Clinical Outcome and Viral Genome Variability of Hepatitis B Virus–Induced Acute Liver Failure

Anastasiou, Olympia E.; Widera, Marek; Westhaus, Sandra; Timmer, Lejla; Korth, Johannes; Gerken, Guido; Canbay, Ali; Todt, Daniel; Steinmann, Eike; Schwarz, Tatjana; Timm, Jörg; Verheyen, Jens; Ciesek, Sandra

doi:10.1002/hep.30279

Cited by 20 publications

(17 citation statements)

References 32 publications

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“…All ALF patients presented with or developed sepsis and MODS. Interestingly, ALF patients were exclusively male, indicating that male sex may be a risk factor for ALF in SARS-CoV-2 infection, contrary to what has been shown for ALF due to other pathologies [ 14 , 15 ].…”

Section: Discussionmentioning

confidence: 90%

Mild versus Severe Liver Injury in SARS-CoV-2 Infection

Anastasiou

Korth

Herbstreit

et al. 2020

Dig Dis

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Background Abnormal liver function has been reported in patients with COVID-19 infection. The aim of our study was to report on the prevalence of liver injury in our cohort, to evaluate the association of mild versus severe liver injury with mortality in COVID-19 patients and to scrutinize the temporal pattern of viral detection and liver injury. Methods We present data from a German cohort of 147 SARS-CoV-2 infected patients. The patients were divided into 3 groups according to their liver status during treatment. The first group included patients without elevated alanine aminotransferase or bilirubin, the third group patients meeting the biochemical criteria of acute liver failure (ALF), and the second group all other patients. Results Liver injury was detected in 75 (50.7%) and 93 (63%) patients by admission and during treatment, respectively. ALF was associated with the male sex, younger age, and higher BMI. Mortality was associated with the presence of ALF (OR = 9.423, 95% CI: 2.410–36.858) in contrast to milder liver injury (OR 1.101, 95% CI: 0.435–2.791). In 30% of patients with mild liver injury and in 50% of ALF patients, peak liver injury was observed at a time point when the virus was no longer detectable in the respiratory tract. Conclusion Mild liver injury was not associated with worse outcome in our cohort, and the pattern of liver injury did not fit well to the theory of SARS-CoV-2 directly causing liver impairment. Instead, severe liver injury in our cohort was associated multiple-organ failure and acute vascular events.

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Section: Discussionmentioning

confidence: 90%

Mild versus Severe Liver Injury in SARS-CoV-2 Infection

Anastasiou

Korth

Herbstreit

et al. 2020

Dig Dis

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“…DNA extraction was performed with QIAamp DNA mini kit (Qiagen). PCR for the whole HBV genome was performed as previously described [12]. For genotype assessment, detection of immune escape mutations and stop codon mutations in HBsAg the geno2pheno platform was used [17].…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have demonstrated that viral factors, such as increased variability in HBV core, preS2 region, and HBsAg, as well as host factors (e.g., the presence of certain human leukocyte antigen (HLA) class II locus alleles), are associated with the development of ALF in the case of an acute HBV infection [12,13,14]. Furthermore, HBV reactivation has been shown to correlate with HBsAg mutations associated with enhanced capability to evade immune response, some of them were only present as minority variants as shown per next-generation sequencing (NGS) [15].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure

Anastasiou

Theissen

Verheyen

et al. 2019

Viruses

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Hepatitis B virus (HBV) reactivation in immunosuppressed patients can cause considerable morbidity and mortality. The aim of our study was to evaluate factors associated with acute liver failure (ALF) in HBV reactivation. Clinical, laboratory, and virological data of 87 patients with HBV reactivation were analyzed retrospectively. Teno torque virus (TTV) plasma loads were measured as a measure of immune competence. HBV genomes isolated from 47 patients were analyzed by next-generation sequencing. A functional analysis of identified HBsAg mutants was performed. In patients with ALF the diagnosis was significantly later confirmed than in the non-ALF group. Patients diagnosed during immunosuppression had a milder clinical course compared to later diagnosed patients (p = 0.018, OR = 4.17). TTV viral loads did not differ significantly between the two groups. The HBV genomes isolated from ALF patients had higher viral complexity. A mutation in C-region of HBsAg (L216*), was associated with reduced HBsAg production and secretion. Patients diagnosed with HBV reactivation during immunosuppression had a milder clinical course compared to patients diagnosed during immune reconstitution. ALF was associated with higher viral complexity. An HBsAg mutation (L216*) was found to be more frequent in ALF patients and was associated with reduced HBsAg production and secretion.

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“…There are 120 million carriers of HBV and 20 million patients with chronic hepatitis B 2 . A study showed 0.1%‐0.5% HBV‐infected patients would develop ALF 3 . HBV infection is a major risk factor for ALF patients.…”

Section: Introductionmentioning

confidence: 99%

“…HBV infection is a major risk factor for ALF patients. However, current treatments for HBV‐ALF, which include antiviral treatment and other support measures, are not satisfying except liver transplantation 3 . But owing to dramatic clinical course and shortage of donor organ, many patients die during the waiting for the proper donor liver.…”

Section: Introductionmentioning

confidence: 99%

Systematic analysis on multiple Gene Expression Omnibus data sets reveals fierce immune response in hepatitis B virus‐related acute liver failure

Chen

Zhao

Zhang

et al. 2020

J Cellular Molecular Medi

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Acute liver failure (ALF) caused by hepatitis B virus (HBV) is common type of liver failure in the world, with high morbidity and mortality rates. However, the prevalence, genetic background and factors determining the development of HBV‐related ALF are rarely studied. In this study, we examined three Gene Expression Omnibus (GEO) data sets by bioinformatics analysis to identify differentially expressed genes (DEGs), key biological processes and pathways. Immune infiltration analysis showed high immune cells infiltration in HBV‐related ALF tissue. We then confirmed natural killer cells and macrophages infiltration in clinical samples by immunohistochemistry assay, implying these cells play a significant role in HBV‐ALF. We found 1277 genes were co‐up‐regulated and that 1082 genes were co‐down‐regulated in the 3 data sets. Inflammation‐related pathways were enriched in the co‐up‐regulated genes and synthetic metabolic pathways were enriched in the co‐down‐regulated genes. WGCNA also revealed a key module enriching in immune inflammation response and identified 10 hub genes, differentially expressed in an independent data set. In conclusion, we identified fierce immune inflammatory response to elucidate the immune‐driven mechanism of HBV‐ALF and 10 hub genes based on gene expression profiles.

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Clinical Outcome and Viral Genome Variability of Hepatitis B Virus–Induced Acute Liver Failure

Abstract: HBV GT-D and increased variability in HBV core, preS2 region and SHB are associated with a worse clinical outcome of acute HBV infection. This article is protected by copyright. All rights reserved.

Cited by 20 publications

References 32 publications

Mild versus Severe Liver Injury in SARS-CoV-2 Infection

Mild versus Severe Liver Injury in SARS-CoV-2 Infection

Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure

Systematic analysis on multiple Gene Expression Omnibus data sets reveals fierce immune response in hepatitis B virus‐related acute liver failure

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