Study finds clues to fibrosis progression in chronic HCV infection

Study finds clues to fibrosis progression in chronic HCV infection
By: WHITNEY MCKNIGHT, Hospitalist News Digital Network August 10, 2016

FROM THE JOURNAL OF INFECTIOUS DISEASES

Vitals
Key clinical point: Fibrosis progression is not linear in chronic HCV infection.

Major finding: Between the first and follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Data source: A review of 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013.

Disclosures: Dr. Talal and Dr. Jacobson disclosed numerous industry relationships, including with Abbott, AbbVie, and Gilead. The study was supported by the Troup Fund of the Kaleida Health Foundation and the Greenberg Foundation for Medical Research.

Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with alanine aminotransferase–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study.

Identifying which patients with hepatitis C virus (HCV) infection will likely progress to cirrhosis has historically been a challenge, creating some difficulty adhering to guidelines recommending that patients at greater risk of fibrosis be among those prioritized for treatment. Having an ability to more accurately diagnose those most at risk could help to better guide treatment prioritization and clinical management.

To that end, Marija Zeremski, PhD, and her colleagues at Weill Cornell Medical School, New York, analyzed 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013. At the time of the first biopsy, nearly two-thirds of the patients were white men in their late 40s to mid-50s, with chronic HCV infection. Nearly 88% of all patients were HCV genotype 1 infected.

In a study, investigators found that between the first and a follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Fibrosis progression between the first and last biopsies was associated with less fibrosis on the first biopsy (P less than .001).

Increased necroinflammation and the presence of at least one alanine aminotransferase (ALT) flare greater than 200 U/L during follow-up was also significantly associated with fibrosis progression (odds ratio [OR], 2.64, P less than .007). HCV genotype 3–infected patients were significantly more likely to progress to cirrhosis (P less than .001).

Intrahepatic inflammation at the time of the initial biopsy was at grade 1 or lower in 36.4% of patients, while 56.9% of patients had grade 2 (moderate) inflammation. Severe inflammation (grade 3 or higher) was found in 6.7% of patients reviewed. There was no fibrosis in 11.9% of patients, stage 1 level of fibrosis in 32.3%, stage 2 in 39.4%, and stage 3 in 16.4% of patients.

Moderate to severe fibrosis, defined as equal to or greater than stage 2, was significantly associated with elevated inflammation (greater or equal to grade 2) on the initial biopsy (OR, 9.00; P less than .001). Steatosis testing was performed on 222 patients; 59% tested positive for it. This was significantly associated with stage 2 or higher fibrosis (OR, 2.39; P = .002), and grade 2 or higher levels of inflammation (OR, 4.07; P less than .001) on the initial biopsy.

The highest fibrosis progression rate occurred between stages 0 and 1; the lowest, between stages 2 and 3.

Consecutive biopsies were separated by at least 1 year; patients were either HCV treatment naive or were treatment nonresponders. There were a total of 558 consecutive biopsy pairs available to analyze stage progression. The time between the first and last biopsies was 6.5 years (plus or minus 3 years), while the mean duration between adjacent biopsies was 4.4 years (plus or minus 1.9 years).

Data regarding HCV treatment between liver biopsies were available for all but 45 patients. Forty-three percent of the remaining patients did not achieve a sustained virologic response after treatment.

Patients who’d had a cirrhosis diagnosis according to the first biopsy, those for whom treatment induced viral eradication, or those who’d had liver transplantation between biopsies were all excluded from the review.

The investigators wrote that their finding about the association between genotype 3 and cirrhosis should be “interpreted cautiously” because of the low number of these patients in their study.

Source - Hospitalist News Digital Net