Association Between Severe Serum Alanine Aminotransferase Flares and Hepatitis B e Antigen Seroconversion and HBV DNA Decrease in Untreated Patients With Chronic HBV Infection.
Study Goal
The researchers aimed to determine the incidence and outcomes of alanine aminotransferase (ALT) flares in a racially diverse North American cohort with chronic HBV infection.
Results Summary
The study found that ALT flares occurred in 6% of participants, with higher incidence in males, those with higher baseline HBV DNA, at-risk alcohol use, and higher FIB-4 values. Flares were associated with greater decreases in HBV DNA and HBeAg loss but not HBsAg loss, and no severe adverse outcomes were observed.
Population
Adults with chronic HBV infection (49.9% male, 73.7% Asian, mean age 42.6 years) in the U.S. and Canada.
Effective Dosage
Not specified
Duration
Planned 5-year follow-up (data collected from January 2011 to May 2016).
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
- | increase | ALT flares | participants | 102 participants (6%) | occurred in | #1 |
- | increase | ALT flares | - | 31 flares (30%) | occurring at | #2 |
- | increase | 4-year cumulative incidence of ALT flares | - | 5.7% | was | #3 |
- | increase | median peak level of ALT | - | 450 U/L | was | #4 |
male sex | increase | occurrence of an ALT flare | - | odds ratio [OR], 3.02 | associated with | #5 |
higher baseline HBV DNA values | increase | occurrence of an ALT flare | - | OR per log10, 1.41 | associated with | #6 |
at risk alcohol use | increase | occurrence of an ALT flare | - | OR, 2.27 vs none or moderate | associated with | #7 |
higher FIB-4 values | increase | occurrence of an ALT flare | - | OR, 1.85 per log2 | associated with | #8 |
older age | decrease | odds of an ALT flare | - | OR, 0.63 per 10 years | associated with | #9 |
ALT flare | increase | rate of decrease in level of HBV DNA by 1 log10 or more | HBeAg-positive vs HBeAg-negative patients | 59 vs 23 per 100 person-years | higher in patients with | #10 |
ALT flare | increase | HBeAg loss | - | 47 vs 15 per 100 person-years | higher in patients with | #11 |
ALT flare | no change | rate of HBsAg loss | - | 4 vs 2 per 100 person-years | similar in patients with | #12 |
- | no change | hepatic decompensation, liver transplants, or deaths | ALT flares | No | observed in participants with | #13 |
- | increase | cumulative incidence of severe ALT flares | large racially heterogeneous cohort of adults with chronic HBV infection | low | was | #14 |
ALT flares | increase | greater decreases in HBV DNA and loss of HBeAg | - | - | associated with | #15 |
ALT flares | no change | loss of HBsAg | - | - | not associated with | #16 |
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.