not Receive Anti-Viral Prophylaxis.

BACKGROUND: Reactivation of HBV replication with an increase in serum HBV DNA and alanine aminotransferase (ALT) activity has been reported in 20-50% of hepatitis B carriers undergoing cytotoxic chemotherapy for cancer treatment. Manifestation of HBV reactivation ranges from asymptomatic self-limiting hepatitis to severe progressive hepatic failure and fatal consequences. AIM: To investigate the risk of severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients with solid tumors or hematological malignancies who underwent chemotherapy without antiviral prophylaxis. METHODS: A retrospective review of charts was conducted for HBsAg-positive cancer patients in our institution who underwent chemotherapy and did not receive anti-viral prophylaxis between the periods of July 2007 to January 2013. We investigate the incidence of severe acute exacerbation of chronic HBV infection if these patients with a variety of solid tumors and hematological malignancies. RESULTS: A total of 156 patients (hematological malignancies: 16; solid tumors: 140) were included. The incidence of severe acute HBV exacerbation in the patients with hematological malignancy was higher than that in solid tumors (25.0% [4/16] vs 4.3% [6/140]); P = 0.005). Additionally, patients receiving rituximab-based chemotherapy had higher acute exacerbation rate than those with non-rituximab-based chemotherapy (40.0% vs 4.1%, P = 0.001). Among the patients with solid tumors, the incidences of severe acute exacerbation of chronic HBV in hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, gynecological cancer, urological tract cancer, head/neck cancer and other solid malignancies were 2.3%, 4.0%, 7.1%, 9.0%, 16.7%, 6.7%, 0% and 0%, respectively. CONCLUSION: Severe acute exacerbation of chronic HBV infection may occur in HBsAg-positive patients with a variety of solid tumors who received chemotherapy without adequate anti-viral prophylaxis. Hematological malignancy and rituximab-based chemotherapy are the risk factors related to severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients undergoing chemotherapy.

Ten-day Quadruple therapy comprising proton-pump inhibitor, bismuth, tetracycline, and levofloxacin achieves a high eradication rate for Helicobacter pylori infection after failure of sequential therapy.

BACKGROUND: Sequential therapy has been recommended in the Maastricht IV/Florence Consensus Report as the first-line treatment for Helicobacter pylori eradication in regions with high clarithromycin resistance. However, it fails in 5-24% of infected subjects, and the recommended levofloxacin-containing triple rescue therapy only achieves a 77% eradication rate after failure of sequential therapy. AIM: To investigate the efficacy of a novel quadruple therapy comprising proton-pump inhibitor, bismuth, tetracycline, and levofloxacin for rescue treatment of sequential therapy. METHODS: This was a multicenter study in which H. pylori-infected patients who had failed sequential therapy received a 10-day quadruple therapy (esomeprazole (40 mg b.d), tripotassium dicitrato bismuthate (120 mg q.d.s.), tetracycline (500 mg q.d.s.), and levofloxacin (500 mg o.d.) for 10 days). H. pylori status was examined 6 weeks after the end of treatment. RESULTS: From July 2007 to June 2012, twenty-four subjects received 10-day quadruple therapy. The eradication rates according to intention-to-treat and per-protocol analyses were both 95.8% (23 of 24; 95% confidence interval, 87.8-103.8%). Adverse events were seen in 25.0% (6 of 24) of the patients. Drug compliance was 100.0% (24/24). CONCLUSIONS: The 10-day quadruple therapy comprising proton-pump inhibitor, bismuth, tetracycline, and levofloxacin achieves a very high eradication rate for H. pylori infection after failure of sequential therapy. It is well tolerated and has great potential to become a good choice of rescue treatment following non-bismuth-containing quadruple therapy in regions with high clarithromycin resistance.

Diffuse malignant peritoneal mesothelioma.

Mesothelioma often originates in the pleura and less frequently in the peritoneum. This article describes a rare case of diffuse malignant peritoneal mesothelioma in a 54-year-old male construction worker who was admitted to our hospital with a 2-month history of progressive abdominal distention. Abdominal computed tomography revealed extensive peritoneal nodularity and omental cake along with massive ascites. Imaging findings initially suggested peritoneal carcinomatosis, primary peritoneal carcinoma, and tuberculous peritonitis. Laparoscopic biopsy of the omentum and peritoneum confirmed the diagnosis of malignant peritoneal mesothelioma of epitheloid type. Although systemic chemotherapy was administered, no tumor regression was found. The patient finally died of nosocomial infection.