The rising rates of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) incidence and prevalence highlights the importance and urgency of developing and implementing effective screening, diagnosis, and treatment strategies, according to a report published in Gastroenterology. The report summarizes the results of a national NASH Needs Assessment survey and the virtual conference, “Preparing for a NASH Epidemic: A Call for Action.”

NAFLD and NASH are considered common conditions with an increasing burden. It is estimated that at least 20% to 30% of patients with NAFLD develop NASH. Developing NASH may lead to cirrhosis and associated complications, including hepatocellular cancer (HCC). According to the authors, NASH is also associated with a greater risk for cardiovascular disease and increased cardiovascular and liver-related mortality.

The majority of patients with NAFLD and NASH have traditionally been diagnosed and managed by hepatologists. However, the recent availability of noninvasive diagnostic procedures is increasing the role of other health care professionals likely to see patients with these conditions, especially gastroenterologists, endocrinologists, obesity medicine specialists, and primary care providers (PCPs). Previous research suggests that more education is needed about both NAFLD and NASH among specialists and PCPs. Some published data has also revealed substantial management gaps between published guidance and clinical practice in patients with NAFLD and NASH.


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To address these knowledge gaps, the American Gastroenterological Association (AGA) conducted a needs assessment survey of health professionals likely to be managing adult patients with NAFLD/NASH, followed by a virtual conference, which consisted of international experts representing 7 professional societies. This conference was held to review the current research and summarize the future agenda for clinical practice, research, and policy. The main objective was to call for a unified, international public health response to NAFLD and NASH.

In May 2020, the NASH Needs Assessment Survey was conducted. The survey aimed to evaluate participants’ knowledge related to screening, diagnosis, and management of NAFLD and NASH, compare current diagnostic and treatment patterns with up to date practice guidance on NAFLD/NASH, and determine the educational needs that could be useful targets to improve guideline-based treatment of NAFLD and NASH. Altogether, 751 gastroenterologists, hepatologists, endocrinologists, and PCPs from 46 states in the United States completed the survey. The researchers noted that over 50% of survey participants were PCPs with an average of 19.5 years in practice (range, 2-35 years).

The results from the survey demonstrated substantial gaps in knowledge about who to screen and how to diagnose and treat patients at greater risk for NASH, including disparities between published practice guidance and clinical practice. The majority of the respondents (>80%) wanted additional education about screening, diagnosis, and treatment of NAFLD/NASH.

To address these knowledge gaps, the AGA held a virtual conference on July 10, 2020. The conference consisted of international experts in gastroenterology, hepatology, endocrinology, obesity management, and primary care who practice in the United States, Europe, Australia, and Asia. The sections here summarize the discussion, conclusions, and recommendations for clinical practice and future research that arose from the conference and the process leading up to the meeting.

Burden of NAFLD and NASH

Since the 1980’s, the clinical burden of NAFLD and specifically, NASH,  has increased steadily. Currently, NAFLD affects 25% of the global population and >60% of patients with type 2 diabetes (T2D). Between 2015 and 2030, the prevalence of NASH is anticipated to increase by 63%. By 2030, modeling data estimate that the number of patients with NASH-related advanced fibrosis is expected to double, which will result in 800,000 liver-related deaths.

Risk Factors for NAFLD, NASH, and Related Complications

Patients with obesity or T2D are at a greater risk of developing NAFLD/NASH. Patients with NAFLD are at a higher risk of developing T2D. NAFLD and in particular, NASH, are independently associated with several liver-related complications such as cirrhosis, HCC, and liver-related mortality. With regard to cardiovascular disease, patients with NAFLD have a 2-fold increase in risk. 

The investigators assert that effective screening for and timely diagnosis of NAFLD may prevent progression to NASH. Diagnosing NAFLD/NASH starts with assessing patients for alternative or coexisting causes of liver disease, such as viral hepatitis or significant alcohol intake, which is carried out through history and laboratory testing. Once diagnosis and initial risk stratification is complete, a more detailed evaluation of liver fibrosis is needed.

The majority of patients with NAFLD and many with NASH are considered to have a low risk of clinically significant fibrosis and can be managed by PCPs. NAFLD is not an isolated disease. NAFLD is considered a component of cardiometabolic abnormalities typically associated with obesity. Therefore, the cornerstone of therapy for patients with NAFLD are lifestyle-based therapies (altered diet, such as reduced-calorie or Mediterranean diet and regular, moderate physical activity) and replacing obesogenic medications to reduce body weight and improve cardiometabolic health.

If diabetes is present, the researchers suggest that the PCPs may prescribe a medication for diabetes that can also treat NASH. However, it should be noted that metformin is not effective in treating NASH and guidelines suggest that clinicians should consider using pioglitazone instead.

For individuals with NAFLD, alcohol consumption should be limited to 2 to 3 drinks per week in women and 4 to 5 drinks per week in men. Alcohol consumption should also be avoided in patients with advanced fibrosis.

Previous studies have shown that statins are safe and effective in patients with NAFLD and NASH, and they can be used to treat dyslipidemia in these patients, including those with compensated cirrhosis. However, current data is lacking regarding the safety and risks of statins in patients with decompensated cirrhosis. Therefore, statins should be avoided in these patients until more robust evidence to support their safety is available.

Due to the high frequency of NAFLD and the lack of patient awareness about this disease, the application of artificial intelligence/machine learning tools to the big data repositories of electronic health records may have the potential for efficient disease identification and risk stratification. Several liver-targeted and other potential therapies targeting a broad range of pathologic changes associated with NASH are currently under investigation. Ultimately, given the multiple pathways involved in NASH pathogenesis, combination regimens may be required to treat NASH more efficiently.

Recommendations

Key opinion leaders from the conference recommend more sensitive and specific diagnostic methods for NASH. They also recommend the adoption of a multidisciplinary approach to ensure optimal care of patients with NASH. Care for patients with NASH may require clinicians from different specialties such as primary care, hepatology, obesity management, and endocrinology to address both the hepatic manifestations of the disease and the comorbid metabolic syndrome and cardiovascular risks, as well as screening and treating other comorbid conditions, including obstructive sleep apnea. When NAFLD progresses to NASH, multidisciplinary, team-based care involving the aforementioned specialties is imperative.

The panel emphasizes that the development of clinical care pathways that utilize validation and effective noninvasive tests and calculators is essential to a multidisciplinary approach to managing NAFLD/NASH.

Overall, decreasing the clinical and economic burden of NAFLD and NASH will require fundamental societal changes that address failing public health systems and the social factors of health.

Summary and Conclusions

The Call-to-Action Meeting represents one of the first steps needed to align key stakeholders on a collective plan to address the rising burden of NAFLD/NASH. Improving care for patients with NALFD will require substantial changes and innovations in technology, health care delivery, and policy. Optimum care of patients with NAFLD/NASH will require a multidisciplinary team combining primary care, hepatology, obesity medicine, and endocrinology/diabetology, along with the investigation of high-yield targets for clinical research and practice identified by key opinion leaders.

“These efforts should help the field move toward a collective strategy with shared goals and objectives that will improve care for the growing population of patients with NAFLD/NASH,” the study authors wrote.   

Disclosure: Some study authors declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.

Disclosure: This research was supported by multiple sources. Please see the original reference for a full list of disclosures.

Reference

Kanwal F, Shubrook JH, Younossi Z, et al. Preparing for the NASH epidemic: a call to action. Gastroenterol. Published online July 26, 2021. doi: 10.1016/j.metabol.2021.154822