Nonalcoholic steatohepatitis (NASH) is a serious liver condition, a more severe form of non-alcoholic fatty liver disease (NAFLD). In NASH, fat accumulation in the liver is accompanied by inflammation and liver cell damage. This damage can lead to fibrosis, the formation of scar tissue within the liver. The disease often progresses silently, making early detection challenging. This article explains NASH fibrosis, its identification, management, and long-term implications.
What is NASH Fibrosis?
NASH fibrosis begins with hepatic steatosis, or fatty liver, characterized by excess fat deposits in liver cells. A liver is considered fatty if over 5% of its weight is fat. Simple fatty liver often causes no harm and typically does not progress to severe liver damage.
NASH develops when fat accumulation is accompanied by inflammation and liver cell damage. This inflammatory response injures liver cells, prompting the body’s repair mechanisms. The liver attempts to heal itself by forming scar tissue, a process called fibrosis. Fibrosis progression can lead to severe liver dysfunction.
Fibrosis in NASH is progressive, meaning scar tissue accumulates and stiffens the liver over time. Severity is categorized into stages, F0 to F4. F0 indicates no fibrosis, while F1 signifies mild scarring. As scarring increases, it progresses through F2 (moderate) and F3 (severe) stages. The most advanced stage, F4, represents cirrhosis, a life-threatening condition where extensive, irreversible scar tissue prevents the liver from functioning properly.
NASH is associated with metabolic syndrome conditions, including obesity, type 2 diabetes, high cholesterol, and high blood pressure. These metabolic disturbances contribute to NASH development and progression. For instance, insulin resistance, often present in type 2 diabetes, plays a role in driving NASH. The increasing prevalence of these metabolic conditions contributes to the rise in NASH cases.
Identifying NASH Fibrosis
Detecting NASH fibrosis is challenging because the condition often lacks noticeable symptoms in early stages. Many individuals feel well and are unaware they have a liver problem. The disease is frequently discovered incidentally during routine medical evaluations. Initial findings that may raise suspicion include elevated liver enzymes, such as ALT or AST, in routine blood tests. Imaging performed for other reasons might also reveal fatty changes in the liver.
Once NASH is suspected, healthcare providers use various diagnostic methods to assess liver health and determine fibrosis presence and extent. Blood tests beyond basic liver enzymes can include markers that help evaluate liver damage and rule out other liver diseases. While blood tests can indicate a liver problem, they do not always definitively diagnose NASH or fibrosis.
Imaging techniques provide non-invasive ways to assess liver stiffness and fat content. Ultrasound is often the first imaging test used to detect fatty liver. Specialized techniques include FibroScan, or transient elastography, which measures liver stiffness using sound waves; higher stiffness indicates more scarring. FibroScan can help estimate liver damage and monitor disease progression. Magnetic Resonance Elastography (MRE) combines MRI imaging with sound waves to create a detailed visual map of liver stiffness, offering high accuracy for detecting fibrosis, including earlier stages. However, these imaging methods, while useful for detecting fibrosis, may not always definitively diagnose NASH itself, as they cannot fully assess inflammation or cell damage.
Liver biopsy remains the gold standard for definitive NASH diagnosis and accurate fibrosis staging. During this procedure, a small tissue sample is removed from the liver and examined under a microscope for fat, inflammation, cell damage, and scar tissue. While a biopsy provides comprehensive information, it is an invasive procedure with potential risks, such as bleeding. It also samples only a small part of the liver, which might not fully represent the entire organ. Due to these limitations, non-invasive tests are increasingly used to screen patients and guide biopsy decisions.
Managing NASH Fibrosis
Managing NASH fibrosis primarily focuses on lifestyle modifications, which can improve liver health. Weight loss is a highly effective intervention. Even modest body weight reductions can decrease liver fat deposits. Losing at least 3% to 5% of total body weight can reduce liver fat, while a 7% to 10% weight loss can further reduce liver inflammation and scar tissue, potentially reversing or stabilizing liver scarring. For some, weight loss can even lead to improvements in liver histology.
Dietary changes support weight loss and improve liver health. Adopting a balanced diet, such as the Mediterranean diet, is often recommended. This eating pattern emphasizes fruits, vegetables, whole grains, lean proteins, and healthy fats like olive oil, while minimizing processed foods, sugary drinks, and saturated fats. Reducing caloric intake is a primary focus for dietary interventions.
Regular physical activity complements dietary changes. Both aerobic and resistance exercise can reduce liver fat content and improve insulin resistance, even independently of significant weight loss. Physical activity can improve various metabolic risk factors associated with NASH, such as diabetes and hypertension. Major medical associations recommend physical exercise as a treatment for NAFLD. Current recommendations suggest aiming for at least 150 minutes of moderate-intensity physical activity per week.
Beyond lifestyle changes, medical management involves controlling underlying conditions that contribute to NASH. This includes managing type 2 diabetes, hypertension, and dyslipidemia (abnormal cholesterol and triglyceride levels). Addressing these metabolic risk factors can help slow liver damage progression.
Currently, no medications are specifically approved to treat NASH fibrosis, though research is ongoing. However, some medications are used off-label or are under investigation. Vitamin E, an antioxidant, may be considered for patients with biopsy-proven NASH who do not have diabetes, as it might help reduce inflammation-caused damage. Pioglitazone, a diabetes medication, has shown promise in improving liver histology, including fibrosis, and may be considered for patients with or without diabetes. Resmetirom (Rezdiffra), a new medicine, recently became available to help reduce liver fat in people with NASH and moderate to severe liver scarring, though it is not recommended for those with cirrhosis. The development of new pharmacological treatments targeting NASH fibrosis remains an active area of research.
Living with NASH Fibrosis
Living with NASH fibrosis requires understanding its potential long-term implications for liver health. If the condition progresses without effective management, it can lead to cirrhosis, advanced and irreversible liver scarring. Cirrhosis can impair liver function, potentially resulting in liver failure, a life-threatening condition. Individuals with NASH fibrosis, particularly those who develop cirrhosis, are at an increased risk of developing hepatocellular carcinoma (HCC), a type of liver cancer.
Regular monitoring by healthcare providers is important to track disease progression and manage complications. This ongoing care involves periodic blood tests and imaging to assess liver function and scarring extent. A multidisciplinary approach is often beneficial, involving specialists such as hepatologists, dietitians, and endocrinologists, to address the condition’s various aspects and associated metabolic factors.
For individuals who develop end-stage liver disease due to NASH, liver transplantation may become an option. NASH is becoming a leading indication for liver transplantation, reflecting its increasing prevalence and severity. While transplantation offers a life-saving solution, it is a complex procedure with its own considerations. A multidisciplinary team evaluates candidates carefully. Proactive management and consistent adherence to medical advice are important for individuals with NASH fibrosis to achieve a better prognosis and reduce severe outcomes.