metabolic dysfunction-associated steatohepatitis

Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Severe Form of Liver Disease

Metabolic dysfunction-associated steatohepatitis (MASH) is a severe form of liver disease characterized by inflammation and damage to the liver cells. It is considered an advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD), also known as nonalcoholic fatty liver disease (NAFLD).

Key Features:

• Liver Inflammation: MASH is marked by inflammation in the liver, which can lead to scarring and damage to the liver cells.
• Metabolic Dysfunction: The condition is associated with metabolic dysfunction, including insulin resistance, high blood sugar levels, and abnormal lipid profiles.
• Fatty Liver: Fat builds up in the liver, leading to liver enlargement and discomfort.

Prevalence:

About 20% of people with MASLD have MASH, indicating a significant proportion of individuals with fatty liver disease are at risk of developing this severe form of liver inflammation.

Risk Factors:

• Metabolic Disorders: Conditions such as obesity, type 2 diabetes, and high blood pressure increase the risk of developing MASH.
• Alcohol Consumption: Excessive alcohol consumption can accelerate the progression of MASH.
• Certain Medications: Certain medications, such as cytotoxic drugs, may also contribute to the development of MASH.

References:

• [1] Metabolic dysfunction-associated steatohepatitis (MASH). Driving change through meaningful innovation within fatty liver disease research. (Context 4)
• [2] Metabolic dysfunction-associated steatotic liver disease (MASLD) is when fat builds up in your liver. It once was called nonalcoholic fatty liver disease... (Context 2)
• [3] About 20% of people with MASLD have liver inflammation called metabolic dysfunction-associated steatohepatitis (MASH), a more severe form of MASLD. (Context 3)

Metabolic dysfunction-associated steatohepatitis (MASH) can present with a range of signs and symptoms, which may vary in severity and frequency among individuals.

Common symptoms:

• Severe tiredness (fatigue) [9]
• Pain in the right upper belly (abdomen) [9]

Other possible symptoms:

• Weakness and fatigue [3]
• Abdominal pain, which may be in the center or the right upper part of the abdomen, and sometimes fatigue [4]
• Right upper quadrant discomfort, fatigue, and/or malaise [6]
• Slight enlargement of the liver on physical examination [4]

Silent disease:

• In some cases, MASH can be a silent disease with no noticeable symptoms [11][13]

It's essential to note that not everyone with MASH will experience these symptoms, and in many cases, the condition may only be detected during routine medical check-ups or when liver damage has progressed.

References:

[3] - What are the symptoms of metabolic dysfunction-associated steatohepatitis? [4] - May 13, 2024 [6] - September 18, 2023 [9] - What are the symptoms of metabolic dysfunction-associated steatotic liver disease? [11] - October 15, 2024 [13] - Jun 5, 2019

Metabolic dysfunction-associated steatohepatitis (MASLD) diagnosis involves a combination of blood tests, imaging tests, and sometimes liver biopsy.

Blood Tests Blood tests are used to measure liver function and detect inflammatory activity. They can also be used to rule out viral hepatitis and other causes of liver disease [1][3]. A1C test is one of the blood tests that may be used to diagnose MASLD [2].

Imaging Tests Imaging tests such as ultrasonography, CT scan, and MRI may identify hepatic steatosis (fat accumulation in the liver) [4][5]. These tests can show fat deposits in the liver, which is a characteristic of MASLD.

Liver Biopsy A liver biopsy may be required to confirm MASLD if other causes of liver disease cannot be excluded. This test involves taking a small sample of liver tissue and examining it under a microscope for signs of inflammation and damage [6].

Other Tests Other tests such as ultrasound elastography or MR elastography may also be used to diagnose MASLD [4]. Liver function tests can also be used to detect inflammatory activity in the liver.

In summary, the diagnostic tests for MASLD include:

• Blood tests (A1C test, liver function tests)
• Imaging tests (ultrasonography, CT scan, MRI)
• Liver biopsy
• Other tests (ultrasound elastography, MR elastography)

References: [1] - Context 3 [2] - Context 3 [3] - Context 7 [4] - Context 4 and 9 [5] - Context 5 [6] - Context 6

Current Drug Treatments for Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Several medications have shown promise in treating MASH, a condition characterized by liver inflammation and scarring due to metabolic dysfunction. Here are some of the current drug treatments being explored:

• Resmetirom: The first medication specifically approved to treat MASH and fibrosis, resmetirom works by reducing liver fat and inflammation [1]. It was approved by the FDA in March 2024 for use in adults with well-developed scarring in their liver.
• Tirzepatide: A study published in June 2024 found that treatment with tirzepatide for 52 weeks was more effective than placebo in resolving MASH without worsening fibrosis [2].
• Pioglitazone: Based on grade A and high-strength evidence, pioglitazone is recommended for the treatment of MAFLD (metabolic-associated fatty liver disease) when there is evidence of NASH (raised transaminases) [3].
• Denifanstat: An oral fatty acid synthase inhibitor, denifanstat blocks de-novo lipogenesis, a key pathway driving progressive lipotoxicity in MASH patients [4].

Emerging Treatments and Challenges

While these medications show promise, there are ongoing challenges and potential solutions in drug development for MASH. A review published in 2024 highlights the need for more effective treatments and better understanding of the disease mechanisms [5]. The FDA has recently approved resmetirom to treat patients with MASH and fibrosis, but more research is needed to fully understand its effects.

References

[1] May 7, 2024 — The recently approved treatment, called resmetirom, is the first medication to specifically treat MASH and fibrosis. [2] Jun 8, 2024 — Treatment with tirzepatide for 52 weeks was more effective than placebo with respect to resolution of MASH without worsening of fibrosis. [3] by MS Jeeyavudeen · 2023 · Cited by 30 — Based on grade A and high strength evidence, pioglitazone is currently recommended for treatment of MAFLD when there is evidence of NASH (raised transaminases) ... [4] by R Loomba · 2024 · Cited by 4 — Denifanstat, an oral fatty acid synthase (FASN) inhibitor, blocks de-novo lipogenesis, a key pathway driving progressive lipotoxicity, ... [5] by MA Tincopa · 2024 · Cited by 15 — In this review, we highlight ongoing challenges and potential solutions in drug development for MASH and provide an overview of available data from emerging ...

Differential Diagnosis of Metabolic Dysfunction-Associated Steatohepatitis

Metabolic dysfunction-associated steatohepatitis (MASH) is a condition characterized by inflammation and fat accumulation in the liver, often associated with metabolic disorders. When diagnosing MASH, it's essential to consider alternative causes that may present similar symptoms. Here are some differential diagnoses for MASH:

• Nonalcoholic fatty liver disease (NAFLD): NAFLD is a condition where excess fat accumulates in the liver cells, but without inflammation. It's often associated with obesity, insulin resistance, and metabolic syndrome.
• Metabolic-associated fatty liver disease (MAFLD): MAFLD is another term for MASH, emphasizing its association with metabolic disorders. The diagnostic criteria for MAFLD are similar to those for MASH.
• Nonalcoholic steatohepatitis (NASH): NASH is a more severe form of NAFLD, characterized by inflammation and liver damage. It's often associated with obesity, insulin resistance, and metabolic syndrome.
• Steatotic liver disease: This term refers to any condition where fat accumulates in the liver cells, including MASH, MAFLD, and NAFLD.

Key differences between these conditions:

• Inflammation: MASH is characterized by inflammation of the liver, whereas NAFLD and NASH are not.
• Metabolic associations: MASH is strongly associated with metabolic disorders, such as obesity, insulin resistance, and metabolic syndrome. While NAFLD and NASH may also be associated with these conditions, they are not as strongly linked.

References:

• [8] Oct 16, 2023 — Metabolic dysfunction-associated steatotic ... Metabolic associated steatohepatitis (MASH) ... Differential Diagnosis. Alternate causes ...
• [6] by M Eslam · 2020 · Cited by 3645 — ... diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). ... Histologic features of steatohepatitis in patients with a clinical diagnosis ...
• [9] Jun 27, 2024 — Metabolic dysfunction-associated steatotic liver disease (MASLD) previously known as nonalcoholic fatty liver disease (NAFLD), is the ...

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