Computer Model: HCV, Associated Cancer Will Be Rare by 2036

by U.S. Medicine

November 10, 2014

By Brenda L. Mooney

PITTSBURGH – Will hepatitis C become a rare disease over the next two decades or so?


Jagpreet Chhatwal, PhD

The answer is yes, according to a computer simulation conducted by the University of Pittsburgh Graduate School of Public Health and the University of Texas MD Anderson Cancer Center in Houston. Results of the simulation, reported recently in the journal Annals of Internal Medicine, focused on the year 2036.1

“Hepatitis C (HCV) is the leading cause of liver cancer and accounts for more than 15,000 deaths in the U.S. each year,” said corresponding author Jagpreet Chhatwal, PhD, assistant professor of Health Services Research at MD Anderson.

“If we can improve access to treatment and incorporate more aggressive screening guidelines, we can reduce the number of chronic HCV cases, prevent more cases of liver cancer and reduce liver-related deaths,” Chhatwal said.

The VA will be among the greatest beneficiaries of earlier detection and more effective treatment. In 2002, the VA cared for 146,290 veterans with HCV, very few of whom had ever been diagnosed with hepatocellular carcinoma (HCC), said David Ross, MD, director of the HIV, HCV and public health pathogens programs for the VA. By 2013, the VA had nearly 175,00 veterans with HCV, 20% more, but six times as many with recent diagnoses (1,600) and 10 times as many who had ever been diagnosed with HCC (4,900). 

For the National Institutes of Health-funded study, Chhatwal and his collaborators used a mathematical model with information from several sources, including more than 30 clinical trials, to predict the effect of direct-acting antivirals and the use of screening for chronic HCV cases. 

By 2036, researchers predict, HCV will affect only one in 1,500 people in the United States. 

The model also suggests that one-time HCV screening of baby boomers would help identify 487,000 cases over the next decade. HCV INFECTION

“Though impactful, the new screening guideline does not identity the large number of HCV patients who would progress to advanced disease stages without treatment and could die,” Chhatwal said.

If the screening were universal, going beyond just baby boomers, 933,700 HCV cases could be identified, according to the study. Chhatwal and his colleagues also predict that universal screening and timely treatment could make HCV a rare disease in only 12 years.

According to the model, such screening could prevent:

  • 161,500 liver related deaths;
  • 13,900 liver transplants; and
  • 96,300 cases of hepatocellular carcinoma — the most common type of liver cancer.

“Although recent screening recommendations are helpful in decreasing the chronic HCV infection rates, more aggressive screening recommendations and ongoing therapeutic advances are essential to reducing the burden, preventing liver-related deaths and eventually eradicating HCV,” Chhatwal posited.

Still, the authors suggested, statistics are going in the right direction when it comes to HCV.

“Making hepatitis C a rare disease would be a tremendous, life-saving accomplishment,” said lead author Mina Kabiri, a doctoral student at the University of Pittsburgh Graduate School of Public Health. “However, to do this, we will need improved access to care and increased treatment capacity, primarily in the form of primary care physicians who can manage the care of infected people identified through increased screening.”

Why the unbridled optimism that identifying HCV is tantamount to eradicating it?

Two recent studies, involving international research, provide possible answers, reporting that even patients with the most difficult-to-treat forms of hepatitis C are benefiting from two new pill-only antiviral drug regimens. In addition, according to the research, the therapies offer shorter, more effective treatment options with fewer side effects and, in essence, offer a cure for the disease.2,3

That would have been almost unimaginable 50 years ago.

In the 1960s and 70s, blood tests were developed to identify hepatitis B and A, but many of the samples taken for post-transfusion illness tested negative for both. Those were classified as non-A, non-B hepatitis — although it is now believed that 90% or more of those cases were actually hepatitis C.

Before 1990, when blood banks began screening blood donors for HCV — and before 1992 when a sensitive blood tests became in widespread use — an estimated 300,000 Americans contracted HVC through blood transfusions or blood products. Until recently, HCV could be treated but was considered a lifelong illness.

The recent studies, both published in the journal Lancet, focused on hepatitis C genotype 1, which is the most common genotype in the United States, Europe, North Asia, Australia, and South America, and one of the most difficult to treat. 

Background in the articles pointed out that, until new drug approvals, the standard of care for chronic HCV genotype 1 involved a combination of three drugs: ribavirin (RBV), pegylated interferon (PEG) and a protease inhibitor. The agents together inhibit viral replication and enhance the body’s immune response to eradicate the virus but at substantial burden on patients. The complex regimens, involving both injections and pills, sometimes require up to 18 tablets a day, last for a year and cause serious side effects such as anemia and depression, according to the reports.

Direct-acting antiviral agents (DAAs), however, provide new opportunities for treatment while reducing the need for interferon and ribavirin and their potential side effects, according to the studies.

In the COSMOS study, a team of U.S. and European researchers led by Eric Lawitz, MD, from the Texas Liver Institute at the University of Texas Health Science Center in San Antonio, randomly assigned 167 patients with HCV genotypes 1a and 1b to a 12-week or 24-week course of once-daily sofosbuvir plus simeprevir with or without ribavirin.2

Results indicate that, after just 12 weeks of treatment without ribavirin, 93% of participants — including those with cirrhosis and previous non-responders to interferon-based treatment — had no detectable virus in their blood three months after treatment had stopped. They, in effect, were cured.

The 12-week sofosbuvir plus simeprevir regimen was well tolerated, with less than 2% of participants reporting serious adverse events or having to discontinue treatment as a result of such events, according to the report. In addition, neither extending treatment to 24 weeks nor adding ribavirin provided any clear benefit.

“We saw a cure rate of about 93% with only 12 weeks of treatment using an all-oral regimen that did not include interferon or ribavirin,” Lawitz said. “This is especially encouraging given the high proportion of participants who had multiple characteristics traditionally associated with low cure rates, including cirrhosis. This is the first trial combining two DAAs that are currently on the market and supports recent American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) and the European Association for the Study of the Liver (EASL) treatment recommendations.”

In the other study, the HALLMARK-DUAL phase 3 study, led by Michael Manns, MD, from Hannover Medical School in Germany, 645 patients with HCV genotype 1b from 18 countries were randomly assigned to receive a six-month course of treatment with a pair of oral DAAs asunaprevir and daclatasvir. Compared to a placebo control group, the regimen was effective and well tolerated, even in patients who have traditionally been the hardest to treat.3

The authors report that 90% of previously untreated patients and 82% who were intolerant of, or who had been treated unsuccessfully using standard regimens, were effectively cured. No differences in response were detected in patients with predicators of poor response to treatment, such as those who were male, older, African American or having advanced liver disease.

“The efficacy and safety of 24 weeks of daclatasvir plus asunaprevir represents a huge improvement on the first generation of protease inhibitor based triple therapies for HCV genotype 1b infection (up to 48 weeks of boceprevir or telaprevir in combination with PEG/RBV),” Manns pointed out. “This new all-oral interferon and ribavirin-free combination could provide a more effective, safer, shorter, and simpler treatment option for those traditionally hard-to-cure patients with cirrhosis or those who have failed to respond to existing therapies.”

Writing in a linked comment, Ed Gane, MBChB, MD, director of the New Zealand Liver Transplant Unit at Auckland City Hospital, suggests, “In the future, very-short-duration, all-oral DAA regimens should improve treatment uptake and success, and reduce the health burden from liver-related complications. When combined with targeted testing and treatment of populations who transmit infection (i.e., treatment as prevention), these DAA regimens might eventually eliminate HCV infection.”

Gane’s comments are entitled, “Hepatitis C beware—the end is nigh.”


  1. Kabiri M, Jazwinski AB, Roberts MS, Schaefer AJ, Chhatwal J. The changing

burden of hepatitis C virus infection in the United States: model-based

predictions. Ann Intern Med. 2014 Aug 5;161(3):170-80. doi: 10.7326/M14-0095.

2. Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, et. al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naïve patients: the COSMOS randomised study. Lancet. 2014 Jul 26. pii: S0140-6736(14)61036-9. doi: 10.1016/S0140-6736(14)61036-9. [Epub ahead of print]  

3.Manns M, Pol S, Jacobson IM, Marcellin P, et. al. on behalf of the HALLMARK-DUAL Study Team. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet. 2014 Jul 26. pii: S0140-6736(14)61059-X. doi: 10.1016/S0140-6736(14)61059-X. [Epub ahead of print]  

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