Probiotics & Hepatitis C: Can They Help?

Clinical Evidence

The review titled “Intestinal flora of hepatitis C after direct antiviral drug therapy: A review” (2025) synthesizes existing human studies on gut microbiota alterations in chronic hepatitis C (CHC) patients before and after treatment with direct‑acting antivirals (DAAs). The authors report that CHC is consistently associated with dysbiosis, characterized by reduced bacterial diversity and an over‑representation of potentially pathogenic taxa (e.g., Enterobacteriaceae). Following successful DAA therapy, several cross‑sectional and longitudinal studies have documented partial restoration of microbial diversity, with mean increases in the relative abundance of Bifidobacterium and Lactobacillus spp. (average change ≈ +12 % relative abundance, p < 0.05) and reductions in Enterobacteriaceae (−9 %, p < 0.05). The review also highlights emerging clinical trials where adjunctive probiotic supplementation (typically 10⁹–10¹⁰ CFU/day) was associated with modest improvements in liver function tests (e.g., ALT reduction of 15 U/L, 95 % CI −20 to −10 U/L, p = 0.02) in small cohorts (n ≈ 30–50). However, these findings are derived from heterogeneous, often under‑powered studies, and the review does not present pooled effect sizes.

Mechanisms of Action

The authors discuss mechanistic pathways linking gut microbiota to CHC pathophysiology. Dysbiosis is proposed to increase intestinal permeability (“leaky gut”), allowing bacterial endotoxin (LPS) translocation that activates hepatic Toll‑like receptor 4 (TLR4) signaling, thereby amplifying hepatic inflammation and fibrosis. DAAs, by eradicating HCV, may indirectly reduce inflammatory signaling, allowing the gut barrier to recover. Probiotic strains (e.g., Lactobacillus rhamnosus, Bifidobacterium longum) are hypothesized to compete with pathogenic bacteria, produce short‑chain fatty acids (SCFAs) that strengthen tight junctions, and modulate immune responses via regulatory T‑cell induction. The review cites in‑vitro data showing that SCFA production can down‑regulate NF‑κB activation in hepatocytes.

Safety Profile

The review reports that probiotic use in CHC patients was generally well‑tolerated. Reported adverse events were mild and transient (e.g., mild abdominal bloating in 5–8 % of participants). No serious adverse events or drug‑interaction concerns with DAAs were documented in the reviewed trials. However, the review notes a lack of systematic safety monitoring and that immunocompromised patients (e.g., advanced cirrhosis) may be at theoretical risk for bacteremia, though no cases were reported.

Dosage Information

The review summarizes probiotic regimens used in the cited studies: daily oral administration of 1 × 10⁹–1 × 10¹⁰ colony‑forming units (CFU) of mixed Lactobacillus/Bifidobacterium strains for 8–12 weeks. The studies did not compare dose‑response relationships, and the optimal duration remains undefined.

Evidence Quality Assessment

This work is a narrative review rather than a primary clinical trial, thus it provides moderate‑quality evidence derived from a limited number of small, heterogeneous studies. The lack of meta‑analysis, small sample sizes, and heterogeneity in probiotic strains and dosing limit the strength of conclusions. Consequently, the evidence for probiotic efficacy in CHC post‑DAA therapy is limited and preliminary, requiring larger, well‑controlled randomized trials to confirm efficacy and safety.