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Severity of Acute Portal Hypertension Determines the Clinical Outcomes in Severe Alcoholic Hepatitis

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Abstract

Background

Severe alcohol-associated hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) has high mortality. Severe hepatic inflammation and ongoing hepatocellular cell death lead to rapid rise in portal pressure, a hyperdynamic circulation that might precipitate infections and organ failures.

Methods

Consecutive SAH patients were classified based on baseline HVPG measurement as 6to < 12 mmHg, 12to < 20 mmHg, and ≥ 20 mmHg. We analyzed portal hypertension severity in relation to fibrosis stage, ACLF at presentation, response to prednisolone, severity scores(MELD and Maddrey’s Discriminant Function, mDF), and 90-day mortality.

Results

Of 819 SAH patients (94.6% ACLF, 85.4% histological cirrhosis, median MELD and mDF scores 25 and 66, respectively), 250(30.5%) had HVPG ≥ 20 mmHg. Patients with HVPG ≥ 20 mmHg more often had large esophageal varices (25.2%vs.13.2%; p-0.001), higher baseline MELD (27.1 ± 5.6vs.25.3 ± 5.2; p-0.001), and mDF(76.1 ± 16vs.68.4 ± 15.1; p-0.01) scores. No patient without ACLF had HVPG ≥ 20 mmHg. Moreover, during hospital course these patients had higher incidence of variceal bleed (17.2%vs.8.8%; p-0.001), acute kidney injury (36.4%vs.25.3%; p-0.001), and spontaneous bacterial peritonitis (6.4%vs.3.5%; p-0.05). Of 412(50.3%) eligible patients treated with prednisolone, 69.2% showed response at day 7(Lille’s score < 0.45). 90-day mortality was 27.6%; and baseline MELD > 25.5[HR 1.78], HVPG ≥ 20 mmHg [HR 1.86], the presence of HE[HR 1.63], and prednisolone ineligibility due to sepsis[HR 1.27] were independent predictors. Mortality was unrelated to varices grade, variceal bleed, and histological cirrhosis. Repeat HVPG performed in 114(19.2%) patients after a median of 5.2 months showed significant decrease (3.6 mmHg; p-0.001) which correlated with improvement in MELD score(13points; p-0.05).

Conclusion

Development of ACLF and complications in SAH are likely a result of acute rise in HVPG. “High-risk” SAH are SAH patients with HVPG ≥ 20 mmHg in the presence of ascites. Understanding the drivers for acute rise in portal pressure in SAH ACLF might help introduction of newer therapies.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

SAH:

Severe alcohol-associated hepatitis

ACLF:

Acute-on-chronic liver failure

PHT:

Portal hypertension

mDF:

Maddrey’s Discriminant Function

NSBBs:

Non-selective beta-blockers

HVPG:

Hepatic venous pressure gradient

ILBS:

Institute of Liver and Biliary Sciences

NIAAA:

National Institute on Alcohol Abuse and Alcoholism

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

INR:

International normalization ratio

UGIE:

Upper gastrointestinal endoscopy

APASL:

Asian-pacific Association for the Study of Liver Diseases

WHVP:

Wedged hepatic venous pressure

FHVP:

Free hepatic venous pressure

HCC:

Hepatocellular carcinoma

AKI:

Acute kidney injury

AKIN:

Acute kidney injury network

HE:

Hepatic encephalopathy

MELD:

Model for end-stage liver disease

NSBB:

Non-selective beta-blocker

FMT:

Fecal microbiota transplantation

SD:

Standard deviation

IQR:

Interquartile range

References

  1. Sarin SK, Choudhury A, Sharma MK et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int 2019;13:353–390.

    Article  PubMed  Google Scholar 

  2. Luca A, García-Pagán JC, Bosch J, Feu F, Caballería J, Groszmann RJ, Rodés J. Effects of ethanol consumption on hepatic hemodynamics in patients with alcoholic cirrhosis. Gastroenterology 1997;112:1284–1289.

    Article  CAS  PubMed  Google Scholar 

  3. Rincon D, Iacono OL, Ripoll C et al. Prognostic value of hepatic venous pressure gradient for in-hospital mortality of patients with severe acute alcoholic hepatitis. Aliment Pharmacol Ther 2007;25:841–848.

    Article  CAS  PubMed  Google Scholar 

  4. Patidar KR, Peng JL, Kaur H et al. Severe alcohol-associated hepatitis is associated with worse survival in critically Ill patients with acute on chronic liver failure. Hepatol Commun 2022;6:1090–1099.

    Article  PubMed  Google Scholar 

  5. Kumar M, Kainth S, Choudhury A et al. Treatment with carvedilol improves survival of patients with acute-on-chronic liver failure: a randomized controlled trial. Hepatol Int 2019;13:800–813.

    Article  PubMed  Google Scholar 

  6. Sarin SK, Sharma S. Predictors of steroid non-response and new approaches in severe alcoholic hepatitis. Clin Mol Hepatol 2020;26:639–651.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Crabb DW, Bataller R, Chalasani NP et al. Standard definitions and common data elements for clinical trials in patients with alcoholic hepatitis: recommendation from the NIAAA alcoholic hepatitis consortia. Gastroenterology 2016;150:785–790.

    Article  PubMed  Google Scholar 

  8. de Franchis R, Faculty BVI. Expanding consensus in portal hypertension report of the Baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015;63:743–752.

    PubMed  Google Scholar 

  9. Kumar A, Sharma P, Sarin SK. Hepatic venous pressure gradient measurement: time to learn! Indian J Gastroenterol 2008;27:74–80.

    PubMed  Google Scholar 

  10. Wong F. Acute kidney injury in liver cirrhosis: new definition and application. Clin Mol Hepatol 2016;22:415–422.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ferenci P, Lockwood A, Mullen K et al. Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11thWorld Congresses of Gastroenterology, Vienna, 1998. Hepatology 2002;35:716–721.

    Article  PubMed  Google Scholar 

  12. Llovet JM, Ducreux M, Lencioni R et al. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Eur J Cancer 2012;48:599–641.

    Article  Google Scholar 

  13. Philips CA, Pande A, Shasthry SM et al. Healthy donor fecal microbiota transplantation in steroid-ineligible severe alcoholic hepatitis: a pilot study. Clin Gastroenterol Hepatol 2017;15:600–602.

    Article  PubMed  Google Scholar 

  14. Kumar V, Choudhury AK, Maiwall R et al. Degree of hemodynamic derangements correlate with poor outcomes in acute on chronic liver failure (ACLF) patients AASLD abstract. Hepatol 2018;2018:S1.

    Google Scholar 

  15. Shasthry SM, Sharma MK, Shasthry V, Pande A, Sarin SK. Efficacy of granulocyte colony-stimulating factor in the management of steroid-nonresponsive severe alcoholic hepatitis: a double-blind randomized controlled trial. Hepatology 2019;70:802–811.

    Article  CAS  PubMed  Google Scholar 

  16. Mathurin P, O’Grady J, Carithers RL et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut 2011;60:255–260.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hepatology, Institute of Liver and Biliary Sciences, D – 1, Vasant Kunj, New Delhi, 110070, India

    Ankur Jindal, Manoj K. Sharma, Rajan Vijayaraghavan, Shasthry SM & Shiv K. Sarin

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

    Guresh Kumar

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  1. Ankur Jindal
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  2. Manoj K. Sharma
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  3. Rajan Vijayaraghavan
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  4. Shasthry SM
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  5. Guresh Kumar
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Contributions

AJ contributed toward conceptualization, review and original draft preparation, analysis, and editing of manuscript; MKS contributed toward original draft preparation; GK contributed toward statistical analysis; SKS contributed toward conceptualization, review, and editing of manuscript.

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Correspondence to Shiv K. Sarin.

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Jindal, A., Sharma, M.K., Vijayaraghavan, R. et al. Severity of Acute Portal Hypertension Determines the Clinical Outcomes in Severe Alcoholic Hepatitis. Dig Dis Sci 69, 298–307 (2024). https://doi.org/10.1007/s10620-023-08144-4

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  • DOI: https://doi.org/10.1007/s10620-023-08144-4

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