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Background <p>Cholestatic liver disease disproportionately affects South Asians, yet they remain underrepresented in genomic studies. This recall study aimed to recall volunteers from a British South Asian genetic cohort that were considered to be at high risk of cholestatic liver disease based on their genotype or phenotype.</p> Methods <p>Cases were defined as participants with rare (minor allele frequency &lt;1%) heterozygous loss of function (LoF) variants in <i>ABCB4</i> and <i>ABCB11</i> (genotype re-call) or with a previous intrahepatic cholestasis of pregnancy (ICP) diagnosis (ICD10 O26.6). Cases were matched 1:1 to controls. A detailed medical and family history was taken along with fasting anthropometric and transient elastography (TE) measurements and blood samples.</p> Results <p>Out of 22 eligible volunteers, 9 (41%) participate in the recall (8/9 genotype and 1/9 phenotype recall). Among the recalled cases there are 5 <i>ABCB4</i> LoF, 3 <i>ABCB11</i> LoF, and 1 ICP phenotype. Of these, 5/9 (55.6%) exhibit findings suggestive of liver involvement (genotype re-call). Specifically, 2/5 (50%) have increased liver stiffness on TE with one also demonstrating abnormal liver blood tests. 2/5(40%) report at least 2 cholestatic symptoms and an additional 1/5 (20%) demonstrates abnormal liver blood tests without increased liver stiffness.</p> Conclusions <p>This study shows findings suggestive of liver involvement in 55.6% of volunteers, underscoring the potential of rare heterozygous <i>ABCB4/11</i> variants as markers for identifying individuals at high risk of developing cholestatic liver disease. Consequently, individuals at higher genetic risk benefit from monitoring, personalised treatment and prevention strategies for cholestatic liver disease.</p>

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A genes and health recall study of intrahepatic cholestasis of pregnancy and cholestatic liver disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月23日

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  • Maria Constantinides,
  • Joseph Gafton,
  • Ana Cristina Angel Garcia,
  • Eamonn Maher,
  • Shabana Chaudhary,
  • Joseph Gafton,
  • Karen A. Hunt,
  • Shapna Hussain,
  • Kamrul Islam,
  • Mohammed Bodrul Mazid,
  • Elizabeth Owor,
  • Jessry Russell,
  • Nishat Safa,
  • John Solly,
  • Marie Spreckley,
  • David A. Van Heel,
  • Jan Whalley,
  • Ishevanhu Zengeya,
  • Emily Mantle,
  • Shaheen Akhtar,
  • Samina Ashraf,
  • Dan Mason,
  • John Wright,
  • Daniel MacArthur,
  • Michael Simpson,
  • Richard C. Trembath,
  • Gerome Breen,
  • Raymond Chung,
  • Sang Hyuck Lee,
  • Omar Asgar,
  • Joanne Harvey,
  • Karen Tricker,
  • Caroline Winckley,
  • Hanifa Khatun,
  • Amna Asif,
  • Claudia Langenberg,
  • Grainne Colligan,
  • Ceri Durham,
  • Bill Newman,
  • Ahsan Khan,
  • Hilary Martin,
  • Teng Heng,
  • Matt Hurles,
  • Vivek Iyer,
  • Georgios Kalantzis,
  • Vladimir Ovchinnikov,
  • Iaroslav Popov,
  • Klaudia Walter,
  • Panos Deloukas,
  • David Collier,
  • Ana Angel,
  • Saeed Bidi,
  • Fabiola Eto,
  • Chris Griffiths,
  • Sam Hodgson,
  • Benjamin M. Jacobs,
  • Rohini Mathur,
  • Caroline Morton,
  • Asma Qureshi,
  • Stuart Rison,
  • Annum Salman,
  • Miriam Samuel,
  • Moneeza K. Siddiqui,
  • Daniel Stow,
  • Sabina Yasmin,
  • Julia Zöllner,
  • Sheik Dowlut,
  • Peter H. Dixon,
  • Catherine Williamson,
  • Kenneth Linton,
  • Sarah Finer,
  • Upkar S. Gill,
  • Julia Zöllner

摘要

Background

Cholestatic liver disease disproportionately affects South Asians, yet they remain underrepresented in genomic studies. This recall study aimed to recall volunteers from a British South Asian genetic cohort that were considered to be at high risk of cholestatic liver disease based on their genotype or phenotype.

Methods

Cases were defined as participants with rare (minor allele frequency <1%) heterozygous loss of function (LoF) variants in ABCB4 and ABCB11 (genotype re-call) or with a previous intrahepatic cholestasis of pregnancy (ICP) diagnosis (ICD10 O26.6). Cases were matched 1:1 to controls. A detailed medical and family history was taken along with fasting anthropometric and transient elastography (TE) measurements and blood samples.

Results

Out of 22 eligible volunteers, 9 (41%) participate in the recall (8/9 genotype and 1/9 phenotype recall). Among the recalled cases there are 5 ABCB4 LoF, 3 ABCB11 LoF, and 1 ICP phenotype. Of these, 5/9 (55.6%) exhibit findings suggestive of liver involvement (genotype re-call). Specifically, 2/5 (50%) have increased liver stiffness on TE with one also demonstrating abnormal liver blood tests. 2/5(40%) report at least 2 cholestatic symptoms and an additional 1/5 (20%) demonstrates abnormal liver blood tests without increased liver stiffness.

Conclusions

This study shows findings suggestive of liver involvement in 55.6% of volunteers, underscoring the potential of rare heterozygous ABCB4/11 variants as markers for identifying individuals at high risk of developing cholestatic liver disease. Consequently, individuals at higher genetic risk benefit from monitoring, personalised treatment and prevention strategies for cholestatic liver disease.