Lo Re Research Group

Dr. Lo Re has conducted validation studies to ascertain end-stage liver disease (i.e., hepatic decompensation, hepatocellular carcinoma) events within electronic health data. Since this represents the most important outcome of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, the development and validation of algorithms to identify these endpoints within large electronic health databases has led to the conduct of important epidemiologic studies by Dr. Lo Re examining incidence rates of end-stage liver disease by HIV status, determining the impact of HIV viral suppression on hepatic decompensation, evaluating determinants of end-stage liver disease in HIV/HCV-coinfected patients, and examining outcomes of liver complications. Dr. Lo Re has also led scientific workgroups within the FDA’s Mini-Sentinel Initiative, Veterans Health Administration, and Kaiser Permanente Northern California to identify and validate severe acute liver injury and acute liver failure events. This work led to the first population-based study evaluating the incidence of drug-induced acute liver failure, the development of prognostic models estimating the risk of acute liver failure in patients with drug-induced liver injury, and comparative safety studies evaluating the risk of severe liver injury in users of antiretrovirals and antifungals.

Selected publications:

• Validation of three coding algorithms to identify patients with end-stage liver disease in an administrative database  |  Pharmacoepidemiology & Drug Safety
• Validity of diagnostic codes to identify cases of severe acute liver injury in the US Food and Drug Administration's Mini-Sentinel Distributed Database  |  Pharmacoepidemiology & Drug Safety
• Validity of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events in the Veterans Aging Cohort Study  |  Pharmacoepidemiology & Drug Safety
• Validity of diagnostic codes and laboratory tests of liver dysfunction to identify acute liver failure events  |  Pharmacoepidemiology & Drug Safety
• Validation of a coding algorithm to identify patients with hepatocellular carcinoma in an administrative database  |  Pharmacoepidemiology & Drug Safety
• Validity of The Health Improvement Network (THIN) for epidemiologic studies of hepatitis C virus infection  |  Pharmacoepidemiology & Drug Safety

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Dr. Lo Re received R01 funding from the Agency for Healthcare Research and Quality to evaluate the impact of drug-induced liver disease in HIV-infected and uninfected patients. He has published a seminal paper in Gastroenterology that reported the incidence, etiologies, characteristics, and outcomes of drug-induced acute liver failure. Subsequent studies have led to the development of prognostic models to identify drug-induced liver injury patients at high-risk of acute liver failure, a classification of the most hepatotoxic medications based on real-world incidence rates of severe acute liver injury, and an evaluation of the risk of acute liver injury associated with antiretroviral and antifungal medications. 

Selected publications:

• Population-representative incidence of drug-induced acute liver failure based on an analysis of an integrated health care system  |  Gastroenterology
• Risk of acute liver failure in patients with drug-induced liver injury: Evaluation of Hy's Law and a new prognostic model  |  Clinical Gastroenterology and Hepatology
• Severe acute liver injury after hepatotoxic medication initiation in real-world data | JAMA Internal Medicine
• Oral azole antifungal medications and risk of acute liver injury, overall and by chronic liver disease status  |  The American Journal of Medicine

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Dr. Lo Re has applied the novel methodology described above to identify end-stage liver disease events to produce a seminal study published in Annals of Internal Medicine that demonstrated that despite effective antiretroviral therapy, HIV/HCV-coinfected patients had significantly higher rates of hepatic decompensation compared to those with chronic HCV alone. Notably, HIV/HCV patients who maintained suppressed HIV RNA throughout their follow-up still had higher rates of decompensation than those with chronic HCV alone, suggesting that HIV viral suppression with antiretroviral therapy is not sufficient to reduce rates of end-stage liver disease to those of HCV-monoinfected patients. Subsequent studies evaluated risk factors for the high rate of liver complications in HIV/HCV patients, including non-hazardous alcohol use, uncontrolled HBV, race, obesity, and diabetes mellitus. Recently, Dr. Lo Re has evaluated the impact that medications have on liver disease progression in HIV/HCV, using marginal structural models to determine the risk of hepatic decompensation associated with current and cumulative use of antiretroviral and non-antiretroviral medications. He has also developed prognostic models to estimate the risk of end-stage liver disease in HIV/HCV patients. He has a pending R01 grant from NCI that will extend the above work and evaluate novel mechanisms for hepatocellular carcinoma development in HIV.

Selected publications:

• Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study  |  Annals of Internal Medicine
• Predicting risk of end-stage liver disease in antiretroviral-treated human immunodeficiency virus/hepatitis C virus-coinfected patients  |  Open Forum Infectious Diseases
• Protease inhibitor-based direct-acting antivirals are associated with increased risk of aminotransferase elevations but not hepatic dysfunction or decompensation | Journal of Hepatology
• Accuracy of FIB-4 for cirrhosis in people living with HIV and hepatocellular carcinoma | Journal of Acquired Immune Deficiency Syndromes

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Dr. Lo Re’s background in pharmacoepidemiology has allowed him to make important contributions on adverse effects of anti-HCV therapies, adherence to HCV treatment, and access to the new direct-acting antiviral therapies. Early studies highlighted the risk of significant weight loss and anemia due to pegylated interferon and ribavirin therapy among HIV/HCV patients. Dr. Lo Re then developed methods to measure adherence to anti-HCV agents using pharmacy refill measures and used this methodology to produce an important paper, published in Annals of Internal Medicine, which evaluated the relationship between antiviral adherence and virologic response, changes in adherence over time, and determinants of non-adherence.

In addition, Dr. Lo Re’s team was the first to evaluate the HCV continuum of care via a meta-analysis of existing data, showing the drop-offs in each step of the HCV care cascade over time. Policy makers and the Institute of Medicine have cited this article as helping to determine where to allocate health care resources for the goal of elimination of chronic HCV in the US. Finally, research by Dr. Lo Re has recently found that a significant disparity in access to direct-acting antiviral-based HCV treatments exists, with nearly half of US Medicaid beneficiaries from four states denied access to these therapies. These findings were recently presented as a late-breaking oral abstract at The Liver Meeting 2015 and were reported in the national news and highlighted in a health segment by National Public Radio.

Selected publications:

• Incidence and risk factors for weight loss during dual HIV/hepatitis C virus therapy  |  Journal of Acquired Immune Deficiency Syndromes
• Relationship between adherence to hepatitis C virus therapy and virologic outcomes: a cohort study  |  Annals of Internal Medicine
• The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis  |  PLoS One
• The hepatitis C care cascade during the direct-acting antiviral era in a United States commercially insured population | Open Forum Infectious Diseases
• Disparities in absolute denial of modern hepatitis C therapy by type of insurance  |  Clinical Gastroenterology & Hepatology

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Dr. Lo Re has also focused on evaluating the epidemiology of HIV/HBV coinfection. He conducted a cohort study that determined that over half of HIV/HBV patients in the Delaware Valley region treated with anti-HBV active antiretroviral therapy failed to achieve HBV DNA suppression. He has a R21 grant from NIAID to examine the risk of liver complications (i.e., hepatic decompensation and hepatocellular carcinoma) associated with detectable HBV and HIV viremia among HIV/HBV-coinfected patients.

Selected publications:

• Risk of hepatocellular carcinoma with hepatitis B viremia among HIV/HBV-coinfected persons in North America | Hepatology
• Incidence and risk factors for incomplete HBV DNA suppression in HIV/HBV-co-infected patients initiating tenofovir-based therapy  |  Journal of Viral Hepatitis
• Increased risk of hip fracture associated with dually treated HIV/hepatitis B virus coinfection  |  Journal of Viral Hepatitis
• Prevalence, risk factors, and outcomes for occult hepatitis B virus infection among HIV-infected patients  |  Journal of Acquired Immune Deficiency Syndromes
• Incidence of transaminitis among HIV-infected patients with occult hepatitis B  |  Journal of Clinical Virology

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Recently, Dr. Lo Re has expanded his research interests to the evaluation of the epidemiology of COVID-19. 

Selected publications:

• Association of COVID-19 vs influenza with risk of arterial and venous thrombotic events among hospitalized patients | JAMA
• Risk of admission to hospital with arterial or venous thromboembolism among patients diagnosed in the ambulatory setting with covid-19 compared with influenza: retrospective cohort study | BMJ Medicine
• Risk of arterial and venous thrombotic events among patients with COVID-19: A multi-national collaboration of regulatory agencies from Canada, Europe, and United States | Clinical Epidemiology
• Global covid-19 vaccine rollout and safety surveillance-how to keep pace | BMJ
• A COVID-19-ready public health surveillance system: The Food and Drug Administration's Sentinel System | Pharmacoepidemiology & Drug Safety
• Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study | PLoS Medicine

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