Why Do People Get Liver Cirrhosis?

Understanding the causes of Liver Cirrhosis and reasons why you are at risk even if you don't drink alcohol!
Enhanced view of liver cirrhosis. (Created using Canva by Dr. Aditi Bakshi)
Enhanced view of liver cirrhosis. (Created using Canva by Dr. Aditi Bakshi)
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Have you been losing weight and falling sick too often? Feeling tired and exhausted all the time, even after a good night's sleep? Do you persistently feel bloated and have lost your appetite but that waist seems to be gaining inches? Has your skin lost its healthy glow and turned pale? Have you observed heavy bleeding from your minor injuries, and bruises all over? These could be signs of a hidden problem: cirrhosis of the liver. It might sound scary, but before you panic, let's explore why people develop this condition and, more importantly, how to protect your liver health.


What is Liver Cirrhosis?

Cirrhosis of the liver is a late-stage diseased condition in which healthy liver tissues get replace by scar tissue and rounded fibrous nodules over time. This happens when the liver stays inflamed over an extended period. Several causative factors could be at play here. The liver's reparative function( immune response) in the fight against inflammation results in scar tissue formation in place of healthy spongy liver tissues. Overabundance of scar tissue, formed over time, prevents oxygen and blood from passing through your liver's tissues impacting their normal functioning. [18]

Several culprits are implicated in cirrhosis:

Long-term infection with viral hepatitis B and C

Hepatitis B and C - one of the leading causes of liver cirrhosis. (Representational picture from freepick.com)
Hepatitis B and C - one of the leading causes of liver cirrhosis. (Representational picture from freepick.com)
  • A recent study from 2021 which included extensive research data of 520 prior researches on liver cirrhosis, including 1376503 patients with liver cirrhosis, from 86 countries, indicated 42% of patients with cirrhosis had hepatitis B virus infection (HBV), and 21% had hepatitis C virus infection (HCV). [19]

  • Hepatitis C infections tend to become chronic, though now, curable with antivirals. Likewise, a low percentage of hepatitis B infections become chronic as it is only treatable and not curable. These infections cause persistent inflammation and progressive fibrosis (scarring). 

  • HCV infection is one of the most common causes of chronic liver disease worldwide, with an estimated prevalence of 3% or 170 million infected people [15]

  • Studies also suggest a potential role of HEV (hepatitis E virus) in the development of cirrhosis especially among immunocompromised patients (those with low immunity) [1]

    Early detection and antiviral therapy are crucial to prevent the disease from escalating. [3, 4]

Alcohol abuse [11, 12]

  • Heavy Drinking or alcohol abuse emerges as another major cause. This triggers a toxic reaction, leading to steatosis ( deposition of fat ( triglyceride droplets) in liver cells), inflammation, and finally, fibrosis (formation of fibrous bands). These abnormal changes in healthy liver tissue compromise liver function heavily.

  •  According to studies, drinking more than 40 gram of alcohol daily in men and more than 20 gram of alcohol daily in women for over 10 years significantly increases the risk of liver cirrhosis. [14]

Non-alcoholic fatty liver disease (NAFLD) [12, 1]

Factors that increase the risk of non alcoholic fatty liver disease. image (Created using CANVA by the author)
Factors that increase the risk of non alcoholic fatty liver disease. image (Created using CANVA by the author)

Now called metabolic dysfunction-associated steatotic liver disease or MASLD, NAFLD can also progress to cirrhosis. Sometimes, excess fat gets deposited in liver cells, even if you don't drink alcohol or drink occasionally, this affects several chemical reactions and processes that normally happen in the liver cells, further causing liver cell injury and fibrosis.

Lifestyle diseases and conditions such as: diabetes, high cholesterol, coronary artery disease, hypertension, and dyslipidemia (abnormally high levels of one or more types of fats in the blood) which are often seen to be present in people with NAFLD, act as contributory factors in this process.

Do all people once infected with hepatitis virus (B, C, E , D) or living an unhealthy lifestyle, stand a risk of developing liver cirrhosis?

Image of DNA - Genes studies indicate some inherited genes increase the chances of developing cirrhosis. (istock royalty free images)
Image of DNA - Genes studies indicate some inherited genes increase the chances of developing cirrhosis. (istock royalty free images)

Research suggests not all individuals with hepatitis infections or Lifestyle diseases, and those who regularly drink heavily get the disease

According to the findings obtained from various gene based studies it is known that certain inherited genes increase the chances of developing cirrhosis. 

The impact of genetic risk factors is increased in the presence of environmental factors like excess alcohol consumption or obesity. For example, according to a study the chances of developing cirrhosis by age 75 with genetic risks was 48.2% among those with increased alcohol intake, compared to 13.7% in those with no/occasional light alcohol use. [10]

Dr. Supriya Joshi, MD, GI/Hepatologist, UofT lecturer, took to Instagram to describe the causes and create awareness regarding the myths and facts about liver cirrhosis.

Less known causes

While the aforementioned factors are the primary culprits, there can be some lesser-known contributing factors: [3, 4]

Genetic probability

Q

I don't drink alcohol and never was diagnosed with jaundice or hepatitis, I am safe right?

A

Your "genes" (hereditary characters you obtained from your parents) can also increase your risk of developing liver cirrhosis, as proven by several studies and research.

Genetic factors actually affect the progress of liver disease to cirrhosis. Genes involved in inflammation, fibrosis, and immune responses have been linked to an increased risk of developing cirrhosis in people with chronic liver diseases.[ 6, 8] 

Additionally genes can also  increase the risk of developing liver cirrhosis in otherwise healthy individuals. 

Identifying genes that can increase an individuals’ risk of developing the disease, can help predict whether an individual's chances of liver disease progressing to cirrhosis. Studies have identified some genes ( like PNPLA3, HFE, TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4, and IFNL4) that are associated with an increased risk of cirrhosis. [5]

Additionally genetics interacts with environmental and lifestyle factors to influence the development and progression of cirrhosis.

Inherited Liver Diseases 

These are a group of rare liver illnesses that are passed on from the parents to their children which If left untreated, contribute to development of liver cirrhosis. Some of these inherited diseases are: sarcoidosis, alpha-1 antitrypsin deficiency, cystic fibrosis, budd-chiari syndrome, wilson's disease (copper overload in body, including liver ), haemochromatosis (iron overload), glycogen storage disease, and hereditary fructose intolerance. 

If you have been diagnosed with any of these, speak to your health care team to find out about the ways you can keep your liver healthy and protected.

Conditions that damage, destroy, or obstruct the bile ducts

  1. Primary biliary cholangitis ( inflammation of bile duct) can result in cholestatic injury( halting the flow of bile and swelling and injury to the duct lining) and subsequent fibrosis( fibrous bands formation)

  2. Primary sclerosing cholangitis.

Long-term use of certain medicines

Certain medicines, such as methotrexate or amiodarone, can have harmful effects on the liver (hepatotoxicity), including over-the-counter painkillers, which can result in cirrhosis.

Daily consumption of high doses of vitamin A 

Vitamin A, a fat soluble vitamin tends to deposit in fatty tissues and known to produce toxic effects when present in high doses in the body. [17]

Chronic heart failure with liver congestion

In CHF, the heart's decreased efficiency leads to poor circulation. Blood backs up in the systemic circulation ( called Venous Congestion), this particularly affects the liver which becomes enlarged (hepatomegaly) and can develop fibrosis over time, resembling cirrhosis.

Autoimmune hepatitis:

A disease in which one’s own immune system attacks the healthy cells of the body including liver cells. [2] The body attempts to repair the damage by laying down scar tissue (fibrosis). Over time, extensive scarring replaces healthy liver tissue, hindering its function and potentially leading to cirrhosis.


Cancers affecting the liver and bile duct

 Liver cancer, bile duct cancer, liver adenoma.

Environmental toxins

Cigarette smoke, aflatoxin ( produced from a fungus)

Are you at risk of developing liver cirrhosis?

This picture highlights the risk factors for developing liver cirrhosis
This picture highlights the risk factors for developing liver cirrhosisCreated with canva by Dr Aditi Bakshi

MedBound Times reached out to Dr. Shanjitha J Hussain, MD Internal Medicine for her expert opinion on Liver cirrhosis.

Liver cirrhosis is a preventable condition irrespective of whether it is due to an acquired or inherited cause. Early diagnosis of the causative condition, being mindful of what you consume and what you avoid, staying in touch with your healthcare provider is what you will be needing mostly.

Dr. Shanjitha J Hussain, MD Internal Medicine

Following are some factor that increase your risk of developing  liver cirrhosis: [19]

  • Lifestyle-related factors:

History of heavy alcohol use, smoking, physical inactivity, emotional stress, obesity( deposition of excess body fat, particularly around the waist), high-fat diet, low in PUFA, and antioxidants. [16] 

  • Inadequate dietary behaviors: such as missing breakfast and a lack of feeding schedules. [15,13]

  • Those with type 2 diabetes and chronic insulin resistance.

  • Gender: Men.

  • Aged 40 or older.

  • Certain ethnicities: like Mestizos in Mexico, having a mix of European, Amerindian, and African ancestry are genetically prone to cirrhosis. [9]

  • Have tattoos or body piercings.

  • Shared needles to inject drugs.

  • Those who came in contact with an infected person’s blood or other body fluids.

  • Have sex without protection.

  • Have contact with chemicals or toxins.

  • Have a family history of liver disease.

Liver cirrhosis is a preventable condition irrespective of whether it is due to an acquired or inherited cause. Early diagnosis of the causative condition, being mindful of what you consume and what you avoid, staying in touch with your healthcare provider is what you will be needing mostly.
Dr. Shanjitha J Hussain, MD Internal Medicine

How this knowledge benefits you !

Lifestyle changes might not be enough to treat hereditary diseases that directly cause cirrhosis. However, addressing the environmental factors that interact with the genes, making proper lifestyle changes can significantly reduce the possibility of developing cirrhosis, in those cases where  for genetic factors simply raise the risk of the disease.

Thus, depending on the patient's genetic profile and ethnicity, different treatment options can be  developed. Genetic testing can be used to determine who is more vulnerable so as to initiate early intervention. While current therapies seek to control problems associated with cirrhosis and to halt or reverse the disease's progression. Long-term survival is possible with liver transplantation. [7]

Conclusion

Truly one's risk of acquiring cirrhosis is significantly influenced by the interplay between environmental exposures and genetic susceptibility to the disease. Research indicates that liver cirrhosis is mostly caused by environmental factors, while genetics can elevate an individual's risk to developing the condition. The main environmental offenders include obesity, viral diseases such as hepatitis B and C, and excessive alcohol usage.
Even if a person does not drink alcohol, unhealthy lifestyle choices such as poor eating and sedentary behaviour can exacerbate pre-existing illnesses like diabetes, high blood pressure, and non-alcoholic fatty liver disease (NAFL), can damages the liver.

The good news is that cirrhosis advances slowly, providing a window of opportunity for recovery. Make wise choices about your diet, activity levels (exercise), and alcohol use. Keep in mind that the best medicine is prevention!
 Take charge today for a healthier liver, and a healthier you!

Note: This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits.

References

1. Kamar, Nassim, Harry R. Dalton, Florence Abravanel, and Jacques Izopet. 2014. “Hepatitis E Virus Infection.” Clinical Microbiology Reviews 27 (1): 116–38. doi:10.1128/CMR.00057-13.https://pubmed.ncbi.nlm.nih.gov/24396139

2. Zarrilli, Federica, Ausilia Elce, Manuela Scorza, Sonia Giordano, Felice Amato, and Giuseppe Castaldo. 2013. “An Update on Laboratory Diagnosis of Liver Inherited Diseases.” BioMed Research International 2013: 697940. doi:10.1155/2013/697940.https://pubmed.ncbi.nlm.nih.gov/24222913

3. Symptoms & Causes of Cirrhosis - NIDDK.” 2024. National Institute of Diabetes and Digestive and Kidney Diseases. Accessed July 19. https://www.niddk.nih.gov/health-information/liver-disease/cirrhosis/symptoms-causes.

4. Centre (UK), National Guideline. 2016. “Risk Factors and Risk Assessment Tools.” In Cirrhosis in Over 16s: Assessment and Management. National Institute for Health and Care Excellence (NICE). https://www.ncbi.nlm.nih.gov/books/NBK385224/.

6. https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1140427/full

7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123515/#B6

8. https://www.sciencedirect.com/science/article/pii/S016882781500135X

9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631960/

10. https://pubmed.ncbi.nlm.nih.gov/33310085/

11. https://www.nhs.uk/conditions/cirrhosis/treatment/

12. https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065%2822%2900179-1/fulltext

13. https://www.nhs.uk/conditions/cirrhosis/treatment/

14. https://pubmed.ncbi.nlm.nih.gov/20034030

15. https://pubmed.ncbi.nlm.nih.gov/23197979

16. https://pubmed.ncbi.nlm.nih.gov/24152749

17. https://pubmed.ncbi.nlm.nih.gov/23197979

18. https://pubmed.ncbi.nlm.nih.gov/24966602

19. https://www.ncbi.nlm.nih.gov/books/NBK385224/

By Dr. Aditi Bakshi

Enhanced view of liver cirrhosis. (Created using Canva by Dr. Aditi Bakshi)
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