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      Adenoma Detection Rate (ADR) Irrespective of Indication Is Comparable to Screening ADR: Implications for Quality Monitoring

      One of the key benchmarks of the effectiveness of screening colonoscopy is adenoma detection rate (ADR).
      • Cross A.J.
      • Robbins E.C.
      • Saunders B.P.
      • et al.
      Higher adenoma detection rates at screening associated with lower long-term colorectal cancer incidence and mortality.
      ADR is the proportion of screening colonoscopies in which at least one adenoma is detected. However, colonoscopies are also performed for non-screening purposes (surveillance or diagnostic).
      • Mangas-Sanjuan C.
      • Santana E.
      • Cubiella J.
      • et al.
      QUALISCOPIA Study Investigators
      Variation in colonoscopy performance measures according to procedure indication.
      In this issue of Clinical Gastroenterology and Hepatology, Kaltenbach and colleagues
      • Kaltenbach T.
      • Gawron A.
      • Meyer C.S.
      • et al.
      Adenoma detection rate (ADR) irrespective of indication is comparable to screening ADR: implications for quality monitoring.
      conducted a retrospective review of consecutive colonoscopies at 2 Veterans Affairs centers to address their hypothesis that overall ADRs associated with healthcare site and provider, irrespective of the indication, would be similar to the ADR for screening colonoscopies. They calculated the ADR for screening, non-screening, and all colonoscopies (irrespective of indication) and corrected for within-endoscopist correlation. They also investigated how the effect of different distributions for indication of the colonoscopy would impact the ADRs by designing and performing 8 simulation studies in 2 types of settings, where colonoscopy was the primary screening modality and where annual FIT was the first-line screening method. In this study, the patients were predominantly men (93%) with a mean age of 63.2±10.0 years. There were 2628 colonoscopies performed by 21 gastroenterologists over 6 months in 2015 and the indication was screening in 28.9%, surveillance in 48.2% and diagnostic in 22.9%. There was no significant difference in the ADR between all colonoscopies (50% [95% CI, 45-56]) and screening colonoscopies (49% [95% CI, 43-56]) (P = .55). The ADRs for surveillance and diagnostic colonoscopies was 56% and 38%, respectively. Simulation modeling did not significantly change the calculated ADRs for non-screening indications or screening only indication. Study limitations included that it was retrospective and was conducted in predominantly men at a relatively older mean age. In summary, this study found that overall ADR based on all colonoscopies was not significantly different than the conventional ADR based on screening colonoscopies. Future prospective studies should evaluate the validity of using overall ADR as a quality indicator in other patient populations and settings.
      This article is highlighted by an editorial by Douglas Rex on page 0000.
      See page 1883.

      Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis

      Prior studies and meta-analyses suggest that proton pump inhibitors (PPI) increase the risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and health outcomes. However, many of these studies had significant limitations and thus, the use of PPI and its possible association with risk of COVID-19 infection and disease severity remains uncertain. In this issue of Clinical Gastroenterology and Hepatology, Bastrup Israelsen et al
      • Bastrup Israelsen S.
      • Thomsen Ernst M.
      • Lundh A.
      • et al.
      Proton pump inhibitor use is not strongly associated with SARS-CoV-2 related outcomes: A nationwide study and meta-analysis.
      conducted a nationwide observational study including 83,224 SARS-CoV-2 cases in Denmark as of December 1, 2020. The association of current PPI use with risk of infection was examined in a case-control design. The authors compared the risk of severe outcomes, including mechanical ventilation, admission to the intensive care unit, or death in current PPI users (n = 4473) compared to those who never used PPIs (n = 59,413). In addition to performing propensity score matching to control for confounding, the authors also conducted an updated meta-analysis on risk of SARS-CoV-2 infection and COVID-19 mortality associated with PPI use. They found that current PPI use was associated with increased risk of SARS-CoV-2 infection with an adjusted odds ratio (OR), 1.08 (95% CI, 1.03-1.13). Among SARS-CoV-2 cases, PPI use was associated with increased risk of hospital admission (19% vs 16%; adjusted relative risk (RR), 1.13 [1.03-1.24]), but not with other severe outcomes. Their updated meta-analysis showed no association between PPI use and risk of infection or mortality with a pooled OR, 1.00 (95% CI, 0.75-1.32) and RR, 1.33 (95% CI, 0.71-2.48). The authors noted that all the studies reporting the impact of PPI use in SARS-CoV-2 infected individuals have substantial differences, such as heterogeneous study populations and study design. The authors concluded that PPI use is generally safe with regards to risk of SARS-CoV-2 infection and severe COVID-19 outcomes. The risk of hospital admission was increased for current PPI users, although the minimally elevated relative risk may be explained by confounding factors. The study’s updated meta-analysis demonstrated that current PPI use did not impact COVID-19 outcomes.
      See page 1845.

      Ultra-Long-term Follow-up of Interferon-Alpha Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection

      Functional cure rates (ie, HBsAg loss) for chronic hepatitis B (CHB) with current nucleos(t)ide analogues (NA) has been difficult to achieve despite their potent antiviral effects. Interferon-alpha (IFN-α) treatment for CHB virus infection leads to relatively higher functional cure rates than NA therapy.
      • Alawad A.S.
      • Auh S.
      • Suarez D.
      • et al.
      Durability of spontaneous and treatment-related loss of hepatitis B s antigen.
      • Wu Y.
      • Liu Y.
      • Lu J.
      • et al.
      Durability of interferon-induced hepatitis B surface antigen seroclearance.
      • Chen H.
      • Sun J.
      • Zhou B.
      • et al.
      Variants in STAT4 associated with cure of chronic hbv infection in hbeag-positive patients treated with pegylated interferon-alpha.
      In this issue of Clinical Gastroenterology and Hepatology, Choi et al

      Choi HSJ, van Campenhout MJH, van Vuuren AJ, et al. Ultra long-term follow-up of interferon alfa treatment for HBeAg-positive chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 2021;19:1933–1940.

      conducted a retrospective cohort study of HBeAg-positive patients at a tertiary referral center between 1977-2014 to evaluate the effects of pegylated (PEG)-IFN-α treatment and clinical outcomes in an ultra-long-term follow-up of CHB patients following treatment. Treatment endpoints included HBsAg loss with or without anti-HBs seroconversion and incidence of clinical events. The study included 267 patients (67% male, 58% Caucasian, 34% Asian; median age, 32 years) with a median follow-up of 11.5 years. The cumulative incidence of HBsAg loss was 14% by 5 years and 32% by 10 years. Baseline factors associated with a higher rate of HBsAg loss were male sex, Caucasian race, genotype A, age ≥40 years, and cirrhosis, but not the type IFN-α given, treatment strategy, treatment duration, or baseline ALT or HBV DNA. HBsAg loss rates did not differ significantly between those who received short-term (≤24 weeks) versus long-term (>24 weeks) therapy. However, further studies are needed to adjust for any confounders and confirm this finding. Incidence rates of HBsAg loss were higher and clinical outcomes lower in patients who achieved initial response, which was defined as HBeAg loss within 1-year post-IFN-α treatment. Limitations include the retrospective study design and time-related bias. The authors concluded that high rates of HBeAg and HBsAg loss can be achieved from a single course of PEG-IFN-α, especially in certain patients. The durable, ultra-long-term curative effects suggest that PEG-IFN-α may be an important component of novel combination therapies for a functional cure for CHB.
      See article 1933.

      Liver Stiffness by Magnetic Resonance Elastography Predicts Future Cirrhosis, Decompensation and Death in NAFLD

      There is a lack of effective, noninvasive methods to identify patients with nonalcoholic fatty liver disease (NAFLD) who have a high risk of progressing to cirrhosis and liver-related complications. Magnetic resonance elastography (MRE) is the most accurate method to estimate liver fibrosis, which histologically is a strong predictor of liver-associated outcomes.
      • Hsu C.
      • Caussy C.
      • Imajo K.
      • et al.
      Magnetic resonance vs transient elastography analysis of patients with nonalcoholic fatty liver disease: a systematic review and pooled analysis of individual participants.
      ,
      • Eaton J.E.
      • Sen A.
      • Hoodeshenas S.
      • et al.
      Changes in liver stiffness, measured by magnetic resonance elastography, associated with hepatic decompensation in patients with primary sclerosing cholangitis.
      In this issue of Clinical Gastroenterology and Hepatology, Gidener and colleagues
      • Gidener T.
      • Ahmed O.T.
      • Larson J.J.
      • et al.
      Liver stiffness by magnetic resonance elastography predicts future cirrhosis, decompensation and death in NAFLD.
      studied the role of liver stiffness measurement (LSM) by MRE in predicting the development of cirrhosis in 639 adults with noncirrhotic NAFLD and the development of liver decompensation or death in 194 adults with compensated NAFLD cirrhosis between 2007 and 2019. Twenty patients without baseline cirrhosis developed cirrhosis after a median follow-up of 4 years. Baseline LSM was predictive of cirrhosis development with an age-adjusted hazard ratio (HR), 2.93 (95% CI, 1.86-4.62; P < .0001) per 1 kPa increment. Patients with a baseline LSM of 1 or 2 kPa had ≤1% risk of developing cirrhosis in the next 5 years, and therefore, repeating MRE in a shorter time frame was felt to have a low yield. However, patients with a LSM of 3 kPa should be considered for repeat elastography in 3 years, when the risk to develop cirrhosis was 1.71%. In contrast, those with a baseline LSM of 4-5 kPa had a risk of progression to cirrhosis of 1.78-5.26% in 1 year, and therefore surveillance elastography should be considered within this time period. In patients with baseline compensated cirrhosis, LSM independently predicted decompensation and death with an adjusted HR, 1.32 (95% CI, 1.13-1.56; P = .0007). The 1-year probability of future decompensation or death in cirrhosis with baseline LSM of 5 kPa vs 8 kPa was 9% vs 20%, respectively. In this largest study to date, LSM measurement by MRE was shown to predict the risk of developing cirrhosis or decompensation in patients with NAFLD. Limitations include the retrospective design, lack of paired liver biopsies, and cost and lack of availability of MRE.
      See page 1915.

      References

        • Cross A.J.
        • Robbins E.C.
        • Saunders B.P.
        • et al.
        Higher adenoma detection rates at screening associated with lower long-term colorectal cancer incidence and mortality.
        Clin Gastroenterol Hepatol. 2020 Sep 12; (S1542-S3565(20)31280-5. https://doi.org/10.1016/j.cgh.2020.09.020. Epub ahead of print)
        • Mangas-Sanjuan C.
        • Santana E.
        • Cubiella J.
        • et al.
        • QUALISCOPIA Study Investigators
        Variation in colonoscopy performance measures according to procedure indication.
        Clin Gastroenterol Hepatol. 2020; 18: 1216-1223
        • Kaltenbach T.
        • Gawron A.
        • Meyer C.S.
        • et al.
        Adenoma detection rate (ADR) irrespective of indication is comparable to screening ADR: implications for quality monitoring.
        Clin Gastroenterol Hepatol. 2021; 19: 1883-1889
        • Bastrup Israelsen S.
        • Thomsen Ernst M.
        • Lundh A.
        • et al.
        Proton pump inhibitor use is not strongly associated with SARS-CoV-2 related outcomes: A nationwide study and meta-analysis.
        Clin Gastroenterol Hepatol. 2021; 19: 1845-1854
        • Alawad A.S.
        • Auh S.
        • Suarez D.
        • et al.
        Durability of spontaneous and treatment-related loss of hepatitis B s antigen.
        Clin Gastroenterol Hepatol. 2020; 18: 700-709.e3
        • Wu Y.
        • Liu Y.
        • Lu J.
        • et al.
        Durability of interferon-induced hepatitis B surface antigen seroclearance.
        Clin Gastroenterol Hepatol. 2020; 18: 514-516.e2
        • Chen H.
        • Sun J.
        • Zhou B.
        • et al.
        Variants in STAT4 associated with cure of chronic hbv infection in hbeag-positive patients treated with pegylated interferon-alpha.
        Clin Gastroenterol Hepatol. 2020; 18: 196-204.e8
      1. Choi HSJ, van Campenhout MJH, van Vuuren AJ, et al. Ultra long-term follow-up of interferon alfa treatment for HBeAg-positive chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 2021;19:1933–1940.

        • Hsu C.
        • Caussy C.
        • Imajo K.
        • et al.
        Magnetic resonance vs transient elastography analysis of patients with nonalcoholic fatty liver disease: a systematic review and pooled analysis of individual participants.
        Clin Gastroenterol Hepatol. 2019; 17: 630-637.e8
        • Eaton J.E.
        • Sen A.
        • Hoodeshenas S.
        • et al.
        Changes in liver stiffness, measured by magnetic resonance elastography, associated with hepatic decompensation in patients with primary sclerosing cholangitis.
        Clin Gastroenterol Hepatol. 2020; 18: 1576-1583.e1
        • Gidener T.
        • Ahmed O.T.
        • Larson J.J.
        • et al.
        Liver stiffness by magnetic resonance elastography predicts future cirrhosis, decompensation and death in NAFLD.
        Clin Gastroenterol Hepatol. 2021; 19: 1915-1924

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