Large VA study reveals hidden liver damage in US military veterans
Up to 1 in 4 may have irreversible liver scarring at PBC diagnosis
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As many as 1 in 4 U.S. military veterans with the liver disease primary biliary cholangitis (PBC) may have irreversible liver scarring, or cirrhosis, by the time of diagnosis.
That’s according to a large study using Department of Veterans Affairs (VA) national data, which revealed that approximately one-quarter of U.S. veterans found to have PBC also showed signs of cirrhosis. The researchers noted that disease prevalence, or the population of veterans in the study group found to have PBC, was also high.
“Among a national cohort [of] US veterans, the prevalence of PBC ranged from 19.5 to 76.2 per 100,000 persons when evaluating various diagnostic criteria,” the researchers wrote.
The suspected large numbers of veterans with cirrhosis at diagnosis “is alarming and emphasizes the importance of raising awareness for early recognition and diagnosis, followed by prompt referral to specialty care and treatment,” the researchers wrote, noting that “disease severity at time of diagnosis is a reflection of potential delays in timely diagnosis and treatment.”
The study, “Up to 1 in 4 Veterans With Primary Biliary Cholangitis May Have Cirrhosis by the Time of Its Diagnosis,” was published in the journal Gastro Hep Advances by a trio of VA scientists in California. Two of the three authors are also affiliated with Stanford University School of Medicine.
In cholangitis, the bile ducts — the tubes that carry the digestive fluid bile from the liver to the small intestine — become inflamed. PBC is an autoimmune form of the condition that affects only the bile ducts inside the liver.
Without treatment, it can lead to scarring, cirrhosis, and liver failure over time. However, PBC diagnosis is often slow across all patient populations, in part due to a lack of distinctive symptoms.
“Delays in timely diagnosis and treatment contribute … to continued liver disease progression to cirrhosis and subsequent liver-related mortality” for patients, the team wrote.
Info needed on PBC frequency, symptom severity at diagnosis
According to the researchers, better understanding PBC’s frequency and how severe symptoms are at diagnosis could help focus public health efforts in this area.
To address this, the trio turned to a dataset covering more than 5.13 million veterans with at least one VA health record from January 2010 through April 2025. The team used two main methods — diagnostic codes and blood test results — to identify people with PBC.
More specifically, International Classification of Diseases (ICD)-9/10 diagnostic codes are a standardized system for recording medical diagnoses, and there are specific ICD-9/10 codes for PBC. Blood tests for self-reactive antimitochondrial antibodies (AMA) can also help define PBC diagnosis. AMAs are highly specific to PBC, so a record of a positive AMA test strongly suggests the condition is present.
Depending on the combination of ICD-9/10 and AMA criteria that was used, the prevalence of PBC, or the proportion of the population affected at a given time, varied widely, the researchers noted.
The broadest definition of PBC — involving everyone with at least one recorded ICD-9/10 diagnostic code — resulted in a prevalence of 76.2 cases per 100,000 people, the data showed. Using a definition that required both an ICD-9/10 code and a positive AMA test, the prevalence dropped to 19.5 cases per 100,000.
“These variations in prevalence, when using different diagnostic criteria, also mirror the variations in PBC prevalence that has been reported in previous studies,” the team wrote.
Liver disease is more common among female US veterans
Also consistent with previous studies, PBC was significantly more common among female U.S. veterans. This gap was largest when the team used more specific criteria, such as both an ICD-9/10 code and positive AMA test, to define PBC. Using that definition, the prevalence among women was more than three times higher than among men.
In addition, PBC’s frequency was higher in older age groups across most diagnostic criteria and highest among Hispanic and Asian/Pacific Islander veterans.
The researchers also found relationships between age and sex.
“While increasing age was associated with increasing PBC prevalence among both men and women, the gender gap became more prominent in older age groups,” the team wrote.
Next, the team assessed the severity of symptoms at the time of PBC diagnosis. Depending on the diagnostic criteria, 10.7% to 26.4% of participants already had cirrhosis when they received their diagnosis. This indicates that the disease had already progressed substantially, potentially suggesting diagnostic delays, according to the researchers.
“Since many patients with PBC are asymptomatic [do not show symptoms], it is likely that development of advanced liver disease such as cirrhosis prompts further workup and diagnosis of PBC,” the researchers wrote.
While it is not entirely clear why men with PBC have higher risk of disease progression and liver-related mortality, the ‘myth’ that PBC is less common in men may contribute to delays in diagnosis, leading to more advanced disease at time of diagnosis, which is associated fewer options for successful treatment and worse outcomes.
For most diagnostic criteria, the proportion of men with cirrhosis was higher than that of women.
“While it is not entirely clear why men with PBC have higher risk of disease progression and liver-related mortality, the ‘myth’ that PBC is less common in men may contribute to delays in diagnosis, leading to more advanced disease at time of diagnosis, which is associated fewer options for successful treatment and worse outcomes,” the team wrote.
Using existing medical records allowed the researchers to examine a very large population. The findings indicate that “across different PBC diagnostic criteria, up to one-quarter of patients had already developed cirrhosis at time of diagnosis,” the researchers wrote.
That result “[emphasizes] the need for improved efforts toward early recognition and diagnosis, followed by prompt referral to specialty care for monitoring and treatment,” the team wrote.
However, the study also had limitations. Differences in the application of diagnostic codes and the availability of AMA test results may have varied throughout the group, the researchers noted.
Further, these findings may be specific to U.S. military veterans, the team suggested, noting that “the predominantly male and older demographic of the VA population limits the generalizability of the findings to other populations.”
In the future, similar studies could more closely review medical records and clinical notes to more accurately determine if participants had PBC, the researchers suggested.
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