Meet the expert: microbiology case presentation

Abstract

A 64-year-old man underwent an orthotopic liver transplant in October 2008 for end-stage cirrhosis secondary to hepatitis C virus (HCV) infection. His HCV infection (genotype 1A) had previously been unresponsive to treatment with pegylated-interferon-α and ribavirin. He suffered an episode of mild acute rejection 6 days post-operatively, which was responsive to steroids, and his subsequent immunosuppressive regime consisted of cyclos-porine and prednisone. Given that there was cytomegalovirus (CMV) serostatus mismatch (D+/R-), he was also given prophylactic valganciclovir for 12 weeks post-operatively. One week after discontinuation of valganciclovir, he developed malaise, anorexia, spiking fevers and dyspnoea. He was admitted to hospital, and was profoundly hypoxic, with bilateral chest infiltrates. He was commenced on iv ganciclovir, pending CMV levels. However, his CMV viral load was undetectable, as was his Epstein-Barr virus (EBV) viral load and no CMV was detected in a bronchoalveolar lavage specimen. However, his white blood cells and plasma were strongly positive for human herpes virus-6 (HHV-6), as was his broncho-alveolar lavage specimen and a diagnosis of HHV-6 pneumonitis was made. He was treated with 2 weeks of iv ganciclovir, and 2 months of valganciclovir, and made a good clinical response. One month after discontinuation of his valganciclovir, he developed worsening graft dysfunction, fevers and diarrhoea. A liver biopsy revealed recurrent HCV infection, and his CMV viral load was elevated. He was again commenced on ganciclovir, although after one week there was no clinical response, and his high CMV viraemia remained unchanged. A molecular and clinical diagnosis of ganciclovir resistance was made, and he received 2 weeks of foscarnet therapy, to which he responded, although this was discontinued due to renal impairment and neurotoxicity. He was commenced on low-dose cidofovir for 3 months, and during this time also developed a CMV IgG response. He has remained free of HHV-6 or CMV-related disease for 6 months to date. This case posed several management and diagnostic dilemmas: •the role of HHV-6 as a true pathogen given that it can reactivate in many transplant recipients; •duration of prophylactic therapy in CMV mismatch patients; •development of ganciclovir resistance and toxicity of second-line agents. A 64-year-old man underwent an orthotopic liver transplant in October 2008 for end-stage cirrhosis secondary to hepatitis C virus (HCV) infection. His HCV infection (genotype 1A) had previously been unresponsive to treatment with pegylated-interferon-α and ribavirin. He suffered an episode of mild acute rejection 6 days post-operatively, which was responsive to steroids, and his subsequent immunosuppressive regime consisted of cyclos-porine and prednisone. Given that there was cytomegalovirus (CMV) serostatus mismatch (D+/R-), he was also given prophylactic valganciclovir for 12 weeks post-operatively. One week after discontinuation of valganciclovir, he developed malaise, anorexia, spiking fevers and dyspnoea. He was admitted to hospital, and was profoundly hypoxic, with bilateral chest infiltrates. He was commenced on iv ganciclovir, pending CMV levels. However, his CMV viral load was undetectable, as was his Epstein-Barr virus (EBV) viral load and no CMV was detected in a bronchoalveolar lavage specimen. However, his white blood cells and plasma were strongly positive for human herpes virus-6 (HHV-6), as was his broncho-alveolar lavage specimen and a diagnosis of HHV-6 pneumonitis was made. He was treated with 2 weeks of iv ganciclovir, and 2 months of valganciclovir, and made a good clinical response. One month after discontinuation of his valganciclovir, he developed worsening graft dysfunction, fevers and diarrhoea. A liver biopsy revealed recurrent HCV infection, and his CMV viral load was elevated. He was again commenced on ganciclovir, although after one week there was no clinical response, and his high CMV viraemia remained unchanged. A molecular and clinical diagnosis of ganciclovir resistance was made, and he received 2 weeks of foscarnet therapy, to which he responded, although this was discontinued due to renal impairment and neurotoxicity. He was commenced on low-dose cidofovir for 3 months, and during this time also developed a CMV IgG response. He has remained free of HHV-6 or CMV-related disease for 6 months to date. This case posed several management and diagnostic dilemmas: •the role of HHV-6 as a true pathogen given that it can reactivate in many transplant recipients; •duration of prophylactic therapy in CMV mismatch patients; •development of ganciclovir resistance and toxicity of second-line agents.