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Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (liquid biopsy) could improve screening participation. Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMS min) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses. CMS min reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%–79% and 73%–81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMS min cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMS min would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120–$140) would be cost-effective vs FIT at comparable participation. CMS min could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only. [Display omitted] Blood tests to screen for colorectal cancer could be effective in people who decline stool tests or colonoscopy, but they should not substitute for established methods unless they achieve high detection rates for colorectal cancer and its precursors. [ABSTRACT FROM AUTHOR]

Overweight and obese persons have not only elevated rates of colorectal cancer (CRC), but also higher competing mortality and healthcare spending. We examined the cost-effectiveness of intensified CRC screening in overweight and obese persons. We adapted our validated decision analytic model of CRC screening to compare screening starting at 45 or 40 years of age instead of at 50 years of age, or shortening screening intervals, in women and men with body mass index (BMI) ranging from normal to grade III obesity. Strategies included colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual fecal immunochemical test. Without screening, sex-specific total CRC deaths were similar for persons with overweight or obesity I–III, reflecting the counterbalancing of higher CRC risk by lower life expectancy as BMI rises. For all BMI and sex groups, Colo10 starting at 45 years of age or FIT starting at 40 years of age were cost-effective at a threshold of $100,000 per quality-adjusted life year gained. Colo10 starting at 40 years of age was cost-effective only for men with obesity II–III, at $93,300 and $80,400 per quality-adjusted life year gained, respectively. Shifting Colo10 to earlier starting ages was always preferred over Colo5 starting at later ages. Results were robust in sensitivity analysis, including varying all-cause mortality, complication, and BMI-specific CRC risks. CRC screening starting at 45 years of age with colonoscopy, or at 40 years of age with FIT, appears cost-effective for women and men across the range of BMI. In men with obesity II–III, who have the highest CRC but also all-cause mortality risks, colonoscopy starting at 40 years of age appears cost-effective. It remains to be decided whether BMI should be used as a single predictor or incorporated into a multivariable tool to tailor CRC screening. [Display omitted] [ABSTRACT FROM AUTHOR]

The adenoma detection rate at screening (ADR) predicts interval colorectal cancer. Monitoring other lesion detection rates and colonoscopy indications has been proposed. We developed a comprehensive, automated colonoscopy audit program based on standardized clinical documentation, explored detection rates across indications, and developed the Adenoma Detection Rate – Extended to all Screening / Surveillance (ADR-ESS) score. In a prospective cohort study, we calculated overall and advanced adenoma and sessile serrated lesion (SSL) detection rates among 15,253 colonoscopies by 35 endoscopists from 4 endoscopy units across all colonoscopy indications. We explored correlations between detection rates, and the precision and stability of ADR-ESS versus ADR. The overall "screening, first" ADR was 36.3% (95% confidence interval [CI], 34.5%–38.1%). The adenoma detection rate was lower for "screening, not first" (relative rate [RR], 0.80; 95% CI, 0.74–0.87) and "family history" (RR, 0.84; 95% CI, 0.74–0.96), and higher for "surveillance" (RR, 1.22; 95% CI, 1.15–1.31) and "follow-up, FIT" (RR, 1.21; 95% CI, 1.07–1.37). For "screening, first," the detection rates for advanced adenoma, SSL, and advanced SSL were 6.7% (95% CI, 5.7%–7.7%), 7.2% (95% CI, 6.2%–8.2%), and 2.6% (95% CI, 2.0%–3.2%), respectively. Adenoma and SSL detection were correlated (r = 0.44; P =.008). ADR-ESS had substantially narrower confidence intervals and less period-to-period variability than ADR, and was not improved by weighting for indication volume and correction for detection by indication. Comprehensive, automated colonoscopy audit based on standardized clinical documentation is feasible. Adenoma detection is a fair but imperfect proxy for SSL detection. ADR-ESS increases the precision of adenoma detection assessments and emphasizes quality across colonoscopy indications. [ABSTRACT FROM AUTHOR]

Persistent serum alanine aminotransferase (ALT) elevation in nucleotide/nucleoside analogue (NA)-treated patients with chronic hepatitis B (CHB) has been associated with unfavorable long-term outcomes.1 It has been consistently shown that a higher proportion of patients receiving tenofovir alafenamide (TAF) achieve normal ALT in comparison with recipients of tenofovir disoproxil fumarate,2–5 the mechanism for which remains unknown.2 [ABSTRACT FROM AUTHOR]

The American Cancer Society has recommended initiating colorectal cancer (CRC) screening at age 45 years instead of 50 years. We estimated the cost effectiveness and national effects of adopting this recommendation. We compared screening strategies and alternative resource allocations in a validated Markov model. We based national projections on screening participation rates by age and census data. Screening colonoscopy initiation at age 45 years instead of 50 years in 1000 persons averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), cost $33,900/QALY gained, and required 758 additional colonoscopies. These 758 colonoscopies could instead be used to screen 231 currently unscreened 55-year-old persons or 342 currently unscreened 65-year-old persons, through age 75 years. These alternatives averted 13–14 CRC cases and 6–7 CRC deaths and gained 27–28 discounted QALYs while saving $163,700–$445,800. Improving colonoscopy completion rates after abnormal results from a fecal immunochemical test yielded greater benefits and savings. Initiation of fecal immunochemical testing at age 45 years instead of 50 years cost $7700/QALY gained. Shifting current age-specific screening rates to 5 years earlier could avert 29,400 CRC cases and 11,100 CRC deaths over the next 5 years but would require 10.7 million additional colonoscopies and cost an incremental $10.4 billion. Improving screening rates to 80% in persons who are 50–75 years old would avert nearly 3-fold more CRC deaths at one third the incremental cost. In a Markov model analysis, we found that starting CRC screening at age 45 years is likely to be cost effective. However, greater benefit, at lower cost, could be achieved by increasing participation rates for unscreened older and higher-risk persons. [ABSTRACT FROM AUTHOR]

Tenofovir alafenamide (TAF) is the latest agent approved for chronic hepatitis B virus (HBV) treatment. In its registrations trials, TAF demonstrated better renal safety and improvement in alanine aminotransferase (ALT) activities compared with tenofovir disoproxil fumarate (TDF).1–3 However, data are scarce regarding these outcomes in liver transplantation (LTx) recipients.4 In this study, we determine effects of switching from other antivirals to TAF on ALT and renal function in LTx recipients. [ABSTRACT FROM AUTHOR]

All major U.S. guidelines now endorse average-risk colorectal cancer (CRC) screening at 45–49 years of age. Concerns exist that endoscopic capacity may be strained, that low-risk persons may self-select for screening, and that calculations of the adenoma detection rate may be diluted. We analyzed age-specific screening colonoscopy volumes and lesion detection rates before vs after the endorsement of CRC screening at 45–49 years of age. We compared colonoscopy volumes and lesion detection rates in our healthcare system during period 1 (October 2017 to December 2018), before the first change in guidelines, vs period 2 (January 2019 to August 2021), the era of new guidelines. The proportion of first-time screening colonoscopies performed in 45- to 49-year-olds increased from 3.5% to 11.6% (relative risk, 3.36; 95% CI, 2.45–4.61). The period 2 detection rates for adenoma, advanced adenoma, sessile serrated lesion, advanced sessile serrated lesion, adenomas per colonoscopy, and lesions per colonoscopy were very similar for 45- to 49-year-olds (34.3%, 6.3%, 8.6%, 2.9%, 0.58, and 0.69, respectively) and 50- to 54-year-olds (38.2%, 5.8%, 9.4%, 3.0%, 0.63, and 0.76, respectively) at first-time screening, and for 60- to 64-year-olds at rescreening (33.4%, 6.1%, 7.2%, 2.3%, 0.61, and 0.70, respectively). All detection rates, adenomas per colonoscopy, and lesions per colonoscopy increased from period 1 to period 2 (eg, overall adenoma detection rate 35.1% vs 42.6%; P <.0001), without any decreases among 45- to 49-year-olds. In our healthcare system, a lower CRC screening initiation age has modestly affected colonoscopy volume by age without compromising screening yield. Lesion detection rates, including for advanced adenomas, in average-risk 45- to 49-year-olds approximate those in 50- to 54-year-olds at first-time screening and 60- to 64-year-olds at rescreening. National monitoring is needed to assess fully the impact of lowering the CRC screening initiation age. [Display omitted] [ABSTRACT FROM AUTHOR]

Background & Aims Cirrhosis from hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma worldwide. We determine the prevalence of cirrhosis among HCV-infected American adults including those unaware of their infection. Methods Using the National Health and Nutrition Examination Survey (NHANES) data, we identified participants aged ⩾20 years with detectable serum HCV RNA. The prevalence of advanced fibrosis and cirrhosis was determined for eras 1 (1988–94), 2 (1999–2006) and 3 (2007–2012) by using FIB-4 >3.25 and APRI >2.0, respectively. Results Out of 52,644 NHANES examinees, 49,429 were tested for HCV, of whom 725 met the inclusion criteria (positive HCV RNA with available data for FIB-4 and APRI). Based on APRI, 6.6% (95% confidence interval [CI]: 2.2–11.0) of HCV-infected adults in era 1, 7.6% (95% CI: 3.4–11.8) in era 2 and 17.0% (95% CI: 8.0–26.0) in era 3 had cirrhosis. In the multivariable regression analysis, this era effect was attributable to increasing age (odds ratio [OR]:1.04, 95% CI: 1.02–1.07), diabetes (OR: 2.33, 95% CI: 1.01–5.40) and obesity (OR: 2.96, 95% CI: 1.15–7.57). Cirrhosis was as common among respondents who were unaware of their infection as those who were aware (both 11%). Results were identical when FIB-4 was used. Conclusions Among HCV-infected American adults, the proportion with cirrhosis has increased rapidly. Cirrhosis prevalence remains high in individuals unaware of their HCV infection. These data highlight the urgency for HCV screening regardless of symptoms, systematic assessment for liver fibrosis in those with HCV infection and institution of antivirals to prevent advanced liver disease. Lay summary Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis, creating a large public health burden. Based on the U.S. National Health and Nutrition Examination Survey sample, we found the proportion of patients with cirrhosis among Americans with HCV infection increased from 6.6% to 17.0% over the past two decades. Patients who were unaware of their infection were just as likely to have cirrhosis as those who knew about their infection, which highlights the need for screening and treatment for HCV at the population level. [ABSTRACT FROM AUTHOR]

Policy changes in the United States have lengthened overall waiting times for patients with hepatocellular carcinoma (HCC). We investigated temporal trends in utilization of locoregional therapy (LRT) and associated waitlist outcomes among liver transplant (LT) candidates in the United States. Data for primary adult LT candidates listed from 2003 to 2018 who received HCC exception were extracted from the Organ Procurement and Transplantation Network database. Explant histology was examined, and multivariable competing risk analysis was used to evaluate the association between LRT type and waitlist dropout. There were 31,609 eligible patients with at least 1 approved HCC exception, and 34,610 treatments among 24,145 LT candidates. The proportion with at least 1 LRT recorded increased from 42.3% in 2003 to 92.4% in 2018. Chemoembolization remains the most frequent type, followed by thermal ablation, with a notable increase in radioembolization from 3% in 2013 to 19% in 2018. An increased incidence of LRT was observed among patients with tumor burden beyond Milan criteria, higher α-fetoprotein level, and more compensated liver disease. Receipt of any type of LRT was associated with a lower risk of waitlist dropout; there was no significant difference by number of LRTs. In inverse probability of treatment weighting–adjusted analysis, radioembolization or ablation as the first LRT was associated with a reduced risk of waitlist dropout compared with chemoembolization. In a large nationwide cohort of LT candidates with HCC, LRT, and in particular radioembolization, increasingly was used to bridge to LT. Patients with greater tumor burden and those with more compensated liver disease received more treatments while awaiting LT. Bridging LRT was associated with a lower risk of waitlist dropout. [ABSTRACT FROM AUTHOR]

The Model for End-Stage Liver Disease (MELD) has been established as a reliable indicator of short-term survival in patients with end-stage liver disease. The current version (MELDNa), consisting of the international normalized ratio and serum bilirubin, creatinine, and sodium, has been used to determine organ allocation priorities for liver transplantation in the United States. The objective was to optimize MELD further by taking into account additional variables and updating coefficients with contemporary data. All candidates registered on the liver transplant wait list in the US national registry from January 2016 through December 2018 were included. Uni- and multivariable Cox models were developed to predict survival up to 90 days after wait list registration. Model fit was tested using the concordance statistic (C-statistic) and reclassification, and the Liver Simulated Allocation Model was used to estimate the impact of replacing MELDNa with the new model. The final multivariable model was characterized by (1) additional variables of female sex and serum albumin, (2) interactions between bilirubin and sodium and between albumin and creatinine, and (3) an upper bound for creatinine at 3.0 mg/dL. The final model (MELD 3.0) had better discrimination than MELDNa (C-statistic, 0.869 vs 0.862; P <.01). Importantly, MELD 3.0 correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women. In the Liver Simulated Allocation Model analysis, MELD 3.0 resulted in fewer wait list deaths compared to MELDNa (7788 vs 7850; P =.02). MELD 3.0 affords more accurate mortality prediction in general than MELDNa and addresses determinants of wait list outcomes, including the sex disparity. An updated version of the Model for End-Stage Liver Disease (MELD) affords improved prediction of mortality risk for patients with cirrhosis and corrects the sex disparity. [ABSTRACT FROM AUTHOR]

Patients in need of liver transplantation may travel to improve their chance of receiving an organ. We evaluated factors to determine which transplant candidates travel to other regions to increase their chances of receiving a liver and effects of travel on waitlist outcomes. We performed a retrospective cohort study of all adult patients registered for primary deceased donor liver transplantation in the United States from January 2004 to December 2016. Zip code data were used to calculate the travel distance from a patient's residence to centers at which they were on the waitlist or received a liver transplant. Distant listing and migration were defined as placement on a waitlist and receipt of liver transplantation, respectively, outside the home transplantation region and greater than 500 miles from the home zip code. We assessed the effect of distant listing on outcomes (death and liver transplantation) and predictors of distant listing or migration using multivariable analyses. There were 104,914 waitlist registrations during the study period; of these, 2930 (2.8%) pursued listing at a distant center. Of waitlist registrants, 60,985 received liver transplants, of whom 1985 (3.3%) had migrated. In a multivariable competing risk analysis in which liver transplantation was considered as a competing event, distant listing was associated with a 22% reduction in the risk of death within 1 year (subhazard ratio, 0.78; 95% CI, 0.70–0.88). Distant listing and migration were associated with non-black race, non-Medicaid payer, residence in a higher income area, and education beyond high school. Placement on a liver transplant waitlist outside the home transplantation region is associated with reduced waitlist mortality and an increased probability of receiving a liver transplant. Geographic disparities in access to liver transplantation have disproportionate effects on patients who are minorities, have lower levels of education, or have public insurance. [ABSTRACT FROM AUTHOR]

Background The full spectrum of serious non-gastrointestinal post-colonoscopy complications has not been well characterized. We analyzed rates of and factors associated with adverse post-colonoscopy gastrointestinal (GI) and non-gastrointestinal events (cardiovascular, pulmonary, or infectious) attributable to screening or surveillance colonoscopy (S-colo) and non-screening or non-surveillance colonoscopy (NS-colo). Methods We performed a population-based study of colonoscopy complications using databases from California hospital-owned and nonhospital-owned ambulatory facilities, emergency departments, and hospitals from January 1, 2005 through December 31, 2011. We identified patients who underwent S-colo (1.58 million), NS-colo (1.22 million), or low-risk comparator procedures (joint injection, aspiration, lithotripsy; arthroscopy, carpal tunnel; or cataract; 2.02 million) in California’s Ambulatory Services Databases. We identified patients who developed adverse events within 30 days, and factors associated with these events, through patient-level linkage to California’s Emergency Department and Inpatient Databases. Results After S-colo, the numbers of lower GI bleeding, perforation, myocardial infarction, and ischemic stroke per 10,000-persons were 5.3 (95% confidence interval [CI], 4.8–5.9), 2.9 (95% CI, 2.5–3.3), 2.5 (95% CI, 2.1–2.9), and 4.7 (95% CI, 4.1–5.2) without biopsy or intervention; with biopsy or intervention, numbers per 10,000-persons were 36.4 (95% CI, 35.1–37.6), 6.3 (95% CI, 5.8–6.8), 4.2 (95% CI, 3.8–4.7), and 9.1 (95% CI, 8.5–9.7). Rates of dysrhythmia were higher. After NS-colo, event rates were substantially higher. Most serious complications led to hospitalization, and most GI complications occurred within 14 days of colonoscopy. Ranges of adjusted odds ratios for serious GI complications, myocardial infarction, ischemic stroke, and serious pulmonary events after S-colo vs comparator procedures were 2.18 (95% CI, 2.02–2.36) to 5.13 (95% CI, 4.81–5.47), 0.67 (95% CI, 0.56–0.81) to 0.99 (95% CI, 0.83–1.19), 0.66 (95% CI, 0.59–0.75) to 1.13 (95% CI, 0.99–1.29), and 0.64 (95% CI, 0.61–0.68) to 1.05 (95% CI, 0.98–1.11). Biopsy or intervention, comorbidity, black race, low income, public insurance, and NS-colo were associated with post-colonoscopy adverse events. Conclusions In a population-based study in California, we found that following S-colo, rates of serious GI adverse events were low but clinically relevant, and that rates of myocardial infarction, stroke, and serious pulmonary events were no higher than after low-risk comparator procedures. Rates of myocardial infarction are similar to, but rates of stroke are higher than, those reported for the general population. [ABSTRACT FROM AUTHOR]

Background & Aims We developed a model to determine whether a multitarget stool DNA (MT-sDNA) test that detects colorectal cancer (CRC) and polyps with higher sensitivity and lower specificity, but at a higher cost, than the fecal immunochemical test (FIT) can be used in screening. Methods We used a Markov model of average-risk CRC screening to compare the effectiveness and cost effectiveness of screening with the MT-sDNA test vs FIT or colonoscopy. We accounted for the complex longitudinal participation patterns observed in organized programs vs opportunistic screening, as well as organized programs’ patient support costs and differential payment rates by commercial insurers vs Medicare. Results With optimal adherence, yearly FIT and colonoscopy every 10 years were dominant (more effective and less costly) than MT-sDNA every 3 years. Compared with successful organized FIT programs (50% consistent and 27% intermittent participation; patient support costs, $153/cycle), the patient support program for the MT-sDNA test would need 68% of subjects to participate consistently and 32% to participate intermittently every 3 years, or the MT-sDNA test would need to cost 60% less than in the base case ($260 commercial payment and $197 Medicare payment), for the MT-sDNA test to be preferred over FIT at a threshold of $100,000 per quality-adjusted life-year (QALY) gained. Compared with opportunistic yearly FIT screening (15% consistent and 30% intermittent participation), performing the MT-sDNA test every 3 years would cost less than $100,000 per QALY gained if the MT-sDNA test achieved a participation rate more than 1.7-fold that of FIT. The results were robust in sensitivity analyses. Assuming equal participation across strategies and a threshold of $100,000 per QALY gained, FIT was preferred in 99.3% of iterations in Monte Carlo simulation. Conclusions In a Markov model, we found FIT and colonoscopy to be more effective and less costly than the MT-sDNA test when participation rates were equal for all strategies. For the MT-sDNA test to be cost effective, the patient support program included in its cost would need to achieve substantially higher participation rates than those of FIT, whether in organized programs or under the opportunistic screening setting that is more common in the United States than in the rest of the world. [ABSTRACT FROM AUTHOR]