High baseline levels of circulating bacterial DNA increased the odds of serious infections by nearly fivefold in patients receiving prednisolone for severe alcoholic hepatitis, even after controlling for MELD score and white blood cell count, investigators reported in the April issue of Gastroenterology (2016 Dec 31. doi: 10.1053/j.gastro.2016.08.029).
“Patients with severe alcoholic hepatitis given prednisolone are at greater risk for developing serious infections and infections after treatment than patients not given prednisolone, which may offset its therapeutic benefit,” Nikhil Vergis, MD, and his associates wrote in Gastroenterology. “Level of circulating bacterial DNA before treatment could identify patients at high risk of infection if given prednisolone, which could be used to select therapies for patients with severe alcoholic hepatitis.”
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To further explore rates and predictors of infections in STOPAH, the researchers analyzed longitudinal data on incident infections for 1,092 trial participants who received either prednisolone (40 mg daily) or pentoxifylline (400 mg three times daily). For 731 patients, they also examined whether baseline circulating levels of 16s ribosomal bacterial DNA were associated with infections.
A total of 135 patients (12%) had an infection at baseline, 251 (23%) developed infections during treatment, and 89 (8%) developed infections after treatment, the investigators reported. Prednisolone therapy was not associated with infections during treatment, but was associated with a nearly 30% rise in the odds of serious posttreatment infections compared with pentoxifylline (odds ratio, 1.27; 95% confidence interval, 1.27-2.92; P = .002). Prednisolone recipients who developed infections were significantly more likely to die within 90 days than those who did not, even after controlling for end-stage liver disease or Lille score (OR, 2.5; 95% CI, 1.4-4.3; P = .002). Antibiotic therapy appeared to significantly reduce the risk of mortality among infected prednisolone recipients (13% vs. 52%; OR, 0.13; 95% CI 0.04-0.47; P = .002).
There was “a striking association between bacterial DNA and the development of infection within 7 days in patients treated with prednisolone,” the researchers reported. These patients had a median baseline circulating DNA level of 20.9 pg/mL, while prednisolone recipients who did not develop infections had a median baseline bacterial DNA level of 8.3 pg/mL (P = .004). Bacterial DNA predicted infections with an area under receiver operating characteristic curve of 0.70 (95% CI, 0.58-0.83; P = .003), which substantially exceeded the curve for white blood cell count (0.58).
A cut-off value of 18.5 pg/mL was 80% specific for predicting infection within 7 days of prednisolone therapy, the investigators also reported. Bacterial DNA level did not, however, predict infections within 7 days of pentoxifylline therapy, and pentoxifylline was not linked with infections that were serious, infections during treatment, or infections after treatment. (P =.08).
Using bacterial DNA levels to guide prednisolone prescription also appeared to reduce 90-day mortality in this patient population, although the effect achieved borderline statistical significance, the researchers said. “Larger prospective randomized studies are needed to definitely report whether bacterial DNA-guided therapy can [have an] impact on mortality in severe alcoholic hepatitis, and perhaps in other acute inflammatory conditions” in which immunosuppression is required, they added.
The National Institute for Health Research and Wellcome Trust and Medical Research Council provided funding. Dr. Vergis and 10 coinvestigators disclosed no conflicts of interest. Senior author Dr. Mark Thursz and one coinvestigator disclosed ties to Gilead, Bristol-Myers Squibb, AbbVie, Abbott, and Norgine.
Source: American Gastroenterological Association