Stellar-3 is a randomised, double-blind and placebo-controlled trial that evaluated the safety and efficacy of selonsertib in patients with bridging fibrosis
(F3) due to NASH.
Gilead Sciences announced that STELLAR-3, a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib, an investigational, once daily, oral inhibitor of apoptosis signal-regulating kinase 1, or ASK1, for patients with bridging fibrosis
, or F3, due to nonalcoholic steatohepatitis, or NASH, did not meet the pre-specified week 48 primary endpoint of a greater than or equal to 1-stage histologic improvement in fibrosis without worsening of NASH.
(6, 7) On the other hand, if UIP pattern is recognized, it should be specified if ancillary findings suggesting chronic hypersensitivity pneumonitis or collagen vascular disease or asbestosis (eg, chronic lymphoplasmacytic inflammation with or without lymphoid follicles, interstitial granulomas/giant cells, bronchiolitis, pleuritis, bridging fibrosis
, asbestos fibers, eosinophilic infiltrate) are present or absent/minimal.
The following are the fibrosis stages (F0-F4): F0, non-fibrosis; F1, portal tract expansion by fibrosis (Figure 1); F2, <50% bridging fibrosis
; F3, >50% bridging fibrosis
(Figure 2); and F4, established cirrhosis.
Practitioners must remain engaged, however, with patients cured of their HCV who have bridging fibrosis
or cirrhosis, as the HCC risk after pharmacologic cure persists, and it is critical that such patients continue with HCC screening.
The fibrosis stage score was categorized into five stages (0-4): 0: none, 1: zone 3 perisinusoidal fibrosis; 2: zone 3 perisinusoidal fibrosis plus portal fibrosis; 3: perisinusoidal fibrosis and portal fibrosis, plus bridging fibrosis
; and 4: cirrhosis.
Liver biopsy showed steatohepatitis with bridging fibrosis
Degree of steatosis and NASH (grade 0 [less than or equal to] 5%; 1 = 5-33%; grade 2 = 34%-66%; grade 3 [greater than or equal to] 66%), lobular inflammation (0: no foci, 1 < 2 foci per 200x field, 2: 2 to 4 foci per 200x field, and 3: foci per 200x field), hepatocyte ballooning (0: none; 1: rare or few; 2: many), and fibrosis (0: no fibrosis, 1: perisinusoidal or periportal fibrosis, 2: perisinusoidal and portal/perioral fibrosis, 3: bridging fibrosis
, and 4: cirrhosis).
A single expert hepatopathologist reviewed all liver biopsies and utilized the scoring system established by Brunt and colleagues  for grading and staging of steatohepatitis (staging of fibrosis is as follows: Stage 0, no fibrosis, Stage 1, zone 3 perisinusoidal fibrosis, Stage 2, as above with portal fibrosis, Stage 3, as above with bridging fibrosis
, and Stage 4, cirrhosis).
"No fibrosis; Fibrosis portal expansion; Bridging fibrosis
; Bridging fibrosis
with lobular degeneration and Cirrhosis".
Brunts criteria (13) include the following parameters: the amount of fat (graded 1 to 3 according to the percentage of fatty droplets [1, 096-3396; 2, 34-66%; 3, 67-100%]); fibrosis (graded 0 [absent] to 4 [l, perisinusoidal/pericellular fibrosis; 2, periportal fibrosis; 3, bridging fibrosis
; 4, cirrhosis]); and necroinflammation (graded 0 [absent] to 3 [l, occasional ballooned hepatocytes and no or very mild inflammation; 2, ballooning of hepatocytes and mild to moderate portal inflammation; 3, intra-acinar inflammation and portal inflammation]).