Good morning. I'd like to thank the organizers and moderators for giving me the chance to address you this morning. I'm going to talk about disease that we can actually treat for a change. So my topic is screening for viral hepatitis in special population and my talk will be more US-centric than globally, so I apologize for people who are not familiar with the US data. This is my disclosure study and for those of you who are not familiar with the US system, there have been some activities by the USPSTF, which is United States Preventive Services Task Force, which is an organization that reviews all the evidence and make recommendations about how we should practice and their recommendation is important because that's the basis of insurance reimbursement in common situations. So they are so powerful. They published a recent paper in Journal of JAMA recently by just affirming their old recommendation. So it's remarkable that they said screening for hepatitis B virus infection in pregnant women is a good thing. Yes, we agree. They also are proposing to do something different for hepatitis C. So in this proposed policy, they are making a recommendation that we should screen everybody, all adults, for hepatitis C in the US. The actual statement reads the USPSTF recommends screening for hepatitis C virus infection in adults ages 18 to 79 years. So that is an interesting recommendation. I'm going to show or share my perspective on that with you in the next few minutes. If you look at NHANES type population survey and track the prevalence of hepatitis C in the US, it has decreased. So this is a paper in press compared to the peak prevalence in the US in the early 2000s where it was almost 2% If you look at the most recent survey data, it's about 0.5%. So significant reduction in hepatitis C. In my view, this is people who have died as well as people who have been successfully treated. If you look at the actual number of people in the population, this is a recent hepatology paper where they looked at the NHANES estimates. About 2 million people in the US. About 2 million people with hepatitis C, and then they added sort of a non-standard population, incarcerated, homeless, and so forth. That adds a quarter million, additional quarter million Americans, adding up to 2.4 million Americans with hepatitis C, and that's about 1% of the population. So hepatitis C is still quite common. It's not going away as easily as us hepatologists. We think. And part of that trend is this. If you look at the new infection, reported new infection, hepatitis C, this is a CDC data. Actually, it has gone up. And if you look at the age distribution, it's people in the 20s and 30s and 40s, and you notice that these are all people born after the baby boomer birth cohort whom we think traditionally is at high risk of hepatitis C. So if you just zero in on the baby boomer cohort, you will miss all these new infections and that's the rationale for perhaps for the USPSTF report. Americans know this. This is the reason why we are seeing resurgence of hepatitis C infection and that's opioid epidemic, the so-called opioid epidemic. So if you ignore the gray bars where the epidemiology data is missing, the tallest bar with regard to risk factor is injection drug use for hepatitis C acquisition followed by sexual risk factors and so forth. So injection drug use is what's driving this. There isn't a lot of data that supports that universal screening is justified and Professor Canval is going to talk about cost effectiveness right after me. So I won't belabor on this study, but suffice to say that at least in one analysis, if your prevalence is greater than 1%, the healthcare system actually saves money by screening everybody, look for those people and treat them before they become ill. If you apply the traditional cost effectiveness threshold, that prevalence goes down to 0.1%, which applies to most of the settings in the US. So I think that's part of the calculation. So I actually pulled up the recommendation document. It's a long document. I tried to condense it into one table, but you can't read that. Well, the bottom line here is that the reason why they changed their stance from screening selected member of the population to universal screening is not because epidemiology changed. It's not because we have a more useful diagnostic test. It's because we have better treatment. So that's the basis of their recommendation, high SVR and SVR impacting on the patient outcome. So that's all good. So, so far we've journeyed through risk-based screening in the old days and the current recommendation as of today is age-based testing plus risk-based testing and now USPSTF is asking or proposing to go to universal testing. The baby boomer birth core testing comes from this type of data. These two lines are prevalence data from prior NHANES surveys. So both surveys show that there's a bump in the middle group, which is people born between 1945 and 1965, baby boomer generation where hepatitis C prevalence is high. So that makes sense, but I just want to draw your attention. What is the expected prevalence if you did baby boomer cohort screening? The antibody prevalence, 4.5%. You should see at least 3% RNA positivity if you look for hepatitis C in baby boomers. There's an ongoing study at my place called ERASE-C. These are electronic health record driven messaging system to encourage hepatitis C testing in baby boomer generation. So patients who have no upcoming appointments with their primary care doctor and people who have upcoming primary care doctor appointments, we send electronic message and then the control group is not doing anything, but the intervention group is we send EPIC message that we are doing this. We actually put an order for anti-HCV in the record and we do that for people with and without upcoming appointments. And you can see that reminder system and encouragement works. So people who have no upcoming visits, their uptake is lower than people who have upcoming visits, so that makes sense. But the net effect of the messaging is significantly higher than without messaging. So that's all good. The point that I didn't put on slide is we tested about 500 patients by this mechanism. We found zero case of new hepatitis C. So that's interesting, but that's not unusual. If you look at this paper published in 2013, brilliant idea of combining screening colonoscopy with hepatitis C testing catch two birds with a stone. So they had a viral hepatitis screening offered patients undergoing colonoscopy. They both tested anti-HCV and surface antigen. Patients were 50 to 65 years old. Bottom line, they found zero cases of surface antigen and one case of HCV RNA positivity. They invited 500 individuals. Some already had been tested. About 75... 85% accepted to go in the study and 350 patients were tested. There were four patients that was antibody positive. Only one of the four were RNA positive. So if you test anti-HCV in a low prevalent situation, the true positivity rate will be even lower than the population screen. So yield is fairly low in the baby boomer screening efforts. There is another paper from last year that combined three trials, Detroit, New York, and Birmingham. Detroit study had repeated mailing for hepatitis C screening. EHR trigger like our study in New York and the third one was in-clinic patient solicitation for hepatitis C. If you zoom down here, these interventions were more effective than without. So compared to usual care active 5.3-fold increase in the screening rate, 2.68. So these things work to get people tested, but if you look at what we find is the net yield is 0.3%, 0.3%, 0.7% with the intervention arm lower in the usual stand-off care arm. Again, we're supposed to see 3%. We're seeing nowhere near that. So what's going on? This is my hypothesis that if you look at the populations... or average from systemic survey, systematic survey, you will see certain RNA positivity 3% in baby boomer cohort, but when we do a trial or implementation in practice we see much fewer cases. Why is that? And that's because there are people who are not in the system who has a high prevalence of hepatitis C and you can kick the dead horse all you want, but if patients are not there, you're not going to find them. Therefore, it is so important that for those patients who are not in your clinic already, we need to go out and discover and encourage those patients to come into the system and be tested, but how to do that, that's the big question. For patients who are already in the system where we expect to see 0.2% prevalence, we still need to find them. But in my opinion, screening everybody in that population is really pushing the limit of cost-effectiveness of HCV screening. So this is a poster that we're presenting today. I encourage everyone to go visit. So what we considered was still using ALT cutoff or using APRE or FIP4 for population screening and then narrow down the denominator to look for hepatitis C cases. In our estimation, ALT with a cutoff of 25 for women and 30 for men is the best... It seems to be the best one, because if you look at the post-baby boomer cohort, 74 million Americans. With this criterion applied according to the NHANES data, we will need to test about 20 million people and discover most of the hepatitis C patients leaving 36,000 undiscovered with regard to the NHANES population. If you use more stringent criteria to look for fibrosis, yes, you do fewer testing, but you will be missing a lot more patients with hepatitis C. And then we considered combining those criteria with ALT. It is mainly driven by ALT. The result is just the same as if you used ALT alone. So that may be another system-wide approach that can be applied with very little effort to trigger hepatitis C testing when certain ALT criteria are met for patients who are already undergoing healthcare within our system. I'm going to turn to hepatitis B now. This data compares impact of hepatitis B, hepatitis C, alcohol versus NAFLD and this is US data with regard to mortality. So if you look at end-stage liver disease mortality, number one, alcoholic liver disease as of 2016. Hepatitis C, number two, and NAFLD, important going up, but in terms of grand scale of things, not so much. Hepatitis B is at the bottom, but if you look at the actual estimate of the mortality rate for 100,000 individuals, 3 versus 0.3. So approximately a tenth of a hepatitis B impact compared to hepatitis C. Similar story in HCC, 1.0 hepatitis C is the driving risk factor for hepatocellular carcinoma for hepatitis C, lower for hepatitis B, slightly more than 10%, but roughly one-tenth of the impact of hepatitis C. It's not a secret for everyone, whether US or not, hepatitis B burden is highest in Asians, but in this recent publication that is in press, if you compare foreign-born versus US-born, in all racial categories, foreign-born individuals have higher prevalence of hepatitis B, the surface antigen positivity, Asians, black Americans, white Americans, and so forth. This is a publication that Chris Cowdery put together some years ago looking at foreign-born individuals in the US. The estimate is that as of 2008, 733,000 Asian-born Americans were living with hepatitis B in the US. So that's again, no surprises. What I'd like to focus on is actually African-Americans. People who came from Africa, people who came from Caribbean who are mostly black, if you combine the two, that's about half of Asian-Americans with hepatitis B, but we don't think as much about hepatitis B in our African-American patients. We were able to put together a study on African-American... people of African descent in our hepatitis B research network. This map shows where our patients came from. East Africa, West Africa is the geographic divide that we will talk about in the slide. If you look at the immigration statistics, there has been an exponential increase in the number of individuals coming to the US from Africa. Two million individuals as of 2016. If you draw numbers from the Chris Cowdery paper, the average prevalence in African countries is 10%. East Africa, the top three countries where patients come from or immigrants come from are Ethiopia, Kenya, and Somalia. Altogether, East Africa, about 560,000 individuals with expected prevalence of 10%. West Africa, Nigeria, Ghana, Liberia are the top three countries, overall 750,000 immigrants to the US with expected prevalence of 13%. So these are humongous numbers that we need to pay attention to. I don't think we're doing that so carefully. In the HBRN study, we were able to compare the characteristics of East African versus West African patients and there were interesting differences. West African patients had more likely to have abnormal ALT, higher levels of HPV DNA, and consequently clinician assigned phenotype was more likely to be immune active than immune inactive carrier. Genotype data was also interesting. That if you compare US-born African-Americans, most of them have genotype A. West African patients mostly had genotype E. And if you think about our African-American colleagues originating mostly from West Africa, the genotype difference really tells a story about the anthropology of that group. East Africa is genotype A. But within genotype A, there's a difference. So our African-Americans have European A, East African A1, and West Africans have A3. So the point of this slide is when you see an African patient with hepatitis B, they are not a single entity. You need to think about where they were born, what part of the continent they have come from and that may have some implication on your evaluation and treatment strategy. So take-home hepatitis C part, US prevalence of hepatitis C infection has decreased. However, recently its instance is increasing due to the resurgence of transmission by injection drug use. USPSTF is poised to recommend one-time universal hep C screening for US adults, largely in response to improved treatment. Data from birth cohort screening indicates that hep C prevalence is lower than expected for Americans who are under usual care. In order for universal screening to make an impact, this is my opinion, outreach efforts to those outside the healthcare system need to be redoubled and it needs to be implemented. In patients with low prevalence setting, additional measures may be needed to improve the yield of screening. For hepatitis B, hep B has approximately a tenth of the impact of hepatitis C, remains a disease of foreign-born Americans. Burden of hep B in foreign-born African-Americans, in my opinion, is underappreciated and for them tailored approach is needed to address diversities in clinical characteristics. So all in all for hepatitis B and C, coordinated strategies are needed to implement surveillance, education, clinical services, and prevention. Thank you very much for your attention. Thank you.

viral hepatitis screening

hepatitis B

hepatitis C

USPSTF recommendations

foreign-born individuals