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Ask the Experts
Q: Why do those who are perinatally infected with HBV develop chronic infection while adults have acute HBV? A: Dr. Di Bisceglie replied: Q: Would you treat a 33-year-old Asian woman with HBV who is 4 months pregnant; HBeAg positive; ALT level 308; AST level 108; and whose HBV DNA viral load is greater than 7 log IU, 5 million copies? No liver biopsy, no recent ultrasound with tenofovir. Her last ALT levels 1 year ago were within normal limits. What is the prognosis for this patient? Is breastfeeding recommended while on tenofovir or should the patient switch to lamivudine? A: Dr. Gish replied: Q: If the HBV DNA has not decreased at all at 24 weeks of treatment with pegylated interferon, should the interferon be stopped and the person be started on an oral anti HBV agent, or should we continue pegylated interferon for the full 48 weeks? A: Dr. Adrian M. Di Bisceglie replied: Q: How would you manage a 28-year-old Asian female who wants to start a family, and has HBeAg-negative HBV with a viral load varying from 4-6 log IU over the past 2 years, ALT and AST ranges 18-24, and a recent liver biopsy showing 1/18 HAI and 0/6 fibrosis? A: Dr. Robert G. Gish replied: Q: I use anti-HBc, rather than anti-HBs, to screen patients for hepatitis B. Can you discuss the advantages and disadvantages of anti-HBc, anti-HBs, and HBsAg for screening purposes? A: Dr. Robert G. Gish replied: Posting #8Q: What is the current protocol for withdrawing HBIG post-OLT in chronic hepatitis B patients at your institution, Dr. Kim? A: We have recently implemented a short-term HBIG protocol where we discontinue HBIG after a month in patients whose HBV-DNA <10,000 IU/ml at the time of transplantation. Depending on the prior treatment exposure history, we use emtricitabine in combination with tenofovir from the time of transplantation. We follow HBV DNA monthly during the first year then at their regular laboratory interval. We have not started withdrawing stable existing patients at the present time. Thus, our existing patients are being maintained on IM or IV HBIG program, in whom we plan to systematically discontinue HBIG, once we are satisfied with our experience with the short term HBIG protocol in the next few (~5?) patients. We are on the conservative side, as I am aware of several transplant centers where HBIG is discontinued after the first few months. I am not aware of any particular procedure to follow to withdraw HBIG, other than it is obviously important to use an effective antiviral regimen in a given patient. For example, in patients who broke through lamivudine prior to transplantation, one should avoid using lamivudine. Q: What is considered an effective response to 150 mg of lamivudine daily if a patient's HBV DNA levels are greater than 1 million after 3 months of treatment? A: Dr. Robert G. Gish replied: Posting #4Q: An African American male, age 45, with chronic HBV, positive HBV DNA, negative HBeAb, positive HBeAg. He also has ulcerative colitis that is quiet at this time. He has failed lamivudine, and HBV DNA levels increased on adefovir. What would you suggest as the next step in therapy? A: Before changing drug regimens, it is worthwhile to make sure that the patient is compliant with the current therapy. Provided that this is the case, there are several options. First, of the approved oral agents for treatment of hepatitis B, one that should still work is entecavir. It has been shown in a randomized study to effectively suppress HBV DNA in patients with lamivudine resistance. Although no formal study has been done to prove its efficacy in patients with adefovir resistance, there is no cross resistance between adefovir and entecavir. However, the potency of entecavir in lamivudine-refractory patients is lower than that in treatment-naive patients. Second, what is commonly done in this setting is to use tenofovir alone or in combination with emtricitabine (Truvada®). Tenofovir is equipotent as adefovir but without renal toxicity, which allows larger doses (300mg/d) to be used. Recently, the efficacy of tenofovir in this specific setting has been reported [van Bommel F, et al. Hepatology. 2006;44(2):318]. Third, it is worth remembering that there is no cross resistance between interferon and oral agents. However, in this patient with ulcerative colitis, the risk of colitis flare makes this option less attractive. Q: Three Vietnamese family members—father, age 55, a girl, age 16, and a son, age 21. No clinical complaints. All 3 have HBV DNA >100,000,000 copies/ml, and normal ALT levels. The father had a liver biopsy showing minor inflammation and grade 1 fibrosis. Should I treat, and, if so, how? A: Although the ALT and HBV DNA status look the same between the father and the children, it is highly likely that they are in different phases of HBV infection. The children are probably HBeAg-positive and in the 'immune tolerant' phase of the infection, where the virus replicates freely without being recognized by the host immune system. Classically, they have no liver disease, even if a biopsy were to be performed. There is no data to date to suggest that treatment in this setting leads to either sustained suppression of the virus or changes in long term outcome. The current AASLD guideline recommends following their ALT every 3-6 months [Lok AS, et al. Hepatology. 2004;39(3):857]. In my practice, I recommend follow-up with ALT every six months and clinical examination every year. I try to make the follow-up schedule as easy as possible in these asymptomatic individuals. The father, on the other hand, is probably HBeAg-negative and HBeAb-positive, and from the fact that he has active viremia, he likely has HBeAg-negative chronic hepatitis B (by so-called precore mutant). The biopsy and ALT suggest that he has a very mild case of that. This is one of the cases where it is difficult to decide to treat. The patient has minimal liver disease, and how much improvement will be gained by antiviral therapies (which will undoubtedly decrease the viral load) may be questionable. One must recognize the downside of jumping into antiviral therapy in this situation, as the therapy is likely indefinite, which increases the likelihood of viral resistance. Viral resistance will limit our ability to treat the patient, if and when he develops more serious hepatitis later on. One caveat here is that some patients with HBeAg-negative chronic hepatitis B present with a fluctuating course where apparently inactive disease is interrupted by flares of hepatitis activities [Bonino F, et al. J Hepatol. 2003;39 Suppl 1:S160]. Those patients are at a high risk of developing cirrhosis and thus, this patient needs close monitoring. In this patient, I would recommend monitoring every six months. Finally, recent data show that these patients (normal ALT, no cirrhosis, and high viral load) are at a high risk of developing hepatocellular carcinoma (HCC) [Chen CJ, et al. JAMA. 2006;295(1):65]. What remains unknown is whether reduction of viral load with antiviral therapy will decrease the risk of HCC. In my practice, I discuss the data with them and try to arrive at a consensus. Family history often is an important element in this decision. Regardless, it cannot be overemphasized that this patient needs to be under HCC surveillance [Sherman M. Am J Gastroenterol. 2006;101(Suppl 1):S26-31]. Q: Please comment on strategies for reactivation of hepatitis B infection. I have a patient who has HBeAb, is HBsAg-positive, HBsAb-negative, and has a history of prior infection in the early 1990's. He now has high enzymes 700/800 (ALT/AST), a Pos Core IgM Atb, neg delta virus, and DNA level of 3 million IU/ml. On a followup visit the enzymes came down slightly. Do I wait or consider Rx...an oral analog or interferon? Also, do strategies vary with reactivation cases? A: The clinical course in patients with HBeAg-negative chronic hepatitis B may be divided into two patterns. The first type is patients with persistently increased serum ALT levels, which tend to be mild elevation (>x3-4 ULN). The second type entails fluctuating pattern of ALT flares mixed with periods of apparent inactivity. With the latter type, severe flares of hepatitis, resembling acute hepatitis B with positive IgM anti-HBc and high levels of ALT (sometimes exceeding 1,000 IU/L) may occur.1 These second type of patients should be strongly considered for treatment because they are at high risk of progressive liver disease leading to cirrhosis and then to end stage liver disease.2 With regard to choice of agents, both interferon and oral agents are acceptable, perhaps with a slight advantage for interferon, as patients with IgM core have been reported to have higher likelihood of sustained response to interferon (and presumably to pegylated interferon).3 Obviously, if the patient has a contraindicaiton for interferon, oral agents should be used, with a realistic expecatation that the therapy will continue indefinitely. References
Posting #1Q: Your first answer is fine, as blood donors who are HBsAg negative, Anti HBc total (+) & Anti HBs positive are accepted. However, those who are HBsAg negative, Anti HBc total (+) & Anti HBs negative are advised to take a hepatitis B vaccine, and if they develop anti HBs positive, they are re-entered as blood donors. Do you believe that this practice is acceptable? A: If the patient developes an excellent anamnestic response to one dose of HBV vaccine (i.e., with titers > 50-100 IU) then I believe this would be evidence of good immune response to HBV. Q: In Saudi Arabia, blood donors who repeatedly test positive for HBc total antibody and negative for HBsAg are given HB vaccination. After vaccination, if they are found positive for Anti-HBs, even with positive Anti-HBc, they are accepted as blood donors. Do you think that this is an acceptable practice? Please comment. A: This is based on the assumption that patients with Anti-HBc who also have Anti-HBs are immune and, therefore, are unlikely to infect others. However, it has been shown that a small proportion of patients who are Anti-HBc and Anti-HBs positive may, in fact, have low levels of circulating HBV DNA in the serum. Although this does not represent a problem in the immunocompetent individual, it is theoretically possible that infants, children and immunosuppressed individuals may develop HBV infection. By contrast, such patients can be utilized as donors if their serum shows no HBV by PCR assay. Also, recipients who are already immune to HBV (Anti-HBs positive) will probably do fine with the transfusion. This is my opinion. |
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