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A 35-year-old Asian man with jaundice and markedly high aminotransferase levels

Cleveland Clinic Journal of Medicine. 2009 August;76(8):449-456 | 10.3949/ccjm.76a.08006
August 1, 2009|Cleveland Clinic Journal of Medicine
Ibrahim A. Hanouneh, MD;Rami Khoriaty, MD;Nizar N. Zein, MD, FAASLD
Author and Disclosure Information

Ibrahim A. Hanouneh, MD
Department of General Internal Medicine, Cleveland Clinic

Rami Khoriaty, MD
Department of General Internal Medicine, Cleveland Clinic

Nizar N. Zein, MD
Mikati Foundation Endowed Chair in Liver Diseases; Chief, Section of Hepatology; Medical Director of Liver Transplantation, Department of Gastroenterology and Hepatology, Transplantation Center, Cleveland Clinic

Address: Nizar N. Zein, MD, Digestive Disease Institute, A30, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail zeinn@ccf.org

WHAT IS THE NEXT STEP?

4. Which of the following is the most appropriate next step in the management of this patient?

  • Liver transplantation
  • HBV immunoglobulin only
  • Interferon and a nucleoside analogue
  • Liver-assist devices
  • Continue supportive care only

Liver transplantation. Since the patient’s severe acute hepatitis is accompanied by coagulopathy and encephalopathy, he meets the definition of having acute liver failure. Liver transplantation remains the only definitive therapy.

The most commonly used prognostic criteria in patients with acute liver failure are those developed at the King’s College Hospital (Table 3).13 Several studies have shown these criteria to have positive predictive values ranging from slightly less than 70% to nearly 100% and negative predictive values ranging from 25% to 94%.14–16 According to the King’s College Hospital criteria, our patient has a poor prognosis (having a prothrombin time > 50 seconds, total bilirubin > 18 mg/dL, and jaundice for more than 7 days before the onset of encephalopathy) and may benefit from liver transplantation.

HBV immune globulin immunoprophylaxis is indicated in patients with HBV infection undergoing liver transplantation, to prevent recurrence of hepatitis B after the transplant, particularly in those with a high pretransplant viral load.17 The use of pretransplant antiviral therapy and the posttransplant combination of antiviral therapy and HBV immune globulin has reduced the rate of hepatitis B recurrence to less than 10%. However, immune globulin is by no means the best single next step in managing this patient, who clearly needs a new liver.

Interferon, nucleoside analogues. Options for antiviral treatment are interferon alfa and nucleoside analogues. Interferon therapy is contraindicated in patients such as ours, who have decompensated liver disease, because it can exacerbate the disease.18

Figure 2. Evaluation of patients with chronic hepatitis B virus infection. ALT = alanine aminotransferase; HBsAg = hepatitis B virus surface antigen; HBeAg = hepatitis B virus e antigen
Treatment with a nucleoside analogue—lamivudine (Epivir), adefovir (Hepsera), entecavir (Baraclude), telbivudine (Tyzeka), or tenofovir (Viread)—is a safe and well-tolerated alternative in those with decompensated liver disease. The major complication of long-term lamivudine therapy is the emergence of resistant viral strains. There is no evidence that combination therapy with interferon and lamivudine is superior to antiviral monotherapy in improving the treatment outcome; however, combination therapy may decrease the rate of lamivudine-resistant mutations.

The suggested evaluation of patients with chronic HBV infection is shown in Figure 2. Table 4 shows the current recommendations for treating it.18,19

Liver-assist devices. Because liver allografts are in short supply, there has been a strong interest in developing a device that would provide the same benefits for patients with liver failure as hemodialysis does for patients with renal failure. Trials are under way to determine the efficacy and safety of these devices.20

Case continues: He receives a liver

The patient undergoes liver transplantation. He is given HBV immune globulin during and after the surgery.

Pathologic review. Under the microscope, his old liver has widespread necrosis and hemorrhage as well as inflammatory changes suggesting a chronic viral process. Regenerative nodules are present in the small amount of surviving liver parenchyma, consistent with early cirrhosis. Iron staining shows +3 depositions in areas of hepatic collapse (a nonspecific finding). Periodic acid-Schiff staining after diastase (used to detect alpha-1 antitrypsin deficiency) is negative. Herpetic viral inclusions are not present.

An immunoassay for herpes simplex virus antigen is negative. Immunostaining with antibodies to the HBV core antigen is negative. HBV surface antigen is strongly and diffusely positive in the cytoplasm of 80% to 90% of hepatocytes. The immunohistologic staining pattern is consistent with integration of HBV DNA into the DNA of hepatic tissue.

Postoperative course. Lamivudine is continued after surgery, and the patient is sent home. He has resumed the level of functioning he had before becoming ill.

Comment. The outcome of liver transplantation for hepatitis B has notably improved since HBV immune globulin and nucleoside analogues were introduced. The results of liver transplantation for hepatitis B, particuarly patient and graft survival rates, are now better than those in transplant patients with hepatitis C and similar to those in transplant patients with other types of liver disease.21 The combination of HBV immune globulin and lamivudine has cut the rate of HBV reinfection after liver transplantation to approximately 10% and increased the 5-year survival rate after transplantation to about 80%.17,22

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