Primecuts – This Week in the Journals

August 27, 2021

Army Spc. Angel Laureano holds a vial of the COVID-19 vaccine, Walter Reed National Military Medical Center, Bethesda, Md., Dec. 14, 2020. (DoD photo by Lisa Ferdinando)

By Sue Dong, MD

Peer reviewed

Introduction: With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature. This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose. 

Association of Bezafibrate with Transplant-Free Survival in Patients with Primary Biliary Cholangitis [1]

Ursodeoxycholic acid (UDCA) and obeticholic acid are the only two treatments currently FDA-approved for primary biliary cholangitis (PBC). However, many patients exhibit suboptimal responses to these therapies. Fibrates have been touted as promising adjuvant therapies, but long-term efficacy data are lacking. This study investigated whether the addition of bezafibrate (BZF) to UDCA conferred survival benefits to those diagnosed with PBC.

This retrospective cohort study included survey data on 3,908 patients diagnosed with PBC in Japan. Over 500 medical institutions including tertiary care centers were surveyed. In the study population, 81% were treated with UDCA, and 19% received both UDCA and BZF. Primary outcomes were (1) survival without liver-related death or liver transplantation and (2) survival without all-cause death or liver transplantation. Those in the combination therapy group experienced not only lower transplant-free liver-related mortality (adjusted hazard ratio (aHR) 0.27; 95% CI, 0.13-0.57; p < 0.0001) but lower transplant-free all-cause mortality (aHR 0.33; 95% CI, 0.19-0.55; p < 0.0001) as well. The NNT to prevent one patient from progressing to liver transplantation or death over five years was 29 (95% CI, 22 – 46).

Some caveats to this study should be noted. Several patient characteristics differed between the UDCA only group and the UDCA + BZF group. Patients in the combination therapy group were younger, had more advanced disease on histology at diagnosis, and were more likely to be cared for at tertiary medical centers than at primary or secondary centers. Additionally, starting dates for therapies were inferred if they were not available in the survey data, which has the potential of skewing results. The authors addressed this limitation by including a data model that did not use inferred dates, and the positive effects of BZF addition were still significant with this latter model. Overall, this study provides evidence for the use of BZF as adjunctive therapy in the treatment of PBC.

Effectiveness of Covid-19 Vaccines Against the B.1.617.2 (Delta) Variant [2]

August 2021 finds many countries grappling with yet another resurgence of Covid-19, this time involving the B.1.617.2 (delta) variant of SARS-CoV-2. The effectiveness of various existing Covid-19 vaccines against this variant is largely unknown. This study addresses this knowledge gap.

Using a test-negative case-control study design, this study compared the effectiveness of the BNT162b2 vaccine (Pfizer–BioNTech) and the ChAdOx1 nCoV-19 vaccine (AstraZeneca) against the alpha and delta variants. (Effectiveness of these vaccines against the alpha variant is similar to that seen in clinical trials for these vaccines.) 19,109 cases of Covid-19 infection in England were included in the analysis. Vaccine effectiveness after one dose was lower against the delta variant (30.7%; 95% CI, 25.2-35.7) than against the alpha variant (48.7%; 95% CI, 45.5-51.7). Vaccine effectiveness after two doses remained lower against the delta variant (79.6%; 95% CI, 76.7-82.1) than the alpha variant (87.5%; 95% CI, 85.1-89.5), but overall effectiveness was high. Comparing the two vaccines, the BNT162b2 vaccine was more effective after two doses against both alpha and delta variants (93.7%; 95% CI, 91.6-95.3, and 88.0%; 95% CI, 85.3-90.1; respectively) than the ChAdOx1 nCoV-19 vaccine (74.5%; 95% CI, 68.4-79.4, and 67.0%; 95% CI, 61.3-71.8; respectively).

This study has several strengths and limitations, some of which will be highlighted here.  This study followed a test-negative case-control design, in which all subjects (both cases and controls) have presented for testing. This design minimizes potential differences related to presenting for testing between those who are vaccinated and those who remain unvaccinated. A limitation of this study is that measures of vaccine effectiveness are dependent on the test characteristics of different PCR tests. PCR tests have differing sensitivities and specificities, which may skew results. This study found a marked difference in effectiveness of a single vaccine dose against the alpha variant and the delta variant. This suggests that greater emphasis should be placed on ensuring individuals receive both vaccine doses, now more than ever.

All Coffee Types Decrease the Risk of Adverse Clinical Outcomes in Chronic Liver Disease: A UK Biobank Study [3] 

The global disease burden of chronic liver disease (CLD), including alcohol-related liver disease, non-alcoholic fatty liver disease, and viral hepatitis, is growing. Prior studies have found that coffee consumption protects against development and progression of chronic liver disease, but whether the type of coffee consumed matters for this protective effect remains to be elucidated.

This prospective observational cohort study recruited 494,585 UK men and women without existing diagnosis of CLD over a four-year period. Of participants, 78% were coffee drinkers consuming a median of 2 cups of coffee a day. Study subjects were surveyed on whether they drank decaf, instant, or ground coffee, or other. The primary outcomes were (1) incidence of CLD, (2) incidence of liver cancer, and (3) death due to CLD. The median follow-up duration was 10.7 years. Those who drank coffee experienced lower rates of CLD (HR: 0.79, 95% CI 0.72-0.86) and death due to CLD (HR: 0.51, 95% CI, 0.39-0.67) than those who abstained from coffee. The effect of coffee drinking on development of liver cancer did not reach significance (HR: 0.80, 95% CI 0.54-1.19), but the follow up period (ten years) is relatively short considering the usual time course of cancer development. These effects were seen across all coffee types.

Some limitations to this study bear mentioning. Subjects were surveyed about their coffee consumption habits (or lack thereof) at only one point in time. Over a ten year follow up period, participants could have started drinking coffee, increased or decreased the amount of coffee consumed, or stopped drinking coffee altogether, and these changes are not currently accounted for in the analysis. Additionally, the study population was overwhelming white (>90%), which limits generalization of findings to those of other ethnic backgrounds. Even so, this study provides intriguing evidence for the benefits of coffee consumption in the prevention of CLD and CLD-related mortality.


Non-Vitamin K Antagonist Oral Anticoagulants, Proton Pump Inhibitors and Gastrointestinal Bleeds [4]

Non-vitamin K antagonist oral anticoagulants (NOACs) are known to lead to higher rates of upper GI bleeding. This study investigated whether PPI therapy changed rates of upper GI bleeding in patients with atrial fibrillation treated with a NOAC. Study authors found that those treated with PPI therapy had lower rates of upper GI bleeding (incidence rate ratio (IRR): 0.75; 95% CI, 0.59-0.95). For those age ≥85 years, the number needed to treat for 1 year (NNTY) was 667; for those with HAS-BLED score ≥3, the NNTY was 378. These findings support concurrent PPI therapy in AF treated with NOACs.

Association of Remdesivir Treatment with Survival and Length of Hospital Stay Among US Veterans Hospitalized with COVID-19 [5]

There remains a lack of consensus on remdesivir therapy in the treatment of Covid-19. This study of US veterans found no difference in 30-day mortality between those treated with remdesivir and controls not treated with remdesivir (12.2% compared to 10.6%; aHR: 1.06; 95% CI, 0.83-1.36). Moreover, remdesivir increased the length of hospital stay of recipients compared to controls (6 days [interquartile range, 4-12 days] compared to 3 days [interquartile range, 1-7 days]; P < 0.001). These findings suggest remdesivir therapy in Covid-19 may do more harm than good.

Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease [6]

The DAPA-CKD trial found slower progression of kidney disease and improved survival in CKD patients with or without diabetes treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors. This study investigated a subgroup within the DAPA-CKD trial of patients with advanced (stage 4) CKD with albuminuria and whether SGLT2 inhibitors conferred similar benefits. Treatment with dapagliflozin was associated with decreased progression of kidney disease and kidney or CV-related mortality compared to placebo (HR: 0.73; 95% CI, 0.53-1.0). This extension of the DAPA-CKD trial found that SGLT2 inhibitors may be beneficial even in advanced CKD with albuminuria.

Sue Dong is a resident at NYU Langone Health

Peer reviewed by Alexandria Imperato, MD, Inpatient Chief Resident, Medicine, NYU Langone Health

Image courtesy of Wikimedia Commons, source: Pfizer-BioNTech COVID-19 vaccine (2020) B.jpg


[1] Tanaka A, Hirohara J, Nakano T, et al. Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis. Journal of Hepatology. 2021;75(3):565-571. doi:10.1016/j.jhep.2021.04.010

[2] Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. New England Journal of Medicine. 2021;385(7):585-594. doi:10.1056/NEJMoa2108891

[3] Kennedy OJ, Fallowfield JA, Poole R, et al. All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: A UK Biobank study. BMC Public Health. 2021;21(1):970. doi:10.1186/s12889-021-10991-7

[4] Komen J, Pottegård A, Hjemdahl P, et al. Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds. Heart. Published online July 31, 2021. doi:10.1136/heartjnl-2021-319332

[5] Ohl ME, Miller DR, Lund BC, et al. Association of Remdesivir treatment with survival and length of hospital stay among US veterans hospitalized with COVID-19. JAMA Network Open. 2021;4(7):e2114741-e2114741. doi:10.1001/jamanetworkopen.2021.14741

[6] Chertow G, Vart P, Jongs N, et al. Effects of Dapagliflozin in stage 4 chronic kidney disease. JASN. Published online July 16, 2021. doi:10.1681/ASN.2021020167