Interview with HCV Expert Paul Kwo, MD

We recently sat down to discuss current topics in management of hepatitic C virus (HCV) infection with Paul Kwo, MD, Professor of Medicine (Gastroenterology and Hepatology) at Stanford University Medical Center. Dr Kwo most recently was the lead author on the American College of Gastroenterology's clinical guideline on abnormal liver chemistries. Read on to hear Dr. Kwo’s thoughts on new HCV guideline updates, screening rates, and the evolving role of the gastroenterologist in HCV care.The AASLD/IDSA guidelines have recently been updated to reflect new recommendations for women of reproductive age. Why is testing and management so important in this cohort?

Dr. Kwo: For years, when we thought of the HCV birth cohort, we thought of the baby boomer or Woodstock generation. The need for screening in that 1945 to 1965 birth cohort is well established. Now, there is a second HCV cohort between the ages of 20 to 39. We know this in part because of a report published in the Annals of Internal Medicine showing that the number of reproductive-aged women with acute and past or present HCV infection doubled from 2006 to 2014. This is unfortunately related primarily to our opiate epidemic. We are finding that because of widespread injection drug use, particularly heroin, many younger women of childbearing age have now contracted hepatitis C.

"...the number of reproductive-aged women with acute and past or present HCV infection doubled from 2006 to 2014. This is unfortunately related primarily to our opiate epidemic."

If we can find these individuals prior to pregnancy and achieve SVR with DAA therapy, we are going to reduce the spread of HCV to infants. The guidelines are now emphasizing this population so practitioners are aware of this as another opportunity to find undiagnosed hepatitis C. Specifically, the guidelines state that women of reproductive age with HCV should be counseled about the benefits of antiviral treatment, and that therapy before considering pregnancy should be considered to reduce the risk of transmission to offspring.

In addition, the guidelines recommend universal testing of pregnant women for HCV infection, so when we think of TORCH infections such as toxoplasmosis, rubella, and CMV, we need to be adding hepatitis C to this list. Obviously, we don't treat during pregnancy, but these are the individuals that should be referred immediately post-pregnancy for DAA therapy.

Next: Best Practices in Managing Acute HCV Infection

Recent guidelines also emphasize best practices in managing acute infection. What is important to know in this scenario?

Dr. Kwo: A certain proportion of individuals with acute hepatitis C are going to clear virus spontaneously. The precise numbers are not clear, but it appears to be somewhere in the range of 20 to 50 percent. Nonetheless, there are others who don't have spontaneous resolution, and if they’re not documented to have cleared virus by month 6, they should receive a course of DAA therapy.

"There are now multiple studies showing that if we do find individuals with acute Hepatitis C and they are appropriately linked to care, we can ensure that the vast majority of them will not go on to chronic infection."

That includes one study recently presented by the AIDS Clinical Trials Group showing that an 8-week course of ledipasvir/sofosbuvir for HCV genotype 1 in men having sex with men with HIV infection led to an overall sustained response rate of 100 percent. Other trials have looked at other treatment durations for acute hepatitis C. For example, one German study showed that a 6-week duration was associated with some treatment failures in those with acute hepatitis C. However, the cohorts in these studies are small because it can be challenging to find large numbers of individuals with acute hepatitis C.

Next: Managing HCV in Correctional Settings

Another notable addition to the guidelines is a section of management of patients with HCV in correctional settings. What kind of impact could opt-out HCV testing and antiviral therapy have in this population, both in the facilities, and when they are returned to the community?

Dr. Kwo: I think it’s wonderful that the guidelines now discuss this not only in terms of prisons, or long-term facilities for individuals with felony convictions, but also jails, or short-stay facilities that typically house individuals with sentences of up to a year. The recommendations call for both prisons and jails to implement out-out HCV testing, as well as antiviral therapy if the sentence is sufficiently long enough to complete the recommended course of treatment. With the shorter duration of DAA therapy and high sustained response rates, there is an opportunity to find these individuals with HCV infection who are incarcerated and successfully treat them.

Correctional facilities are also called upon to facilitate linkage to community health care. The guidelines cite research showing that 48% of detainees with chronic HCV referred for management after release attended a follow-up appointment. That linkage is actually very helpful, because these are people who are going to require extra effort to engage in care.

"The guidelines cite research showing that 48% of detainees with chronic HCV referred for management after release attended a follow-up appointment."

This was not in the guidelines, but there was recently a very nice pilot study from California where a VA hospital worked with primary care providers to seek out homeless veterans with HCV for diagnosis and treatment. These people are still going to be out there transmitting the virus, so we absolutely need to be able to have a mechanism that can be scaled to programs where individual are able to be sought out and then linked effectively to care. And again, the beauty of HCV therapy is that it's a finite therapy, at just eight to twelve weeks. As I have stated often, there are very few diseases you can cure with a finite course of therapy.

Next: Thoughts on How to Boost Screening Rates

Adoption of HCV screening for baby boomers remains slow despite clear recommendations. In one recent study, a primary care practice increased screening rates from 24% to 90% through interventions such as adding EMR prompts and informing physicians of their screening rates in relation to the practice as a whole. Do you think either of these strategies may be effective in other practices?Dr. Kwo: There have been now several studies, including one from the University of Michigan, that showed increased screening rates with EMR prompts. Since EMRs are without question here to stay, I think prompts like this are going to be helpful. We are certainly sympathetic, however, to primary care providers who have multiple quality metrics that they have to satisfy with regard to screening. It would also not surprise me in any way that another way to improve screening rates is if the physicians receive feedback on their performance.

Next: Gastroenterologists are the Gatekeepers

What do you think is the most important role of the gastroenterologist now that we are several years into the era of highly effective DAA therapy?

Dr. Kwo: I think gastroenterologists will continue to have an important role to play. We are the gatekeepers and the ones who are going to be caring for those with advanced liver fibrosis. That's something we are uniquely qualified to do, so our role will persist in the treatment and eradication of hepatitis C. Having said that, because of the large number of untreated patients with hepatitis C, there's no reason we should not be able to help other providers assess these individuals, and this can be done through telemedicine or a variety of other venues. We can help make sure that we are not missing those with advanced fibrosis who can develop other complications like decompensated cirrhosis or liver cancer.

"We [gastroenterologists] are the gatekeepers and the ones who are going to be caring for those with advanced liver fibrosis. That's something we are uniquely qualified to do, so our role will persist in the treatment and eradication of hepatitis C."

Biography

Dr. Kwo is currently Professor of Medicine and Director of Hepatology at the Stanford University where he joined the faculty in November 2016. Prior to joining the faculty at Stanford, he was at Indiana University for 21 years where he served as the Medical Director of Liver Transplantation. He has distinguished himself in the field of Hepatitis C therapeutics and has been the principal investigator on multiple international trials. He recently authored the ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries.