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Liv.52 Update
P R O B E
• V o l . L I I I • N o . 3 • A p r – J u n 2 0 1 4
mutants, it is critical to develop new
antiretroviral agents and HD-03/ES is
one such agent.
HD-03/ES capsule is a herbal
formulation consisting of 125 mg each
of hydroalcoholic extracts of the herbs
Cyperus rotundus
and
Cyperus scariosus
.
Acute and subacute toxicity studies
conducted in rats indicated that
HD-03/ES is devoid of significant
toxicity following acute and repeated
administration in rats (Data on file).
Therefore, the objective of the present
clinical study was to determine
whether HD-03/ES administration
is safe and effective for human
administration in the management of
chronic hepatitis B (CHB).
Aim
To determine the safety and efficacy
of HD-03/ES therapy in patients with
CHB
Patients andMethods
Patients
An open prospective controlled
clinical trial was carried out in the
Department of Medicine, RG Kar
Medical College (Calcutta, India)
between March 2003 and February
2005 to evaluate the safety and
efficacy of the herbal formulation
HD-03/ES capsules alone in the
management of hepatitis B. They were
selected from those attending the
Outpatient Department of Medicine,
RG Kar Medical College. Informed
written consent was obtained from all
study participants and the protocol
of the study was approved by the
ethical committee of the institute.
The study in general was conducted
in accordance with Declaration
of Helsinki and GCP Guidelines
issued by the Ministry of Health,
Government of India.
Diagnostic criteria
Patients with a history of hepatitis B or
hepatitis B surface antigen (HBsAg)
carriers for at least 6 months, who still
had symptoms and signs of hepatitis
as well as abnormal liver function and
positive HBsAg, were diagnosed as
having CHB infection in the present
study.
Criteria for enrollment
Patients, aged 18 to 60 years with
their serum alanine aminotransferase
(ALT) level being 41 to 240 IU/L and
who had positive serum HBsAg were
enrolled.
Criteria for exclusion
Patients aged over 60 years or < 18
years, patients in pregnancy or in
breastfeeding period; patients who
had hepatitis C or other hepatic viral
infection, autoimmune hepatitis and
drug-induced hepatitis or alcoholic
hepatitis; patients with severe
complications of the cardiovascular,
renal or hematopoietic system and
patients with mental diseases were
excluded. Patients were excluded if
they had decompensated liver disease
(defined by serum albumin ≤ 36 g/dL,
bilirubin ≥ 15 mg/dL, prothrombin
time ≥ 2 s prolonged, or a history of
ascites, variceal hemorrhage or hepatic
encephalopathy), pancytopenia
(defined as hemoglobin < 11 g/dL,
white cell count < 4000/mm
3
or
platelets < 105/mm
3
). Patients with
a history of using interferon or
antiviral agents or corticosteroids or
immunosuppressive drugs were also
excluded.
Treatment
Each patient was asked to take 2
capsules of HD-03/ES—1 capsule in
the morning after breakfast and
1 capsule at bedtime for a period of
24 weeks.
Recording and observation
of symptoms and signs
At the time of entry into the study the
signs and symptoms of hepatitis, such
as, loss of appetite, nausea/vomiting,
fatigue, weight loss, sense of well
being, jaundice and hepatomegaly
were assessed as present or absent and
if present the severity was noted as
mild, moderate, or severe.
Etiological markers of
hepatitis B
Serum samples collected from patients
were stored at - 20°C until analysis.
Serum was assayed for HBsAg,
hepatitis B e antigen (HBeAg),
and HBV DNA at baseline, 16,
and 24 weeks after therapy using
commercially available enzyme-linked
immunosorbent assay (ELISA) kits
(Roche).
Liver function
The patients had liver function
examination every month during
the treatment, including content
of serum proteins, total bilirubin,
and activities of ALT and aspartate
aminotransferase (AST).
Safety analysis
Safety analysis included data for
all treated patients during dosing.
The primary safety endpoint was
discontinuation of study medication
because of adverse events. Other safety
evaluations included incidence of
adverse effects.
Endpoints
The primary endpoint was HBsAg
clearance; secondary endpoints
included HBV DNA levels and ALT
normalization to 40 IU/L at the end of
treatment as well as clinical signs and
symptoms.
Statistical analysis
The intention-to-treat analysis
included all randomized patients who
