In April, the Edward Hines Jr. VA Hospital in Chicago had the distinction of treating the 100,000th veteran, Darrell A. Mason Sr. for hepatitis C. Mason, center, is shown with VAMC staff. The VA says it will have eliminated hepatitis C infections among all patients willing and able to be treated by next spring.
Photo from VAntage Point blog.

SEATTLE — In March, then-VA Secretary David Shulkin, MD, announced at the annual Wharton Health Care Business Conference that the VA will have eliminated hepatitis C infections among all patients willing and able to be treated by next spring. In comparison, more than 146,000 VA-enrolled veterans had hepatitis C in 2014.

Hepatitis C (HCV) has been the driving factor in the steady rise of hepatocellular carcinoma (HCC), but the VA for a variety of reasons does not expect to see a decline in liver malignancies any time soon.

“Due to the progressive liver damage over decades caused by untreated hepatitis C, there are increasing numbers of HCV-positive veterans with advanced liver disease, cirrhosis, hepatocellular carcinoma (HCC) and other life-threatening, costly liver conditions,” said the 2017 Annual Report of the VA’s HIV, Hepatitis, & Related Conditions (HHRC) Programs.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, which is the fastest-growing cause of cancer deaths in the United States. Veterans develop the disease at about five times the rate seen in the general population, according to the VA.

“As of FY17, VHA had approximately 8,050 HCC patients in its care,” said Lauren Beste, MD, MSc, director of the HHRC Data and Analysis Group and director of the VA National Liver Disease Database at the VA Puget Sound Healthcare System in Seattle.

HHRC stepped up efforts to address HCC and other types of advanced liver disease in 2017 with the creation of an Advanced Liver Disease Technical Advisory Group and by designating hepatic innovation teams to focus on advanced liver disease (ALD). The teams include providers, industrial engineers and system redesign experts to create and share best practices in care that increase access, support high performance and involve both patients and VA staff.

The hepatic innovation team “model has been incredibly successful in spreading innovation in HCV prevention, care and treatment with incredible potential to impact ALD by building on the foundation built to address HCV across the system,” noted the HHRC annual report.

The advisory group has identified key metrics for ensuring quality care for HCC and other advanced liver diseases and contributed to the development of educational materials for patients and clinicians, as well as informatics tools tailored to the challenges of advanced liver diseases.

Based on a VA study published in Gastroenterology, the teams and advisory group have their work cut out for them. The study reported that relatively few VAMCs have the multidisciplinary teams—radiologists, hepatologists, oncologists, interventional radiologists and transplant surgeons—needed to manage the complexities of liver cancer and offer a full range of recommended therapies.1

The lack of deep teams prepared to address advanced liver disease poses serious risk to patients. “Because death in patients with HCC generally results from progressive liver failure, often requiring careful temperance of treatment decisions, patients require collaborative or multidisciplinary care,” the authors wrote.

The researchers also found that patients who received care at university-affiliated VA hospitals had almost twice the odds of receiving active therapy for HCC, including liver transplantation, resection, local ablation, transarterial therapy or treatment with the multikinase inhibitor sorafenib. Based on the differences in treatment provided at VAMCs and the impact of those differences on outcomes, the authors concluded that “multidisciplinary methods of care delivery for HCC should be prospectively evaluated and standardized to improve access to HCC therapy and optimize outcomes.”

Hepatitis B Concerns

The hepatic innovation teams also might find their systems tested in the near future by rising HCC rates caused by an explosion in hepatitis B virus infections. In 2015, acute hepatitis B rates rose 20% in the U.S., and the skyrocketing rate of infection has continued, with some states seeing much higher increases. The rise in HBV has been driven largely by increasing use of injection drugs associated with the opioid crisis, according to the U.S. Department of Health and Human Services (HHS).

The increasing rates have serious implications for the VA, as veterans historically have a higher than average rate of infection and have been significantly impacted by the opioid epidemic. Patients with chronic hepatitis B infection have five to 15 times the risk of developing HCC as non-infected individuals.2

“As of April 2018, VA oversees care for approximately 10,300 users with chronic hepatitis B,” Maggie Chartier, PsyD, MPH, deputy director and national infectious diseases officer of HHRC, told U.S. Medicine.

That number could be understated, as a recent VA study published in the Journal of Clinical Gastroenterology found that 21,419 veterans tested positive for hepatitis B surface antigen, but less than half of those patients had received confirmatory testing.3

Antiviral therapy and ongoing surveillance to detect early signs of cirrhosis or liver cancer form the backbone of chronic HBV treatment and HCC risk management. Only 39% of veterans with HBV received antiviral therapy, according to the study.

“Antiviral treatment considerations for HBV are complex, and treatment is not indicated for all infected individuals,” Beste noted. The VA follows the American Association for the Study of Liver Disease (AASLD) guidelines, she said, which provides an algorithm for antiviral therapy that factors in the patient’s phase of chronic HBV and levels of serum HBV DNA levels and ALT.

In addition to ameliorating the symptoms of hepatitis B infection itself, “antiviral treatment for patients among those with indications for therapy may reduce the future risk of developing hepatocellular carcinoma,” Beste told U.S. Medicine.

Screening and surveillance are important in preventing development of HCC in veterans with chronic HBV, as cirrhosis frequently occurs without symptoms and HBV, an oncogenic virus, can promote HCC without cirrhosis. The Journal of Clinical Gastroenterology study found that only 47% of all veterans with HBV had one-time liver imaging.

The AASLD recommends imaging studies every six to 12 months in patients with chronic HBV who have cirrhosis or high risk for HCC. Asian or black men over age 40 and Asian women older than age 50 are considered high risk, as are individuals with a family history of HCC or co-infection with hepatitis D.

Regular imaging can save lives. Another study of veterans found that 24.6% of veterans with HCC and cirrhosis did not know they had cirrhosis until they received their cancer diagnosis. Patients with unrecognized cirrhosis had more than six times the risk of having advanced HCC at diagnosis.3

1Serper M, Taddei TH, Mehta R, D’Addeo K, Dai F, Aytaman A, Baytarian M, Fox R, Hunt K, Goldberg DS, Valderrama A, Kaplan DE; VOCAL Study Group. Association of Provider Specialty and Multidisciplinary Care With Hepatocellular Carcinoma Treatment and Mortality. Gastroenterology. 2017 Jun;152(8):1954-1964. doi: 10.1053/j.gastro.2017.02.040. Epub 2017 Mar 7.

2Gowda C, Sheikh U, Maier AW, Chang KM, Kaplan DE, Lo Re V, Amorosa VK. Strategies to improve hepatocellular carcinoma surveillance in veterans with hepatitis B infection. Fed Pract. 2017 Jun;S20-29.

3Kushner T, Lam R, Gray DL, Kaplan DE, Serper M. Identifying Patient and Provider-specific Gaps in Care Among Patients With Hepatitis B. J Clin Gastroenterol. 2017 Nov/Dec;51(10):900-906.

4Wazir A, Azar I, Mehdi S. Treatment Rates and Outcomes for Patients with Metastatic Pancreatic Cancer at a Single VA Hospital: An Exploratory Analysis. Abstract 52: 2017 AVAHO Meeting. Fed Prac. 2017 August 1.

5Wainberg ZA, Hochster HS, George B, Gutierrez M, Emery M, et al. Phase I study of nivolumab (nivo) + nab-paclitaxel (nab-P) ± gemcitabine (Gem) in solid tumors: Interim results from the pancreatic cancer (PC) cohorts. J Clin Oncol. 2017 Feb 1;35(4):S412.

6Hingorani SR, Zheng L, Bullock AJ, Seery TE, Harris WP, et al. HALO 202: Randomized Phase II Study of PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma. J Clin Oncol. 2018 Feb 1;36(4):359-366.