Nezam Afdhal, MD, on Monitoring Patients After Treatment for Hepatitis C
Dr Afdhal discusses how to determine which patients warrant additional monitoring after sustained virologic response to treatment for hepatitis C and the tests that should be conducted to ensure the best outcomes.
Nezam Afdhal, MD, is chief of gastroenterology, hepatology, and nutrition at Beth Israel Deaconess Medical Center and a professor of medicine at Harvard University Medical School in Boston, Massachusetts.
Hello and welcome. My name is Ned Afdhal. I'm the chief of gastroenterology, hepatology, and nutrition at Beth Israel Deaconess Medical Center in Boston and professor of medicine at Harvard Medical School.
I'm going to talk to you today about hepatitis C, about some of the monitoring that we do for patients who are undergoing treatment, with a focus on monitoring for fibrosis to diagnose cirrhosis pretreatment, and then focusing on the best policies for the management of patient's post‑sustained virological response or SVR.
We all know that today, the new direct‑acting antiviral therapies which are pangenotypic regimens cure approximately 95% to 97% of patients in real practice with hepatitis C. This high cure rate really means that most of our patients with an 8- or 12‑week course of treatment can essentially be considered hepatitis C‑free.
However, there are patients in whom there is the need for continuous monitoring to occur even after sustained biological response, and what's very important is to identify those patients and to give them appropriate follow‑up and care.
When we start with a patient with hepatitis C at their first visit, we do evaluate them fully in terms of a full physical exam, look at all their concomitant medications to make sure that there will be no drug‑drug interactions, and then we personally do genotype our patients although with the pangenotypic regimens that's not necessary.
The decision is then made to treat the patient. What else do we need to know? I think it's very important that we know the stage of fibrosis of all of our patients undergoing treatment. The reason for this is that the stage of fibrosis is predictive of the final outcomes post‑cure and SVR.
We utilize very simply the technology of elastography to look at staging liver fibrosis. We use the commercially available FibroScan device, and all of our patients have the FibroScan prior to treatment. If a patient has a FibroScan score of greater than 12.5, we consider them to have potentially advanced fibrosis, and above 15, they probably have cirrhosis.
Now there are false positives for elastography. These false positives include a high ALT. They also include the presence of right heart failure, the presence of hepatic congestion, and if there is any evidence of jaundice.
Once we've evaluated the patient and established pretreatment staging of fibrosis, we will undertake the treatment. After treatment, very quickly, usually within the first 3 months but sometimes even right at the end of treatment, there are changes that occur in the hepatic microenvironment.
These changes include significant reductions in inflammation and in hepatocyte swelling, and both of these result in a reduction in the elastography scores. How do we deal with this change?
We know that perhaps the patient has cirrhosis, but now we've come post‑treatment and that elastography score has fallen and may have fallen from 16 or 17, which is in the cirrhosis range, down to 9 or 10. We don't know whether the patient does or does not have cirrhosis and whether this reduction is just related to the decrease in inflammation, and in liver swelling, and liver injury.
There are studies now that have been done, that have looked at post‑SVR changes in elastography, and also looked at what are the predictors of poor outcomes post‑viral cure for hepatitis C. These poor outcomes are really focused on the development and the risk of development of hepatocellular carcinoma.
There are studies that have taken place from Asia, Europe, and also the US that have looked at these issues. There are a variety of parameters that one has to realize are important and if present post‑SVR require the patient to undergo continued monitoring. Let's take our hypothetical patient again.
A hypothetical patient came in to see you. He had an evaluation. It was genotype 1a hepatitis C, never been treated. He had liver elastography which showed a score of 17.5 kilopascals. Because he was in the cirrhotic range, he had an ultrasound performed which showed a coarsened liver, no splenomegaly, no esophageal varices on endoscopy.
We've now got this patient who has got a high liver stiffness. Potentially, we have labelled him ‑‑ since we haven't done a biopsy ‑‑ as liver cirrhosis. We give him a 12‑week course of treatment, and as expected, he has a sustained biological response.
At his 12‑week post‑SVR visit, the patient comes in. We performed a repeat elastography, and his score is now 9.7. Does the patient have cirrhosis? What is his risk? How do we monitor him?
We can't say that the patient absolutely has cirrhosis. There is no splenomegaly. The platelet count is OK. There is no evidence of esophageal varices. There's no portal hypertension, but he had this high baseline liver stiffness.
What do we look at? We look at and see, are there any other associated features that put him at risk for having more advanced liver disease? We would look at his FIB‑4. We would look at his platelets. We would reimage his liver to see if there were any changes, any nodularity, any features to suggest more advanced disease.
One doesn't have to do this by ultrasound. One can also use MRI‑based technologies if one wants to get a better imaging of the liver. However, this patient has nothing. There is nothing there. No splenomegaly. Platelet count is fine. AST/ALT are now normal. His bilirubin is normal. His albumin is normal. His liver stiffness is 9.7. Is he still at risk?
The answer here is probably not. Even though his baseline score was high, he probably does not have established cirrhosis. Can we be 100% sure? No, but for this particular patient, we can look at the parameters that predict risk of hepatocellular carcinoma post‑SVR.
These include, especially from the Asian literature, one, any elevation in AFP of above normal. Our patient’s AFP is now completely normal. Two, a FibroScan score of greater than 11 that persists post‑SVR. Our patient is 9.6. Three, an albumin less than 3.5. Our patient score is now 4.2. Any persistent elevation in ALT or AST, he doesn't have those either and no imaging features of cirrhosis.
We could probably tell this patient, "No, you don't have cirrhosis," but should we just tell him to leave, that he is finished, he is cured, he can move on? The answer to this question is probably no. He probably still needs some post‑SVR monitoring.
What we do at the Beth Israel for this type of patient is we do a post‑SVR monitoring 6 months later, then 1 year later. At both of those visits, we re‑evaluate the biochemistries. We re‑evaluate the platelet count. We repeat the elastography which in the noncirrhotic patient will continue to go down.
In fact, what you will see is that his liver stiffness from 9.7 will probably go down to 7 or to 6 even. Then what we will do is we will image his liver 2 more times. At that stage, I feel pretty comfortable that the patient has no cirrhosis.
Certainly, liver elastography less than 7, and a normal ultrasound, and a normal platelet count. I'm very contented. I usually do one more visit 1 year later. At that stage, if everything is the same, I can discharge the patient from my clinic. You might say this is a conservative approach, but of course, what we are all worried about is the risk for hepatocellular carcinoma.
This has focused on our patient with hepatitis C, our virtual patient, but there are other factors that one has to take into account post‑SVR. These are common factors because they are common diseases in the United States today.
Those 2 factors are, 1, are there any concomitant liver diseases; and 2, what is the risk of alcohol consumption or reinfection? In some of our patients, about 30%, they have clear risk factors for nonalcoholic fatty liver disease. In those patients, they're usually diabetic. They might be overweight or obese.
One of the key factors is that in this group the ALT and AST does not return to normal. You've now taken a patient who has both hepatitis C and nonalcoholic fatty liver disease and turned them into nonalcoholic fatty liver disease, and you'd have to follow that patient appropriately. Those patients require continued care for their nonalcoholic fatty liver disease.
The second group is the group that has some high‑risk behaviors. One of those high‑risk behaviors is alcohol. We do see patients who, after SVR, go back to increased alcohol consumption, and this is on top of an already damaged liver from the hepatitis C.
They may have stopped alcohol consumption because they were told that they had hepatitis C. It's always important to take a good alcohol history from these patients and to continue to advise them to avoid alcohol.
The third group of patients is those whose risk factor for hepatitis C, whether it'd be men who have sex with men or intravenous drug use, remains still at risk. Here, it's very important that the correct social and psychological support systems are present.
It's very important that harm reduction and risk reduction advice is given either by you as the primary hepatologist, or ID physician, or else by affiliated healthcare specialties with an expertise in this area. Reinfections do occur for hepatitis C.
The high‑risk populations are those that continue with active intravenous drug use, where reinfection rates can be quite significant at 2% to 3% per year or in men who have multiple sexual partners with other men. Again, harm reduction, risk reduction is very important.
Overall, the good news is that for the majority of our patients, they're going to come in, you're going to evaluate them as we discussed, stage their fibrosis, most of them will not have significant fibrosis, treat them, cure them, and then they can go back out into the community hepatitis C‑free.
For those who have high baseline evaluations for a significant liver fibrosis and for those the harm reduction is important, long‑term care remains essential to avoid reinfection and risk of hepatocellular carcinoma and further worsening of liver injury.
I hope this is helpful as a primer on how to look after our patients in the era of direct‑acting antivirals and hepatitis C. I thank you for your attention.