TITLE PAGE:
Original Research Article
CORRELATION OF VIROLOGICAL AND CLINICAL PROFILE IN PATIENTS WITH
BC-COINFECTION IN OUR SET-UP
JAVED IQBAL FAROOQI, RIAZMUHAMMAD, ZAFAR ALI, ABDURREHMAN,
INTEKHABALAM, NOORULLAH KHAN, MOHAMMAD JAMSHED KHAN
MUHAMMADASGHAR, FAROOQ AHMAD
Department of Medicine, PGMI, LRH, Peshawar
ABSTRACT
OBJECTIVE:to find out and correlate the virological and clinical profile in our patients with
chronic hepatitis B and C co-infection.
MATERIAL AND METHODS:This observational, descriptive and cross-sectional study was
conducted at Medical A Ward, PGMI, LRH Peshawar and Author’s Private Hepatology Clinic,
Akber Medical Center, Peshawar, from July 2010 to June 2014. All patients with HBsAg and
Anti-HCV Reactive by ELISA for more than 6 months were included in the study. Following
investigations were carried out in these patients: Serum ALT, HBeAg, anti-HBe, HBV DNA
PCR, HCV RNA PCR, and abdominal ultrasound. Data was entered and analyzed using SPSS
version 16.0.
RESULTS: A total of 130 patients were included in the analysis, out of which 81 (62.3%) were
males. Mean age of patients was 40.52±14.27 years. Majority of patients belonged to age-group
of 21-30 years. Mean serum ALT of patients was 83.69±60.48 U/L. Majority of patients
belonged to ALT-Group of 41-80 U/L. Hepatitis C Virus was the dominant virus in 53% of
patients. Chronic Hepatitis was the dominant clinical profile in 73% of patients.
CONCLUSION:Hepatitis C Virus is the dominant virus in our patients with BC co-infection.
There is no statistically significant association between virological and clinical profile of these
patients.
KEY WORDS:Hepatitis B Virus, Hepatitis C Virus, BC Co-infection, Chronic Hepatitis,
Cirrhosis, Hepatocellular Carcinoma
INTRODUCTION
Hepatitis B and hepatitis C viruses are the most commoncauses of chronic liver disease
worldwide. Approximately 350 million people are infected with HBV1and another 170 million
people with HCV2.Both chronic Hepatitis B and Ccan progress to cirrhosis and later on
hepatocellular carcinoma (HCC).Chronic hepatitis B leads to cirrhosis and HCC in 5-40% of
patients3, with an annual death rate of an over a million people worldwide4,5. Similarly, chronic
hepatitis C leads to cirrhosis and HCC in 32% of patients, with an annual death rate of half a
million people worldwide6.
As hepatitis B and C share same modes of transmission, co-infection with these viruses is
possible7. Infection with multiple viruses leads to management problems with higher incidence
ofmorbidity and mortality8. Therefore, BC Co-infection may potentially lead to moresevere liver
disease, with an increased risk of progressionto cirrhosis and HCC9-12.HBV super-infection in
patientswith chronic hepatitis C, and HCV super-infection inpatients with chronic hepatitis B
have both been reported13-15. In Pakistan, overall national prevalence of HBsAg is 2.5%, antiHCV is 4.9%, and BC Co-infection is 0.1%16. Several studies have shown that the HBV and
HCV interactwith each other and affect immune responses17-22.
The present study was conducted to find out the virological and clinical profile in patients
with chronic hepatitis B and C co-infection in our set-up.
MATERIAL AND METHODS
This observational, descriptive and cross-sectional study was conducted at Medical A
Ward, PGMI, LRH Peshawar and author’s private practice setup, over4 years’ time period (from
July 2010 to June 2014). All patients with HBsAg and Anti-HCV Reactive by ELISA for more
than 6 months were included in the study by convenience sampling. Patients, who were currently
receiving or had received in past antiviral therapy, were excluded from the study. As per routine
clinical practice protocol, following investigations were carried out in all of these patients:
Serum ALT, HBeAg, anti-HBe, HBV DNA Qualitative PCR, HCV RNA Qualitative PCR, and
abdominal ultrasound.
According to virological profile, patients were divided in four groups: 1) Both Active:
those patients in whom both HBV and HCV PCRs were detected; 2) HBV Active: those patients
in whom HBV PCR was detected and HCV PCR was not-detected; 3) HCV Active: those
patients in whom HCV PCR was detected and HBV PCR was not-detected; and 4) Both Inactive:
those patients in whom both HBV and HCV PCRs were not-detected.
Chronic hepatitis B patients were classified into: 1) CHB-ITP (Chronic Hepatitis B
Immune Tolerant Phase): those patients, who were having HBV-DNA PCR detected, HBeAg
Reactive, Anti-HBe Non-Reactive, with normal serum ALT; 2) CHB-IRP (Chronic Hepatitis B
Immune Reactive Phase): those patients, who were having HBV-DNA PCR detected, HBeAg
Reactive, Anti-HBe Non-Reactive, with raised serum ALT; 3) CHB-ICP (Chronic Hepatitis B
Immune Control Phase): those patients, who were having HBV-DNA PCR not-detected, HBeAg
Non-Reactive, Anti-HBe Reactive, with normal serum ALT; and 4) CHB-IEP (Chronic Hepatitis
B Immune Escape Phase): those patients, who were having HBV-DNA PCR detected, HBeAg
Non-Reactive, Anti-HBe Reactive, with raised serum ALT.
According to clinical profile, patients were divided in three groups: 1) Chronic Hepatitis:
those patients in whom ultrasound was showing normal liver with portal vein of normal size,
spleen of normal size, and no evidence of ascites; 2) Cirrhosis: those patients in whom
ultrasound was showing liver with coarse echogenic parenchyma to small nodular liver,
increased portal vein diameter, enlarged spleen with or without ascites; and 3) Hepatocellular
Carcinoma (HCC): those patients in whom ultrasound showing space occupying lesion,
confirmed as hepatocellular carcinoma by triphasic CT liver with raised serum alpha fetoproteins
(AFP).
SPSS Version 16.0 was used to analyze the data. After entry, descriptive statistics was
used to calculate Mean + SD (Standard Deviation) for numerical variables like age (in years) and
ALT levels. Frequencies/Percentages were calculated for gender, virological and clinical profile
of patients. Chi-square (in Crosstabs analysis) was used to identify significant association
between virological and clinical profile of the patients.
RESULTS
A total of 130 patients with BC Co-infection were assessed during the study period.
Among them 81(62.3%) were males and 49 (37.7%) were females. Mean age was 40.52±14.272
years. Their age range was from 10 to 85 years. Majority of patients belonged to age-group of
21-30 years, followed by age-group of 41-50 years (Table-1). Mean serum ALT was 83.69 ±
60.482 U/L. Their Serum ALT range was from 18 to 377 U/L. Majority of patients belonged to
ALT-Group of 41-80 U/L, followed by ALT-Group of 81-120 U/L (Table-2). Among the four
virological profile groups, majority of patients belonged to “C Active” group, followed by “Both
Active” group (Table-3). Among the four HBV virological profile groups, majority of patients
belonged to “CHB-ICP”-group, followed by “CHB-IRP”-group (Table-4). Among three clinical
profile groups, majority of patients belonged to “Chronic Hepatitis”group, followed by
“Cirrhosis”-group (Table-5). Majority of patients with “Chronic Hepatitis”was females and
majority of patients with “Cirrhosis”was males (Table-6). Majority of patients with “Chronic
Hepatitis” was in the age-group of 21-30 years whereas majority of patients with “Cirrhosis” was
in the age-group of 41-50 years (Table-7). Majority of patients with “Chronic Hepatitis”as well
as “Cirrhosis” was having ALT in the range of 41-80 U/ (Table-8). Pearson Chi-Square test
showed that there is no statistically significant association between virological and clinical
profile of these patients, and similarly Phi and Cramer’s V systemic measures showed that the
strength of association between virological and clinical profile is very weak (Table-9).
DISCUSSION
In our study, male to female ratio was 1.6:1 among 130 patients studied. Results of the
current study revealed that 74% of chronic liver disease patients were in 3rd to 5th decade oflife.
Chronic hepatitis patients were a decade younger than cirrhotic patients, whereas HCCpatient
was a decade older at an average. Increasing age is a higher risk to have thedisease, probably due
to longer exposure to multiple risk factors23-29. In our study, 62% of chronic liver disease
caseswere younger than 50-years of age, out of which 31% younger than 30 years of age; the
percentage gradually decreased in the later decades. The reason could be an earlychildhood
infection with the hepatitis viruses. The chronic infection with hepatitis virusesleads to slow
progressive liver disease. It may end up in cirrhosis, chronic liver failure,and hepatocellular
carcinoma (HCC) over a period of up to 30 years30,31.Since the route of transmission for these
viruses are similar, so patientscould have co-infection with one or two viruses. Co-infection with
HBV and HCV has been reported from Pakistan32,33.
Studies have shown that the HBV and HCV interact with each other and affect immune
responses. Four virological profiles have been described: Active HCV, Active HBV, Dual Active
BC, and Inactive BC. In our study, HCV was active in more than half of the patients (53%) with
inactive HBV. Many studies have shown the same trend in BC Co-infected17-19. Chronic hepatitis
B patients who become superinfected with HCV can undergo seroconversion of HBeAg and
HBsAg to respective antibodies20-22. Longitudinal studies have found 2.08% annual incidence of
HBsAg seroconversion in BC Co-infected patients as compared to 0.43% in patients with HBV
monoinfection34,35. Several authors have reported that HBV can reciprocally inhibit HCV
replication as well36-38. In our study, only 11% of patients were having active HBV and inactive
HCV. An Italian study reported 71% HCV RNA clearance in BC Co-infected patients as
compared to 14% in HCVmonoinfection39. Furthermore, mutual suppression of each other in
BCCo-infected patients hasalso been reported40. In our study, 14% of patients were having both
inactive HBV and HCV.
Chronic hepatitis BC coinfected patients can present in three possible clinical phases:
Chronic Hepatitis, Cirrhosis, and Hepatocellular carcinoma. In our study, 73% patients belonged
to chronic hepatitis stage. Majority of them was females, in the age-group of 21-40 years, and
having ALT in the range of 41-80 U/L. In majority of these HCV was active alone or in
combination of active HBV (dual active infection). These patients are at highest risk of
progressionto cirrhosis and decompensated liver disease, and therefore,should be considered for
treatment.In our study, Cirrhosis was found in 26% of BC-coinfected patients irrespective of
their virological profile. Majority of patients were males and in the age-group of 31-50 years. No
specific trend was seen regarding ALT levels.Studies have reported higher rates of cirrhosis in
BC-coinfected patients as compared to mono-infected patients17, 38, 41, but we our study did not
reveal statistically significant association between virological and clinical profile of BCcoinfected patients.We found only one case of HCC, a male patient over 70 years of age. BCcoinfected patients have an increased risk ofdeveloping HCC9,10,12,41,42. Because of thelikely
increased risk of developing HCC, coinfectedpatients should receive regular 6-month and
possiblemore frequent screening with ultrasound of the liver andserum alfa-fetoprotein levels.
CONCLUSION
Co-infection with HBV and HCV is not uncommon, especiallywithin areas of high
prevalence of hepatitis B. We could not find any statistically significant association between
virological and clinical profile of these patients, rather the strength of association between
virological and clinical profile was very weak.
Dualinfections present unique management challenges giventhe complex interaction of
HBV and HCV, and the propensityfor developing more severe liver disease. Treatment decisions
should bemade based upon the determination of the "dominant"hepatitis virus. Caution must be
exercised in treatingcoinfected patients, as flares of the untreated virus mayoccur. No standard of
care has been established for treatmentof coinfected patients, and larger randomized,
controlledtrials are needed to clarify the optimal treatmentfor such patients and the role of newer
antiviral agents.
Table-1: Age-wise distribution of patients
Age group (years)
No of Patients
1-10
1
11-20
4
21-30
37
31-40
26
41-50
33
51-60
21
61-70
6
71-80
1
81-90
1
Total
130
Percent
0.8
3.1
28.5
20.0
25.4
16.2
4.6
0.8
0.8
100
Table-2: ALT Levels of patients
ALT Levels (U/L)
No of Patients
<40
23
41-80
60
81-120
28
121-160
5
161-200
7
>200
7
Total
130
Percent
17.7
46.2
21.5
3.8
5.4
5.4
100
Table-3: Virological Profile of Patients
Virological Profile
No of Patients
Both Active
28
HBV Active
15
HCV Active
69
Both Inactive
18
Total
130
Percent
21.5
11.5
53.1
13.8
100
Table-4: HBV Virological Profile of patients
HBV Virological Profile
No of Patients
CHB-ITP
1
CHB-IRP
31
CHB-ICP
87
CHB-IEP
11
Total
130
Table-5: Clinical Profile of Patients
Clinical Picture
No of Patients
Chronic Hepatitis
95
Cirrhosis
34
Percent
0.8
23.8
66.9
8.5
100
Percent
73.0
26.2
HCC
1
0.8
Total
130
100
Table-6: Gender-wise distribution of Clinical Profile of patients
Age group
Clinical Status of Patients
Chronic Hepatitis
Cirrhosis
No of pts Percent
No of pts Percent
Male (n=81)
52
64.2
28
34.6
Female (n=49)
43
87.8
6
12.2
Total
95
73.0
34
26.2
HCC
No of pts
1
0
1
Percent
1.2
0
0.8
Table-7: Age-wise distribution of Clinical Profile of patients
Age Group Clinical Status of Patients
Chronic Hepatitis
Cirrhosis
No of pts
Percent
No of pts
Percent
1-10
1
0.77
0
0
11-20
4
3.07
0
0
21-30
35
26.93
2
1.54
31-40
20
15.38
6
4.62
41-50
21
16.15
12
9.23
51-60
12
9.23
9
6.92
61-70
2
1.54
4
3.08
71-80
0
0
0
0
81-90
0
0
1
0.77
Total
95
73.0
34
26.2
HCC
No of pts
0
0
0
0
0
0
0
1
0
1
Percent
0
0
0
0
0
0
0
0.77
0
0.8
Table-8: ALT levels regarding Clinical Profile of patients
ALT Levels Clinical Status of Patients
(U/L)
Chronic Hepatitis
Cirrhosis
No of pts Percent
No of pts
Percent
<40
17
13.07
6
4.61
41-80
46
35.37
14
10.77
81-120
22
16.91
6
4.61
121-160
2
1.54
3
2.31
161-200
4
3.08
2
1.54
>200
4
3.08
3
2.31
Total
95
73.0
34
26.2
HCC
No of pts
0
0
0
0
1
0
1
Percent
0
0
0
0
0.8
0
0.8
Table-9: Correlation of Virological and Clinical Profiles of patients
Virological
Clinical Status of Patients
Profile
Chronic Hepatitis
Cirrhosis†‼*
No of pts Percent
No of pts
Percent
Both Active†
20
15.36
8
6.15
HBV active‼
13
10.00
2
1.54
HCV Active*
47
36.13
21
16.15
Both Inactive
15
11.51
3
2.31
HCC
No of pts
0
1
0
0
Percent
0
0.8
0
0
Total
95
73.0
34
26.2
1
0.8
*Both-Active vs Rest = Pearson Chi-square p value = 0.552, Phi & Cramer’s V p value = 0.552
‼HBV-Active vs Rest = Pearson Chi-square p value = 0.186, Phi & Cramer’s V p value = 0.186
†HCV-Active vs Rest = Pearson Chi-square p value = 0.966, Phi & Cramer’s V p value = 0.966
Correspondence:
Javed Iqbal Farooqi
FCPS (Medicine), FCPS (Gastroenterology)
Associate Professor of Medicine
Medical A Unit, PGMI, LRH, Peshawar
E-mail: dr_farooqi@hotmail.com
Phone: 0333-9123818