In some areas of the world, particularly Japan and Europe, the hepatitis C population is ageing. In Germany, for example, many of the infections occurred in the 1960s,70s and 80s through blood transfusions, until de novo infections via blood and blood products were stopped in 1990 due to blood bank screening. These patients are now in their 60s and 70s and more and have concomitant diseases requiring cholesterol lowering drugs, antihypertensive drugs, antidiabetic drugs and drugs for arrhythmias.
In China, the major route of HCV transmission was blood transfusion, but there are now other transmission routes. Similar to the Western countries, patients are also aging. In general though, our patients are not as old as those in Western countries - 40-60 years of age is the peak. And our older patients are fewer than in the West. But similarly, older patients with diabetes, hypertension and renal disease are common..
In the era of peg-interferon and ribavirin, comorbidities did affect the efficacy of antiviral therapy for HCV. Now it seems that thecomorbitities themselves do not negatively affect the efficacy of DAAs in HCV RNA clearance, whether the patient has cirrhosis or renal disease or other comorbidities. It does not seem to be a big issue.
I must say, in China, one issue for the use of DAAs is concurrent use of herbal medicine, which is widely used and the safety data is not often available. We do not know what would happen if aherbal medicine is used together with the DAAs. It is also difficult, if not impossible, to check against online or other resources. This is a potential issue for Chinese patients where they are using DAAs as well as herbal medicine.
DDI is not as difficult as it was previously. There are the three classes of DAAs - the polymerase inhibitors, the NS5A inhibitors and the protease inhibitors. In general, the protease inhibitors have the biggest problems with DDIs because they are metabolized by cytochrome p450 3A4, like many of the other drugs we use for treating hypertension and cholesterol, for example.
However, we can choose between these classes. Sometimes it is not only a class effect and we have to specifically look at the particular drug and, as Professor Jia mentioned, we can use the wonderful website from Liverpool University, which we all refer to. Once we know the specific drugs, we can look up the potential interactions.
In addition, we are not only dealing with an ageing population and treating hypertension and arrhythmias, we also have patients who are co-infected with HIV and using HIV drugs, as well as transplant patients who are using immunosuppressive drugs. So in these cases as well, we have to look at the DAA that is given and what specific co-medication the patient is using.
In general, if you have two drugs and they have the same route of metabolism, if exposure to one of the drugs is increased, for example, the exposure to the other drug is decreased. We have to assess if a potential toxicity can occur by increasing exposure to one or more drug.
DAAs are not available right now in China, so we have little experience. Butwe can follow the guidelines and we need to clearly understand the metabolic pathways of the different DAAs. We need to know what other diseases patients are dealing with and what medications they are using.
For that information, we can check the Liverpool website to see how the DAAs and many other medications will interact. But I wouldsay again, that Chinese patients who take herbal medicine should be very careful with DAAs because there is very little data available.
Very recently, there was a specific drug-drug interaction between the nucleoside polymerase inhibitor, sofosbuvir, and an anti-arrhythmic drug, but this was a very particular situation, and otherwise there are very few drug-drug interactions with that DAA. With the protease inhibitors, we have to consider the cytochrome P450 3A4 metabolism. But in general, we always have possibilities for alternatives, and if we are aware of this, we can easily manage the patient. Nowadays, with the various possibilities and the three different classes of drugs and various combinations, this is less of a problem than before.
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