Hamidreza Karimi-Sari

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are increasingly used in gastrointestinal and liver cancers. However, antibiotic-induced gut microbiota disruption may influence ICI effectiveness. The objective of this study was to evaluate association between antibiotic use and clinical outcomes among patients with gastrointestinal and liver cancers receiving ICI therapy. METHODS: In this meta-analysis, we searched studies involving adults with gastrointestinal or liver cancers treated with ICIs, comparing outcomes between patients with and without antibiotic use. Eligible studies reported hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for overall survival (OS), progression-free survival (PFS), objective response rate, or disease control rate. Random-effects models were used for pooled analyses. RESULTS: Twenty-eight studies were included. Antibiotic use was associated with worse OS (HR 1.56; 95% CI: 1.23–1.98; I ² = 87.3%), PFS (HR 1.48; 95% CI: 1.15–1.90; I ² = 88.3%), and disease control rate (OR 0.55; 95% CI: 0.33–0.90; I ² = 65.0%), but no significant difference in objective response rate (OR 1.01; 95% CI: 0.78–1.31; I ² = 0%). Results were consistent in subgroup analyses by ICI type and timing of antibiotic administration. Antibiotic use was associated with worse OS and PFS in hepatocellular carcinoma (HR for OS: 1.49; 95% CI: 1.24–1.79; HR for PFS: 1.25; 95% CI: 1.01–1.56) and upper gastrointestinal cancers (HR for OS: 2.40; 95% CI: 1.48–3.90; HR for PFS: 2.15; 95% CI: 1.18–3.91), whereas colorectal cancer studies showed improved OS (HR: 0.58; 95% CI: 0.45–0.75). DISCUSSION: Antibiotic use is associated with worse outcomes in patients with gastrointestinal or liver cancer receiving ICIs and should be carefully justified. Prospective studies are needed to validate these results.

Background/Objectives: Chronic hepatitis B and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with risk of advanced hepatic fibrosis and cirrhosis. Given the increased risk, the presence of insulin resistance, metabolic syndrome, and hepatic fibrosis should be assessed in individuals with chronic hepatitis B. The Lipoprotein Insulin Resistance Index (LP-IR) is a simple method of assessing insulin resistance in the general population, and lipoprotein profiles have been shown to reflect hepatic steatosis and fibrosis in patients with MASLD. However, LP-IR and lipoprotein profiles have not been evaluated in patients with chronic hepatitis B. Methods: Lipoprotein profiles and LP-IR scores were evaluated in a cohort of patients with chronic hepatitis B using NMR spectroscopy. Results: Serum samples from 50 patients with chronic hepatitis B and 44 with chronic hepatitis B and metabolic syndrome were analyzed. A cut-off value was defined that differentiates patients with and without insulin resistance. Increased large VLDL and reduced small VLDL particles were observed, suggesting the presence of hepatic steatosis and fibrosis. Conclusions: In this largely Asian cohort of chronic hepatitis B patients, where BMI and conventional markers are less reliable, LP-IR scores differentiated patients with and without insulin resistance and metabolic syndrome. In addition, distinctive lipoprotein profiles such as increased large VLDL and reduced small VLDL particles were observed in these chronic hepatitis B patients, suggesting the presence of hepatic steatosis and fibrosis. Future studies with larger sample sizes are necessary to confirm the utility of these NMR-measured lipoprotein parameters in predicting metabolic disease and fibrosis among patients with underlying liver disease.

Background: Hepatitis C virus (HCV) infection and hazardous alcohol use are both preventable causes of morbidity and mortality among people who inject drugs (PWID). In the general population, hazardous alcohol is associated with a reduced likelihood of HCV treatment initiation. Less is known about the prevalence and impact of hazardous alcohol use on direct-acting antiviral (DAA) therapy initiation among PWID with active injection drug use. Methods: PWID were recruited via street outreach in Baltimore, Maryland, between 2018 and 2019 and were enrolled in a study cohort. Participants completed a study survey and underwent HCV testing. Self-reported DAA therapy initiation was evaluated at follow-up visits every six months. Hazardous alcohol use was determined based on an AUDIT-C score of ≥4 for men or ≥3 for women. Data were analyzed using multivariable logistic regression with generalized estimating equations. Results: Of the 720 PWID recruited, 291 had detectable HCV RNA, and only 134 were aware of their HCV infection. The mean (±standard deviation) age of those that were aware of their infection was 48.7 (±10.3) years, with a slight majority (53.0%) being male and predominantly African American (64.9%). The majority (80/134, 59.7%) met criteria for hazardous alcohol use. Only 16 (11.9%) PWID reported DAA therapy initiation within six months, and 20 (14.9%) reported it within 12 months of follow-up. Hazardous alcohol use (aOR = 1.23, 95% CI = 0.43–3.53) was not associated with DAA treatment initiation. Conclusions: There was a high prevalence of hazardous alcohol use, low rates of oral DAA therapy initiation, and no association between self-reported hazardous alcohol use and initiation of oral DAA therapy in our sample of PWID that were aware of their chronic HCV infection. Strategies to increase HCV treatment uptake in PWID with active drug use are urgently needed and should integrate alcohol and drug use evaluation and care.

Background: People who inject drugs (PWID) experience high rates of drug overdose death with the risk of mortality increasing after each non-fatal event. Racial differences exist in drug overdose rates, with higher rates among Black people who use drugs. Psychological factors may predict drug overdose. Methods: Cross-sectional data from a survey administered to PWID in Baltimore, MD enrolled in a social network-based intervention were analyzed. Linear regression methods with generalized estimating equations were used to analyze data from indexes and network members to assess for psychological factors significantly associated with self-reported number of lifetime drug overdoses. Factors associated with number of overdoses were assessed separately by race. Results: Among 111 PWID enrolled between January 2018 and January 2019, 25.2% were female, 65.7% were Black, 98.2% reported use of substances in addition to opioids, and the mean age was 49.0 ± 8.3 years. Seventy-five individuals (67.6%) had a history of any overdose with a mean of 5.0 ± 9.7 lifetime overdoses reported. Reports of feeling fearful (β = 9.74, P = 0.001) or feeling lonely all of the time (β = 5.62, P = 0.033) were independently associated with number of drug overdoses. In analyses disaggregated by race, only the most severe degree of fearfulness or loneliness was associated with overdose among Black participants, whereas among White participants, any degree of fearfulness or loneliness was associated with overdose. Conclusions: In this study of PWID loneliness and fearfulness were significantly related to the number of reported overdose events. These factors could be targeted in future interventions.

We aimed to evaluate the effect of hepatitis C virus cure on serum inflammatory markers among people with HIV. Among 127 people with HIV, serum alanine aminotransferase, soluble tumor necrosis factor receptor 1, and inflammatory index score were significantly lower at the 24-week time point in patients who achieved sustained virologic response as compared with those who did not.

People who inject drugs (PWID) have a high prevalence of hepatitis C virus (HCV) infection. However, HCV treatment rates among PWID remain low. Previous data suggest that hazardous alcohol use is negatively associated with direct-acting antiviral (DAA) therapy initiation in the general population. We aimed to evaluate the effect of hazardous alcohol use on DAA therapy initiation among PWID. PWID were recruited through street outreach in Baltimore, Maryland 2018–2019. Participants completed a study survey and HCV testing (antibody reflex to RNA) at study visits. DAA initiation (self-report) was assessed at study follow-up in 6-month increments. Hazardous alcohol use was defined as Alcohol Use Disorders Identification Test-C (AUDIT-C) ≥4 for men or ≥3 for women. Frequency of injection drug use was categorized as ≤3 vs. >3 times/day. Longitudinal data were analyzed using descriptive statistics and multivariable logistic regression analyses with generalized estimating equations (GEE). Among our sample of PWID with HCV infection, oral DAA treatment was not associated with self-reported hazardous alcohol use. The overall very low rates of HCV treatment are concerning and need to be addressed by effective interventions, especially for younger PWID. Oluwaseun Falade-Nwulia, MBBS ,MPH, Abbvie Inc: Grant/Research Support|Gilead Sciences: Advisor/Consultant