Treatment of severe psoriasis with biological therapies in patients with viral hepatitis B and C
Authors: R.B. Warren, A. Al-Ri Fai
Journal: British Journal of Dermatology (2013)

Randomized controlled trials of biological therapies for the treatment of psoriasis are key resources that dermatologists may utilize when deciding in whom, and how, to prescribe certain therapies. In the fast-evolving field of psoriasis therapeutics there is no shortage of trials to review. However, by their very nature, rarely do they cover scenarios of drug use that may be more challenging, yet faced on a regular basis by the practising dermatologist. One such scenario is the use of biological therapies in patients infected with potentially chronic viral infections such as hepatitis (hep) B or C. In this edition of the British Journal of Dermatology (BJD), a retrospective case series of patients infected with hep B and C, who have been treated with either antitumour necrosis factor (anti-TNF) therapies or ustekinumab, is presented alongside a single case report about reactivation of hep B virus while on ustekinumab.1, 2 It is estimated that up to 210 million people worldwide are chronically infected with hep C.3 In Western Europe the prevalence is estimated to be in the range of 0·4–3%.4 Dermatologists can expect a similar incidence of hep C among their patients. In patients who have received solid organ transplants, hep C has a more rapid and aggressive course with worse outcomes, an effect thought to be mediated in part by the use of immunosuppressive therapy.5 In addition, treating hep C with interferon, the current gold-standard therapy, can lead to a flare of psoriasis.6 Therefore, initial assessment of these patients and close monitoring and follow-up are essential, with decisions on treatment being made jointly between the dermatologist and hepatologist. However, in the case of hep C there is now considerable evidence documenting the safety of anti-TNF treatment in such patients.7 Concomitant treatment of hep C with interferon-based regimens, in the presence of anti-TNF agents, has been shown to be safe with no reduction in efficacy. Indeed, concomitant etanercept and interferon has even been associated with improved outcomes in the treatment of hep C.8 The data in the case series, presented in this edition of the BJD, support these findings, in addition showing that the use of ustekinumab may also be safe.1 It is important to note that, in this report, two cases of hepatocellular carcinoma (HCC) developed in the cohort of 20 patients. As this was a retrospective cohort, firm conclusions are hard to draw, but a detailed examination of the two cases is worthwhile. In case 3 the patient had had a diagnosis of hep C for 9 years and had not been treated. He had received ustekinumab for only 9 months. The report does not say whether the patient had cirrhosis or not, whether treatment of his hep C was contraindicated, or what his viral load was. In the absence of further information no conclusions can be made regarding this case. In case 18, the 47-year-old man already had established cirrhosis due to alcoholic liver disease, and his hep C was diagnosed only on screening. The HCC in this case is likely to be related to the natural history of the disease. The incidence of HCC in patients with hep C and cirrhosis is between 1 and 8% per year, with heavy alcohol intake increasing this risk two- to fourfold.9 Hep B infection appears to be more problematical than hep C in the setting of concomitant immunosuppression. Reactivation of hep B in patients treated with chemotherapy and immunosuppressive agents has been well documented and can occur in up to 50% of cases.10 However, patients who have cleared a previous hep B infection seem to have a much lower rate of reactivation, which is estimated to be around 1–2%. In their recent meta-analysis, Lee et al.11 found this rate to be 1·7% in patients treated with anti-TNF agents, and who were hep B surface antigen (HBsAg) negative but hep B core antibody (Anti-HBc) positive. These data show that the use of these agents in patients with hep B is risky and even potentially fatal if the appropriate screening tests and prophylaxis are not initiated. Screening for hep B is now recommended for all patients before starting biological therapy.12 However, what tests to request and the interpretation of these tests can still be a challenge for the nonspecialist. When screening for hep B we suggest that the following tests should be carried out to categorize the patients into four groups. (i) HBsAg positive, the presence of which indicates that the person is a carrier and infectious, (ii) Anti-HBc, which appears with the acute infection and persists for life. The presence of this represents a previous infection, (iii) Hep B surface antibody (Anti-HBs), which indicates either recovery or immunity due to vaccination. Checking Anti-HBs is recommended if both (i) and (ii) are negative, (iv) Hep B virus (HBV) DNA, which represents the viral load detected in the serum. This usually indicates activity. The viral load should be checked if (i) and/or (ii) are positive. The first group consists of the patients who have chronic hep B, identified as HBsAg positive. Although these patients will normally require antiviral treatment when their disease is active, in the context of starting these patients on anti-TNF agents or ustekinumab they should be started on antivirals first, regardless of their viral load. The five patients reported by Navarro et al.1 belong to this group and were all on antiviral treatment prior to starting anti-TNF therapy. The second group, and the more tricky one, is those who have the so-called ‘resolved infection’. These are identified as being HBsAg negative, but Anti-HBc positive, as was the case in the report by Koskinas et al.2 The risk of reactivation in this group of patients is low, but it can be catastrophic if it occurs. These patients should have a baseline viral load (HBV DNA) measurement at the start of treatment with the biological agent. If they have a detectable viral load then antiviral treatment should be considered. If the HBV DNA is undetectable, this should be monitored every 1–3 months on treatment, and if it becomes detectable then oral antiviral treatment should be started regardless of the liver-function tests. The third and fourth groups are those who are negative for HBsAg and for Anti-HBc. These patients are either susceptible and Anti-HBs negative, or they are vaccinated, in which case their Anti-HBs will be positive. We propose that susceptible patients are offered vaccination. No action is needed for the vaccinated group. It is clear that careful monitoring of patients on biological therapies, especially those with concomitant infections, must be robust and multidisciplinary. Ultimately, registers, such as the British Association of Dermatologists’ Biologic Interventions Register, will be crucial to informing the longer-term safety of biological agents in complex clinical scenarios, such as those reported in this edition of the BJD.13 None declared.