Background & aims

We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in patients with hepatitis C virus infection who achieved a sustained virologic response (SVR).

Methods

We searched the literature through October 2016 for observational studies or randomized controlled trials of adults with hepatitis C virus infection who received antiviral therapy (either direct-acting antiviral agents or interferon-based therapies), underwent liver stiffness measurement using VCTE before starting therapy, and had at least 1 follow-up VCTE after completion of therapy; studies also provided data on mean or median liver stiffness measurements for patients who did and did not achieve an SVR. We identified 24 studies, and estimated weighted mean difference (and 95% confidence interval) in liver stiffness in patients with versus without SVR using random-effects meta-analysis.

Results

In patients who achieved SVR, liver stiffness decreased by 2.4 kPa at the end of therapy (95% CI, -1.7 to -3.0), by 3.1 kPa 1-6 months after therapy (95% CI, -1.6 to -4.7), by 3.2 kPa 6-12 months after therapy (90% CI, -2.6 to -3.9), and 4.1 kPa 12 months or more after therapy (95% CI, -3.3 to -4.9) (median decrease, 28.2%; interquartile range, 21.8-34.8). In contrast, there was no significant change in liver stiffness in patients who did not achieve an SVR (at 6-12 months after therapy, decrease of 0.6 kPa; 95% CI, -1.7 to 0.5). Decreases in liver stiffness were significantly greater in patients treated with direct-acting antiviral agents than with interferon-based therapy (decrease of 4.5 kPa vs decrease of 2.6 kPa; P = .03), cirrhosis at baseline (decrease of 5.1 kPa vs decrease of 2.8 kPa in patients with no cirrhosis; P = .02), or high pretreatment levels of alanine aminotransferase (P < .01). Among patients with baseline liver stiffness >9.5 kPa, 47% (95% CI, 27%-68%) achieved posttreatment liver stiffness of <9.5 kPa.

Conclusions

In a systematic review and meta-analysis, we associated eradication of hepatitis C virus infection (SVR) with significant decreases in liver stiffness, particularly in patients with high baseline level of inflammation or patients who received direct-acting antiviral agents. Almost half the patients considered to have advanced fibrosis, based on VCTE, before therapy achieved posttreatment liver stiffness levels <9.5 kPa. Clinical Trial Registration no: CRD42016051034.

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

There is high demand in environmental health for adoption of a structured process that evaluates and integrates evidence while making decisions and recommendations transparent. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework holds promise to address this demand. For over a decade, GRADE has been applied successfully to areas of clinical medicine, public health, and health policy, but experience with GRADE in environmental and occupational health is just beginning. Environmental and occupational health questions focus on understanding whether an exposure is a potential health hazard or risk, assessing the exposure to understand the extent and magnitude of risk, and exploring interventions to mitigate exposure or risk. Although GRADE offers many advantages, including its flexibility and methodological rigor, there are features of the different sources of evidence used in environmental and occupational health that will require further consideration to assess the need for method refinement. An issue that requires particular attention is the evaluation and integration of evidence from human, animal, in vitro, and in silico (computer modeling) studies when determining whether an environmental factor represents a potential health hazard or risk. Assessment of the hazard of exposures can produce analyses for use in the GRADE evidence-to-decision (EtD) framework to inform risk-management decisions about removing harmful exposures or mitigating risks. The EtD framework allows for grading the strength of the recommendations based on judgments of the certainty in the evidence (also known as quality of the evidence), as well as other factors that inform recommendations such as social values and preferences, resource implications, and benefits. GRADE represents an untapped opportunity for environmental and occupational health to make evidence-based recommendations in a systematic and transparent manner. The objectives of this article are to provide an overview of GRADE, discuss GRADE's applicability to environmental health, and identify priority areas for method assessment and development.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4-12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti-interleukin-5 therapy, anti-interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4-12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti-interleukin-5 therapy, anti-interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy.