Menopause Linked to Liver Fibrosis Acceleration in HIV, HCV Co-Infection

Menopause speeds up liver fibrosis in women co-infected with HIV and hepatitis C virus (HCV), new findings show.

In the United States, up to 15% of individuals with HIV are co-infected with HCV, according to NAM. This figure is at least 3 times the rate of HCV infection found in the general population. When HIV is left untreated, it is linked with accelerated HCV-related liver fibrosis.

In a study published in Clinical Infectious Diseases, investigators enrolled 405 women with HIV/HCV co-infection who were pre-menopausal at baseline. Menopause and liver fibrosis progression were monitored longitudinally.

The investigators also collected patient data on chronological age, race, alcohol use, metabolic syndrome, HCV viral load, and HIV-related factors.

Serial measures of anti-Müllerian hormone (AMH) were used to assess menopausal status. Pre-menopause was defined as the presence of detectable AMH and peri-menopause was defined as the period within 5 years of AMH becoming undetectable. Post-menopause was more than 5 years after AMH loss.

Fibrosis was assessed using APRI and FIB-4, according to NAM. The medial follow-up was 9.1 years, and during this period, one-fifth of the women took some form of hormone replacement therapy.

At the start of the study, 6% of women had stage 3 fibrosis or higher—–which increased to 32% during follow-up when using FIB-4 and 20% using APRI.

Eighty-eight percent of patients were undergoing antiretroviral therapy (ART), but only 23% received any kind of HCV treatment, with only 2% treated with direct-acting antiviral agents (DAAs).

Approximately a quarter of patients had a history of diabetes and 11% had ever been diagnosed with metabolic syndrome, according to NAM. Only 6% of patients reported heavy alcohol use.

After adjusting for chronological age, the findings showed liver fibrosis was accelerated during peri-menopause compared with pre-menopause. Furthermore, accelerated fibrosis progression as present post-menopause compared with pre-menopause; however, the authors noted the difference was short of statistical significance for both FIB-4 and APRI.

Further adjustments were made, including Hispanic ethnicity, ART use, and alcohol consumption. But peri-menopause continued to be associated with faster fibrosis progression.

“We found that liver fibrosis rates … increased as women transitioned through menopause,” the authors said, as reported by NAM. “Importantly, we employed a robust statistical approach to account for potential confounding effects of chronological aging, and evaluated reproductive states by hormonal confirmation of ovarian reserve. Acceleration of hepatic fibrosis also began during peri-menopausal years, suggesting that women may be at increased risk of liver scarring earlier than suggested by prior data relying on self-reported menopausal age.”

The authors noted that the findings demonstrate clinical significance, suggesting that peri- and post-menopausal women should be prioritized as candidates for DAA therapy to prevent further liver fibrosis.

“The current study represents an important advance in our understanding of the effects of reproductive ageing on liver fibrosis by highlighting the accelerated fibrosis that begins as early as pre-menopausal years,” the authors said, as reported by NAM. “Using AMH as a gold standard measurement of ovarian reserve we were able to evaluate each woman’s fibrosis rate as she transitioned across reproductive stage.”

Based on the findings, the authors conclude that fibrosis progression in women with HIV/HCV co-infection is accelerated with reproductive age that is independent of chronological age.

“Accelerated fibrosis began in peri-menopausal years, highlighting a previously unrecognized group of women at increased risk of progressive fibrosis and associated complications,” the authors said, as reported by NAM. “Similar analyses using serial measures of fibrosis should be conducted in non-HCV related liver diseases, including women without HIV infection, given potential implications of ovarian reserve on fibrosis progression in women with a broad spectrum of liver diseases.”