for Health Care Providers
1: He has prior psychiatric issues but a very low viral load: A case for shorter duration of treatment?
The patient is a 43-year-old white man with chronic hepatitis C virus (HCV) genotype 1, a viral load of 64 IU/mL, and mild elevation of aspartate aminotransferase (AST) and total bilirubin levels. An ultrasound examination of the abdomen indicated the presence of fatty liver disease. The patient has not consented to undergo a liver biopsy. He also has a history of bipolar disorder, schizophrenia, panic attacks, and depression, for which he is not well controlled.
Question 1: Given the patient's low viral load, if he is able to be treated in the future, would one treat with a full course of therapy for 48 weeks or with a modified schedule?
Speaker 1: We have a patient with HCV genotype 1, but we do not know the levels of alanine aminotransferase (ALT), other liver enzymes, or albumin. It would be ideal if we could determine the stage of his liver disease to help us make decisions about treatment, as issues in his history suggest he may experience decompensation of mental health during treatment. In particular, it would be useful to know whether he has developed cirrhosis, but he has not consented to a biopsy.
There are three ways to think about cirrhosis: biochemically, clinically, and histologically. For this patient, we would need more biochemical, clinical, and histologic information by means of a liver biopsy in order to determine whether he has cirrhosis.
We do know that the patient's viral load is remarkably low. Nevertheless, enough virus was present to allow laboratory technicians to determine the genotype. Given the patient's low viral load and the risk of mental decompensation while he is on treatment, the question is whether to consider modifying the duration of treatment, if he is to be treated at all.
This introduces the concept of "rapid virologic response," or RVR. If a patient is undergoing hepatitis C treatment and becomes HCV RNA qualitative negative at 4 weeks, then this is considered an RVR.
If an RVR occurs, could we treat him for less than 48 weeks and still achieve a sustained virologic response (SVR)? This was successfully done for genotype 2 and genotype 3 patients in a study reported by the New England Journal of Medicine in which patients who were RNA qualitative negative at 4 weeks were able to achieve an SVR at 12 weeks instead of the usual 24 weeks of treatment. For genotype 1 patients, in a study reported in Hepatology, if patients were RNA qualitative negative at 4 weeks, 89% were able to achieve an SVR after 24 weeks of treatment -- instead of the usual 48 weeks of treatment.
At the same time, because this patient has such a low pretreatment viral load of only 64 IU, there is good reason to believe an RVR could be achieved. Thus, we could perhaps shorten his course of treatment if side effects occurred, and still achieve an SVR.
If this were an otherwise uncomplicated genotype 1 patient, we would predict a 55-60% likelihood of an SVR after the standard 48 weeks of treatment. We do not have data to determine the likelihood of his achieving an SVR with such a low viral load, and with only 24 weeks of treatment. However, given the possibility of serious side effects, one could consider treating for a shorter duration and reducing the likelihood of mental health complications by attempting to achieve an RVR at 4 weeks and then treating with a shortened course of 6 months (24 weeks).
This also highlights the importance of trying to maximize the patient's dosage of interferon and ribavirin during the first weeks of treatment and then checking the viral load at week 4.
Let's further discuss his mental health, with the history of bipolar disorder, schizophrenia, and panic attacks. Many of our patients do have psychiatric comorbidities. The patient's mental health would be the biggest red flag in this case--not his genotype, or the lack of a biopsy--but his psychiatric history and the potential impact of ribavirin and interferon on his mental health.
Speaker 2: Absolutely. The incidence of mental health issues is very high in the veteran population. Answering the question of whether to use hepatitis C therapies in such patients often comes down to issues of individual resources and individual comfort. We recommend that patients with significant mental illness such as schizophrenia and bipolar disorder should be followed very closely with psychiatric evaluation, if possible. The Hepatitis C Resource Center put together a program on the management of depression and hepatitis C to improve coordination with psychiatrists and increase the availability of resources for our patients.
If possible, we would assign a case manager who could see this patient frequently, probably even if he weren't being treated for hepatitis C.
Speaker 1: Moving to other points, we also note that ultrasound has detected significant fatty liver. This finding should prompt us to attempt to determine whether the patient has the metabolic syndrome and to check his glucose level and body mass index (BMI).
Speaker 2: A number of studies have shown that BMI is an important predictor of hepatitis C treatment outcome. I think that, by encouraging and helping our patients to lose weight, we are also helping them increase the likelihood of a positive response to hepatitis C treatment.
Participant: Given the mild elevation of AST and total bilirubin, I would be very concerned that this is a cirrhotic patient. Bilirubin should not be mildly abnormal, and isolated elevation of the AST is also suggestive of cirrhosis. Certainly, thrombocytopenia, even a mild degree, would be another indication. Ultrasound really cannot distinguish between fat and fiber in the liver, so several factors would suggest this is a cirrhotic patient. I think a biopsy should be performed on this patient in order to confirm that, because you're going to follow him differently.
Speaker 1: Even though this patient has a low peripheral viral load, we cannot determine the stage of fibrosis. In fact, patients with low peripheral viral loads may fibrose much faster than others. To determine whether or not a patient has advanced liver disease, a biopsy would be useful, and one should not rely too heavily on AST and ALT measurements for determining stage of liver disease.
A biopsy is almost always helpful. Unless a patient is already decompensated with ascites and so forth, a biopsy will almost always reveal more information about the patient's stage of disease.
Question 2: If the patient is unable to be treated at this time, how and at what intervals should he be followed?
Participant: For our patients who are not being treated but are "tenuous" in terms of the stage of their liver disease, we usually follow them every 6 months, checking ASTs, LFTs, and their appropriate clotting, and their CBCs and platelet counts.
Speaker 1: I think most people would agree with following up every 6-12 months. But, what the follow-up should include depends on the stage of the liver disease, and this goes back to whether we think the patient has cirrhosis. When we know whether or not there is cirrhosis, then we know who we should be screening for hepatocellular carcinoma, who is at risk of variceal bleeding, and so forth. So, we want to determine the stage of disease for all patients, but we all know that some patients refuse to have a biopsy. If mental health issues are the most prominent concern, we try to bring hepatitis C care to the forefront, but some patients will do OK regardless, without interferon-based therapy.
Participant: Because the projection of cirrhosis was high, would you recommend that the subspecialists do the follow-up CT scans every 6 months and that the primary care physician measure alfa-fetoprotein levels every 3 months (4 times a year), with scanning twice a year, only if we think the patient is really cirrhotic?
Speaker 2: I think you should screen with alfa-fetoprotein only in patients who are being assessed for liver cancer. There is no need for alfa-fetoprotein testing in somebody who has only stage 1 liver disease and, therefore, who you really do not consider to be at much risk of hepatocellular carcinoma. Unfortunately, providers frequently request alfa-fetoprotein levels even for patients without cirrhosis. However, I definitely recommend that you screen patients for liver cancer only if they are at risk (have cirrhosis); and, when you screen them, measure the alfa-fetoprotein level along with the imaging. Does anyone have another opinion?
Speaker 1: In fact, 2005 AASLD guidelines The Management of Hepatocellular Carcinoma are not putting too much weight at all on AFP screening. In other words, what cutoff would we take as a worrisome AFP level? If somebody's AFP measurement 20, would you send that patient for an MRI of the liver?
Speaker 2: Well, that is the difficulty with AFP for the purpose of screening. It is not specific enough for cancer screening. For example, if the ALT is 200, even if the patient has minimal liver disease, I think you will tend to see a high AFP level because the ALT level is high. So, AFP screening is problematic and not a perfect test, which is all the more reason you should request it only for cirrhotic patients you are screening for liver cancer. Also, the guidelines do not recommend cancer screening in patients with early-stage liver disease at all. In those patients, there is no reason for screening with AFP or imaging.
- Low viral load is a predictor of achieving an SVR.
- RVR is a predictor of SVR.
- Genotype 1 patients with an RVR may be able to achieve an SVR after only 24 weeks of treatment, rather than the usual 48 weeks.
- Genotype 2 or 3 patients with an RVR may be able to achieve an SVR after only 12 weeks of treatment, rather than the usual 24 weeks.
- High BMI is a negative predictor of treatment outcome and disease progression.
- Patients with a significant psychiatric history would need very careful monitoring while on HCV treatment, ideally in conjunction with a mental health specialist.
- Patients with cirrhosis are at increased risk for hepatocellular carcinoma.
- Guidelines recommend screening patients with cirrhosis for HCC with abdominal imaging such as ultrasound, but the AFP is not sensitive or specific for detecting HCC.
- Patients with cirrhosis who are not undergoing treatment should be seen and evaluated approximately every 6-12 months.
- Patients with compensated cirrhosis can be safely treated with pegylated interferon and ribavirin but it is not usually safe to treat decompensated patients.
- Decompensated patients should be considered for liver transplant, if appropriate.
- Ann Busch, Liver Transplant Clinical Nurse Specialist, Portland VAMC
- Sue Currie, Associate Director, HCRC, San Francisco VAMC
- Guadalupe Garcia-Tsao, Director, HCRC, Connecticut VAMC
- Douglas Heuman, Liver Transplant Program Director, Richmond VAMC
- Alexander Monto, Director, HCRC, San Francisco VAMC
- Roberta Ruimy, Manager, Liver/Kidney Transplant Programs, Portland VAMC
- Brenda Salvas, Health System Specialist, Manager, Liver and Kidney Transplant Program, VA Transplant Program, VA Central Office, Washington, DC
- Anna Sasaki, Staff Physician, Portland VAMC
- Kristine Stick, Nurse Practitioner for Hepatology, San Francisco VAMC
- Suchat Wongcharatrawee, Associate Director HCRC, Connecticut VAMC
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