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Cited by 2,089Liver Disease and TransplantationLiver physiology and pathologyLiver Diseases and Immunity

Liver cirrhosis

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Schuppan, Detlef, Afdhal, Nezam H·2008·The Lancet
DOI 10.1016/s0140-6736(08)60383-9PMC PMC2271178
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Abstract

Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease. Recent advances in the understanding of the natural history and pathophysiology of cirrhosis, and in treatment of its complications, have resulted in improved management, quality of life, and life expectancy of patients. Liver transplantation remains the only curative option for a selected group of patients, but pharmacological treatments that can halt progression to decompensated cirrhosis or even reverse cirrhosis are currently being developed. This Seminar focuses on the diagnosis, complications, and management of cirrhosis, and new clinical and scientific developments.

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  • Chronic liver injury from viruses, alcohol, or overnutrition leads to cell death, regeneration, inflammation, fibrosis, and ultimately hepatocellular carcinoma.

    “In the liver, chronic injury from viruses, alcohol, or overnutrition leads to cell death, regeneration, inflammation, fibrosis, and ultimately hepatocellular carcinoma (HCC) (5, 6).”

    From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [5]

    The Introduction identifies viral hepatitis, alcohol-related disease, and obesity-associated NASH as causes or risk factors for cirrhosis. Its fibrosis and hepatocellular carcinoma passages describe fibrogenesis after chronic injury, regenerative nodules, and cirrhosis as a major risk factor for HCC. They do not establish the claimed sequence beginning with cell death or imply that chronic injury inevitably ends in HCC. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • HSCs have fibrosis-independent roles through RSPO3, regulating critical parameters that affect CLD progression and outcomes, including metabolic hepatocyte functions, liver regeneration and hepatocyte death.

    “The current study amends this fibrocentric concept by demonstrating fibrosis-independent roles for HSCs through RSPO3, regulating critical parameters that affect CLD progression and outcomes, including metabolic hepatocyte functions, liver regeneration and hepatocyte death2,49,50.”

    From Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 (2025) · cites this paper as [49]

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Cited by

Sorted by citations

Authors
Schuppan, D., & Afdhal, N. H.
Affiliations
Beth Israel Deaconess Medical Center (US)
Corresponding author
Schuppan, Detlef
ORCID
Afdhal, Nezam H
Venue
The Lancet
Publisher
Elsevier BV
Published
2008-03
Volume
371
Issue
9615
Pages
838-851
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(08)60383-9
PMC
PMC2271178
OpenAlex
W4210990778
Cited by
2,089
References
4
Citations by year
2026: 72 · 2025: 114 · 2024: 140 · 2023: 122 · 2022: 172 · 2021: 172 · 2020: 168 · 2019: 156 · 2018: 145 · 2017: 135 · 2016: 129 · 2015: 133 · 2014: 106 · 2013: 91 · 2012: 72
FWCI
6.42
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Public Health Service (U19 A1 066313)
  • National Institute of Allergy and Infectious Diseases (U19AI066313)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R21DK076873)
  • National Center for Complementary and Integrative Health (U01AT003571)
Topics
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
liver cirrhosis, regenerative nodules, liver fibrosis, chronic liver injury, portal hypertension, end-stage liver disease, cirrhosis complications, cirrhosis diagnosis, cirrhosis management, liver transplantation, decompensated cirrhosis, cirrhosis reversal, pharmacotherapy
MeSH terms
Contraindications, Animals, Female, Carcinoma, Hepatocellular, Humans, Liver, Liver Cirrhosis, Liver Neoplasms, Male, Liver Transplantation

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