"It has been estimated that once treatment programs get going, it will probably be thirty years and you could eradicate this disease."

 

　　Since almost all HCV infections could be cured by currently available oral direct-acting antivirals, could we expect an opportunity for the eradication of HCV worldwide? In an interview with APASL Daily, Professor Eugene R. Schiff, Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, USA told us that we could expect the eradication of HCV but it would be over a thirty-year period. Because there is no vaccine for hepatitis C, it would mean treating everyone. Of course we can never get rid of every last case but we could get it where it is really very well contained. Something that is analogous to that was polio and the polio vaccine.

 

　　Eradication of HCV would be dependent for the large part on access: access to someone who is going to test and that means getting to a facility or service and  access to the drugs, which is limited by cost.

 

　　As far as access to a diagnosis, there are a lot of things that are being developed that may have a place in facilitating this. One is called point-of-care testing. The other issue is the access to the drug and that is variable. There are regions that are being used to demonstrate that HCV can be eradicated from that region where the resources do not otherwise exist. Prof. Schiff gave 3 examples of such regions, Egypt, the country of Georgia and  Mongolia. For example, 15% of the population in Egypt is hepatitis C positive and disproportionately genotype 4. They obtained drug (a nucleotide polymerase inhibitor, sofosbuvir) at a much-reduced cost from one of the major manufacturers, Gilead. The cost of the course of the nucleotide polymerase inhibitor from Gilead for the patients in Egypt was $900. They coupled that with an NS5a inhibitor made by a company in San Francisco called Presidio. It is not licensed for use in the United States but now Egyptian interests own a significant proportion of the company. It is now been administered very effectively in Egypt. That program may well come close to eliminating HCV in Egypt of the next five or six years.

 

　　Prof. Schiff said, "In general, we are going to start to see more people being diagnosed and more people being treated. In some of these countries, drugs that are not licensed in the United States are being used that might be considered “counterfeit”, but if they are effective and safe then fine. .I think we will see these drugs become much more widely available and more affordable. The talk I am giving at APASL is related to this in part. In Japan, one of the most common liver diseases is chronic hepatitis C. It is disproportionately genotype 1b. Now that these drugs are available, they are producing cure rates >95% on finite therapy. "

 

　　"Even when the cures for hepatitis C increase, they are going to have a significant component of patients who will need to be followed because of the advanced liver disease and cirrhosis that gives rise to hepatocellular carcinoma despite the eradication of HCV."

 

　　However, the question there might be, what is the future of hepatology going to be because a large part of the discipline currently focuses on hepatitis C? If we start with HCV itself, we know (particularly in Japan where the epidemic started well before that in the United States) that there is significantly more cirrhosis and cancer of the liver in their population related to HCV. Even when the cures for hepatitis C increase, they are going to have a significant component of patients who will need to be followed because of the advanced liver disease and cirrhosis that gives rise to hepatocellular carcinoma despite the eradication of HCV. Where there is advanced cirrhosis, the complications of cirrhosis need to be managed even though the underlying cause has been stopped.

 

　　" The problem with HBV is that, unlike what we see with HCV, in the majority of cases, therapy is not finite."

 

　　When asking about the future of treatment of hepatitis B, Prof. Schiff thought it was particularly relevant to Asia. The predominant hepatitis in South-east Asia or sub-Sahara Africa is HBV. In those regions in particular, HBV has been transmitted in the past from mother to newborn (perinatal or vertical transmission). Right now, there is underway around the world, universal vaccination against hepatitis B. There is a long way to go in some of these countries particularly in Africa, but when the newborn is vaccinated against HBV, even though the mother is positive, infection in the infant can be prevented.

 

　　For those already with hepatitis B, treatment has come a long way. There are some similarities with HCV in that these are very effective pills. The first-line drugs are nucleotide and nucleoside analogs (entecavir and tenofovir from Bristol-Meyers Squibb and Gilead respectively). These pills can render a person with HBV negative for virus in their blood (i.e. HBV DNA-negative) and that returns liver chemistry to normal and histology reversal just as with HCV. Where there is fibrosis without advanced cirrhosis, removing the virus allows the fibrosis to regress over time. When the underlying inflammation that causes fibrosis is removed, there is no new fibrosis and there will be regression of existing fibrosis. The problem with HBV is that, unlike what we see with HCV, in the majority of cases, therapy is not finite. Even though the medications we have are very effective in stopping the progression to cirrhosis and reducing the risk for cancer of the liver, they have to be given continuously. When therapy is stopped, in most cases, it recurs. HCV can be cured with finite treatment, but that is not true with HBV in the vast majority of cases.

 

　　" The point is that for HBV, the new advance will be to accomplish finite therapy ? to be able to give it for a given period of time and to achieve cure.  "

 

　　To Prof Schiff, the challenge for hepatology in the field of HBV is to produce drugs that will get rid of cccDNA from the nuclei of infected liver cells. Currently, giving medication gets rid of the virus circulating in the blood, but because of the cccDNA in the nuclei of the liver cells, when therapy is stopped, the virus can begin replicating again. In people  who appears to have recovered from HBV, even where HBsAg-negative, the cccDNA will persist in the core nuclei so if immunosuppression occurs with drugs like rituximab for example, HBV will be reactivated. The point is that for HBV, the new advance will be to accomplish finite therapy ? to be able to give it for a given period of time and to achieve cure.  We cannot do that now. We can achieve some good outcomes, but we can’t cure it. Because patients need to stay on therapy indefinitely, cost and compliance come into play. The promising drugs are those that are focusing on cccDNA, but they are not there yet.

 

　　（Want to know more future perspective of  hepatology？Let's meet with professor Schiff in his speech on 23rd Feburary, in Room 1BC.）