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Etiologic fractions in patients of hepatocellular carcinoma in India with and without a background of cirrhosis: a multi-centric study

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Abstract

Background

Hepatocellular cancer (HCC) typically arises in the background of cirrhosis. The epidemiology of HCC has changed in recent years due to availability of newer antivirals, changing life-styles and greater possibility for early detection. We undertook a multicentric national sentinel surveillance for liver cirrhosis and HCC to assess the attributable risk factors for the development of HCC, both with and without a background of cirrhosis.

Methods

Data from January 2017 till August 2022 from hospital-based records of eleven participating centers were included. Diagnosed cases of cirrhosis [radiological (multiphase and/or histopathological] and HCC [as per AASLD 2018] were included. History of significant alcohol intake was elicited by AUDIT-C questionnaire.

Results

Altogether 5798 enrolled patients were assessed, of which 2664 patients had HCC. The mean age was 58.2 ± 11.7 years and 84.3% (n = 2247) were males. Diabetes was found in over a third of those with HCC (n = 1032;39.5%). The most common etiology of HCC was NAFLD (n = 927;35.5%) followed by viral hepatitis B and C and harmful levels of alcohol. Among those with HCC, 27.9% (n = 744) had no cirrhosis. Higher proportion of cirrhotic HCC patients had alcohol as an etiological factor as compared to non-cirrhotic (17.5 vs. 4.7%, p ≤ 0.001). NAFLD was an etiological factor for a higher proportion of non-cirrhotic HCC patients as compared to cirrhotic HCC (48.2 vs. 30.6%, p ≤0.001). Diabetics more commonly had non-cirrhotic HCC (50.5 vs. 35.2%). The following factors were associated with an occurrence of cirrhotic HCC: male gender (OR 1.372 and 95% CI 1.070–1.759), age above 60 years (OR 1.409 and 95% CI 1.176–1.689), HBV (OR 1.164 and 95% CI 0.928–1.460), HCV (OR 1.228 and 95 CI 0.964–1.565) and harmful consumption of alcohol (OR 3.472 and 95% CI 2.388–5.047). The adjusted odds of non-cirrhotic patients having NAFLD was 1.553 (95% CI 1.290–1.869).

Conclusion

This large multi-centric study demonstrates that NAFLD is the most important risk factor for development of both cirrhotic and non-cirrhotic HCC in India and has overtaken viral hepatitis. Awareness campaigns and large-scale screening are required to reduce the high burden of NAFLD-related HCC in India.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

HCC:

Hepato-cellular carcinoma

AASLD:

American Association for the Study of Liver Diseases

AUDIT-C:

Alcohol use disorders identification test-concise

NAFLD:

Non-alcoholic fatty liver disease

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

ILBS:

Institute of Liver and Biliary Sciences

CT:

Computed tomography

MRI:

Magnetic resonance imaging

OPD:

Outpatient department

IPD:

Inpatient department

IBM:

International business machines

SPSS:

Statistical package for the social sciences

IQR:

Interquartile range

AFLD:

Alcoholic fatty liver disease

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Acknowledgements

We appreciate the efforts of all the collaborators for WHOCC study titled ‘Surveillance of Etiological factors for Cirrhosis and Hepatocellular Carcinoma’.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Institute of Liver and Biliary Sciences, New Delhi, India

    Tushar Prabhakar, Kanica Kaushal & Manya Prasad

  2. Department of Virology, Institute of Liver and Biliary Science, New Delhi, India

    Ekta Gupta

  3. Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India

    Ajit Sood

  4. Department of Gastroenterology, Choithram Hospital and Research Centre, Indore, India

    Ajay K. Jain

  5. Department of Gastroenterology, GS Medical College and KEM Hospital, Mumbai, India

    Akash Shukla

  6. Department of Hepatology, Christian Medical College, Vellore, India

    Ashish Goel

  7. Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Ajay Duseja

  8. Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India

    Anoop Saraya

  9. Department of Transplant Hepatology, HPB, Liver Intensive Care, Global Hospital, Mumbai, India

    Samir Shah

  10. Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India

    Guresh Kumar

  11. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

    Shiv Kumar Sarin

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  1. Tushar Prabhakar
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  11. Samir Shah
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Contributions

All authors contributed to the study conception and design. Material preparation, data analysis and first draft was done by TP. SKS commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shiv Kumar Sarin.

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Conflict of interest

Tushar Prabhakar, Kanica Kaushal, Manya Prasad, Ekta Gupta, Ajit Sood, Ajay K. Jain, Akash Shukla, Ashish Goel, Ajay Duseja, Anoop Saraya, Samir Shah, Guresh Kumar, Shiv Kumar Sarin have no relevant financial or non-financial interests to disclose.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was waived off due to the record review and surveillance mode of data collection. Institutional Ethics Committee allowed the same (No. IEC/2020/73/NA06).

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Prabhakar, T., Kaushal, K., Prasad, M. et al. Etiologic fractions in patients of hepatocellular carcinoma in India with and without a background of cirrhosis: a multi-centric study. Hepatol Int 17, 745–752 (2023). https://doi.org/10.1007/s12072-023-10498-w

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