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Lamivudine for Chronic Hepatitis B

Phase 2
Not Enrolling
Chronic Hepatitis B, Chronic Hepatitis D, Glomerulonephritis, Polyarteritis Nodosa

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Trial Information

Lamivudine for Chronic Hepatitis B

To assess the safety, antiviral activity and clinical benefit of lamivudine (3-thiacytidine:
3TC) in chronic hepatitis B, we will treat 60 patients with oral lamivudine in a dose of 100
mg daily for up to five years. Lamivudine is a nucleoside analogue which is used
extensively in patients with HIV infection and is being studied in controlled trials in
chronic hepatitis B. In this study, we will evaluate lamivudine in patients with four
different forms of chronic hepatitis B: (A) Atypical serology (HBeAg negative), (B)
extra-hepatic manifestations, (C) chronic delta hepatitis, (D) typical HBeAg- positive
chronic hepatitis B. After evaluation and liver biopsy, patients will receive lamivudine,
100 mg orally once daily for 1 year, being monitored at regular intervals for symptoms of
liver disease, side effects of lamivudine, serum biochemical and hematologic indices, and
serologic markers of hepatitis B (and D) virus replication. At one year, patients will have
a repeat medical evaluation and liver biopsy. If there is virologic, biochemical or
histologic evidence of benefit, therapy will be continued thereafter for up to 5 years.
Patients who develop viral resistance to lamivudine may be offered therapy with higher doses
of lamivudine (300 mg per day). The activity of lamivudine will be assessed by changes in
levels of HBV DNA or HDV RNA during treatment and its efficacy by loss of viral markers and
improvements in aminotransferases and liver histology.

Inclusion Criteria


Age 18 years or above, male or female.

Known presence of HBsAg in serum for at least 6 months.

Liver biopsy histology showing chronic hepatitis with or without cirrhosis.

Previous therapy with alpha interferon without a lasting effect or intolerance to alpha
interferon, due to side effects.

Written informed consent.

Group A: For patients with chronic hepatitis B with atypical serology: absence of HBeAg
from serum despite elevations in serum aminotransferases, such as that the average levels
are greater than 55 U/L (approximately 1.3 times the upper limit of the normal range)
based upon two determinations taken at least one month apart during the 6 months before

Group B: For patients with glomerulonephritis: proteinuria of greater than 1 gm per 24
hours. For patients with polyarteritis, radiological proof of arteritis and involvement
of at least on organ system outside of the liver.

Group C: For patients with chronic delta hepatitis: anti-HDV in serum and HDV antigen in
liver biopsy or HDV RNA in serum and elevations in serum aminotransferases, such that the
average levels are greater than 55 U/L based upon two determinations taken at least one
month apart during the 6 months before entry.

Group D: For patients with chronic hepatitis B and typical serology: HBeAg and HBV DNA in
serum but ineligibility to enter the multicenter trial of lamivudine either because of
previous receipt of interferon and intolerable side effects, refusal to receive interferon
again, because of normal serum aminotransferases, or lack of availability of the trial.


Pregnant or if capable of bearing or fathering children must practice adequate

Significant systemic illnesses other than liver diseases, including congestive heart
failure, renal failure, chronic pancreatitis, diabetes mellitus with poor control.

Pre-existing bone marrow compromise: hematocrit must be greater than 30%, white blood
cell count must be greater than 2000 mm(3), platelets must be greater than 70,000 mm(3).

Creatinine clearance must be greater than 50 cc/min.

A history of clinically apparent pancreatitis or evidence of subclinically pancreatitis as
shown by serum amylase values twice the upper limits of the normal range and abnormalities
of the pancreas on computerized tomography or other imaging studies of the abdomen.

Irreversibly severe cirrhosis as defined by Child's stage C.

Presence of anti-HIV or anti-HCV with HCV RNA in serum.

Immunosuppressive therapy requiring use of more than 10 mg of prednisone (or its
equivalent) per day.

Other antiviral therapy for chronic hepatitis B within the previous 3 months.

Sensory or motor neuropathy apparent from medical history and physical examination.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

September 1995

Completion Date:

September 2005

Related Keywords:

  • Chronic Hepatitis B
  • Chronic Hepatitis D
  • Glomerulonephritis
  • Polyarteritis Nodosa
  • Nucleoside Analogues
  • Delta Hepatitis
  • Glomerulonephritis
  • Polyarteritis Nodosa
  • Hepatitis Mutants
  • 3TC
  • Chronic Hepatitis B
  • Chronic Hepatitis D
  • Cirrhosis
  • Lamivudine
  • Hepatitis D
  • Glomerulonephritis
  • Hepatitis
  • Hepatitis A
  • Hepatitis B
  • Hepatitis, Chronic
  • Polyarteritis Nodosa
  • Hepatitis B, Chronic
  • Hepatitis D, Chronic



National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Bethesda, Maryland  20892