Long-term benefit of DAAs on gut dysbiosis and microbial translocation in HCV-infected patients with and without HIV coinfectionOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study asked whether curing hepatitis C virus (HCV) with direct-acting antivirals (DAAs) produces lasting improvement in gut dysbiosis and microbial translocation. It followed patients long after treatment. Fecal samples at baseline and 72 weeks after treatment completion were analyzed by 16S rRNA sequencing. Butyryl-CoA:acetate CoA transferase (BCoAT), a butyrate-production gene, was measured by real-time PCR. Plasma lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) were measured by ELISA as markers of translocation and gut damage.
Who was studied?
The prospective longitudinal cohort was 69 HCV-infected adults treated with DAAs at King Chulalongkorn Memorial Hospital in Bangkok, Thailand. This included 50 patients with HCV monoinfection and 19 with HCV/HIV coinfection, plus 20 healthy controls. HCV/HIV patients were on antiretroviral therapy with undetectable HIV RNA. Patients were grouped by liver fibrosis stage, from no or early fibrosis (F0-F1) to significant fibrosis or cirrhosis (F2-F4). Sustained virological response reached 94 percent in monoinfection and 100 percent in coinfection.
What were the most important findings?
Among treatment responders, gut microbial richness improved and stayed improved at 72 weeks. Chao1 rose from a baseline of about 99 to about 128, while non-responders showed no improvement. Fourteen short-chain fatty acid producing genera increased, including Blautia, Fusicatenibacter, Subdoligranulum, and Bifidobacterium. BCoAT expression rose to levels comparable with healthy controls. Plasma LBP fell significantly in responders, from about 17,700 to about 13,900, matching healthy levels, and its change correlated inversely with BCoAT (r=-0.315, p=0.011). Gains were strongest in HCV-monoinfected patients with mild fibrosis. I-FABP did not decline significantly.
What are the greatest implications of this study?
The results indicate HCV cure can durably restore gut microbiota and butyrate production and reduce microbial translocation, supporting guidelines that recommend early DAA treatment regardless of fibrosis stage. Because improvement was limited in HCV/HIV coinfection and in advanced fibrosis, coinfected patients may retain residual dysbiosis and need additional gut-directed strategies. The unchanged I-FABP suggests translocation reduction is tied to microbiota composition more than to repaired gut barrier. The study reports associations, not proven causation, and had few coinfected patients.