Systematic review: microbial manipulation as therapy for primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested. AIM: To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis. METHODS: We conducted a comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC. RESULTS: A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking. CONCLUSIONS: The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease.

High rates of treatment stage migration for early hepatocellular carcinoma and association with adverse outcomes: An Australian multicenter study.

Background and Aim: The rate of contraindications to percutaneous ablation (PA) for inoperable early hepatocellular carcinoma (HCC) and subsequent outcomes is not well described. We investigated the prevalence and outcomes of inoperable early HCC patients with contraindications to PA, resulting in treatment stage migration (TSM). Methods: Barcelona Clinic Liver Cancer (BCLC) 0/A patients diagnosed between September 2013 and September 2019 across five hospitals were identified. Primary endpoint was proportion of BCLC 0/A HCCs with contraindications to PA. Secondary endpoints included overall survival (OS), local tumor control (LTC), and recurrence-free survival (RFS). The causal effects of PA versus TSM were assessed using a potential outcome means (POM) framework in which the average treatment effects (ATEs) of PA were estimated after accounting for potential selection bias and confounding. Results: Two hundred twenty patients with inoperable BCLC 0/A HCC were identified. One hundred twenty-two patients (55.5%) had contraindications to PA and received TSM therapy, 98 patients (44.5%) received PA. The main contraindication to PA was difficult tumor location (51%). Patients who received TSM therapy had lower median OS (2.4 vs 5.3 years), LTC (1.0 vs 4.8 years), and RFS (0.8 vs 2.9 years); P < 0.001, respectively, compared with PA. The ATE for PA versus TSM yielded an additional 1.11 years (P = 0.019), 2.45 years (P < 0.001), and 1.64 years (P < 0.001) for OS, LTC, and RFS, respectively. Three-year LTC after PA was suboptimal (65%). Conclusion: Our study highlights high rates of contraindication to PA in early HCCs, resulting in TSM and poorer outcomes. The LTC rate for PA appears suboptimal despite being considered as curative therapy. Both findings support the exploration of improved treatment options for early HCCs.