How lifestyle factors and coinfections drive liver fibrosis progression in the MASH cohort
Participants
Higher mortality with cocaine use
Food insecurity prevalence
Years follow-up
The same medical advances that turned HIV from a death sentence into a manageable condition have uncovered a hidden epidemic—progressive liver disease that now threatens the long-term health of people living with HIV.
When we think about HIV management today, we typically picture antiretroviral therapy that suppresses the virus to undetectable levels. But behind this medical success story lies a growing concern: advanced liver disease has emerged as a leading cause of non-AIDS related death among people living with HIV. The Miami Adult Studies on HIV (MASH) Cohort has been at the forefront of investigating this silent threat, revealing surprising connections between lifestyle factors, co-infections, and liver health that extend far beyond what we traditionally associate with liver damage. 1
For years, researchers at the University of Miami have followed a group of primarily economically disadvantaged, middle-aged Black and Hispanic participants—both with and without HIV—in what's known as the Miami Adult Studies on HIV (MASH) Cohort. This long-term observational study has become a treasure trove of information about how HIV and its associated conditions affect the body over time. 4
Recent findings from this cohort have been eye-opening. While viral hepatitis co-infection certainly contributes to liver damage in people with HIV, the MASH research reveals that other factors play equally important roles: food insecurity, substance use, and the HIV virus itself all appear to independently damage the liver.
To appreciate the significance of the MASH findings, we first need to understand what liver fibrosis is and why it matters. Imagine your liver as a sophisticated processing plant with thousands of specialized workers (hepatocytes) and support staff. When this factory sustains damage—from viruses, toxins, or inflammation—it attempts to repair itself by laying down scar tissue, much like skin forms a scar after a deep cut.
This scar tissue formation process involves the activation of hepatic stellate cells, the liver's repair specialists. In their normal state, these cells store vitamin A and help maintain the liver's structure. But when persistently activated by injury, they transform into collagen-producing factories. 5
The problem with this repair process is that unlike skin scars that eventually fade, liver scars tend to persist and expand, slowly compromising the liver's essential functions. When fibrosis progresses to its end stage—cirrhosis—the damage becomes largely irreversible. 5
Viruses, toxins, or inflammation damage liver cells, triggering repair response.
Hepatic stellate cells transform into collagen-producing factories.
Collagen deposits form fibrous bands that replace healthy tissue.
Liver architecture is disrupted, function is severely compromised.
One of the most surprising connections emerging from the MASH research involves food insecurity—limited access to sufficient nutritious food—and its impact on both cognitive and liver health. In a two-year longitudinal analysis of 394 participants (247 with HIV), researchers made a startling discovery: the frequency of food insecurity directly correlated with cognitive impairment. 4
Food insecurity often leads to poor nutritional quality and metabolic dysfunction, which can promote liver fat accumulation and inflammation. This creates a vicious cycle: liver dysfunction impairs nutrient processing and toxin clearance, which may further exacerbate cognitive issues.
Perhaps even more striking is the MASH finding regarding cocaine use and mortality. In a analysis of 487 HIV-positive participants followed for at least two years, researchers discovered that cocaine users were nearly five times more likely to die than non-users among HIV mono-infected participants.
Cocaine use generates oxidative stress—an imbalance between harmful free radicals and protective antioxidants—that directly damages liver cells.
Lifestyle factors associated with substance use may compound the problem, including poor nutrition, inconsistent medication adherence, and limited healthcare access.
For those living with both HIV and Hepatitis C, the liver faces a dual assault. Research extending beyond the MASH cohort reveals that HIV/HCV coinfection leads to accelerated hepatic fibrosis progression, higher rates of liver failure, and increased mortality compared to those with either infection alone. 3
Even in the era of effective HCV treatments that can cure the infection, the legacy of coinfection may persist. The MASH research and related studies show that elevated fibrosis biomarkers often remain elevated after HCV treatment, suggesting ongoing liver dysfunction even after the virus is cleared. 2
Understanding how scientists detect and measure liver fibrosis helps appreciate the significance of their findings. Researchers in the MASH cohort and similar studies employ multiple tools to assess liver health without resorting to invasive biopsies in all participants. 7
| Tool | Type | What It Measures | Advantages |
|---|---|---|---|
| FIB-4 Index | Blood test | Age, AST, ALT, and platelet count | Non-invasive, easily calculated from routine blood work |
| APRI Score | Blood test | AST levels relative to platelet count | Simple, inexpensive, requires basic lab values |
| Transient Elastography (FibroScan) | Imaging | Liver stiffness using ultrasound | Quick, painless, directly measures tissue properties |
| Liver Biopsy | Tissue sample | Direct visualization of liver architecture | Gold standard, provides detailed structural information |
To understand how MASH cohort research works in practice, let's examine the food insecurity study that yielded such striking results. This investigation exemplifies the careful, longitudinal approach needed to unravel complex relationships between social factors and health outcomes. 4
The findings remained significant even after excluding participants with cognitive impairment at baseline, strengthening the evidence that food insecurity preceded—and likely contributed to—cognitive decline rather than merely correlating with it.
The work emerging from the MASH cohort represents a paradigm shift in how we view health in people living with HIV. It reveals that successful long-term management requires looking beyond viral loads and CD4 counts to consider the whole person—their nutritional status, substance use patterns, and organ health.
"Our understanding of the natural history and pathogenesis of liver diseases in HIV has advanced and adapted to the changing landscape of liver disease in this population." 2
Identify at-risk patients during routine HIV care for early intervention.
Address substance use as part of comprehensive HIV care.
Regularly assess liver function and fibrosis in all HIV patients.
What begins as silent fibrosis today may determine tomorrow's health outcomes for people living with HIV. Thanks to studies like the MASH cohort, we're beginning to understand how to intervene before the damage becomes irreversible.