Most Read Articles
Tristan Manalac, 11 Jul 2018
Gestational exposure to grain products fortified with folic acid appears to be linked to a lower risk of psychosis in offspring, according to a recent study.
Pearl Toh, 10 Jul 2018
A dual-hormone artificial pancreas (DAP) with a rapid delivery of insulin and pramlintide in a fixed ratio improves glycaemic control and reduces glucose variability in adults with type 1 diabetes (T1D) compared with first-generation artificial pancreas delivering insulin alone, according to a study presented at ADA 2018.
4 days ago
Chocolate consumption is not associated with risk of coronary heart disease (CHD), stroke or both combined in postmenopausal women free of pre-existing major chronic disease, a study suggests.
Pearl Toh, 4 days ago
More intensive lowering of LDL-C levels was associated with a progressively greater survival benefit than less intensive approach, when the baseline LDL-C levels were ≥100 mg/dL, reveals a meta-analysis of 34 randomized trials.

ASK1 inhibition shows potential in nonalcoholic steatohepatitis

14 Nov 2017

The apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib appears to have favourable effects on liver fibrosis in patients with nonalcoholic steatohepatitis (NASH) and stage II to III fibrosis, according to the results of a phase II exploratory trial.

A total of 72 patients were randomized to receive 24 weeks of open-label treatment with either 6 or 18 mg of selonsertib orally once daily alone or in combination with once-weekly injections of 125 mg of simtuzumab, or simtuzumab alone.

Assessments included paired pre- and post-treatment liver biopsies, magnetic resonance elastography (MRE), and magnetic resonance imaging-estimated proton density fat fraction, quantitative collagen content, and noninvasive markers of liver injury.

Simtuzumab showed no effect on histology or selonsertib pharmacokinetics. As a result, selonsertib groups with and without simtuzumab were pooled. Following 24 weeks of treatment, the number of patients with a ≥1-stage reduction in fibrosis was 13 of 30 (43 percent) in the 18-mg selonsertib group, eight of 27 (30 percent) in 6-mg selonsertib group and two of 10 (20 percent) in the simtuzumab-alone group.

Reductions in fibrosis were associated with improvements in the following: liver stiffness on MRE, collagen content and lobular inflammation on liver biopsy, and serum biomarkers of apoptosis and necrosis.

Adverse events (AEs) were comparable, with at least one AE occurring in majority of the patients in the two selonsertib groups and the simtuzumab group. Most AEs were mild to moderate in severity. Among the most commonly reported were headache, nausea, sinusitis, nasopharyngitis, upper abdominal pain, back pain and fatigue.

The present data suggest that AK1 inhibition with selonsertib has the potential to address an important unmet need for an effective antifibrotic therapy for patients with NASH and advanced fibrosis, researchers said.

“Since fibrosis is a key predictor of liver mortality in NAFLD, further studies are needed to assess the benefits of selonsertib in improving long-term outcomes associated with NASH-related fibrosis in a larger, randomized controlled trial,” they added.

Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Doctor - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
Tristan Manalac, 11 Jul 2018
Gestational exposure to grain products fortified with folic acid appears to be linked to a lower risk of psychosis in offspring, according to a recent study.
Pearl Toh, 10 Jul 2018
A dual-hormone artificial pancreas (DAP) with a rapid delivery of insulin and pramlintide in a fixed ratio improves glycaemic control and reduces glucose variability in adults with type 1 diabetes (T1D) compared with first-generation artificial pancreas delivering insulin alone, according to a study presented at ADA 2018.
4 days ago
Chocolate consumption is not associated with risk of coronary heart disease (CHD), stroke or both combined in postmenopausal women free of pre-existing major chronic disease, a study suggests.
Pearl Toh, 4 days ago
More intensive lowering of LDL-C levels was associated with a progressively greater survival benefit than less intensive approach, when the baseline LDL-C levels were ≥100 mg/dL, reveals a meta-analysis of 34 randomized trials.