Browsing by Author "Serfaty, Lawrence"

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    Current and Future Therapeutic Regimens for Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH)
    (Wiley, 2018) Younossi, Zobair M.; Loomba, Rohit; Rinella, Mary E.; Bugianesi, Elisabetta; Marchesini, Giulio; Neuschwander-Tetri, Brent A.; Serfaty, Lawrence; Negro, Francesco; Caldwell, Stephen H.; Ratziu, Vlad; Corey, Kathleen E.; Friedman, Scott L.; Abdelmalek, Manal F.; Harrison, Stephen A.; Sanyal, Arun J.; Lavine, Joel E.; Mathurin, Philippe; Charlton, Michael R.; Chalasani, Naga P.; Anstee, Quentin M.; Kowdley, Kris V.; George, Jacob; Goodman, Zachary D.; Lindor, Keith; Medicine, School of Medicine
    NASH/NAFLD is rapidly becoming one of top causes of cirrhosis, hepatocellular carcinoma and indication for liver transplantation. Except for life style modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is hard to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD and has been shown to improve liver histology. In order to have approved regimens for treatment of NASH/NAFLD, a number of issues that must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced stage of fibrosis, it is not an independent predictor of long term mortality. In contrast, there is significant data to suggest that stage of fibrosis is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, a number of important secondary endpoints, including non-invasive biomarkers, long term outcomes, and patient reported outcomes, must be considered. In 2017, a few phase 3 clinical trials for treatment of NASH are in progress. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH enriches the pipeline of emerging therapies. Conclusion: Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD.
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    Diagnostic Modalities for Non-alcoholic Fatty Liver Disease (NAFLD), Non-alcoholic Steatohepatitis (NASH) and Associated Fibrosis
    (Wiley, 2018) Younossi, Zobair M.; Loomba, Rohit; Anstee, Quentin M.; Rinella, Mary E.; Bugianesi, Elisabetta; Marchesini, Giulio; Neuschwander-Tetri, Brent A.; Serfaty, Lawrence; Negro, Francesco; Caldwell, Stephen H.; Ratziu, Vlad; Corey, Kathleen E.; Friedman, Scott L.; Abdelmalek, Manal F.; Harrison, Stephen A.; Sanyal, Arun J.; Lavine, Joel E.; Mathurin, Philippe; Charlton, Michael R.; Goodman, Zachary D.; Chalasani, Naga P.; Kowdley, Kris V.; George, Jacob; Lindor, Keith; Medicine, School of Medicine
    NAFLD is a spectrum comprised of isolated steatosis, NASH, advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and don't carry a significant risk for adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high prevalence rates to low rates are noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition as an important liver disease, the diagnosis of NASH still requires a liver biopsy which is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, it suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathologic features. A number of non-invasive modalities to diagnose NASH and stage liver fibrosis are being developed. These include predictive models (NAFLD fibrosis score) and serum biomarkers such as Enhanced Liver Fibrosis, (ELF). Other tests are based on radiologic techniques such as transient or MR elastography (MRE) which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have AUROC between 0.76 to 0.90% with MRE having the best predictive performance. In summary, developing accurate, safe and easily accessible non-invasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease but to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH.