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Abstract Background Patients with hepatitis C virus (HCV) frequently remain at risk for cirrhosis after sustained virologic response (SVR). Existing cirrhosis predictive models for HCV do not account for dynamic antiviral treatment status and are limited by fixed laboratory covariates and short follow up time. Advanced fibrosis assessment modalities, such as transient elastography, remain inaccessible in many settings. Improved cirrhosis predictive models are needed. Methods We developed a laboratory-based model to predict progression of liver disease after SVR. This prediction model used a time-varying covariates Cox model adapted to utilize longitudinal laboratory data and to account for antiretroviral treatment. Individuals were included if they had a history of detectable HCV RNA and at least 2 AST-to-platelet ratio index (APRI) scores available in the national Veterans Health Administration from 2000 to 2015, Observation time extended through January 2019. We excluded individuals with preexisting cirrhosis. Covariates included baseline patient characteristics and 16 time-varying laboratory predictors. SVR, defined as permanently undetectable HCV RNA after antiviral treatment, was modeled as a step function of time. Cirrhosis development was defined as two consecutive APRI scores > 2. We predicted cirrhosis development at 1-, 3-, and 5-years follow-up. Results In a national sample of HCV patients (n = 182,772) with a mean follow-up of 6.32 years, 42% (n = 76,854) achieved SVR before 2016 and 16.2% (n = 29,566) subsequently developed cirrhosis. The model demonstrated good discrimination for predicting cirrhosis across all combinations of laboratory data windows and cirrhosis prediction intervals. AUROCs ranged from 0.781 to 0.815, with moderate sensitivity 0.703–0.749 and specificity 0.723–0.767. Conclusion A novel adaptation of time-varying covariates Cox modeling technique using longitudinal laboratory values and dynamic antiviral treatment status accurately predicts cirrhosis development at 1-, 3-, and 5-years among patients with HCV, with and without SVR. It improves upon earlier cirrhosis predictive models and has many potential population-based applications, especially in settings without transient elastography available.

Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and its complications, including hepatocellular carcinoma. Given that the majority of patients with NASH are asymptomatic, developing screening strategies to identify those individuals at risk for progressive NASH remains a highly unmet need. Furthermore, noninvasive tests that accurately predict disease progression as part of the natural history of NASH or regression in response to treatment are urgently needed to decrease the reliance on repeat liver biopsies. To date, there are no US Food and Drug Administration (FDA)‐approved medications for NASH that can resolve steatohepatitis and lead to fibrosis regression. The lack of FDA‐approved therapy has led to apathy in diagnosis and referral for specialty care. However, several therapeutic agents are rapidly progressing through the different phases of clinical trials with several already in phase 3 programs. In this review, we provide a summary of recent developments in NASH diagnostics and therapeutics that are likely to shape the future management of this underdiagnosed and undertreated disease.

Child pedestrian road traffic injuries (RTIs) are an important cause of death and disability in poorer nations, however RTI prevention strategies in those countries largely draw upon studies conducted in wealthier countries. This research investigated personal and environmental risk factors for child pedestrian RTIs relevant to an urban, developing world setting.This is a case control study of personal and environmental risk factors for child pedestrian RTIs in San Juan de Miraflores, Lima, Perú. The analysis of personal risk factors included 100 cases of serious pedestrian RTIs and 200 age and gender matched controls. Demographic, socioeconomic, and injury data were collected. The environmental risk factor study evaluated vehicle and pedestrian movement and infrastructure at the sites in which 40 of the above case RTIs occurred and 80 control sites.After adjustment, factors associated with increased risk of child pedestrian RTIs included high vehicle volume (OR 7.88, 95%CI 1.97-31.52), absent lane demarcations (OR 6.59, 95% CI 1.65-26.26), high vehicle speed (OR 5.35, 95%CI 1.55-18.54), high street vendor density (OR 1.25, 95%CI 1.01-1.55), and more children living in the home (OR 1.25, 95%CI 1.00-1.56). Protective factors included more hours/day spent in school (OR 0.52, 95%CI 0.33-0.82) and years of family residence in the same home (OR 0.97, 95%CI 0.95-0.99).Reducing traffic volumes and speeds, limiting the number of street vendors on a given stretch of road, and improving lane demarcation should be evaluated as components of child pedestrian RTI interventions in poorer countries.