Management of hepatitis B and C virus infections among people with Hemophilia

Magnitude of the problem

The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among the general population in India is 4% and 0 – 1.7%, respectively. The prevalence of these infections are much higher among people with Hemophilia with HBV infection occurring in 5-10% and HCV infection in 30-35% of multiply transfused patients. These infections therefore contribute to significant morbidity and mortality among them.

Diagnosis of infection

A battery of serologic and molecular tests are available to diagnose HBV and HCV infection. These tests are expensive and should be chosen depending on the clinical indication.

Screening tests for HBV and HCV infection are HBV antigen (Ag.) and HCV antibody, respectively.

IgM core antibody: Indicates acute HBV infection.
AntiHBV antibody: Protective antibody against HBV infection.
HBV DNA PCR } Indicates replicative HBV infection.
HCV RNA PCR: Indicate viremic status.

The last 3 markers mentioned above are done, when antiviral treatment is being considered. (Please see section on antiviral treatment.)

Spectrum of disease caused by HBV or HCV infection
When we see a patient with either of these infections, we aim to categories the patient into one of the following categories:

Acute infection  
Acute hepatitis Typical illness has 3 phases – prodromal, hepatitic and cholestatic. Lasts < 6 months.
Fulminant hepatic failure Onset of hepatic encephalopathy within 6 weeks of the first symptom (no evidence of underlying chronic liver disease).
Subacute hepatic failure Fluid overload state occurring 8 weeks after the first symptom (with no evidence of underlying chronic liver disease).
Chronic infection  
Chronic hepatitis Is a histologic diagnosis, > 6 months of illness
Cirrhosis Is a histologic diagnosis showing necrosis, regenerating nodules and fibrosis in the liver.
Hepatocellular carcinoma Proven by histology and elevated serum alphafetoprotein level.
Carrier Implies chronic infection with no symptoms or signs, been         suggested that this term should be no longer used.

Antiviral Treatment
When is antiviral therapy indicated?

HBV/HCV Related Chronic Hepatitis And Cirrhosis
The complications of chronic liver disease occur more frequently in the following subsets of patients with HBV / HCV related chronic hepatitis or cirrhosis:
Replicative HBV infection (ie: patients who are HBe antigen or HBV DNA positive).

HCV RNA positive.
Hence, antiviral treatment is advocated in these patient groups, aimed to convert the patient to non-replicative HBV infection or HCV RNA negative status. Antiviral treatment has also been shown to reduce the risk of developing liver cancer among patients with HBV and HCV related chronic liver disease.

Acute Hepatitis B Or C
As the risk of deleloping chronic infection is low (10%) in acute hepatitis B, antiviral therapy is not required. Acute hepatitis C, on the other hand, is treated with antiviral therapy (if patient is viremic), as the risk of chronicity is high (85%).

Other Situations Lamivudine is reported to be beneficial in patients with HBV related fulminant and sub- acute hepatic failure, who have replicative HBV infection.

HBV Treatment    
Drugs available Duration of treatment Cost in Rupees (2003)
PEG Interferon alpha 2A or 2B 4 months 2.1 lakhs
Interferon alpha 2A or 2B 4 months 80,000
Lamivudine 6 months 6000
Drugs available Duration of treatment Cost in Rupees (2003)
PEG Interferon alpha 2A or 2B 4 months 3.2 lakhs
Interferon alpha 2A or 2B 4 months 80,000
Ribavarin 6 month 50000

Genotyping and quantification of viral load are helpful in predicting effectivenessof treatment and deciding duration of treatment in chronic hepatitis C.

Management of complications of liver disease
Portal hypertension: Drugs to reduce portal pressure (ex: Propranolol) are used as both primary and secondary prophylaxis against variceal bleed. Endoscopic therapy (ex: sclerotherapy / variceal ligation) or porto-systemic shunt surgery are indicated, once variceal bleed has occurred. Fluid overload state: Salt and fluid restriction is the cornerstone of treatment. Spironolactone is the preferred diuretic, as patients often have secondary hyper-aldosteronism. Hepatic encephalopathy: Anti-hepatic coma measures (nil protein diet, oral ampicillin, bowel wash, lactulose) are instituted. Any precipitant for hepatic encephalopathy ex: hypokalemia, should be quickly identified and corrected.

Liver transplantation
This is advised when a patient’s liver functions deteriorate such that major complications ex: hepatic encephalopathy occurs. The engrafted liver produces the deficient coagulation factor as well, thus cures the Hemophilia.

Hepatitis B vaccination should be given to all Hemophiliacs, after checking their HBsAg status. It is not clear whether a booster dose is needed or not. No vaccine is available against hepatitis C.

Dietary misconceptions are common among patients with liver disease. Patients with liver disease should have a normal diet. They can eat any food that they can tolerate. Patients who develop fluid overload (ascites / pedal oedema) are advised to restrict salt intake. Protein restricted diet is advised only if patient develops altered mentation.