Publications

Department of Medicine faculty members published more than 3,600 peer-reviewed articles in 2024.

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Health and quality of life outcomes

Incorporating development of a patient-reported outcome instrument in a clinical drug development program: examples from a heart failure program.

2016

Authors: Wiklund I, Anatchkova M, Oko-Osi H, von Maltzahn R, Chau D, Malik FI, Patrick DL, Spertus J, Teerlink JR

Metabolomics : Official journal of the Metabolomic Society

The alpha-1A adrenergic receptor agonist A61603 reduces cardiac polyunsaturated fatty acid and endocannabinoid metabolites associated with inflammation in vivo.

2016

Authors: Willis MS, Ilaiwy A, Montgomery MD, Simpson PC, Jensen BC

The American journal of cardiology

Effect of Diffuse Subendocardial Hypoperfusion on Left Ventricular Cavity Size by 13N-Ammonia Perfusion PET in Patients With Hypertrophic Cardiomyopathy.

2016

Authors: Yalçin H, Valenta I, Yalçin F, Corona-Villalobos C, Vasquez N, Ra J, Kucukler N, Tahari A, Pozios I, Zhou Y, Pomper M, Abraham TP, Schindler TH, Abraham MR

American journal of public health

Moderation of the Relation of County-Level Cost of Living to Nutrition by the Supplemental Nutrition Assistance Program.

2016

Authors: Basu S, Wimer C, Seligman H

Malaria journal

Characterizing microscopic and submicroscopic malaria parasitaemia at three sites with varied transmission intensity in Uganda.

2016

Authors: Rek J, Katrak S, Obasi H, Nayebare P, Katureebe A, Kakande E, Arinaitwe E, Nankabirwa JI, Jagannathan P, Drakeley C, Staedke SG, Smith DL, Bousema T, Kamya M, Rosenthal PJ, Dorsey G, Greenhouse B

European journal of medicinal chemistry

4-Aminoquinoline-ferrocenyl-chalcone conjugates: Synthesis and anti-plasmodial evaluation.

2016

Authors: Singh A, Gut J, Rosenthal PJ, Kumar V

Volume 66 of Issue 2 | Journal of hepatology

Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B.

2016

Authors: Lai CL, Wong D, Ip P, Kopaniszen M, Seto WK, Fung J, Huang FY, Lee B, Cullaro G, Chong CK, Wu R, Cheng C, Yuen J, Ngai V, Yuen MF

View Abstract

BACKGROUND AND AIMS

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), a mini-chromosome essential for HBV replication, is supposed to be resistant to nucleos(t)ide analogue treatment. We investigated the effect of long-term nucleos(t)ide analogue treatment on cccDNA.

METHODS

Among 129 patients who had been enrolled in previous international nucleos(t)ide analogue clinical trials and had liver biopsies at baseline and one year after treatment, we recruited 43 patients on long-term continuous treatment for 72 to 145months for a third liver biopsy. Serum HBV DNA, hepatitis B surface antigen (HBsAg) levels, total intrahepatic HBV DNA (ihHBV DNA), cccDNA, HBV pregenomic RNA (pgRNA) as well as histologic changes were examined.

RESULTS

At the time of the third biopsy, serum HBV DNA levels were undetectable in all but one patient. The median levels of HBsAg, ihHBV DNA, and cccDNA were 2.88logIU/ml, 0.03copies/cell, and 0.01copies/cell, respectively. Compared to baseline levels, there was reduction of HBsAg levels by 0.54log (71.46%), ihHBV DNA levels by 2.81log (99.84%), and cccDNA levels by 2.94log (99.89%), with 49% having cccDNA levels below the detection limit. One patient had undetectable HBsAg. The median pgRNA level, measured only in the third biopsy, was 0.021copies/cell, with 40% of patients having undetectable pgRNA.

CONCLUSIONS

Long-term nucleos(t)ide analogue treatment induced marked depletion of cccDNA in the majority of patients while serum HBsAg levels, though reduced, were detectable in all but one patient. Whether cccDNA depletion is sustained and associated with better patient outcome requires further study.

LAY SUMMARY

It is generally presumed that a form of hepatitis B virus DNA, called covalently closed circular DNA (cccDNA), which hides inside the nuclei of liver cells of patients with chronic hepatitis B, cannot be reduced by antiviral treatment. The present study showed that with prolonged treatment (median period 126months), cccDNA can be markedly reduced, with 49% of liver biopsies having undetectable cccDNA. This suggests that viral replication capacity would be very low after prolonged antiviral treatment.

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Science translational medicine