Office of Research & Development

VA research on

Hepatitis C


Introduction

Hepatitis C, caused by the hepatitis C virus (HCV), is a condition marked by inflammation of the liver. Inflammation is swelling that occurs when tissues of the body become injured and infected. It can cause organs to not work properly.

HCV is spread through contact with infected blood or contaminated IV needles, razors, tattoo tools, or other items.

The symptoms of hepatitis C infection are often very mild. Most people can carry the virus for years and will not notice any symptoms. The most common symptoms are vague abdominal discomfort, fatigue, and joint pains. Over time, HCV can cause other health problems, such as cirrhosis and liver cancer. Because the virus stays in the body, an infected person can give hepatitis C to someone else.

People at risk for hepatitis C should consider getting tested. (A list of reasons to consider testing can be found here.) Blood tests are required to determine if HCV is present in the body.

VA is the single largest HCV care provider in the United States. Veterans who served in the Vietnam War era, those with alcohol or substance use disorders, and those with psychiatric conditions or who are homeless are particularly likely to be affected. VA is proactive in identifying Veterans with HCV through its screening processes, and is committed to providing them with the highest-quality care and treatment.

VA has treated more than 76,000 Veterans infected with hepatitis C and approximately 60,000 have been cured. Since the beginning of 2014, more than 42,000 patients have been treated with new, highly effective antiviral medications. In fiscal year 2015, VA allocated $696 million for new hepatitis C drugs, which is 17 percent of VA's total pharmacy budget. In fiscal year 2016, VA anticipates spending approximately $1 billion on hepatitis C drugs.

In March 2016, the department announced that it is now able to fund care for all Veterans with hepatitis C for fiscal year 2016 regardless of the stage of the patient's liver disease.

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Selected Major Accomplishments

  • 2001: Established the VA National Hepatitis C program (now the National Viral Hepatitis Program) within VA's Office of Public Health
  • 2013: Determined that patients with both anemia and the HCV virus can benefit from intensive treatment for the virus
  • 2015: Learned that cure rates from new HCV treatments were much better than previous treatments, but not as good as rates reported in clinical trials
  • 2015: Developed a new model to help identify which patients chronically identified with HCV have the greatest need for new antiviral drugs
  • 2016: Found that patients with HCV infections are at increased risk of developing osteoporosis and fractures

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New, Ongoing, and Published Research

VA research on hepatitis C includes clinical trials of treatments, epidemiologic studies, investigations of the biological mechanisms of infection, and studies on identifying and removing barriers to treatment.

Some VA researchers are working on projects to improve screening and testing methods for HCV. Others are working to improve the assessment and treatment of patients traditionally excluded from hepatitis C treatment, including those with mental illness, substance use, or who also are infected with the human immunodeficiency virus (HIV), the virus that causes AIDS.

Another area of interest to VA researchers is developing and disseminating models of interdisciplinary care to optimize treatment and clinical standards for treating patients at all stages of HCV infection.

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➤ New treatments for HCV

New drug treatments—In 2013, the U.S. Food and Drug Administration (FDA) approved a new drug for the treatment of HCV: sofosbuvir (sold as Sovaldi). In 2014, FDA also approved the combination pill Harvoni, which includes sofosbuvir and another new drug, ledipasvir.

These drugs are very expensive, but have been hailed as a cure for HCV. Up to 95 percent of patients in clinical trials achieved a state in which the virus was undetectable in the blood and stayed that way for at least three to six months after treatment, meaning that there was little chance of the virus returning.

In 2015, however, researchers based at the VA Palo Alto Health Care System conducted an observational study of more than 4,000 Veterans who were treated with sovosbuvir-based regimens during 2014. Harvoni was not included in the trial, as the drug was not FDA-approved at the time the trial was conducted.

They found that cure rates ranged from 67 to 79 percent, far better than that of previous HCV treatments, but short of the rates seen in clinical trials.

According to the team, the study serves as a reminder that in the real world, response rates may not be as high as in clinical trials. Patients and providers need to temper their expectations appropriately. The team is now evaluating outcomes for Harvoni, and also testing other newly developed treatments.

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➤ Optimizing the response rate to HCV treatment

New risk protection tool—Researchers with the VA Ann Arbor Health Services Research and Development Center for Clinical Management Research and the University of Michigan have developed a new model that uses routine laboratory tests and machine-learning methods to help identify which patients chronically identified with HCV have the greatest need for new antiviral drugs. The results of the their study were published in 2015.

According to the research team, hepatitis C will remain stable without treatment, perhaps for many years, in most patients. One-third of patients, however, are at high risk of complications and need immediate care to prevent the virus from causing further liver damage. These are the patients who would most benefit from the costly new HCV treatments.

Clinical data such as age, body mass index, virus type, and routine lab measurements estimated patients' risk of progression of their liver disease. Among the patients the model predicted would have a low risk of progression, only 6 percent developed cirrhosis (liver scarring) complications in the next year, compared with 56 percent in the high-risk group.

The team believes that the risk-protection tool can be added to an existing electronic medical record, such as VA's, to help doctors make treatment recommendations. It can also establish how often patients should come in for doctor visits or have monitoring tests done.

HCV and mental health care—A 2015 study led by researchers at the VA San Diego Healthcare System looked at 363 Veterans with substance use or psychiatric disorders with HCV infections. They found that those Veterans who receive care that fully integrated support for their mental health issues and hepatitis C infection under the supervision of a care manager were more likely to receive antiviral therapy than those whose care was not integrated, and were more likely to successfully complete that therapy and have undetectable virus loads..

Over a mean follow-up period of 28 months, 31.9 percent of Veterans with HCV infections receiving integrated care began receiving antiviral therapy, compared with 18.8 percent of those who did not. In addition, 15.9 percent of those who received integrated care completed the treatment regiment successfully, compared with 7.7 percent of those who received only usual care.

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➤ HCV and osteoporosis

Osteoporosis is a condition in which bones become brittle and fragile from loss of tissue. It typically occurs as a result of hormonal changes, or a deficiency of calcium or vitamin D. It leads to bones that are at an increased risk for fractures.

A number of studies have established that many people with HIV are developing osteoporosis as they age.

Higher fracture risk—Researchers at the VA North Texas Health Care System and the University of Texas Southwestern looked at patients with HCV infections in a study published in 2016, and found that they, too, are at increased risk of developing osteoporosis and fractures—and that the risk is greatest for patients who have both HIV and HCV infections.

They found that patients with HIV and HCV have a threefold greater risk of developing fractures compared with people who have neither infection, and that those with both infections also have significant additional risk compared to patients who are only infected with HIV.

The team believes that new tools that have recently been developed to assess the quality of people's bones may help researchers better understand why this is the case.

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➤ HCV and statin use

Veterans with HCV and liver cirrhosis are significantly less likely to die or to progress to a stage in the disease called decompensated cirrhosis if they use statins to control blood cholesterol. Decompensated cirrhosis is a stage of liver disease in which patients are at significant risk of dying unless they receive a liver transplant.

Statins and cirrhosis risk—In a study published in 2016, a team from the VA Connecticut Healthcare System and Yale University looked at the health records of 685 statin users with HCV and cirrhosis seen at VA outpatient clinics between 1996 and 2009. Their health status was compared to that of 2,062 patients with the same illnesses who did not use statins.

Over a follow-up period of more than two years, statin use was associated with more than a 40 percent reduction in the risk of death or decompensated cirrhosis. These associations persisted after statistical adjustments for other health care variables associated with liver disease.

The team concluded that until randomized controlled trials are conducted, statins cannot be widely recommended for all people with HCV and cirrhosis, but patients with HCV who would require statins for other health issues such as high cholesterol should be prescribed those drugs.

Statins and antiviral treatments—Another 2015 study, led by researchers from the VA Pittsburgh Healthcare System, found that statins improved outcomes among Veterans receiving antiviral treatment for hepatitis C. The researchers followed 7,248 hepatitis C patients who received antiviral treatment and were followed for at least 24 months after completing their therapy. Of those patients, 45 percent received statins.

Those who used statins were significantly more likely to have a sustained response to antiviral therapy, compared with those who did not (39 percent versus 33 percent.) Statin users were also less likely to progress to cirrhosis (17 percent versus 25 percent) or to develop liver cancer (1.2 percent versus 2.6 percent.)

According to the research team, the data support the use of statins in patients with HCV.

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➤ Hepatitis B

Hepatitis B (HBV) is a contagious liver condition that can range from a severe acute illness lasting a few weeks to a slow-progressing but serious lifelong ailment. It shares symptoms and some risk factors with HCV, but HCV is more common in the United States.

Most acute cases of HBV clear up within a few months, with no lasting effects—but about 1 in 10 adults develops a chronic infection, and 1 in 5 patients with chronic infections might develop liver failure, cirrhosis, or liver cancer. The infection is tied to as many as 4,000 deaths each year in the U.S.

HBV screening follow-up—Researchers at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia looked at the records of more than 21,400 Veterans who had screened positive for HBV between 1999 and 2013. These screens should have been followed up with other blood tests to confirm the presence of the virus and to gauge how active it is.

According to the researchers, however, that happened less than half the time, although 97 percent of those who screened positive did get a follow-up test for their liver function that could indicate how active and dangerous the virus was in their system. Most patients with liver damage did not get proper follow-up care, however.

The study's authors called for improvements in provider education and clinical processes to help VA physicians and other health care providers better adhere to testing and treatment guidelines.

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More on Our Website

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Selected Scientific Articles by Our Researchers

Association between facility characteristics and the process of care delivered to patients with hepatitis C virus infection. Kanwal F, Hoang T, Chrusciel T, Kramer JR, El-Serag HB, Durfee J, Mominitz JA, Yano EM, Asch SM. Healthcare facility factors are potentially modifiable and may enhance process quality in HCV treatment. Dig Dis Sci. 2014 Feb;59(2):273-81.

All-cause mortality and liver-related outcomes following successful antiviral treatment for chronic hepatitis. C. Dieperink E, Pocha C, Thuras P, Knott A, Colton S, Ho SB. Despite significant medical and psychiatric comorbidities, sustained virological response markedly reduced liver-related outcomes without a significant change in non-liver-related mortality after a median follow-up of 7.5 years. Dig Dis Sci. 2014 Apr;59(4):872-80.

Improvement of predictive models of risk of disease progression in chronic hepatitis C by incorporating longitudinal data. Konerman MA, Zhang Y, Zhu J, Higgins PD, Lok AS, Waljee AK. Predictive models that incorporate longitudinal data can capture nonlinear disease progression in chronic hepatitis C, and thus outperform baseline models. Hepatology, 2015 Jun:61(6):1832-41.

Effect of addition of statins to antiviral therapy in hepatitis C virus-infected persons: results from ERCHIVES. Butt AA, Yan P, Bonilla H, Abou-Samra AB, Shaikh OS, Simon TG, Chung RT, Rogal SS, ERCHIVES Study Team. Statin use was associated with improved virological response rates to antiviral therapy and decreased progression of liver fibrosis and incidence of hepatocellular cancer among a large cohort of HCV-positive Veterans. Hepatology, 2015 Aug;62(2):365-74.

Effectiveness of sofosbuvir-based regimens in genotype 1 and 2 hepatitis C virus infection in 4026 U.S. Veterans. Backus LI, Belperio PS, Shahoumian TA, Loomis TP, Mole LA. In a real world cohort, sustained virological response rates for sofosbuvir-based regimens were lower than in clinical trials. Aliment Pharmacol Ther. 2015 Sep;42(5):559-73.

Integrated care increases treatment and improves outcomes of patients with chronic hepatitis C virus infection and psychiatric illness or substance abuse. Ho SB, Brau N, Cheung R, Liu L, Sanchez C, Sklar M, Phelps TE, Marcus SG, Wasil MM, Tisi A, Huynh L, Robinson SK, Gifford AL, Asch SM, Groessl EJ. Integrated care increases the proportion of patients with HCV infection and psychiatric illness or substance abuse who begin antiviral therapy and achieve a sustained virologic response without serious adverse effects. Clin Gastroenterol Hepatol. 2015 Nov:13(11):2005-14.e1-3.

Care delivery and outcomes among U.S. Veterans with hepatitis B: a national cohort study. Serper M, Choi G, Forde KA, Kaplan DE. The research team observed a low prevalence of recommended laboratory testing, antiviral therapy initiation, and liver imaging among a national cohort of Veterans with hepatitis B infection. Hepatology, 2015 Nov 11. (Epub ahead of print.)

Cost-effectiveness of new antiviral regimens for treatment-naïve U.S. Veterans with hepatitis C. Chidi AP, Rogal S, Bryce CL, Fine MJ, Good CB, Myaskovsky L, Rustgi VK, Tsung A, Smith KJ. Managing any treatment-naïve genotype 1 hepatitis C patient with ombitasvir-based therapy is the most economically efficient strategy, although price and efficacy can impact cost-effectiveness. Hepatology, 2016 Feb:63(2):428-36.

Cascade of care for hepatitis C virus infection within the US Veterans Health Administration. Maier MM, Ross DB, Chartier M, Belperio PS, Backus LI. This article provides a clinically relevant model to measure the quality of HCV care within a health care system and to compare HCV care across health systems. Am J Public Health, 2016 Feb;106(2):353-8.

Statins are associated with a decreased risk of decompensation and death in Veterans with hepatitis C-related compensated cirrhosis. Mohanty A, Tate JP, Garcia-Tsao G. Statin use among patients with HCV and compensated cirrhosis is associated with a more than 40 percent lower risk of cirrhosis decompensation and death. Gastroenterology, 2016 Feb;150(2):430-440.e.1.

Hepatitis C virus coinfection as a risk factor for osteoporosis and fracture. Bedimo R, Maalouf NM, Re VL 3rd. Chronic HCV infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis. Curr Opin HIV AIDS. 2016 Feb 17. (Epub ahead of print)

Chronic hepatitis C: treatment, complications, and long-term outcomes in a population of Latino Veterans. Santiago-Rolon A, Purcell D, Grigg N, Toro DH. Although the prevalence of chronic hepatitis C in the Latino Veteran population of Puerto Rico is high, relatively few patients have received treatment. PR Health Sci J. 2016 Mar;35(1):30-4.

Treatment of dyslipidemia with statins by primary care providers in Veterans with and without chronic Hepatitis C. Among Veterans, statins are used less frequently in patients with HCV compared to those without HCV. Both groups had similar achievement of LDL goals, though. Am J Health Syst Pharm. 2016 Mar 1;73(5 Suppl 1):S30-4.

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