Can liver cirrhosis occur in the absence of risk factors, such as hepatitis (infection of the liver) or alcohol use?

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Last updated: March 16, 2025View editorial policy

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From the Guidelines

Liver cirrhosis can occur in the absence of traditional risk factors, such as hepatitis or alcohol use, although this is relatively rare. According to the most recent and highest quality study, approximately 10-15% of liver cancer cases are attributed to causes other than hepatitis B or C, or alcohol intake 1. The development of cirrhosis is a complex process involving inflammation and fibrosis, and can be driven by various factors, including genetic conditions, autoimmune disorders, and metabolic syndrome. Some people may develop cryptogenic cirrhosis, where no clear cause can be identified despite thorough evaluation. Certain genetic conditions, such as hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency, can cause cirrhosis without traditional risk factors 1. Additionally, some medications can cause drug-induced liver injury that progresses to cirrhosis in rare cases. Key points to consider include:

  • The annual risk of HCC development in cirrhotic patients is between 1% and 8% 1
  • Increasing age and male sex are associated risks for HCC development 1
  • Obesity and type 2 diabetes mellitus can cause chronic liver disease and increase the risk of HCC development 1
  • Smoking may also increase the risk of HCC synergistically in those already predisposed to liver disease and cancer 1. It is essential for individuals experiencing symptoms like fatigue, jaundice, abdominal swelling, or unexplained weight loss to seek medical evaluation, as early diagnosis and management can help slow disease progression.

From the Research

Liver Cirrhosis without Risk Factors

  • Liver cirrhosis can occur due to various causes, including obesity, non-alcoholic fatty liver disease, autoimmune diseases, cholestatic diseases, and iron or copper overload 2.
  • The disease can develop after a long period of inflammation, resulting in the replacement of healthy liver parenchyma with fibrotic tissue and regenerative nodules, leading to portal hypertension 2.
  • Chronic liver inflammation from any etiology can lead to cirrhosis, and it is potentially reversible through management of the cause 3.

Autoimmune Liver Diseases

  • Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) are classic autoimmune liver diseases that can lead to liver cirrhosis 4, 5.
  • These diseases result from the effects of multiple genes in combination with environmental factors, and recent genome-wide association studies have identified numerous risk loci for PBC and PSC 5.
  • Liver transplantation is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC, and PSC 4, 5.

Lifestyle Factors

  • Lifestyle-related factors, such as malnutrition, obesity, sedentary lifestyle, alcohol and smoking habits, and poor oral hygiene, can increase the risk of progression of liver cirrhosis 6.
  • Correcting these lifestyle factors can be an attractive approach to add to etiological and pharmacological therapy in patients with cirrhosis 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Liver cirrhosis.

Lancet (London, England), 2021

Research

Liver Disease: Cirrhosis.

FP essentials, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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