Primary Care Screening for Nonalcoholic Fatty Liver Disease Among People With HIV in the United States: A Real-World Provider Survey

Abstract

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people with HIV (PWH) and increases the risk of hepatic fibrosis and hepatocellular carcinoma. We sent an online survey to providers of the American Academy of HIV Medicine. Of respondents (n = 214, 8% response rate), 65% reported screening for NAFLD in PWH, with 28% routinely screening all patients. Most respondents refer patients to hepatology if workup suggests another coexisting liver disease or cirrhosis, with the primary goals of referral being additional diagnostic testing (60%) or specific treatments (75%). The most common barriers to screening were feeling unsure of what tests to order (28%) and how to conclusively diagnose NAFLD (29%). Most respondents were interested in society guidelines (73%) and NAFLD education for patients (57%) and providers (55%). Our findings support the development of NAFLD clinical practice guidelines for HIV providers and the inclusion of PWH in clinical trials of novel agents.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent among people with HIV (PWH), affects more than one third of the population, and is an indication for liver transplantation in PWH (Campos-Varela et al., 2021; Kalligeros et al., 2023). Although HIV is not an independent risk factor for steatosis, studies have demonstrated a higher prevalence of nonalcoholic steatohepatitis (NASH) and fibrosis among PWH compared with those without, suggesting that HIV may adversely alter the natural history of NAFLD (Kardashian et al., 2017; Kirkegaard-Klitbo et al., 2020, 2021; Price et al., 2014; Vodkin et al., 2015). Indeed, a meta-analysis found that among studies of PWH monoinfection who underwent liver biopsy, the pooled prevalence of histologic NASH and significant fibrosis (≥F2) were 49% and 23%, respectively (Kalligeros et al., 2023). Despite this high disease burden, there are no expert guidelines in the United States on the clinical assessment and management of NAFLD in PWH. The recently updated American Association for the Study of Liver Diseases (AASLD) Practice Guidance on NAFLD does not include special considerations for PWH (Rinella, Neuschwander-Tetri, et al., 2023). To better inform recommendations for NAFLD screening among PWH, we surveyed U.S. HIV providers on their NAFLD screening patterns and management needs.

Methods

Survey Population

We designed an anonymous online survey that was sent to member and nonmember HIV providers of the American Academy of HIV Medicine (AAHIVM). The AAHIVM is the leading independent organization of HIV health care providers in the United States and provides HIV Specialist Credentialing for physicians (MD and DO) and advanced practice providers (APPs) who provide clinical care for PWH. Our survey was restricted to physicians and APPs working in the United States, Puerto Rico, and U.S. Virgin Islands (n = 2,753; 61% physicians, 30% nurse practitioners, and 9% physician assistants). The survey link was delivered through electronic mail through the AAHIVM listserv three times over 6 weeks from January to February 2023—the initial survey followed by electronic reminders at 3 and 6 weeks. No incentives were offered for survey completion. Notably, the survey was designed and administered before the adoption of new nomenclature for NAFLD (Rinella, Lazarus, et al., 2023). The terms fatty liver disease and NAFLD have been replaced with steatotic liver disease and metabolic dysfunction–associated steatotic liver disease, respectively, to more accurately reflect the disease pathophysiology and remove stigma. We chose to keep the old terminology of NAFLD in this article to be consistent with the nomenclature used in the survey.

Survey Design and Methods

The 16-question survey was designed by us and reviewed by AAHIVM staff. Questions assessed (a) NAFLD screening and referral practices, (b) barriers to screening, and (c) attitudes toward hypothetical support tools to assist NAFLD diagnosis and management (Table S1, Supplemental Digital Content 1, http://links.lww.com/JNC/A61). The survey was administered through the REDCap electronic data capture tools hosted at the University of California, San Francisco (UCSF). REDCap is a secure and HIPAA-compliant web-based system for managing online surveys (Harris et al., 2019). Our study was approved by the UCSF Institutional Review Board.

Results

The survey had 214 respondents (8% response rate) with a similar proportion of professional backgrounds as compared with the AAHIVM providers who were sent the link: 60% physician, 28% nurse practitioner, and 12% physician assistants (Table 1). Most providers were primary care practitioners, with 38% in family practice and 24% in internal medicine, and the majority had been in practice for more than 10 years (Table 1).

Table 1.

Characteristics of Survey Respondents

	n (%)
Professional title
Physician	129 (60)
Nurse practitioner	59 (28)
Physician assistant	26 (12)
Years in practice
21+	85 (40)
11–20	48 (22)
6–10	34 (16)
0–5	43 (20)
Trainee	3 (1)
Missing	1
Medical specialty
Family practice	82 (38)
Internal medicine	52 (24)
Infectious diseases	59 (28)
Other	21 (10)
Practice type
Hospital based	53 (25)
Large group (>5 providers)	77 (36)
Small group (≤5 providers)	32 (15)
Individual practice	6 (3)
Other	44 (21)
Missing	2

Two thirds of participants reported screening PWH for NAFLD, including 28% who routinely screened all patients with HIV for NAFLD (Figure 1). The most cited reasons for screening were persistently elevated liver enzymes (89%), metabolic syndrome (64%), obesity (61%), and prediabetes/diabetes (56%). Most participants use liver enzymes and abdominal ultrasound to screen for NAFLD, whereas only one third use vibration-controlled transient elastography (VCTE), and very few use magnetic resonance imaging. Most respondents refer patients with suspected NAFLD to hepatology at least some of the time (Figure 1). The majority refer to hepatology if abdominal imaging suggests cirrhosis (71%) or if workup suggests another coexisting liver disease (56%), and most placed referrals seeking specific treatments (75%) and additional diagnostic testing (60%).

Figure 1.

Nonalcoholic fatty liver disease screening and referral practices. d-drugs = dideoxynucleoside analog drugs; NAFLD = nonalcoholic fatty liver disease; MRE = magnetic resonance elastography; MRI = magnetic resonance imaging; VCTE = vibration controlled transient elastography

Sixty-four percent of participants reported barriers to NAFLD screening, the most common of which were feeling unsure of what tests to order (28%) and not knowing when there is enough data to make the diagnosis (29%; Figure 2). A minority of respondents reported screening being a low priority (17%), not having enough time to screen (7%), or not having access to hepatology referrals as barriers (7%). In addition, 13% reported that they do not screen for NAFLD because the diagnosis would not impact their management of the patient. When asked what tools would help in diagnosing and managing NAFLD in PWH, 73% were interested in society guidelines, and the majority were interested in NAFLD education for patients and providers (Figure 2). More than 40% reported that electronic medical record tools would assist NAFLD workup. A sizeable minority of respondents indicated that access to additional resources would improve NAFLD diagnosis and management, including access to VCTE (35%), hepatology specialty care (24%), or abdominal ultrasound (21%).

Figure 2.

Barriers to nonalcoholic fatty liver disease screening and perceptions of provider support tools. EMR = electronic medical record; NAFLD = nonalcoholic fatty liver disease

Discussion

Despite numerous studies documenting a high prevalence of NAFLD among PWH and rising awareness of NASH and advanced fibrosis as a concern in this population, society guidelines addressing NAFLD diagnosis and management in PWH are lacking (Bulteel & Leen, 2015; Sebastiani et al., 2023). To our knowledge, this is the first survey to assess the NAFLD screening and management needs of frontline HIV providers.

Two thirds of survey respondents reported screening for NAFLD in at least some of their patients with HIV, with various indications prompting screening. Most, but not all, respondents screened for NAFLD in PWH with prediabetes/diabetes, obesity, metabolic syndrome, or persistently elevated liver enzymes, consistent with the European AIDS Clinical Society recommendations to screen PWH who have any of the following: obesity, metabolic syndrome, persistent ALT elevation, or exposure to “d-drugs” (e.g., stavudine, didanosine; European AIDS Clinical Society, 2022) After our survey was conducted, the AASLD guidance on NAFLD was updated to recommend targeting screening for advanced fibrosis among patients at an elevated risk, including patients with diabetes, medically complicated obesity, or first degree relative with NAFLD/NASH cirrhosis (Rinella, Neuschwander-Tetri, et al., 2023). However, general population-based screening for advanced fibrosis in PWH was not recommended (Rinella, Terrault, et al., 2023).

Given that the estimated prevalence of ≥ F2 fibrosis among PWH is 12%, which is higher than that in the general population, PWH may be at sufficiently high risk to warrant targeted screening (Kalligeros et al., 2023). Approximately 85% of survey respondents place referrals to hepatology in at least some patients with suspected NAFLD, and only 7% reported not having access to hepatology referral. This suggests that an algorithm including primary care–based screening to identify PWH at risk for NASH or cirrhosis for hepatology referral would be effective. Indeed, more than 70% of respondents referred patients with suspected cirrhosis to hepatology. Studies on the utility of universal screening to identify PWH with at-risk NAFLD would help inform future guidance. Importantly, the most common reason for hepatology referral was to access further treatment options. This is notable because few therapeutic studies specifically address treatment for NAFLD/NASH among PWH, and most investigational trials explicitly exclude PWH (Guaraldi et al., 2020). An important limitation of our study is that we did not assess awareness of the existing AASLD NAFLD guidance. However, our findings suggest that despite the current guidance, HIV providers are seeking more education on NAFLD among PWH.

It is encouraging that most respondents are motivated to screen for NAFLD among PWH and that few lacked the time to screen or believed that NAFLD was not a priority. However, many expressed uncertainties around NAFLD testing, and some believed that a diagnosis would not affect patient management. Our findings underscore the need for NAFLD clinical practice guidelines aimed for HIV providers, increased education on NAFLD among PWH, and the inclusion of PWH in NAFLD/NASH therapeutic trials of novel agents.

Supplementary Material

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and in the HTML and PDF versions of the article at www.janacnet.org.

Key Considerations.

• Most HIV providers surveyed screen for nonalcoholic fatty liver disease (NAFLD) in at least some people with HIV (PWH), particularly in those with metabolic dysfunction or persistently elevated liver enzymes.

• Many expressed uncertainties around NAFLD testing, and some believed that a diagnosis would not affect patient management.

• NAFLD clinical practice guidelines aimed for HIV providers and increased education on NAFLD among PWH are needed.

• Most providers surveyed place specialty referrals seeking treatment options, underscoring the importance of including PWH in NAFLD/nonalcoholic steatohepatitis therapeutic trials of novel agents.

Data Accessibility

Data for this study are available upon request.