Summary Background Non‐alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. It is not well understood, however, which individuals with NAFLD are at highest risk for cardiovascular disease. Aims To determine the factors associated with incident cardiovascular events in a prospective cohort of individuals with biopsy‐proven NAFLD without pre‐existing cardiovascular disease. Methods From 2011 to 2018, adults with biopsy‐proven NAFLD without cardiovascular disease were enrolled in a tissue repository and were followed prospectively to the first recorded date of incident cardiovascular disease, death or the end of follow‐up (11/1/2018). Competing risks analysis was performed to identify predictors of incident cardiovascular disease. Results After a median follow‐up time of 5.2 years, 26/285 (9.1%) individuals experienced an incident cardiovascular event. Advanced fibrosis (stage 3‐4) on biopsy was a significant predictor of incident cardiovascular disease, and this persisted on multivariable analysis (SHR 2.86, 95% CI 1.36–6.04) after considering relevant covariates, including cardiovascular risk scores, which were not independent predictors. Of the non‐invasive indicators of fibrosis, the NAFLD fibrosis score was the only independent predictor of cardiovascular disease. Other histologic features, including steatohepatitis, were not associated with incident cardiovascular disease. Conclusions In adults with biopsy‐proven NAFLD, advanced fibrosis on biopsy and higher NAFLD fibrosis score were significant and independent predictors of incident cardiovascular disease, even after considering traditional risk factors and cardiovascular risk scores. These findings should be considered when evaluating NAFLD patients for primary prevention of cardiovascular disease, and further evaluation into the link between advanced fibrosis and cardiovascular disease is needed.

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Hepatitis C virus (HCV) infection is not only an important cause of chronic liver disease, but extrahepatic manifestations are common and include chronic kidney disease (CKD). HCV is classically associated with cryoglobulinemic glomerulonephritis in the context of mixed cryoglobulinemia syndrome, but other glomerular diseases also occur and may be significantly under-recognized. HCV may cause glomerular disease by immune complex deposition; however, other potential mechanisms by which HCV promotes CKD include a direct cytopathic effect of the virus on renal tissue, and by its association with accelerated atherosclerosis, insulin resistance, and chronic inflammation. Epidemiologic studies show HCV infection confers an increased risk of incident CKD and accelerates progression of CKD to end-stage renal disease (ESRD) in the general population, as well as subpopulations including diabetic patients, those coinfected with human immunodeficiency virus (HIV), and kidney transplant recipients. Patients with CKD and HCV infection experience inferior clinical outcomes, including poorer quality of life and an increased risk of mortality. Treatment with interferon-based regimens is associated with decreased risk of incident CKD and ESRD, though prior studies are limited by the small number of patients with HCV and CKD who underwent treatment. With the advent of new, well-tolerated direct-acting antiviral combinations that are not cleared by the kidneys, it is possible to treat all genotypes of HCV infection in patients with CKD and ESRD. More data on the effectof direct-acting antivirals on CKD incidence and progression are necessary. However, there is every expectation that with improved access to HCV treatment, the burden of CKD in patients with HCV could significantly decline.

CAM use, particularly herbs and supplements, is prevalent among US adults with liver disease. Many do not disclose their CAM use to their providers, despite some using potentially hepatotoxic substances.