68 Gastroenterology I NTERNAL M EDICINE N EWS • April 1, 2005 Investigational Agent Promising for B

BY MARTHA KERR “The objective here is to prevent the having unmeasurable virus levels (below arms at 7%. The most commonly report- Contributing Writer progression of liver disease,” said Dr. Gish, 400 copies/mL) after 48 weeks on the in- ed adverse effects were headache (about medical director of the California Pacific vestigational agent, compared with 38% 25% of both groups), upper respiratory in- B OSTON — Entecavir, an investigation- Medical Center in San Francisco. The on . Mean HBV DNA viral log fection ( about 20% of all patients), cough al oral antiviral agent, “achieves superior HBeAg wild-type strain accounts for 25%- scores dropped 6.78 log10 copies/mL in in about 15%, nasopharyngitis in 14%, up- histologic, virologic, and biochemical im- 40% of virus (HBV) cases. the entecavir group and 5.46 log10 per abdominal pain in 10%, fatigue in provement” in patients with e-antigen- At 48 weeks, histologic improvement copies/mL in the control group. “This is 10%, and fever in about 10%. Treatment positive chronic infection, had occurred in 72% of patients on ente- unprecedented,” Dr. Gish commented. “I was discontinued because of adverse Robert Gish, M.D., reported at the annu- cavir, compared with 62% on lamivudine, know of no other modality that suppress- events in 1% of patients on entecavir and al meeting of the American Association a statistically significant difference. Histo- es the virus to this extent.” 3% of patients on lamivudine. for the Study of Liver Diseases. logic improvement was defined as a re- No significant differences between the Bristol-Myers Squibb Co. has submitted In an international phase III study, 715 duction in the Knodell necroinflammato- lamivudine and entecavir groups were a new drug application to the U.S. Food patients with chronic hepatitis B who were ry score of at least 2 points plus no found for the percentages of patients with and Drug Administration and a marketing nucleoside naive and positive for hepatitis worsening of Knodell fibrosis. seroconversion, normalization of ALT lev- authorization application to the European B e-antigen (HBeAg) were randomized to There was a significantly greater re- els, or loss of HBeAg DNA. Medicines Evaluation Agency for ente- receive either entecavir 0.5 mg daily or duction in HBV DNA with entecavir than The incidence of serious adverse events cavir that includes data from this and oth- lamivudine 100 mg daily for 1 year. with lamivudine, with 70% of patients was low and equal in the two treatment er phase III trials of the drug. ■ Treatment Timing Tricky for Coinfection With HIV, HCV

BY ROBERT FINN treatment of HIV, Teresa L. Wright, M.D., with HIV and hepatitis C virus (HCV): . The guidelines recommend that San Francisco Bureau said at a meeting on HIV management Ǡ If the patient is in an early stage of HIV the dosage of combination ribavirin sponsored by the University of California, disease, consider HCV therapy prior to should reach 400 mg b.i.d. But Dr. Wright S AN F RANCISCO — In patients coin- San Francisco. HIV treatment. said, “we know from a lot of experience fected with HIV and hepatitis C, the pres- Based on recently published studies and Ǡ If the patient’s HIV disease is progress- with hepatitis C monoinfected patients ence of HIV disease complicates the treat- current U.S. and Canadian guidelines, Dr. ing, optimize HIV control that this dose of ribavirin is ment of hepatitis C, and, likewise, the Wright of UCSF listed some key principles first. Then, once the patient If the patient’s going to be inadequate and presence of hepatitis C complicates the in the management of patients coinfected is on a stable HIV regimen, suboptimal, particularly in consider HCV therapy. HIV disease is patients with genotype 1 in- Ǡ Treat psychiatric disease progressing, fections. So I think most of and substance abuse, which us now are increasingly try- can lead to reinfection. optimize HIV ing to get patients up at high- Ǡ When treating HCV, control first and er doses of ribavirin if toler- peginterferon alfa-2a should ated.” She mentioned a daily be administered subcuta- then consider dosage of 1,000-1,200 mg. neously at a fixed dosage of HCV therapy. Ǡ Especially with the higher 180 mcg once a week. dosages of ribavirin, patients Peginterferon alfa-2b should be adminis- are likely to require growth hormone sup- tered subcutaneously at a dosage of 1.5 port with epoetin alfa and/or granulocyte mcg/kg once per week. Two recently pub- colony-stimulating factor. lished studies indicate that total HCV viral Ǡ When treating HCV, avoid HIV regi- suppression is more likely with either of the mens containing didanosine (Videx) be- pegylated plus ribavirin than cause of ribavirin-associated increases in with standard plus ribavirin. Nei- drug levels and mitochondrial toxicity. ther of the studies compared pegylated in- Ǡ Monitor patients closely for side effects terferon alfa-2a (Pegasys) directly with pe- and drug-drug interactions. gylated interferon alfa-2b (Peg-Intron). Dr. Wright said she had no financial re- Ǡ Start patients on a reduced dosage of lationships relevant to her presentation. ■ Antiviral Tx May Cause Graft Rejection In Liver Transplant Patients With HCV

O RLANDO, FLA. — Antiviral therapy tion of HCV RNA from the serum, said for recurrent hepatitis C infection in pa- Dr. Rockey of Duke University, Durham, tients who have had orthotopic liver trans- N.C. Three patients died from complica- plantation promotes a sustained virologic tions associated with profound cholestasis. response, but also appears to contribute to Other reports of allograft rejection dur- a substantial number of allograft failures, ing antiviral therapy in transplant patients Don C. Rockey, M.D., reported at the an- have raised questions about the appropri- nual meeting of the American College of ateness of such treatment. Although ag- Gastroenterology. gressive anti-HCV therapy led to a sus- Of 49 patients who had liver transplan- tained virologic response in nearly a third tation for chronic hepatitis C virus (HCV) of the transplant patients with recurrent infection between 1991 and 2004 and who HCV who did not experience allograft re- received antiviral therapy with interferon jection, there is an apparent tradeoff in and ribavirin for recurrent HCV, 12 had a terms of an increased risk of rejection in sustained virologic response, 18 had a some patients, Dr. Rockey noted. measurable improvement in liver test re- Large randomized, controlled studies sults, and 7 developed acute and/or duc- are needed to better assess the effects of topenic allograft rejection during therapy. antiviral therapy on liver transplant pa- In each case, the development of ab- tients, he concluded. normalities was associated with elimina- —Sharon Worcester

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