From Silent Killer to Solvable: India's Growing Focus on NASH Management

Nonalcoholic Steatohepatitis (NASH), the more severe form of Non-alcoholic Fatty Liver Disease (NAFLD), is rapidly emerging as a silent epidemic in India, posing a significant public health challenge. With a high prevalence closely linked to metabolic disorders like obesity and diabetes, the demand for effective therapeutics and non-invasive diagnostics for NASH is driving substantial innovation and investment across the country.

The Growing Burden: A Silent Threat

Recent studies indicate that NAFLD affects an estimated 38.6% of adults in India, with a significant proportion progressing to NASH. The prevalence of NASH in the general population is estimated to range from 1.5% to 6.45%, but can be much higher in specific populations, with some studies showing a prevalence of over 30% in regions like North Karnataka. Experts warn that the number of cases is alarming, particularly in urban centers where sedentary lifestyles, lack of exercise, and poor sleep contribute to increased fat deposits in the liver.

One of the biggest challenges is the insidious nature of NASH; it often progresses slowly with few or no symptoms, leading to late diagnosis when the disease may have advanced to fibrosis, cirrhosis, or even liver cancer. The Union Health Ministry in September 2024 revised its Operational Guidelines and Training Module for NAFLD, underscoring its recognition as a major public health concern.

Diagnostic Advancements: Moving Beyond Biopsy

Historically, liver biopsy has been the gold standard for diagnosing NASH and assessing fibrosis, but its invasive nature, sampling bias, and patient reluctance have highlighted the urgent need for non-invasive alternatives. Significant progress is being made in this area:

Non-Invasive Biomarkers: Researchers are increasingly investigating non-invasive circulating biomarkers and imaging biomarkers to diagnose fibrosis and minimize the need for biopsies. Serum biomarkers like cytokeratin-18 (CK-18) and fibrosis biomarkers are showing promise.
Advanced Imaging Modalities: Techniques like Magnetic Resonance Imaging (MRI) derived Proton Density Fat Fraction (MRI-PDFF) and Magnetic Resonance Elastography (MRE) are being used in early-phase trials to accurately measure liver fat content and fibrosis stage. Sequential ultrasound molecular imaging (USMI) is also being explored for its potential in visualizing hepatic steatosis and inflammation non-invasively.
Algorithms Integrating Biomarkers: There's a growing focus on developing algorithms that combine various non-imaging and imaging biomarkers to improve diagnostic accuracy and enable earlier detection of NASH and its progression.

Therapeutic Pipeline: A Race for the First Approved Drug

Globally, and in India, there is a huge unmet need for approved drugs specifically for NASH. While lifestyle changes (diet and exercise) remain the cornerstone of management, pharmacological interventions are crucial for many patients, especially those with advanced fibrosis.

Indian Innovation: India has been proactive in this space. In March 2020, India became the first country to approve Saroglitazar Mg (Lipaglyn), a dual peroxisome proliferator-activated receptor α/γ agonist, for NASH. Zydus Cadila, the developer, has reported positive results from clinical trials for Saroglitazar Magnesium in NAFLD and NASH patients.
Global Pipeline Activity: Many global pharmaceutical companies are engaged in a fierce race to develop the first globally approved drug for NASH. Companies like Madrigal Pharmaceuticals recently received FDA approval for Resmetirom (Rezdiffra) in the US, marking a significant milestone. Indian companies like Morepen Laboratories have secured regulatory clearance from CDSCO to conduct bioequivalence studies for Resmetirom tablets, signaling their early entry into this rapidly expanding therapeutic area.
Promising Drug Classes: The pipeline includes various drug classes targeting different aspects of NASH pathophysiology, such as FGF21 analogues (e.g., Efruxifermin), FXR agonists (e.g., Obeticholic Acid, though its approval in the US for NASH has been complex), GLP-1 receptor agonists (like Semaglutide), and others that aim to reduce inflammation, fibrosis, and metabolic dysfunction.

Challenges in Clinical Trials and Adoption

Despite the advancements, several challenges remain in India:

Under-recognition and Late Diagnosis: Many non-cirrhotic NASH patients are asymptomatic, and there are no established nationwide screening guidelines, leading to diagnoses often being incidental findings.
Patient Recruitment: Clinical trials for NASH in India face challenges related to patient recruitment and retention, partly due to the asymptomatic nature of the disease and reluctance for invasive biopsies.
Regulatory Consistency: While India has approved Saroglitazar Mg, harmonizing regulatory pathways with global standards for new NASH therapies is crucial for international collaboration and faster patient access.
Cost and Access: Once approved, the cost of novel NASH therapies could be a barrier to widespread adoption in a diverse market like India.

As awareness grows and the prevalence of NASH continues its upward trend, India's focus on both indigenous drug development and the adoption of cutting-edge non-invasive diagnostics will be vital in addressing this significant public health challenge and improving liver health outcomes across the nation.