Genomic Profiling of Combined Hepatocellular Cholangiocarcinoma Reveals Genomics Similar to Either Hepatocellular Carcinoma or Cholangiocarcinoma

PURPOSE Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare, aggressive primary liver carcinoma, with morphologic features of both hepatocellular carcinomas (HCC) and liver cholangiocarcinomas (CCA). METHODS The genomic profiles of 4,975 CCA, 1,470 HCC, and 73 cHCC-CCA cases arising from comprehensive genomic profiling in the course of clinical care were reviewed for genomic alterations (GA), tumor mutational burden, microsatellite instability status, genomic loss of heterozygosity, chromosomal aneuploidy, genomic ancestry, and hepatitis B virus status. RESULTS In cHCC-CCA, GA were most common in TP53 (65.8%), TERT (49.3%), and PTEN (9.6%), and 24.6% cHCC-CCA harbored potentially targetable GA. Other GA were predominantly associated with either HCC or CCA, including, but not limited to, TERT, FGFR2, IDH1, and presence of hepatitis B virus. On the basis of these features, a machine learning (ML) model was trained to classify a cHCC-CCA case as CCA-like or HCC-like. Of cHCC-CCA cases, 16% (12/73) were ML-classified as CCA-like and 58% (42/73) cHCC-CCA were ML-classified as HCC-like. The ML model classified more than 70% of cHCC-CCA as CCA-like or HCC-like on the basis of genomic profiles, without additional clinico-pathologic input. CONCLUSION These findings demonstrate the use of ML for classification as based on a targeted exome panel used during routine clinical care. Classification of cHCC-CCA by genomic features alone creates insights into the biology of the disease and warrants further investigation for relevance to clinical care.

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How to Clear HBV cccDNA: CRISPR/Cas9 Might Be Promising

10.20944/preprints201710.0065.v1 ◽

2017 ◽

Author(s):

Yan Qiu ◽

Ying Liu ◽

Wen Ren ◽

Jing Ren

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Health Concern ◽

Liver Carcinoma ◽

Major Health ◽

Circular Dna ◽

Hbv Cccdna ◽

B Virus

BACKGROUND: Chronic hepatitis B infected with Hepatitis B virus remains a major health concern worldwide. Despite standard interferon-α and nucleotide analogues have been shown to reduce the deterioration of liver disease among chronic hepatitis B patients, covalently closed circular DNA was still difficult to eradicate. METHODS: A literature search of Pubmed and Web of science was performed with the following key words: ‘CRISPR’, ‘CRISPR/Cas9’, ‘hepatitis B’, ‘HBV’, ‘chronic hepatitis B’ and ‘HBV cccDNA’. The information about CRISPR/Cas9 for the treatment of HBV cccDNA or hepatitis B was reviewed. RESULTS: CRISPR/Cas9 could treat hepatitis B through suppressing or clearing HBV cccDNA with different gRNAs. CONCLUSION: With the emergence of CRISPR/Cas9 (the RNA-guided clustered regulatory interspaced short palindromic repeats, CRISPR) editing technology, clearance of hepatitis B virus and better prevention of liver carcinoma seemed to be possible.

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Anti-Hepatitis B Virus Activity of Esculetin from Microsorium fortunei In Vitro and In Vivo

Molecules ◽

10.3390/molecules24193475 ◽

2019 ◽

Vol 24 (19) ◽

pp. 3475 ◽

Cited By ~ 3

Author(s):

Si-Xin Huang ◽

Jun-Fei Mou ◽

Qin Luo ◽

Qing-Hu Mo ◽

Xian-Li Zhou ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Antiviral Drug ◽

Liver Carcinoma ◽

Dependent Manner ◽

Duck Hepatitis ◽

B Virus

Coumarins are widely present in a variety of plants and have a variety of pharmacological activities. In this study, we isolated a coumarin compound from Microsorium fortunei (Moore) Ching; the compound was identified as esculetin by hydrogen and carbon spectroscopy. Its anti-hepatitis B virus (HBV) activity was investigated in vitro and in vivo. In the human hepatocellular liver carcinoma 2.2.15 cell line (HepG2.2.15) transfected with HBV, esculetin effecting inhibited the expression of the HBV antigens and HBV DNA in vitro. Esculetin inhibited the expression of Hepatitis B virus X (HBx) protein in a dose-dependent manner. In the ducklings infected with duck hepatitis B virus (DHBV), the levels of DHBV DNA, duck hepatitis B surface antigen (DHBsAg), duck hepatitis B e-antigen (DHBeAg), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) decreased significantly after esculetin treatment. Summing up the above, the results suggest that esculetin efficiently inhibits HBV replication both in vitro and in vivo, which provides an opportunity for further development of esculetin as antiviral drug.

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Genomic alterations (GA) and tumor mutational burden (TMB) in large cell neuroendocrine carcinoma of lung (L-LCNEC) as compared to small cell lung carcinoma (SCLC) as assessed via comprehensive genomic profiling (CGP).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8517 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8517-8517 ◽

Cited By ~ 8

Author(s):

Young Kwang Chae ◽

Keerthi Tamragouri ◽

Jon Chung ◽

Alexa Betzig Schrock ◽

Bhaskar Kolla ◽

...

Keyword(s):

Small Cell Lung Carcinoma ◽

Clinical Care ◽

Large Cell ◽

Smoking History ◽

Genomic Profiling ◽

Wild Type ◽

Cell Lung Carcinoma ◽

Mutational Burden ◽

Comprehensive Genomic Profiling ◽

Tumor Mutational Burden

8517 Background: SCLC and L-LCNEC are aggressive neoplasms that are both associated with smoking history and are thought to overlap in clinical, histogenetic, and genomic features. We reviewed the genomic profiles of >1187 patients to assess the genomic similarities of these diseases. Methods: Comprehensive genomic profiling (CGP) of tumors from 300 L-LCNEC and 887 SCLC patients in the course of clinical care was performed to suggest pathways to benefit from therapy. Results: Commonly altered genes in both diseases included TP53, RB1, MYC/MYCL1, MLL2, LRP1B and PTEN; alterations in other genes occurred at somewhat differing frequencies (table). For both diseases, RB1 mutation significantly co-occurred with TP53 mutations (p<0.001), but occurred in a mutually exclusive fashion to STK11 and CDKN2A (p<0.001). RB1 was mutually exclusive with KRAS for L-LCNEC but not for SCLC. The interquartile range for SCLC and L-LCNEC TMB is 7.9 and 12.6 with the 75% quartile being 14.4 and 17.1 respectively. Cases of both diseases will be presented with radiographic response to genomically matched targeted therapy and immunotherapy, particularly in cases of high TMB. Conclusions: Given the similar overall genomic profiles and clinical behavior of a subset of these diseases, they could be conceived of as a single disease to be further classified by genomically defined classes such as SCLC-type ( TP53/ RB1mutated) and NSCLC-like (wild type for one or both). By analogy to NSLC and melanoma, benefit from immunotherapy appears most likely for only the upper quartile of cases in TMB. [Table: see text]

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Classification of Hepatitis A Virus as Enterovirus Type 72 and of Hepatitis B Virus as Hepadnavirus Type 1

Intervirology ◽

10.1159/000149313 ◽

1982 ◽

Vol 18 (3) ◽

pp. 105-106 ◽

Cited By ~ 60

Author(s):

Joseph L. Melnick

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis A ◽

Hepatitis A Virus ◽

B Virus ◽

Enterovirus Type

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Taxonomic Classification of Human Hepatitis B Virus

Intervirology ◽

10.1159/000149651 ◽

1986 ◽

Vol 25 (1) ◽

pp. 14-29 ◽

Cited By ~ 45

Author(s):

Ian D. Gusf ◽

Christopher J. Burrell ◽

Anthony G. Coulepis ◽

William S. Robinson ◽

Arie J. Zuckerman

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Taxonomic Classification ◽

Human Hepatitis ◽

B Virus

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Hepatitis B virus-related combined hepatocellular-cholangiocarcinoma

European Journal of Gastroenterology & Hepatology ◽

10.1097/meg.0b013e3283625df9 ◽

2014 ◽

Vol 26 (2) ◽

pp. 192-199 ◽

Cited By ~ 27

Author(s):

Kai-jian Chu ◽

Chong-de Lu ◽

Hui Dong ◽

Xiao-hui Fu ◽

Hong-wei Zhang ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

B Virus ◽

Combined Hepatocellular Cholangiocarcinoma

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Electronic Health Informatics Data To Describe Clearance Dynamics of Hepatitis B Surface Antigen (HBsAg) and e Antigen (HBeAg) in Chronic Hepatitis B Virus Infection

mBio ◽

10.1128/mbio.00699-19 ◽

2019 ◽

Vol 10 (3) ◽

Cited By ~ 10

Author(s):

Louise O. Downs ◽

David A. Smith ◽

Sheila F. Lumley ◽

Meha Patel ◽

Anna L. McNaughton ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Clinical Data ◽

Health Informatics ◽

Clinical Care ◽

Hepatitis B Virus Infection ◽

Clearance Time ◽

Stratified Care ◽

Chronic Hepatitis B Virus ◽

B Virus

ABSTRACT HBsAg and HBeAg have gained traction as biomarkers of control and clearance during chronic hepatitis B virus infection (CHB). Improved understanding of the clearance correlates of these proteins could help inform improvements in patient-stratified care and advance insights into the underlying mechanisms of disease control, thus underpinning new cure strategies. We collected electronic clinical data via an electronic pipeline supported by the National Institute for Health Research Health Informatics Collaborative (NIHR HIC), adopting an unbiased approach to the generation of a robust longitudinal data set for adults testing HBsAg positive from a large UK teaching hospital over a 6-year period (2011 to 2016 inclusive). Of 553 individuals with CHB, longitudinal data were available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 13 (4%) cleared HBsAg completely. Among these 13, the HBsAg clearance rate in individuals on nucleos(t)ide analogue (NA) therapy (n = 4 [31%]; median clearance time,150 weeks) was similar to that in individuals not on NA therapy (n = 9 [69%]; median clearance time, 157 weeks). Those who cleared HBsAg were significantly older and less likely to be on NA therapy than nonclearers (P = 0.003 and P = 0.001, respectively). Chinese ethnicity was associated with HBeAg positivity (P = 0.025). HBeAg clearance occurred in individuals both on NA therapy (n = 24; median time, 49 weeks) and off NA therapy (n = 19; median time, 52 weeks). Improved insights into the dynamics of these biomarkers can underpin better prognostication and patient-stratified care. Our systematized approach to data collection paves the way for scaling up efforts to harness clinical data to address research questions and support improvements in clinical care. IMPORTANCE Advances in the diagnosis, monitoring, and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical data sets that can help to inform advances in patient care and provide insights that may help to inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been underrepresented in the literature. By tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualized clinical care and may provide important clues into the immune events that underpin disease control.

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Hepatitis B Virus Genotype Study in West Africa Reveals an Expanding Clade of Subgenotype A4

Microorganisms ◽

10.3390/microorganisms9030623 ◽

2021 ◽

Vol 9 (3) ◽

pp. 623

Author(s):

Rayana Maryse Toyé ◽

Damien Cohen ◽

Flor Helene Pujol ◽

Amina Sow-Sall ◽

Gora Lô ◽

...

Keyword(s):

Amino Acid ◽

Hepatitis B Virus ◽

Hepatitis B ◽

The Gambia ◽

The Other ◽

Virus Genotype ◽

Hbv Genotype ◽

Entire Genome ◽

B Virus

Hepatitis B virus (HBV) classification comprises up to 10 genotypes with specific geographical distribution worldwide, further subdivided into 40 subgenotypes, which have different impacts on liver disease outcome. Though extensively studied, the classification of subgenotype A sequences remains ambiguous. This study aimed to characterize HBV isolates from West African patients and propose a more advanced classification of subgenotype A. Fourteen HBV full-length genome sequences isolated from patients from The Gambia and Senegal were obtained and phylogenetically analyzed. Phylogenetic analysis of HBV genotype A sequences isolated from Senegalese and Gambian patients exhibited separate clusters from the other known and confirmed subgenotypes A (A1, A2, A6). Most of the sequences (10/14) clustered with an isolate from Cuba, reported as subgenotype A4 (supported by maximal bootstrap value). Four isolates from The Gambia and Senegal clustered separately from all other subgenotypes and samples sequenced in the study. Three of which from The Gambia, designated as an expanding clade of subgenotype A4, exhibited a mean inter-subgenotypic nucleotide divergence over the entire genome sequence higher than 4% in comparison with the other subgenotypes and the other isolates sequenced in the study, except with subgenotype A4 isolates (3.9%), and this was supported by a maximal bootstrap value. The last one from Senegal seemed to be an expanding subgenotype close to the new clade of A4. Amino acid analysis unveiled a novel motif specific to these isolates. This study revealed an expanding evolution of HBV subgenotype A and novel amino acid motifs. It also highlighted the need for a consensus regarding the analysis and classification of HBV sequences.

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