Novel H1N1 in fluenza A virus infection in a patient with acute rejection after liver transplantation

Hangzhou,China

Introduction

The year 2009 was notable for the outbreak of a novel strain of in fluenza A (H1N1).Since April 2009,thousands of cases of this novel in fluenza have been reported worldwide,resulting in thousands of deaths.In fluenza A (H1N1) pneumonia in immunosuppressed patients after transplant has been reported; severely affected patients present pneumonia,respiratory failure and acute respiratory distress syndrome.[1-4]Here we report a case of a liver transplant recipient who developed H1N1 virus infection and had a favorable outcome.

Case report

A 52-year-old man underwent adult-to-adult living donor liver transplantation for end-stage liver cirrhosis due to hepatitis B on October 14,2008.He received tacrolimus-based immunosuppressive therapy and steroids were tapered in 3 months.However,he was admitted again for abnormal liver function on December 8,2009,with alanine aminotransferase 218 IU/L and total bilirubin 56 μmol/L.After vascular and biliary complications were excluded,acute rejection was first considered.As the patient refused a liver biopsy,we had to increase the tacrolimus concentration from 2.5 to 7.8 ng/ml by adjusting the dose.One week later,the level of total bilirubin remained almost the same.Then moderate acute rejection was confirmed by liver biopsy.High-dose steroids (500 mg methylprednisolone for three days) were immediately administered for acute rejection,but unfortunately there was no response.The level of total bilirubin dose to 215 μmol/L within one week,so the condition was defined as steroid-resistant acute rejection.A new cycle of steroids at the same dose was used on day 20 after admission,however this was relatively ineffective.

On day 28 after admission,the patient presented with a fever of 39.1 ℃ accompanied by in fluenza-like symptoms including cough,sore throat,headache and stuffy nose.His respiratory condition and blood gas analysis remained normal.A chest CT showed a small left basal pleural effusion and some lesion foci.Realtime polymerase chain reaction (PCR) positivity for novel H1N1 in fluenza A from nasal secretions was confirmed on the day after the fever began.Blood and sputum culture results were negative for bacteria and fungi and blood detection of specific IgM antibody for cytomegalovirus was negative.

The patient was transferred immediately to a special isolation ward designed for H1N1 infected patients.After 72-hour treatment with oseltamivir 75 mg orally twice daily,the patient's temperature decreased from 39.1 ℃to normal,coinciding with a resolution of symptoms.Invasive mechanical ventilation was not needed.Fluconazole and antibiotics were also empirically used because bacterial and fungal pneumonia after in fluenza infection are common in immunocompromised patients,especially when high-dose steroids are administered for acute rejection.After his temperature became normal and PCR negative,he was transferred back to an ordinary ward,where oseltamivir was maintained for one week.Chest CT scan showed a significant improvement compared with the previous images.Amazingly,his liver function gradually improved and approached the normal level in the following 20 days.The patient was discharged home on day 50 in good clinical condition with slightly abnormal liver function.Chest CT scan during the follow-up showed a normal radiological demonstration.

Discussion

The 2009 H1N1 in fluenza pandemic has heightened the interest of clinicians in options for the prevention and management of in fluenza virus infection in immunocompromised patients.The Ministry of Health of China has been notified of more than 120 000 cumulative laboratory-confirmed human cases and 648 deaths (data as of December 31,2009),but H1N1 in fluenza A infection in transplant recipients,especially in liver transplant recipients,are seldom reported in the literature from the mainland of China.The spectrum of manifestations and management of this novel virus in transplanted patients is currently of major concern.It ranges from asymptomatic manifestations to the severe complications of acute respiratory distress syndrome,and eventually multi-organ failure and death.[1-5]The infection of a hospitalized transplant recipient we described above was relatively mild.He improved promptly,and prolonged viral shedding was not noted.During the in fluenza pandemic in China,transplant recipients did not receive the in fluenza vaccine routinely; only healthcare workers,students and teachers were predominantly included in the vaccination strategy.Meanwhile,whether liver transplant recipients should receive vaccine is still controversial.Adult liver transplant recipients have also been reported to be adequately protected by the vaccine in the study of Burbach et al,[6]protective post-immunization titers are lower than those in healthy controls,and recipients are thought to be at a higher risk of developing a severe infection from in fluenza because of a decreased immune response.[7-9]To prevent the transmission of novel H1N1 in fluenza A,oseltamivir is widely recommended by international societies; this strain appears to be typically susceptible to oseltamivir.Seville et al[10]reported that 2009 H1N1 in fluenza in their cohort of hospitalized transplant recipients was relatively mild.The majority of the patients improved promptly,and prolonged viral shedding was not noted.However oseltamivir-resistant in fluenza A (H1N1) viruses emerged in several countries and this resulted in prolonged shedding of the virus in immunocompromised patients.[11,12]In conclusion,immunosuppressed patients,despite the greater rate of complications,are able to recover well if prompt measures are taken during the pandemic.Undoubtedly,attention should be paid to its prevention,diagnosis,therapy,and possible complications.

Funding:This study was supported by a grant from the National Key Technology R&D Program of China (2008ZX10002-26).

Ethical approval:Not needed.

Contributors:HJJ wrote the first draft of this commentary.All authors contributed to the intellectual context and approved thefinal version.ZSS is the guarantor.

Competing interest:No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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