Evolving Concepts in Helicobacter pylori Management.

Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain clinically silent. Moreover, individuals with chronic H pylori infection are at risk for gastric preneoplastic lesions, which are also asymptomatic and only reliably diagnosed using endoscopy and biopsy. Thus, to make a significant impact in gastric cancer prevention, a systematic approach is needed to better identify individuals at highest risk of both H pylori infection and its complications, including gastric preneoplasia and cancer. The approach to H pylori eradication must also be optimized given sharply decreasing rates of successful eradication with commonly used therapies and increasing antimicrobial resistance. With growing acceptance that H pylori should be managed as an infectious disease and the increasing availability of susceptibility testing, we now have the momentum to abandon empirical therapies demonstrated to have inadequate eradication rates. Molecular-based susceptibility profiling facilitates selection of a personalized eradication regimen without necessitating an invasive procedure. An improved approach to H pylori eradication coupled with population-level programs for screening and treatment could be an effective and efficient strategy to prevent gastric cancer, especially in minority and potentially marginalized populations that bear the heaviest burden of H pylori infection and its complications.

HES V2.0 outperforms GALAD for detection of HCC: A phase 3 biomarker study in the United States.

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis. APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and HES V2.0 scores within 6, 12, and 24 months of HCC diagnosis. We calculated the AUROC curve and estimated TPR based on an optimal threshold at a fixed false-positive rate of 10%. We analyzed 2331 patients, of whom 125 developed HCC (71% in the early stages). For any HCC, HES V2.0 had higher TPR than GALAD overall (+7.2%), at 6 months (+3.6%), at 12 months (+7.2%), and 24 months (+13.0%) before HCC diagnosis. HES V2.0 had higher TPR than ASAP for all time points (+5.9% to +12.0%). For early HCC, HES V2.0 had higher sensitivity/TPR than GALAD overall (+6.7%), at 12 months (+6.3%), and 24 months (+14.6%) but not at 6 months (+0.0%) and higher than ASAP for all time points (+13.4% to +18.0%). CONCLUSIONS: In a prospective cohort study, HES V2.0 had a significantly higher performance for identifying new HCC, including early stage, than GALAD or ASAP.

PNPLA3, Obesity, and Heavy Alcohol Use in Cirrhosis Patients May Exert a Synergistic Increase Hepatocellular Carcinoma Risk.

BACKGROUND & AIMS: In patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors. METHODS: We analyzed data from 1911 patients in 2 multicenter prospective cohort studies in the United States. We classified patients according to alcohol consumption (current heavy vs not current heavy), obesity (body mass index ≥30 vs <30 kg/m2), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs noncarrier). We examined the independent and joint effects of these risk factors on risk of developing HCC using Cox regression with competing risks. RESULTS: Mean age was 59.6 years, 64.3% were male, 28.7% were Hispanic, 18.3% were non-Hispanic Black, 50.9% were obese, 6.2% had current heavy alcohol consumption, and 58.4% harbored at least 1 PNPLA3 G-allele. One hundred sixteen patients developed HCC. Compared with PNPLA3 noncarriers without heavy alcohol consumption, HCC risk was 2.65-fold higher (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.20-5.86) for carriers who had current heavy alcohol consumption. Compared with noncarrier patients without obesity, HCC risk was higher (HR, 2.40; 95% CI, 1.33-4.31) for carrier patients who were obese. PNPLA3 and alcohol consumption effect was stronger among patients with viral etiology of cirrhosis (HR, 3.42; 95% CI, 1.31-8.90). PNPLA3 improved 1-year risk prediction for HCC when added to a clinical risk model. CONCLUSIONS: The PNPLA3 variant may help refine risk stratification for HCC in patients with cirrhosis with heavy alcohol consumption or obesity who may need specific preventive measures.

Risk factors for HCC in contemporary cohorts of patients with cirrhosis.

BACKGROUND AND AIMS: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk. APPROACH AND RESULTS: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on the risk of HCC. We included 2733 patients with cirrhosis (mean age 60.1 years, 31.3% women). At enrollment, 19.0% had active HCV, 23.3% had cured HCV, 16.1% had alcoholic liver disease, and 30.1% had NAFLD. During 7406 person-years of follow-up, 135 patients developed HCC at an annual incidence rate of 1.82% (95% CI, 1.51-2.13). The annual HCC incidence rate was 1.71% in patients with cured HCV, 1.32% in patients with alcoholic liver disease, and 1.24% in patients with NAFLD cirrhosis. Compared to patients with NAFLD, the risk of progression to HCC was 2-fold higher in patients with cured HCV (HR, 2.04; 95% CI, 1.24-3.35). Current smoking (HR, 1.63; 95% CI, 1.01-2.63) and overweight/obesity (HR, 1.79; 95% CI, 1.08-2.95) were also associated with HCC risk. CONCLUSIONS: HCC incidence among patients with cirrhosis was lower than previously reported. HCC risk was variable across etiologies, with higher risk in patients with HCV cirrhosis and lower risk in those with NAFLD cirrhosis. Current smoking and overweight/obesity increased HCC risk across etiologies.

Recent Trends in the Incidence of Gastric Cancer in the United States.

BACKGROUND: Gastric cancer (GC) incidence rates overall in the United States have declined over recent decades and are predicted to continue declining. However, there have been mixed recent findings regarding the potential stabilization of rates and potential divergent trends by age group. We used the most recent cancer data for the United States and examined trends in GC between 1992 and 2019, overall and in important subgroups of the population. METHODS: Age-adjusted GC incidence rates and trends in adults 20 years or older were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 12 program. Secular trends were examined overall and by age group, sex, race/ethnicity, SEER registry, and tumor location. We used joinpoint regression to compute annual percent changes, average annual percent changes, and associated 95% CI. RESULTS: GC rates decreased by 1.23% annually from 1992 to 2019. Despite overall decreases, GC incidence rates increased for age groups below 50 years, predominately driven by noncardia GC (74.3% of all GCs). Cardia GC (26.7% of GC) rates decreased in all age groups except for 80 to 84 years. Overall GC rates decreased for both sexes, all races, and for all SEER registry regions, with the largest decreases occurring in males, Asians and Pacific Islanders, and in Hawaii. Age-period-cohort analysis revealed that birth cohorts before 1940 and after 1980 both had increased rates of GC compared with the reference birth cohort of 1955. CONCLUSION: GC rates overall have continued to decline through 2019, despite increases in the rate of noncardia GC for younger age groups.

Improving Adherence to Clinical Practice Guidelines for Managing Gastric Intestinal Metaplasia Among Gastroenterologists at a US Academic Institution.

BACKGROUND: Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital. METHODS: This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change in GIM management in a cohort of 50 patients with GIM between April 2020 and January 2021 and surveyed 10 gastroenterologists. The durability of the intervention was assessed in a cohort of 50 GIM patients diagnosed between April 2021 and July 2021. RESULTS: In the preintervention cohort, GIM location was specified (antrum and corpus separated) in 11 patients (22%), and Helicobacter pylori testing was recommended in 11 of 26 patients (42%) without previous testing. Gastric mapping biopsies were recommended in 14% and surveillance endoscopy in 2%. In the postintervention cohort, gastric biopsy location was specified in 45 patients (90%, P <0.001) and H. pylori testing was recommended in 26 of 27 patients without prior testing (96%, P <0.001). Because gastric biopsy location was known in 90% of patients ( P <0.001), gastric mapping was not necessary, and surveillance endoscopy was recommended in 42% ( P <0.001). One year after the intervention, all metrics remained elevated compared with the preintervention cohort. CONCLUSIONS: GIM management guidelines are not consistently followed. A protocol for GIM management and education of gastroenterologists increased adherence to H. pylori testing and GIM surveillance recommendations.

Proton Pump Inhibitors: Rational Use and Use-Reduction - The Windsor Workshop.

BACKGROUND: Despite deprescribing initiatives to curb overutilization of proton pump inhibitors (PPIs), achieving meaningful reductions in PPI use is proving a challenge. SUMMARY: An international group of primary care doctors and gastroenterologists examined the literature surrounding PPI use and use-reduction to clarify: (i) what constitutes rational PPI prescribing; (ii) when and in whom PPI use-reduction should be attempted; and (iii) what strategies to use when attempting PPI use-reduction. KEY MESSAGES: Before starting a PPI for reflux-like symptoms, patients should be educated on potential causes and alternative approaches including dietary and lifestyle modification, weight loss, and relaxation strategies. When commencing a PPI, patients should understand the reason for treatment, planned duration, and review date. PPI use at hospital discharge should not be continued without a recognized indication for long-term treatment. Long-term PPI therapy should be reviewed at least annually. PPI use-reduction should be based on the lack of a rational indication for long-term PPI use, not concern for PPI-associated adverse events. PPI use-reduction strategies involving switching to on-demand PPI or dose tapering, with rescue therapy for rebound symptoms, are more likely to succeed than abrupt cessation.

An Electronic Health Record Model for Predicting Risk of Hepatic Fibrosis in Primary Care Patients.

BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease. AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes. METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic fibrosis (> 8 kPa). Possible predictors included data from the EHR for age, gender, diabetes, hypertension, FIB-4, body mass index (BMI), LDL, HDL, and triglycerides. RESULTS: Of 344 patients (56.4% women), 34 had any hepatic fibrosis, and 15 significant hepatic fibrosis. Three variables (BMI, FIB-4, diabetes) were identified from both approaches. When we used variable cut-offs defined by Youden's index, the final model predicting any hepatic fibrosis had an AUC of 0.75 (95% CI 0.67-0.84), NPV of 91.5% and PPV of 40.0%. The final model with variable categories based on standard clinical thresholds (i.e., BMI ≥ 30 kg/m2; FIB-4 ≥ 1.45) had lower discriminatory ability (AUC 0.65), but higher PPV (50.0%) and similar NPV (91.3%). We observed similar findings for predicting significant hepatic fibrosis. CONCLUSIONS: Our results demonstrate that standard thresholds for clinical risk factors/biomarkers may need to be modified for greater discriminatory ability among populations with high prevalence of obesity and diabetes.

Current Challenges and Future Direction in Surveillance for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.

The burden for hepatocellular carcinoma (HCC) attributed to nonalcoholic fatty liver disease (NAFLD) continues to grow in parallel with rising global trends in obesity. The risk of HCC is elevated among patients with NAFLD-related cirrhosis to a level that justifies surveillance based on cost-effectiveness argument. The quality of current evidence for HCC surveillance in all patients with chronic liver disease is poor, and even lower in those with NAFLD. For a lack of more precise risk-stratification tools, current approaches to defining a target population in noncirrhotic NAFLD are limited to noninvasive tests for liver fibrosis, as a proxy for liver-related morbidity and mortality. Beyond etiology and severity of liver disease, traditional and metabolic risk factors, such as diabetes mellitus, older age, male gender and tobacco smoking, are not enough for HCC risk stratification for surveillance efficacy and effectiveness in NAFLD. There is an association between molecular and genetic factors and HCC risk in NAFLD, and risk models integrating both clinical and genetic factors will be key to personalizing HCC risk. In this review, we discuss concerns regarding defining a target population, surveillance test accuracy, surveillance underuse, and other cost-effective considerations for HCC surveillance in individuals with NAFLD.

Longitudinal changes in fibrosis markers are associated with risk of cirrhosis and hepatocellular carcinoma in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Currently, there is no consistent information on the course of fibrosis-4 (FIB-4) score changes in non-alcoholic fatty liver disease (NAFLD) or their association with subsequent risk of cirrhosis and/or hepatocellular carcinoma (HCC). Thus, we aimed to evaluate the association between longitudinal changes in FIB-4 and subsequent risk of HCC and a composite endpoint of cirrhosis and HCC in patients with NAFLD. METHODS: We conducted a retrospective cohort study of patients with NAFLD seen in 130 Veterans Administration hospitals between 1/1/2004-12/31/2008, with follow-up through to 12/31/2018. We calculated FIB-4 longitudinally and categorized patients based on risk of advanced fibrosis (low-risk FIB-4 <1.45, indeterminate-risk FIB-4 1.45-2.67, and high-risk FIB-4 >2.67). We used landmark Fine-Gray competing risks models to determine the effects of change in FIB-4 between NAFLD diagnosis date and 3-year landmark time on the subsequent risk of HCC and a composite endpoint. RESULTS: Among the 202,319 patients with NAFLD in the 3-year landmark analysis, 473 progressed to HCC at an incidence rate of 0.28 per 1,000 person years (PY) (95% CI 0.26-0.30). The incidence rate of the composite endpoint was 1.31 per 1,000 PY (95% CI 1.25-1.37). At baseline, 74.7%, 21.4%, and 3.8% of patients had a low, indeterminate, and high FIB-4, respectively. Compared to patients who were at stable low FIB-4 at both time points, the risk of HCC and that of the composite endpoint was higher for all other subgroups with the highest risk in patients with persistently high FIB-4 (HCC adjusted sub-distribution hazard ratio 57.7, 95% CI 40.5-82.2 and composite endpoint hazard ratio 28.6, 95% CI 24.6-33.2). CONCLUSION: Longitudinal changes in FIB-4 were strongly associated with progression to cirrhosis and HCC. IMPACT AND IMPLICATIONS: Tools to stratify the risk of HCC development in patients with NAFLD are currently lacking. The fibrosis-4 (FIB-4) score is a widely available non-invasive test for liver fibrosis, a primary determinant of the development of cirrhosis and HCC. In a large retrospective cohort of patients with NAFLD, we found that serial changes in FIB-4 over time were strongly associated with progression to cirrhosis and HCC. Integrating serial measurements of non-invasive tests for fibrosis into the care pathway for patients with NAFLD could help tailor HCC risk prevention.

The Performance of AFP, AFP-3, DCP as Biomarkers for Detection of Hepatocellular Carcinoma (HCC): A Phase 3 Biomarker Study in the United States.

BACKGROUND & AIMS: α-fetoprotein (AFP), AFP Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) in combination or in GALAD (Gender, Age, AFP-L3, AFP, and DCP) were tested for hepatocellular carcinoma (HCC) surveillance in retrospective cohort and case-control studies. However, there is a paucity of prospective data and no phase III biomarker studies from North American populations. METHODS: We conducted a prospective specimen collection, retrospective blinded evaluation (PRoBE) cohort study in patients with cirrhosis enrolled in a 6-monthly surveillance with liver imaging and AFP. Blood samples were prospectively collected every 6 months and analyzed in a retrospective blinded fashion. True positive rate (TPR) and false positive rate (FPR) for any or early HCC were calculated within 6, 12, and 24 months of HCC diagnosis based on published thresholds for biomarkers individually, in combination and in GALAD and Hepatocellular Carcinoma Early Detection Screening (HES) scores. We calculated the area under the receiver operating curve and estimated TPR based on an optimal threshold at a fixed FPR of 10%. RESULTS: The analysis was conducted in a cohort of 534 patients; 50 developed HCC (68% early) and 484 controls with negative imaging. GALAD had the highest TPR (63.6%, 73.8%, and 71.4% for all HCC, and 53.8%, 63.3%, and 61.8 % for early HCC within 6, 12, and 24 months, respectively) but an FPR of 21.5% to 22.9%. However, there were no differences in the area under the receiver operating curve among GALAD, HES, AFP-L3, or DCP. At a fixed 10% FPR, TPR for GALAD dropped (42.4%, 45.2%, and 46.9%) and was not different from HES (36.4%, 40.5%, and 40.8%) or AFP-L3 alone (39.4%, 45.2%, and 44.9%). CONCLUSIONS: In a prospective cohort phase III biomarker study, GALAD was associated with a considerable improvement in sensitivity for HCC detection but an increase in false-positive results. GALAD performance was modest and not different from AFP-L3 alone or HES.

Neighborhood-Level Factors Contribute to Disparities in Hepatocellular Carcinoma Incidence in Texas.

BACKGROUND AND AIMS: Texas has the highest hepatocellular carcinoma (HCC) incidence rates in the continental United States, but these rates vary by race-ethnicity. We examined racial-ethnic disparities through a geospatial analysis of the social determinants of health. METHODS: Using data from the Texas Cancer Registry, we assembled 11,547 HCC cases diagnosed between 2011 and 2015 into Texas's census tracts geographic units. Twenty-nine neighborhood measures representing demographics and socioeconomic, and employment domains were retrieved from the U.S. Census Bureau. We performed a series of aspatial and spatially weighted regression models to identify neighborhood-level characteristics associated with HCC risk. RESULTS: We found positive associations between HCC and proportion of population in census tracts that are Black or African American, Hispanic, over 60 years of age, in the construction industry, and in the service occupation but an inverse association with the proportion of population employed in the agricultural industry. The magnitude of these associations varied across Texas census tracts. CONCLUSIONS: We found evidence that neighborhood-level factors are differentially associated with variations in HCC incidence across Texas. Our findings reinforce existing knowledge about HCC risk factors and expose others, including neighborhood-level employment status.

The Risk of Hepatocellular Carcinoma in Entecavir Versus Tenofovir Treated US Cohort With Chronic Hepatitis B Virus.

The comparative effectiveness of tenofovir (TDF) vs entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) remains unclear. Data from a retrospective Korean cohort study published by Choi et al1 initially suggested a lower-than-expected incidence of HCC in patients on long-term TDF. However, additional studies from Korea did not show a statistically significant difference in HCC incidence rate between TDF and ETV groups,2,3 and subsequent studies reported mixed results ranging from no association or a slight advantage for TDF.4 Most of these studies examined Asian patients from Korea, Taiwan, and China.

Inverse Association Between Gluteofemoral Obesity and Risk of Non-Cardia Gastric Intestinal Metaplasia.

BACKGROUND & AIMS: It is unclear whether obesity confers increased risk of non-cardia gastric adenocarcinoma and its precursor, gastric intestinal metaplasia. Here, we examined whether various dimensions of adiposity independently predispose to the development of non-cardia gastric intestinal metaplasia. METHODS: We compared data from 409 non-cardia gastric intestinal metaplasia cases and 1748 controls without any gastric intestinal metaplasia from a cross-sectional study at the VA Medical Center in Houston, Texas. Participants completed standardized questionnaires, underwent anthropometric measurements, and underwent a study endoscopy with gastric mapping biopsies. Non-cardia gastric intestinal metaplasia cases included participants with intestinal metaplasia on any non-cardia gastric biopsy. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression models. RESULTS: Increasing body mass index (BMI) was not associated with risk of non-cardia gastric intestinal metaplasia (per unit BMI adjusted OR, 0.98; 95% CI, 0.96-1.00). Similarly, we found no associations with increase in waist circumference (per 10-cm increase adjusted OR, 0.94; 95% CI, 0.87-1.03) and waist-to-hip ratio (WHR) (per unit WHR adjusted OR, 2.34; 95% CI, 0.37-14.7). However, there was a significant inverse association with gastric intestinal metaplasia and increasing hip circumference, reflecting gluteofemoral obesity (per 10-cm increase adjusted OR, 0.89; 95% CI, 0.80-0.98). The inverse association was observed for both extensive and focal gastric intestinal metaplasia. CONCLUSIONS: The independent dimensions of adiposity (BMI, waist circumference) are not associated with increased risk of non-cardia gastric intestinal metaplasia. The inverse association between gluteofemoral obesity and risk of gastric intestinal metaplasia warrants additional study.

The Prevalence and Determinants of NAFLD and MAFLD and Their Severity in the VA Primary Care Setting.

BACKGROUND & AIMS: A recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population. METHODS: We conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 dB/m was used to define NAFLD, whereas MAFLD was defined as controlled attenuation parameter median ≥290 dB/m and either body mass index ≥25 kg/m2 or diabetes, or 2 or more of the following: hypertension, high triglycerides, low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol. RESULTS: The mean age of participants was 50.9 years, 55.4% were women, 42.8% were white, and 43.8% were Black. The prevalence of NAFLD was 40.6% (82/202). All 82 patients with NAFLD had a body mass index ≥25 kg/m2, and therefore met our criteria for MAFLD (ie, 100% concordance). Compared with patients with no metabolic trait, patients with ≥3 traits had a 48-fold (adjusted odds ratio, 47.6; 95% confidence interval, 11.3-200) higher risk of NAFLD/MAFLD. Overall, 19 participants (9.4% of the total, 15.9% of those with NAFLD) had at least moderate fibrosis. CONCLUSIONS: NAFLD was present in 40% of Veterans registered in primary care; 9.4% of veterans had at least moderate hepatic fibrosis, with most having concurrent NAFLD. There was perfect concordance between NAFLD and the alternative MAFLD definition.

Admixture Mapping in African Americans Identifies New Risk Loci for HCV-Related Cirrhosis.

BACKGROUND & AIMS: Cirrhosis is the main predisposing condition for hepatocellular carcinoma. Host genetic risk factors have been reported for cirrhosis; however, whether there is a genetic contribution to racial disparities in cirrhosis requires further investigation. METHODS: We used an affected-only mapping by admixture linkage disequilibrium analysis to characterize the genetic risk of cirrhosis in 227 African American patients with cirrhosis genotyped at 19,804 ancestry-informative marker single nucleotide polymorphisms. We additionally performed analyses stratified by hepatitis C virus (HCV) infection status. To replicate our findings, we conducted a case-control analysis in an external study population (452 cases and 196 controls). RESULTS: The mean age of patients was 63.3 years and 98.2% were male. Risk factors for cirrhosis included HCV infection (83.7%) and alcohol abuse (56.4%). In the admixture mapping analysis, we found that European ancestry on chromosome 2q21.1 and African ancestry on chromosome 6p21.2 were associated with increased risk of cirrhosis in African Americans. In the fine-mapping analysis, we identified regions near POTEKP on 2q21.1 (P = .0001) and DNAH8 on 6p21.2 (P = .0017) that were associated with cirrhosis. As the admixture peaks in the HCV-positive patients were the same as those in the overall group, findings in the analysis are reflective of the HCV-positive group. In the replication analysis, the results on chromosome 2 were not significant after adjusting for multiple comparisons, and we could not replicate the results on chromosome 6. CONCLUSIONS: We used admixture mapping to identify novel genomic regions on 2q21.1 and 6p21.2 that may be associated with HCV-related cirrhosis risk in African Americans.

The Predictive Performance of Contemporary Guideline Recommendations for Helicobacter pylori Testing in a United States Population.

BACKGROUND: The Houston Consensus Conference and American College of Gastroenterology (ACG) have recommended Helicobacter pylori screening in United States populations with specific risk factors. However, the performance of these guidelines in clinical practice is not known. METHODS: We identified consecutive patients undergoing upper endoscopy with gastric biopsies for any indication in a safety-net hospital in Houston, TX during January 2015-December 2016. We tested the association between the presence of H pylori (histopathology, stool antigen, urea breath test, immunoglobulin G serology, or prior treatment) and H pylori risk factors using logistic regression models, reported as odds ratios and 95% confidence intervals (CIs). We evaluated the area under the receiver operating characteristic (AUROC) curve for predictive ability of individual risk factors identified by the Houston Consensus Conference and ACG. RESULTS: Of 942 patients, the prevalence of H pylori infection was 51.5%. The risk factors with the highest predictive performance included first-generation immigrant (AUROC, 0.59) and Hispanic or black race/ethnicity (AUROC, 0.57), whereas the remaining 7 risk factors/statements had low predictive value. A model that combined first-generation immigrant status, black or Hispanic race/ethnicity, dyspepsia, and reflux had higher predictive ability for H pylori infection (AUROC, 0.64; 95% CI, 0.61-0.68) than any individual risk factor. CONCLUSIONS: In this contemporary U.S. cohort, the performance of individual risk factors identified by the Houston Consensus Conference and ACG was generally low for predicting H pylori infection except for black or Hispanic race/ethnicity and first-generation immigrant status. A risk prediction model combining several risk factors had improved diagnostic performance and should be validated in future studies.

Using Natural Language Processing to Automatically Identify Dysplasia in Pathology Reports for Patients With Barrett's Esophagus.

BACKGROUND & AIMS: Identifying dysplasia of Barrett's esophagus (BE) in the electronic medical record (EMR) requires manual abstraction of unstructured data. Natural language processing (NLP) creates structure to unstructured free text. We aimed to develop and validate an NLP algorithm to identify dysplasia in BE patients on histopathology reports with varying report formats in a large integrated EMR system. METHODS: We randomly selected 600 pathology reports for NLP development and 400 reports for validation from patients with suspected BE in the national Veterans Affairs databases. BE and dysplasia were verified by manual review of the pathology reports. We used NLP software (Clinical Language Annotation, Modeling, and Processing Toolkit; Melax Tech, Houston, TX) to develop an algorithm to identify dysplasia using findings. The algorithm performance characteristics were calculated as recall, precision, accuracy, and F-measure. RESULTS: In the development set of 600 patients, 457 patients had confirmed BE (60 with dysplasia). The NLP identified dysplasia with 98.0% accuracy, 91.7% recall, and 93.2% precision, with an F-measure of 92.4%. All 7 patients with confirmed high-grade dysplasia were classified by the algorithm as having dysplasia. Among the 400 patients in the validation cohort, 230 had confirmed BE (39 with dysplasia). Compared with manual review, the NLP algorithm identified dysplasia with 98.7% accuracy, 92.3% recall, and 100.0% precision, with an F-measure of 96.0%. CONCLUSIONS: NLP yielded a high degree of sensitivity and accuracy for identifying dysplasia from diverse types of pathology reports for patients with BE. The application of this algorithm would facilitate research and clinical care in an EMR system with text reports in large data repositories.

Prevention of Hepatocellular Carcinoma (HCC). White Paper of the Texas Collaborative Center for Hepatocellular Cancer (TeCH) Multi-stakeholder Conference.

BACKGROUND & AIMS: Texas has the highest age-adjusted incidence rate of hepatocellular carcinoma (HCC) in the United States. The Cancer Prevention and Research Institute of Texas has funded the Texas Collaborative Center for Hepatocellular Cancer (TeCH) to facilitate HCC research, education, and advocacy activities with the overall goal of reducing HCC mortality in Texas through coordination, collaboration, and advocacy. METHODS: On September 17, 2022, TeCH co-sponsored a multi-stakeholder conference on HCC with the Baker Institute Center for Health and Biosciences. This conference was attended by HCC researchers, policy makers, payers, members from pharmaceutical industry and patient advocacy groups in and outside of Texas. This report summarizes the results of the conference. RESULTS: The goal of this meeting was to identify different strategies for preventing HCC and evaluate their readiness for implementation. CONCLUSIONS: We call for a statewide (1) viral hepatitis elimination program; (2) program to increase nonalcoholic steatohepatitis and obesity awareness; (3) research program to develop health care models that integrate alcohol associated liver disease treatment and treatment for alcohol use disorder; and (4) demonstration projects to evaluate the effectiveness of identifying and linking patient with advanced fibrosis and cirrhosis to clinical care.

Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis.

BACKGROUND & AIMS: The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis. METHODS: We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through 2021. RESULTS: We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration. CONCLUSION: The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.