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Understanding Non-Alcoholic Steatohepatitis (NASH): Causes, Diagnosis & Treatment

Doctor Talking to Senior Patient with Stomach Pain During Health Consultation.

Non-Alcoholic Steatohepatitis, or NASH, is a type of Non-Alcoholic Fatty Liver Disease (NAFLD). Unlike alcohol related liver damage, NASH is caused by too much fat accumulating in the liver which causes inflammation and harm to liver cells [1]. Over time this can lead to scarring (fibrosis), cirrhosis or even liver cancer – specifically hepatocellular carcinoma (HCC).

Table of Contents

What is Non Alcoholic Steatohepatitis (NASH)?

In NASH, fat builds up in liver cells and they balloon. The causes of fat in the liver are not fully understood and while certain health conditions may contribute to NAFLD, some people develop NAFLD with no known risk factors. When this balloon-ization persists it damages the liver’s ability to filter out bad stuff and support digestion. Because NASH develops silently people may not notice anything at first. Some may just feel tired or a mild ache on the right side of the upper abdomen. Others may find out they have NASH after a routine blood test shows elevated liver enzymes and they get checked out [1], [2]. This particular form of liver disease is different from others such as Hepatitis B, C, D, E, and NAFLD.

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Causes and Risk Factors

NASH is a complex condition with multiple contributing factors. Obesity is a major risk factor, as excess body weight can lead to fat accumulation in the liver, setting the stage for NASH. Insulin resistance, often preceding type 2 diabetes, is another significant factor, as it can promote fat storage in the liver.

Metabolic syndrome, which includes high blood pressure, high cholesterol, and insulin resistance, increases NASH risk. Women with polycystic ovary syndrome (PCOS) face a higher risk due to hormonal imbalances and insulin resistance. A family history of liver disease or NASH also raises the likelihood of developing the condition.

Other key risk factors include high blood pressure and high LDL cholesterol, both of which can contribute to liver damage and NASH progression. Understanding these risk factors is crucial for early detection and prevention of this serious liver disease.

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Vector illustration. Infographic of fatty liver disease. Symptoms, prevention and risk factors.
(weerasak)

How is NASH Diagnosed?

Doctors diagnose NASH by confirming fat in the liver, ruling out high alcohol use and other liver diseases (like viral hepatitis). Recently the term ‘metabolic dysfunction associated steatohepatitis’ (MASH) has been introduced to better reflect the underlying metabolic issues. Key tests include:*

  • Liver Biopsy: This is the “gold standard” [1]. A small liver tissue sample is examined for cell damage and scarring.
  • Blood Tests: Scores such as the NAFLD Fibrosis Score or Fibrosis-4 (FIB-4) Score estimate how much scarring might be present.
  • Imaging Scans: Transient Elastography (FibroScan) and Magnetic Resonance Elastography (MRE) measure liver stiffness which is linked to the level of fibrosis [2].
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How is NASH Treated?

Treating Non-Alcoholic Steatohepatitis (NASH) involves a combination of lifestyle changes and medical interventions aimed at reducing liver fat, inflammation and scarring. Key strategies include:

Lifestyle Modifications

  • Healthy Diet: Incorporate more fruits, vegetables, whole grains and lean proteins to maintain a balanced weight and control cholesterol and blood sugar levels.
  • Exercise: Engage in regular physical activities such as brisk walking or cycling for at least 150 minutes per week to improve liver health and overall well-being.
  • Weight Loss: Achieve a weight reduction of 3-5% can decrease liver fat, while a loss of 7-10% may also reduce inflammation and scarring.

Medications and Emerging Therapies

  • Vitamin E: This antioxidant may help reduce liver inflammation in individuals without diabetes or cirrhosis.
  • Pioglitazone: Primarily for Type 2 Diabetes, it can also benefit some NASH patients by managing the condition.
  • Emerging Therapies: Drugs like GLP-1 receptor agonists and SGLT2 inhibitors, commonly used for diabetes, are being researched for their potential to decrease liver fat and inflammation in NASH.

Overall, managing NASH involves a comprehensive approach that includes adopting a healthy lifestyle, monitoring by healthcare professionals and considering medications when appropriate. This multi-faceted strategy is essential to prevent complications such as liver cancer, cardiovascular diseases and the need for a liver transplant.

Non-alcoholic steatohepatitis vector concept.
(marina_ua)

NASH can lead to severe complications such as liver cancer and the need for a liver transplant. Chronic liver damage increases the risk of liver cells becoming cancerous. In cases of extensive liver damage a transplant may be required to replace the failing liver. NASH also increases the risk of cardiovascular disease (heart attacks and strokes) due to its association with metabolic syndrome. Type 2 diabetes and kidney disease are also potential complications as insulin resistance and advanced liver damage affects kidney function. Managing NASH is key to preventing these serious health issues.

Follow-Up with Doctors

Since NASH can progress silently doctors often schedule regular checkups and scans every 6-24 months. These may include:

  • Blood tests to monitor liver enzymes.
  • Imaging to measure liver stiffness.
  • Heart health checks as people with NASH are at higher risk of cardiovascular disease.
  • Liver cancer (HCC) screening if cirrhosis is found [2].

Scarring in the liver (fibrosis) can progress to cirrhosis and limit liver functions. People with cirrhosis can experience fluid retention, confusion due to toxin buildup and increased risk of HCC [1]. Those with NAFLD are at higher risk of heart disease which is the leading cause of death in this condition [4]. Managing NASH often means managing overall health including blood pressure, cholesterol and blood sugar.

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Closing Thoughts

NASH is a serious liver disease with fat accumulation, inflammation and potential scarring. Early detection can be difficult as the condition can progress without symptoms. However blood tests and imaging scans can help doctors identify problems before they get worse. The best defense is a balanced diet, regular exercise and moderate weight loss. Meds can support that in certain situations and ongoing studies are exploring new treatments [3]. With regular monitoring and healthier habits many can protect their liver and reduce risk of complications.

References

[1] Tokushige, K., Ikejima, K., Ono, M., Eguchi, Y., Kamada, Y., Itoh, Y., Akuta, N., Yoneda, M., Iwasa, M., Yoneda, M., Otsuka, M., Tamaki, N., Kogiso, T., Miwa, H., Chayama, K., Enomoto, N., Shimosegawa, T., Takehara, T., & Koike, K. (2021). Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020. Hepatology research : the official journal of the Japan Society of Hepatology, 51(10), 1013–1025. https://doi.org/10.1111/hepr.13688

[2] Long, M. T., Noureddin, M., & Lim, J. K. (2022). AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review. Gastroenterology, 163(3), 764–774.e1. https://doi.org/10.1053/j.gastro.2022.06.023

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[3] Harrison, S. A., Bashir, M. R., Guy, C. D., Zhou, R., Moylan, C. A., Frias, J. P., Alkhouri, N., Bansal, M. B., Baum, S., Neuschwander-Tetri, B. A., Taub, R., & Moussa, S. E. (2019). Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet (London, England), 394(10213), 2012–2024. https://doi.org/10.1016/S0140-6736(19)32517-6

[4] Tokushige, K., Ikejima, K., Ono, M., Eguchi, Y., Kamada, Y., Itoh, Y., Akuta, N., Yoneda, M., Iwasa, M., Yoneda, M., Otsuka, M., Tamaki, N., Kogiso, T., Miwa, H., Chayama, K., Enomoto, N., Shimosegawa, T., Takehara, T., & Koike, K. (2021). Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020. Journal of gastroenterology, 56(11), 951–963. https://doi.org/10.1007/s00535-021-01796-x

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