Presentations in Hepatology: Venous Ammonia Concentrations Predict Breakthrough HE in Patients With HE Receiving Rifaximin

30 Jul

In another analysis of RFHE3001, Sanyal and colleagues investigated the relationship between venous ammonia concentrations, breakthrough HE, and rifaximin treatment. Blood ammonia has been proposed as a useful marker of the severity of overt HE, as elevated ammonia levels are associated with the pathogenesis of overt HE and the development of central nervous system effects. In the current study, the investigators measured venous ammonia concentrations at baseline and on Days 24, 84, and 168 of treatment with rifaximin or placebo. Rifaximin was associated with significant reductions in venous ammonia concentrations versus placebo (5.7 vs 0.3 mg/dL; P=.0391). Breakthrough HE, defined as an increase in Conn score to at least 2, or an increase in Conn score to 1 and asterixis grade increase by 1 unit in patients with a baseline Conn score of 0.2, occurred in 35% of patients. Venous ammonia concentrations were significantly higher in patients with breakthrough HE versus those remaining in remission (mean TWA, 102.4 vs 85.4 mmol/L; P=.0079). A significant positive correlation was found between mean venous ammonia TWA and breakthrough HE (Spearman correlation coefficient, 0.22; P=.0005). Moreover, venous ammonia concentrations appeared to be a good predictor of breakthrough HE, as determined by a receiver operating characteristics curve analysis (0.64; 95% confidence interval [CI], 0.57-0.72). Given the significant independent association between venous ammonia concentrations and breakthrough HE, the investigators suggested that the Conn score is a reliable clinical indicator of breakthrough HE.

TDF-associated Resistance Mutations in Patients With Persistent Viremia

Snow-Lampart and colleagues investigated the development of TDF-associated resistance mutations in patients from Studies 102 and 103 with detectable viremia after up to 144 weeks of TDF. Studies 102 and 103 allowed patients with detectable viremia at Week 52 to add emtricitabine (FTC) 200 mg to open-label TDF 300 mg. Overall, 51 of 641 patients (8%) met this criterion; 34 of these patients (67%) elected to add FTC, whereas 17 (33%) patients remained on single-agent TDF. The addition of FTC did not appear to increase the virologic response rate. At Week 144, HBV DNA levels less than 400 copies/mL were observed in 65% of patients receiving FTC and TDF and 71% of patients receiving TDF monotherapy. Population sequencing analyses were conducted on samples from all 17 patients with detectable viremia at Week 144. Conserved site changes were observed in 1 patient each at the following sites: rtR51K, rtG152E, rtA181T±rtL180M±rtM204V, rtR192H, and rtN236T±rtR274Q. Nonadherence was reported by 8 patients (47%). Clonal analysis performed in 5 patients with persistent viremia (all HBeAg-positive) revealed no evidence of viral breakthrough. One patient was found to be nonadherent. In the 4 treatment-adherent patients, the median baseline HBV DNA level was 9.84 log10 copies/mL and the median HBV DNA reduction from baseline was 6.1 log10 copies/mL. Clonal analysis revealed 17 distinct conserved site changes. The only change observed in more than 1 patient was rtF183L, which was observed in 2 patients. The presence of rtF183L did not affect phenotypic susceptibility to TDF in vitro. The investigators concluded that in patients remaining adherent to TDF, persistent viremia was rare, occurring in only 0.6% of patients, and was associated with no demonstrable virologic resistance to TDF.
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