In HCV, Starting Treatment Trumps Staging for Liver Fibrosis

When managing patients with hepatitis C virus (HCV), initiating treatment of the infection promptly is more important than determining the severity of their liver disease with the customary staging tests, a study using microsimulation found.

The study, published in the journal Clinical Infectious Diseases, found that the use of lab testing alone, with the fibrosis-4 index (FIB-4) serum biomarker test, resulted in optimal clinical outcomes, but also found that treatment without staging was a cost-effective approach.

“Our results suggest that treating the patient in front of you for hepatitis C virus infection is more important than determining with the best accuracy how healthy their liver is right now,” Rachel Epstein, MD, an infectious disease specialist at Boston University, Boston, told Medscape Medical News.

“This is because many people are lost to follow-up in the process of completing tests to more accurately stage their liver disease, and treating HCV helps prevent development of liver disease, associated liver cancer, and liver-related death,” she added.

Epstein led a team of researchers that used a microsimulation model to simulate adults with chronic HCV receiving care at US health centers. The microsimulation included five different strategies for managing liver disease in patients with HCV: No staging or treatment, which served as the comparator; FIB-4 testing only; transient elastography (TE) only; a staged approach that involved FIB-4 for all and TE only for intermediate FIB-4 scores; and both tests. It used data from the Rhode Island Medicaid program to calculate costs.

Study Results

FIB-4 testing alone yielded the best clinical outcomes: 87.7% of patients cured, 8.7% developing cirrhosis, and 4.6% having liver-related deaths. Strategies using TE had cure rates of 58.5%-76.5%, cirrhosis rates of 16.8%-29.4%, and liver-related death rates of 11.6%-22.6%.

TE is not always practical or accessible, Epstein said. “Transient elastography is expensive, and for a practice to operate it, it needs to buy a machine and hire a trained technician, so that limits the availability of it,” she said. “It’s generally only available at specialty offices or radiology departments and not at all centers.”

“FIB-4, on the other hand, only depends on a common laboratory test,” she said, adding that in some settings even getting that blood test can be difficult.

The study found that all TE strategies resulted in worse clinical outcomes and higher costs than FIB-4 only, and that FIB-4 was the only cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of $12,869 compared with no staging and no treatment.

However, in a point-of-care test-and-treat scenario, starting treatment without liver disease staging was also a cost-effective and clinically effective strategy, with a cure rate of 87.7% (vs 74.4% for FIB-4 only in this model) and an ICER of $12,681.

The finding that favors FIB-4 testing alone is in line with guidelines from the American Association for the Study of Liver Disease and Infectious Disease Society of America (AASLD/IDSA), Epstein said. But the study also raises questions about the effectiveness of the joint recommendation to combine FIB-4 with TE when available, she added.

Dealing With Patients Lost to Follow-Up

“Our findings demonstrate that this combined approach, doing the indirect serum biomarker (FIB-4) and transient elastography, while the most accurate to stage liver disease, is only the most clinically effective approach on a population level if both tests can be completed without any loss to follow-up,” Epstein said.

But in the real world, many patients do not follow up on their care, she noted. “In those cases, we suggest that only calculating the FIB-4, or if no testing can be done without loss to follow-up, not staging at all and treating the HCV right away.”

In an ideal world, prospective, randomized trials would be done to further validate these findings, Epstein said, “if they were deemed ethical to better determine true linkage to care probabilities for different populations who were staged by each different test.”

However, she added, “Those trials would be difficult to actually conduct in reality, which is why we used simulation modeling.”

The findings may give pause to the AASLD/IDSA guidelines panel to revise the recommendation to combine FIB-4 testing with TE, Vincent Lo Re, MD, an infectious disease specialist at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, told Medscape Medical News.

“Calculating FIB-4 for HCV pretreatment evaluation is simple and saves lives and money compared with requiring transient elastography or other testing approaches for liver fibrosis staging,” Lo Re said. “There remain many obstacles to progressing through the US HCV care cascade, but these data are reassuring since HCV test-and-treat approaches are needed if we are to achieve elimination of HCV infection as a public health problem.”

This study means that clinicians should use the AASLD/IDSA simplified treatment recommendation for FIB-4 for staging liver fibrosis “and identify those with advanced hepatic fibrosis/cirrhosis to streamline the HCV evaluation and reduce barriers to treatment,” Lo Re added.

He noted the simulation model the study used did not specifically account for people who were homeless or incarcerated. “However,” Lo Re said, “the research team gave thoughtful attention to many important sensitivity analyses. Healthcare teams serving these populations could determine which sensitivity analyses fit their population best depending on their resources.”

This study received funding from the National Institutes of Health and the Providence/Boston Center for AIDS Research. Epstein and Lo Re had no relevant financial relationships.

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.