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Liver fibrosis speeds up around the menopause in women with HIV and HCV co-infection
Michael Carter, 2017-08-22 07:20:00
associated with accelerated liver fibrosis in women with HIV and hepatitis C virus
(HCV) co-infection, investigators from the United States report in the
online edition of Clinical Infectious
Diseases. The study showed that liver damage due to fibrosis – the build-up of scar tissue after cell death caused by HCV-related inflammation – begins to speed up as the menopause takes place.
The researchers say that the findings have
important clinical significance, suggesting that peri- and post-menopausal women
should be prioritised as candidates for HCV therapy using direct-acting antiviral agents
(DAAs) to avoid further liver damage.
“We found that
liver fibrosis rates…increased as women transitioned through menopause,”
comment the authors. “Importantly, we employed a robust statistical approach to
account for potential confounding effects of chronological aging, and evaluated
reproductive stages 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.”
Up to 15% of people with HIV in the United States have co-infection with HCV, at least
three times the HCV infection rate seen in the general population. Untreated
HIV infection is associated with accelerated HCV-related liver fibrosis. Sex is
also a risk factor for fibrosis progression, with men having higher rates than
women. This is thought to be because of the protective effects of oestrogen in women, and
higher rates of fibrosis have been observed in post-menopausal women.
research exploring the impact of reproductive ageing on fibrosis progression
has been limited by lack of adjustment for chronological ageing and an absence of
longitudinal follow-up. Moreover, the relationship between oestrogen and
fibrosis progression has not been assessed in HIV-positive women.
the Women Interagency HIV Study (WIHS) designed a study involving 405 women with
HIV/HCV co-infection who were pre-menopausal at baseline. Progression of menopause
and liver fibrosis were monitored longitudinally. To enable the investigators
to robustly assess the relationship between reproductive ageing and the
progression of liver fibrosis, data were also collected on chronological age,
race, alcohol use, metabolic syndrome, HCV viral load and HIV-related factors
(CD4 cell count, use of antiretroviral therapy [ART], viral load).
was assessed using serial measures of anti-Müllerian hormone (AMH). The level of AMH indicates the reserve of eggs left in the ovaries.
Pre-menopause was defined as the presence of detectable AMH; peri-menopause was defined as the period within five
years of AMH becoming undetectable; post-menopause was more than five years
after AMH loss.
assessed using two measures: APRI and FIB-4.The APRI and FIB-4 scales use levels of liver enzymes and platelets to calculate the extent of liver damage.
Median age at
baseline was 37 years, and average age at the onset of menopause was 49 years.
The majority of women were Hispanic (58%). At the start of the study, 6% had
fibrosis stage 3 or above, which increased during follow-up to 32% when
assessed using FIB-4 and 20% using APRI. Only 6% of participants reported heavy
alcohol use. Most were taking ART (88%), but only 23% received any kind of HCV
therapy with just 2% treated with DAAs. Approximately a quarter of participants
had a history of diabetes and 11% had ever been diagnosed with metabolic
was 9.1 years, and a fifth of women took some form of hormone replacement
therapy during this period.
After taking into
account chronological age, the investigators found that fibrosis was
accelerated during peri-menopause compared to pre-menopause using FIB-4 (0.12
units/year faster; 95% CI, 0.02-0.21; p = 0.001) and APRI (0.05- units/year
after; 95% CI 0.002-0.09; p = 0.06). Faster fibrosis progression was also
present post-menopause compared to pre-menopause, though the difference was
short of statistical significance for both FIB-4 (p = 0.07) and APRI (p =
After adjustment for
other potential confounders including Hispanic ethnicity, ART use and alcohol
consumption, peri-menopause continued to be associated with accelerated
fibrosis (0.10 FIB-4 units/year after vs pre-menopause; 95% CI, 0.008-0.20; p
“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,” comment the researchers. “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.”
conclude that fibrosis progression in women with HIV/HCV co-infection accelerates
with reproductive age, 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,”
they note. “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.”