Mayur Brahmania1, Manuel Lombardero2, Bettina E Hansen3, Norah A Terrault4, Anna S Lok5, Robert P Perrillo6, Steven H Belle2, Adrian M Di Bisceglie7, Jordan J Feld1, William M Lee8, Michael W Fried9, Harry L A Janssen10. 1. Division of Gastroenterology, Toronto General Hospital, University Health Network, Toronto, Canada. 2. Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania. 3. Division of Gastroenterology, Toronto General Hospital, University Health Network, Toronto, Canada; IHPME, University of Toronto, Toronto, Canada. 4. Division of Gastroenterology, University of California-San Francisco, San Francisco, California. 5. Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan. 6. Division of Gastroenterology, Baylor University Medical Center, Dallas, Texas. 7. Division of Gastroenterology and Hepatology, Saint Louis University, St Louis, Missouri. 8. Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas. 9. Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina. 10. Division of Gastroenterology, Toronto General Hospital, University Health Network, Toronto, Canada. Electronic address: Harry.Janssen@uhn.ca.
Abstract
BACKGROUND & AIMS: The incidence and outcomes of alanine aminotransferase (ALT) flares during the natural history of chronic HBV infection has not been determined in a large, racially heterogeneous group of patients in North America. METHODS: We collected data from the Hepatitis B Research Network-an observational cohort study of untreated adults with chronic HBV infection enrolled at 21 sites in the United States and Canada. Clinical and laboratory data were collected from 1587 participants (49.9% male, 73.7% Asian, 35.2% genotype B infection, mean age of 42.6 years) at enrollment, at weeks 12 and 24, and every 24 weeks thereafter for a planned 5 years of follow up (from January 2011 through May 2016). Participants were excluded if they had a history of hepatic decompensation, hepatocellular carcinoma, solid organ or bone marrow transplantation, chronic immune suppression, or antiviral therapy within 6 months before enrollment. Levels of ALT were measured in serum samples and flares were defined as at least 10 times the upper limit of normal (300 U/L in males and 200 U/L in females). RESULTS: ALT flares occurred in 102 participants (6%), with 31 flares (30%) occurring at baseline. The 4-year cumulative incidence of ALT flares was 5.7%. The median peak level of ALT was 450 U/L (25th-75th percentile, 330 U/L to 747 U/L) with a maximum of 2578 U/L. In multivariable analysis, factors associated with the occurrence of an ALT flares were: male sex (odds ratio [OR], 3.02; P=.0007), higher baseline HBV DNA values (OR per log10, 1.41; P<.0001), at risk alcohol use (OR, 2.27 vs none or moderate; P=.02), and higher FIB-4 values (OR, 1.85 per log2; P<.0001). Older age was associated with lower odds of an ALT flare (OR, 0.63 per 10 years; P=.004). Rate of decrease in level of HBV DNA by 1 log10 or more (59 vs 23 per 100 person-years for HB e antigen (HBeAg)-positive vs HBeAg-negative patients; P=.003) and HBeAg loss (47 vs 15 per 100 person-years; P=.002) were higher in patients with an ALT flare than in patients without, but the rate of HBsAg loss was similar (4 vs 2 per 100 person-years; P=.26). No hepatic decompensation, liver transplants, or deaths were observed in participants with ALT flares. CONCLUSION: In a large racially heterogeneous cohort of adults with chronic HBV infection, the cumulative incidence of severe ALT flares was low and associated with greater decreases in HBV DNA and loss of HBeAg, but not with loss of HBsAg.
BACKGROUND & AIMS: The incidence and outcomes of alanine aminotransferase (ALT) flares during the natural history of chronic HBV infection has not been determined in a large, racially heterogeneous group of patients in North America. METHODS: We collected data from the Hepatitis B Research Network-an observational cohort study of untreated adults with chronic HBV infection enrolled at 21 sites in the United States and Canada. Clinical and laboratory data were collected from 1587 participants (49.9% male, 73.7% Asian, 35.2% genotype B infection, mean age of 42.6 years) at enrollment, at weeks 12 and 24, and every 24 weeks thereafter for a planned 5 years of follow up (from January 2011 through May 2016). Participants were excluded if they had a history of hepatic decompensation, hepatocellular carcinoma, solid organ or bone marrow transplantation, chronic immune suppression, or antiviral therapy within 6 months before enrollment. Levels of ALT were measured in serum samples and flares were defined as at least 10 times the upper limit of normal (300 U/L in males and 200 U/L in females). RESULTS: ALT flares occurred in 102 participants (6%), with 31 flares (30%) occurring at baseline. The 4-year cumulative incidence of ALT flares was 5.7%. The median peak level of ALT was 450 U/L (25th-75th percentile, 330 U/L to 747 U/L) with a maximum of 2578 U/L. In multivariable analysis, factors associated with the occurrence of an ALT flares were: male sex (odds ratio [OR], 3.02; P=.0007), higher baseline HBV DNA values (OR per log10, 1.41; P<.0001), at risk alcohol use (OR, 2.27 vs none or moderate; P=.02), and higher FIB-4 values (OR, 1.85 per log2; P<.0001). Older age was associated with lower odds of an ALT flare (OR, 0.63 per 10 years; P=.004). Rate of decrease in level of HBV DNA by 1 log10 or more (59 vs 23 per 100 person-years for HB e antigen (HBeAg)-positive vs HBeAg-negative patients; P=.003) and HBeAg loss (47 vs 15 per 100 person-years; P=.002) were higher in patients with an ALT flare than in patients without, but the rate of HBsAg loss was similar (4 vs 2 per 100 person-years; P=.26). No hepatic decompensation, liver transplants, or deaths were observed in participants with ALT flares. CONCLUSION: In a large racially heterogeneous cohort of adults with chronic HBV infection, the cumulative incidence of severe ALT flares was low and associated with greater decreases in HBV DNA and loss of HBeAg, but not with loss of HBsAg.
Authors: Marc G Ghany; Jordan J Feld; Kyong-Mi Chang; Henry L Y Chan; Anna S F Lok; Kumar Visvanathan; Harry L A Janssen Journal: Lancet Gastroenterol Hepatol Date: 2020-02-10
Authors: Simon C Ling; Hsing-Hua S Lin; Karen F Murray; Philip Rosenthal; Douglas Mogul; Norberto Rodriguez-Baez; Sarah Jane Schwarzenberg; Jeffrey Teckman; Kathleen B Schwarz Journal: J Pediatr Date: 2021-05-20 Impact factor: 6.314
Authors: Richard K Sterling; Wendy C King; Mandana Khalili; Raymond T Chung; Mark Sulkowski; Mamta K Jain; Mauricio Lisker-Melman; Marc G Ghany; David K Wong; Amanda S Hinerman; Atul K Bhan; Abdus S Wahed; David E Kleiner Journal: Hepatology Date: 2021-08-25 Impact factor: 17.298
Authors: William M Lee; Wendy C King; Harry L A Janssen; Marc G Ghany; Robert J Fontana; Michael Fried; Richard K Sterling; Jordan J Feld; Junyao Wang; Douglas B Mogul; Stewart L Cooper; Adrian M Di Bisceglie Journal: J Viral Hepat Date: 2021-08-11 Impact factor: 3.728