Serum alanine aminotransferase flares in chronic hepatitis B infection: the good and the bad.
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ABSTRACT:
SUBMITTER: Ghany MG
PROVIDER: S-EPMC7158588 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC6905460 | biostudies-literature
Project description:IntroductionAlterations in the immune system can result in alanine aminotransferase (ALT) flares either during pregnancy or after delivery in women with chronic hepatitis B virus (HBV) infection. The aim of this study was to prospectively assess changes in serum biochemical and virological markers of HBV infection during and after pregnancy in a large North American cohort of pregnant women with chronic HBV.MethodsAdult pregnant women enrolled in the Hepatitis B Research Network between 2011 and 2016 were included. Serum ALT values and HBV DNA viral levels were obtained at <28 weeks and >28 weeks of gestation and <16 weeks, 16-31 weeks, and 32-48 weeks postpartum. Outcomes of ALT flares included severity, duration, and initiation of antiviral therapy.ResultsAmong the 158 pregnant women with chronic HBV, the median age was 33 years, 73% were Asian, and 63% were hepatitis B e antigen (HBeAg) negative. The median HBV DNA level was substantially higher in the HBeAg-positive vs HBeAg-negative women (1.3 × 10 vs 343 IU/mL), but serum ALT levels at their first study visit were similar. Among untreated pregnant women, there was a very mild increase in serum ALT postpartum among both HBeAg-positive and HBeAg-negative women (P < 0.001). Serum ALT flares (range 107-513 U/L) developed in 3.4% (5/149) during pregnancy and in 4.3% (4/92) after delivery. Twenty-two percent were initiated on antiviral therapy. After withdrawal of prophylactic anti-HBV therapy, 17.2% (5/29) developed serum ALT flares (range 107-208 U/L) within 14 weeks of drug discontinuation, and 3 additional women had flares despite continuous anti-HBV therapy during pregnancy or postpartum. Many ALT flares were not associated with significant changes in HBV DNA levels. No flares were severe with elevations of bilirubin or clinical decompensation.DiscussionSpontaneous ALT flares in untreated pregnant women with chronic HBV are infrequent, mild, and self-limited both prepartum and postpartum. Although flares after the withdrawal of antiviral therapy postpartum are more common, they were also mild and self-limited. Further studies of the immunopathogenesis of pregnancy-related flares are needed, as well as effects on long-term outcome of the mother and infant.
| S-EPMC7132838 | biostudies-literature
Project description:Background: Circulating miRNAs, a new family of miRNAs presentin plasma and serum, have shown great potential as novel body fluid biomarkers for non-invasive diagnosis and prognosis of several diseases. Methods: In the present study, we employed next-generation sequencing technology to analyze the expression profiles of circulating miRNAs in the serum of chronic hepatitis B (CHB) patients presenting persistently normal alanine aminotransferase with significant histological features (SPNALT),PNALT patients with no significant histological features (NSPNALT),and healthy control patients. Results: MiRNAs were found to be the major constituents of small RNA-annotated reads by comparing the annotate draw sequence reads with miRNA databases and genome and other small RNA libraries. Our results point to a total of 2767 unique reads that can be mapped to human miRNAs or pre-miRNAs in miRbase, and the pre-miRNAs can be further mapped to the human genome. Thirty novel miRNA genes were identified in three groups. The differential expression levels of 143 miRNAs showed significant variation when the SPNALT and control group were compared. Among these, 22 miRNAs were >4-fold up-regulated (P<0.01) in SPNALT group and 4 were >2-fold down-regulated (P<0.01).When the SPNALT and NSPNALT group were compared, the differential expression levels of 84 miRNAs showed significant variation. Among these, 13 miRNAs showed a >4-fold up-regulation (P<0.01) in the SPNALT group and 21 showed a >2-fold down-regulation (P<0.01). Conclusions: Our results show that circulating miRNAs in the serum of SPNALT patients could be more comprehensively detected by the next-generation sequencing technology. Newly identified miRNAs might be used as biomarkers for diagnosis of chronic hepatitis B patients presenting persistently normal alanine aminotransferase with significant histological features.
2016-12-31 | GSE62290 | GEO
Project description:Our previous studies unexpectedly indicated that the level of serum hepatitis B core antibody (anti-HBc) was positively correlated with the serum alanine aminotransferase (ALT) level. The aim of this study was to determine whether anti-HBc could serve as a potential biomarker for the detection of liver inflammation in chronic hepatitis B (CHB) patients, especially in patients with normal ALT levels. Serum anti-HBc levels were quantified in 655 treatment-naïve CHB patients, including 45 patients who underwent two liver biopsies (baseline phase and the 78th weeks of antiviral-treatment). Serum anti-HBc levels increased significantly along with the increasing histology activity index (HAI) score. After antiviral-treatment, patients with HAI score reduction had significant decline in serum anti-HBc level. Multivariate analysis showed that anti-HBc was independently associated with moderate-to-severe hepatic inflammation in patients with normal ALT level. Furthermore, serum anti-HBc showed a high diagnostic accuracy for predicting moderate-to-severe inflammation in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB patients with normal ALT levels (area under the curve, AUC?=?0.87 and 0.75; respectively). Thus, anti-HBc may be a strong indicator for assessing the hepatic inflammatory degree and used for antiviral treatment decisions in CHB patients with normal ALT levels.
| S-EPMC5459818 | biostudies-literature
Project description:The changes in the gut microbiota of healthy hepatitis B virus (HBV) carriers, including asymptomatic and non-cirrhotic subjects, have been rarely scrutinized. From 1463 faecal samples in health examinees, in total 112 subjects, including 36 hepatitis B surface antigen (HBsAg)-positive and 76 control subjects, were included. Twenty-eight of 36 HBsAg-positive individuals (78%) showed normal alanine aminotransferase (ALT) levels (normal ALT group), whereas eight subjects exhibited elevated ALT levels (22%, high ALT group). By using 16S rRNA gene sequencing, the distance between normal and high ALT groups among HBsAg-positive subjects showed a significant separation after the pairwise comparison of weighted UniFrac distance (permutational analysis of variance q-value = 0.039), when compared with the distances to the control group. In comparison with the control group, the normal ALT group had Anaerostipes as a significant taxon that showed a positive association (Coefficient (Coef.) = 0.028, q = 0.039). Desulfovibrio (Coef. = 0.54, q = 0.014) and Megasphaera (Coef. = 1.41, q = 0.030) showed positive correlations, and Acidaminococcus (Coef. = -1.31, q = 4.15 × 10-75) exhibited a negative correlation with high ALT level. Gut microbial composition was different according to HBV-induced serum ALT levels, indicative of a potential link between gut and liver metabolism.
| S-EPMC6407135 | biostudies-literature
Project description:Background & aimsHepatic elastography (HE) is a noninvasive technique that measures liver stiffness and is used to diagnose hepatic fibrosis. It can help patients who are thought to have early-stage disease avoid a staging liver biopsy, but only when confounding variables that increase liver stiffness are excluded. Chronic inflammation from hepatitis C virus (HCV) infection is not considered to be one of these variables.MethodsWe identified 684 patients with HCV and METAVIR fibrosis scores of 0-2 from a prospective, multi-institutional study of liver stiffness in 2880 patients with chronic liver disease. Patients were 49.6 ± 9.0 years old, 64.3% were male, and they had an average body mass index of 26.7 ± 4.1 kg/m(2).ResultsIn a multivariate analysis, inflammation (based on histologic analysis) and level of alanine aminotransferase (ALT) were associated with liver stiffness. The chances of a patient having a level of stiffness that indicates cirrhosis increased with grade of inflammation and level of ALT. By using a conservative 14.5-kPa cutoff for the diagnosis of cirrhosis, grade 3 inflammation had an odds ratio of 9.10 (95% confidence interval, 2.49-33.4). Likewise, levels of ALT greater than 80 and 120 IU/L had odds ratios of 3.84 (95% confidence interval, 2.10-7.00) and 4.10 (95% confidence interval, 2.18-7.69), respectively. The effect of the level of ALT persisted when analysis was restricted to patients with fibrosis scores of F0 to F1.ConclusionsIn patients with HCV infection and early-stage fibrosis, increased levels of ALT correlate with liver stiffness among patients in the lowest strata of fibrosis (METAVIR scores 0-2). Patients without fibrosis but high levels of ALT could have liver stiffness within the range for cirrhosis. Inflammation should be considered a confounding variable in analysis of liver stiffness.
| S-EPMC3402604 | biostudies-literature
Project description:PurposeAbout 60-80 % of chronic hepatitis B virus (HBV) carriers are characterized with persistently normal alanine transaminase (ALT). Differences of cytokine expression are associated with the prognosis of HBV infection. We investigated the expression pattern of 30 cytokines associated with anti-HBV immunity in patients with normal ALT.MethodsFour patient groups (immune tolerance, inactive hepatitis B surface antigen carriers, resolved hepatitis B, and control; 10 subjects per group) were assigned. Thirty cytokines, including IFN-?, IL-1?, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-17C, IL-21, IL-22, IL-23p19, IL-28A, IL-29, CCL5, CCL16, CCL20, CCL22, CXCL9, CXCL10, CXCL11, TNFRSF8, TNFRSF18, IL-6R, gp130, and TGF-?1, were measured using a human cytokine antibody array. Signal intensities were obtained by laser scanner. Protein-protein interactions were analyzed by STRING (Search Tool for the Retrieval of Interacting Genes/Proteins).ResultsSignificant differences of signal intensities were observed for IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-21, IL-23p19, IL-28A, and IL-29. The lowest intensity was in controls. Among three HBV infection groups, significant differences were observed in IL-2, IL-4, IL-12p70, IL-15, IL-21, IL-23p19, and IL-29. The highest intensity was in the inactive group. All cytokines with significant differences were involved JAK-STAT signaling that up-regulate FOXP3, SOCS3 and MX1.ConclusionDifferential expression of cytokines in JAK-STAT signaling is an important factor associated with prognosis of HBV infection. The elevation of ?C cytokines, IL-12p70, IL-23p19, and IL-29 may promote spontaneous HBeAg seroconversion and HBV clearance.
| S-EPMC3782639 | biostudies-literature
Project description:Background & aimsAn increased level of alanine aminotransferase (ALT) is a marker of liver injury. The mean ALT level has been reported to decrease with age; we performed a longitudinal analysis to determine whether serum levels of ALT changes with age among community-dwelling, older adults in the US.MethodsWe analyzed clinical data from 2 cohorts of individuals who participated in the Rancho Bernardo Study, in Southern CA. The first cohort comprised 1073 community-dwelling participants (59% women); clinical data was collected from 1984-1987 and 1992-1997. The second cohort comprised 416 participants (64% women); data was collected from 1984-1987, 1992-1997, and 1997-1999. Demographic, metabolic covariates, ALT, bilirubin, and albumin were measured. Changes in individual ALT over time were examined in unadjusted and multivariable-adjusted linear and logistic regression analyses.ResultsAt the baseline visit, the patients' mean age was 65.7 years and body mass index was 24.9 kg/m(2). In cohort 1, the mean levels of ALT decreased with age by 10% (from 21 to 19 IU/L) between the time periods of 1984-1987 and 1992-1997 (P < .0001). In cohort 2, they decreased by 20% (from 20 to 16 IU/L) between the time periods of 1984-1987 and 1997-1999 (P < .0001). Categorically-defined increases in ALT also decreased with age (P < .0001). Results remained consistent in sex-specific analyses and after adjusting for metabolic syndrome components, alcohol use, bilirubin, and serum levels of albumin (P < .0001).ConclusionsIn a longitudinal analysis, we observed that levels of ALT decrease with age, independent of sex, metabolic factors, alcohol use, and results from commonly used liver function tests (bilirubin and albumin). When interpreting serum levels of ALT, physicians should consider patients' age especially in the elderly.
| S-EPMC3288181 | biostudies-literature
Project description:Goals and backgroundSerum alanine aminotransferase (ALT) activity has been reported to be greater in the afternoon than the early morning, but data are scarce. We examined diurnal variation of ALT in a national population-based sample.StudyParticipants in the 1999 to 2008 US National Health and Nutrition Examination Survey were randomly assigned to morning (AM; n = 4474 adolescents, 11,235 adults) or afternoon/evening (PM; n = 4887 adolescents, 11,735 adults) examinations. We examined ALT distributions graphically and compared both geometric mean ALT and the prevalence of elevated ALT, defined as >31 IU/L for adolescent boys, >24 IU/L for adolescent girls, >43 IU/L for adult men, and >30 IU/L for adult women, between AM and PM examination groups.ResultsThe examination groups were similar with the exception in the AM group of a longer fasting time and slightly higher prevalence of diabetes among adolescents and viral hepatitis B among adult women. ALT distributions were similar between examination sessions among the 4 groups. Among adolescents and men, neither mean ALT nor prevalence of abnormal ALT differed by examination group. Among women, mean ALT was statistically significant, but minimally higher in the PM group (19.6 IU/L) than the AM group (19.1 IU/L; P = 0.009). Among 1 subgroup, women with chronic viral hepatitis, there was a higher prevalence of abnormal ALT in the PM group (P = 0.018 in unadjusted analysis). Adjusting for liver injury risk factors had little effect on the difference in mean ALT.ConclusionsIn general, clinically significant diurnal variation in ALT activity was not found in the US population.
| S-EPMC3545081 | biostudies-literature
Project description:BackgroundThe clinical and histological features of chronic hepatitis B (CHB) patients who fall into the "grey zone (GZ)" and do not fit into conventional natural phases are unclear.AimTo explore the impact of varying the threshold of alanine aminotransferase (ALT) levels in identifying significant liver injury among GZ patients.MethodsThis retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy. The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines. GZ CHB patients were classified into four groups: GZ-A (HBeAg positive, normal ALT levels, and HBV DNA ≤ 107 IU/mL), GZ-B (HBeAg positive, elevated ALT levels, and HBV DNA < 104 or > 107 IU/mL), GZ-C (HBeAg negative, normal ALT levels, and HBV DNA ≥ 2000 IU/mL), and GZ-D (HBeAg negative, elevated ALT levels, and HBV DNA ≤ 2000 IU/mL). Significant hepatic injury (SHI) was defined as the presence of notable liver inflammation (≥ G2) and/or significant fibrosis (≥ S2).ResultsThe results showed that 50.22% of patients were classified as GZ, and 63.7% of GZ patients developed SHI. The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria (35 U/L for men and 25 U/L for women) can more accurately identify patients with significant liver damage in the GZ phases. In total, the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 64.86% [(221 + 294)/794]. When we lowered the ALT treatment threshold to the new criteria (30 U/L for men and 19 U/L for women), the same outcome was revealed, and the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 75.44% [(401 + 198)/794]. Additionally, the proportion of SHI was 49.1% in patients under 30 years old and increased to 55.3% in patients over 30 years old (P = 0.136).ConclusionThese findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.
| S-EPMC10514758 | biostudies-literature