Contrary to the concept of linear progression, fibrosis progression in patients with hepatitis C virus (HCV) varies according to stage with the highest progression rates occurring between stages 0 and 1 and the lowest between stages 2 and 3, according to a study published in the Journal of Infectious Diseases.1

Marija Zeremski, PhD, of the Division of Gastroenterology and Hepatology at Weill Cornell Medical College in New York, New York and colleagues collected data from electronic medical records of 378 patients with chronic HCV infection “who underwent at least 2 liver biopsies.” Biopsies were separated by at least 1 year and the patients were either HCV treatment naïve or treatment nonresponders. Patients were excluded from the study if their virus was eradicated following medication, or if they had cirrhosis or transplantation between biopsies.

The majority (86.7%) of the patients were infected with HCV genotype 1. The estimated progression rate from stage 0 to stage 1 was “3.08 times higher (95% confidence interval [CI], 1.57 – 6.07) than the progression rate from stage 1 to stage 2.”  The lowest progression rate occurred between stage 2 and 3. “The mean occupancy period of a single stage was the shortest for fibrosis stage 0 (2.55 years; 95% CI, 1.61 – 4.04 years) and the longest for fibrosis stage 2 (18.4 years; 95% CI, 11.5 – 29.4 years).” 


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This trend was consistent when a subgroup analysis was conducted on patients who had > 2 biopsies (Table 1).

Table 1. Subgroup Analysis Results of Patients With > 2 Biopsies

Between Stages Fibrosis Progression Rates 95% CI

0 – 1

0.34

.199 – .588

1 – 2

0.09

.049 – .155

2 – 3

0.07

.04 – .119

3 – 4

0.10

.033 – .279

Hepatic necroinflammation had an effect on fibrosis progression from stage 0 to stage 1.  Elevated alanine aminotransferase levels “between biopsies were found to influence the progression rate at higher stages.”  Patients with HCV genotype 3 were more likely to progress to cirrhosis (P <.001).

Possible limitations of this study included biopsy sampling error and variability of histologic interpretation.  The researchers also did not have “data on infection onset and the amount of alcohol consumption.”

Insufficient data (CD4+ T-cell counts, HIV loads, and HIV treatment information) did not allow the researchers to explore the relationship between fibrosis progression and HIV coinfection.  Furthermore, to accurately identify individuals most likely to have a progressive disease, “prospective studies with larger numbers of patients, particularly among underrepresented ethnic and racial minority subpopulations” would need to be conducted.

The high cost and invasive nature of biopsies make it difficult to evaluate fibrosis progression.  However, “certain parameters that play important roles in modifying fibrosis progression, such as the level of portal and lobular inflammation or steatosis, may not be readily obtainable” from noninvasive methods of fibrosis assessment, such as “transient elastography or multiparameters serum fibrosis indices.”

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Reference

  1. Zeremski M, Dimova RB, Pillardy J, de Jong YP, Jacobson IM, Talal AH. Fibrosis progression in patients with chronic hepatitis C virus infectionJ Infect Dis. 2016;214(8):1164-70. doi: 10.1093/infdis/jiw332.