- Email: [email protected]
Prevalence of hepatitis B and C viral markers in chronic liver disease patients: A single center experience from Yemen
Arab Journal of Gastroenterology 11 (2010) 105–107
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Gastroenterology in Arab Countries
Prevalence of hepatitis B and C viral markers in chronic liver disease patients: A single center experience from Yemen Salem A. Bin Selm * Gastroenterology Unit, Medical Department, Al-Gamhourea Teaching Hospital, Faculty of Medicine, Aden University, P.O. Box 5184, Alden, Yemen
a r t i c l e
i n f o
Article history: Received 11 November 2009 Accepted 9 April 2010
a b s t r a c t Background and study aims: Presence of hepatitis B virus (HBV) anti-core antibodies (anti-HBc) of immunoglobulin G (IgG) type in the absence of surface antigen (HBsAg) in a patient is usually indicative of a past self-limiting HBV infection. This may be associated with hepatitic C virus (HCV) co-infection that can worsen the existing status of a chronic liver disease (CLD). This study evaluates the significance of isolated HBc IgG positivity in CLD patients and also examines the presence of anti-HCV antibodies (anti-HCV Ab) in these patients. Patients and methods: Clinical and biochemical data were collected from all the 67 cases of CLD (which were exposed to B and/or C viral infections) included in this study. Blood samples were taken from these patients and tested using the commercially available enzyme immune assay for the presence of HBsAg, anti-HBc IgG, HBeAg, anti-HBs antibodies (anti-HBsAb), anti-HBe antibodies (anti-HBeAb) anti-HCV Ab. Results: Out of the 67 patients with CLD, anti-HBc IgG positivity in the absence of any other serological markers of HBV infection was detected in 28 patients, whereas 27 had HBV markers, either HBsAg or HBeAb alone or in combination. There was a significant association between isolated anti-HBc IgG positivity and HCV co-infection. Conclusion: All patients with CLD should be tested for anti-HBc IgG, as it is often the only marker of HBV infection in these patients. Patients with anti-HBc IgG positivity should be monitored closely as they can further develop CLD. Co-infection with HCV should be actively investigated in such patients. Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Worldwide, about 350 million persons have chronic hepatitis B virus (HBV) infection, and about 125 million have been infected with hepatitis C virus (HCV), placing viral hepatitis B and C amongst the world’s greatest infectious disease health problems [1–3]. Screening for HBV infection depends in many countries on the presence of surface antigen of HBV (HBsAg), but in 10–20% of patients only anti-HBc IgG can be detected, which is usually indicative of past self-limiting HBV infection [3,4]. The clinical significance of such finding is being recognised and it is seen that, even in HBsAg- and anti-HBs-negative patients, CLD can develop and such patients show anti-HBc IgG positivity as the only marker [4]. Isolated anti-HBc IgG with negative HBs antibodies (HBsAb) is also frequently observed in intravenous drug abusers, human immunodeficiency virus (HIV)-infected individuals, HBV and HCV co-infected patients and pregnant females [3,4]. In cases of co-infection with both HBV and HCV, serious consequences are seen with more severe and aggressive liver disease [5].
* Tel.: +967 2 241482; mobile: +967 777241482. E-mail address: [email protected]
Prevalence of HCC is higher in patients with co-infection than in patients with a single infection [6]. High prevalence of HBV markers such as HBc IgG is seen in patients with HCV-related CLD, particularly those with HCC, suggesting that HBV infection, probably including latent infection, may play an important role in carcinogenesis in these patients [6–8]. Epidemiologic results have also shown that prior exposure to HBV infection is a risk factor for the development of HCC [9]. Hence, in HBV-endemic areas, the possibility of co-infection of HBV in HBsAb- and HBsAg-negative patients with HCV infection should be considered [10]. This study thus evaluates the significance of isolated HBc IgG positivity and investigates the presence of concomitant anti-HCV antibodies (anti-HCV Ab) in a single center in Aden, Yemen where PCR testing is not available.
Patients and methods The present study was conducted in the Department of Internal Medicine, Al-Gamhourea Teaching Hospital (ATH) in Aden, from January 2007 to December 2007. The study group included a total of 67 cases of CLD (all exposed to B and/or C viral infections). Cases with chronic hepatitis, cirrhosis and HCC were included and diagnosed on the basis of clinical,
1687-1979/$ - see front matter Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ajg.2010.04.006
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S.A.B. Selm / Arab Journal of Gastroenterology 11 (2010) 105–107
biochemical, serological, imaging and/or histopathological study. Informed consent was taken from all patients before their inclusion in the study. The patients were evaluated on the basis of a detailed history and detailed physical examination. Autoimmune hepatitis, Wilson’s disease, haemachromatosis and other infective causes were excluded. Serological tests including HBsAg, HBsAb, anti-HBc IgG and anti HCV Ab (anti-HCV Ab) were performed using commercially available enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer’s instructions. The results were statistically analysed using the chi-square test. A p value of <0.05 was considered as statistically significant. Results A total of 67 cases of CLD were found to have evidence of HBV and/or HCV infection. The cases were classified as having chronic hepatitis (21 cases), cirrhosis (43 cases) and HCC (3 cases). Evidence for HBV infection was the most commonly found, which could (55 cases, 82%); none of them had been subjected to HBV vaccination. HBsAg could be detected in only 27 cases (40%), whereas 28 cases (42%) had only HBc IgG and seven of them (12.7%) had both HBc IgG and anti-HBe antibodies. Ten patients with isolated anti-HBc IgG had anti-HCV Ab. The prevalence of HCV infection on the basis of anti-HCV positivity alone was 17.9% (12/67 cases). Anti-HCV could not be detected in any of the HBsAg-positive patients. All the three cases of HCC had evidence of HBV infection, two of whom had HCV Ab (Table 1). Patients showing isolated anti-HBc IgG were further grouped into those with (10 cases) or without (18 cases) anti-HCV Ab. Clinical parameters and the biochemical profile did not show a statistically significant difference between the groups (Table 2).
Table 1 Demographic profile and viral markers in patients with CLD. Variables
CLD (n = 21)
Cirrhosis (n = 43)
HCC (n = 3)
Total (%)
Age Sex M:F (52/15) HBsAg Anti-HBc IgG Anti-HCV Ab
46.5 ± 12.15 16:5 06 12 03
46.4 ± 14.8 33:10 20 13 07
49.3 ± 14.4 3:0 1 3 02
67 67 27 (40%) 28 (42%) 12 (17.9%)
CLD: chronic liver disease and HCC: hepatocellular carcinoma.
Table 2 Clinical and biochemical profile of patients with anti-HBc IgG.a
Abdominal discomfort Jaundice Nausea Vomiting Haematemesis Pruritus AST (normal range: 20–40 U ml 1) ALT (normal range: 20–40 U ml 1) Total bilirubin (normal range: 0.5–1.0 mg/dL) Albumin (normal range: 3.5–5.5 g/dL)
Anti HCV Ab +ve (n = 10)
Anti HCV Ab ve (n = 18)
8 6 6 6 3 3 46 56 3.9 3.12
12 11 08 07 07 05 65 95 4.2 3.1
a Statistical analysis done using the chi-square test. No statistically significant difference was found between the groups.
Discussion HBsAg is still used as the only marker to diagnose the prevalence of HBV infection in some parts of the world, but this can miss a substantial number of cases. Additional tests like anti-HBc IgG and HBV DNA can help to identify further cases of hepatitis B [10,11]. Unfortunately, HBV DNA was not tested for in our study because PCR is still not available in Aden. In our study, HBsAg could be detected in only 27 (40%) out of 67 cases, whereas using additional tests like anti-HBc IgG could be detected in a further 28 cases (42%). This increased the prevalence rate HBV markers from 40% to 82% in CLD patients in our study, approaching, thus, rates reported from other HBV-endemic areas [4]. The prevalence of HCV infection in CLD patients has been reported to be between 10% and 40% [12,13], whereas in a high-risk group like in thalassemias the prevalence can be as high as 60% [14]. In the present study, anti-HCV Ab were detected in 12 cases, that is, in 17.9%; a figure similar to that reported from other regions in Asia [12,13]. Anti-HCV Ab were detected in these 12 patients in isolation, whereas 10 further cases were found to be associated with evidence of past exposure to HBV. These results support the observation that HCV infection occurs more often in association with HBV infection [15–18], and are in agreement with other studies that have reported the presence of HCV in serologically silent HBV infection, with the prevalence ranging between 50% and 87% [3–6]. However, in our study, 10 (35.7%) of the 28 cases with isolated anti-HBc Ab were associated serologically with anti-HCV and may be considered as cases of silent HBV infection. The clinical significance of the silent HBV infection in HCV-associated CLD has not been fully understood. A few studies have reported that the clinical course is generally more severe in patients with HBV/HCV co-infection [6–8], whereas a few have reported decreased severity [16]. However, in our study, the presence of anti-HCV Ab in association with HBV markers did not alter the course of CLD as no significant change in the clinical presentation and biochemical parameters was observed in patients. Isolated anti-HBc IgG positivity is highly prevalent in HCV-infected individuals, raising the possibility of potential interference between HBV and HCV replication [17]. Since HBsAg could not be detected in patients tested positively both for anti-HCV Ab and HBc IgG, it can be hypothesized that HCV reduces HBV replication; a finding that has been documented in other reports [17,18]. The elevated transaminases in patients having isolated HBc IgG positivity confirm the presence of liver disease in such patients. Thus, it can be concluded from the present study that anti-HBc IgG could be the only marker for past HBV infection and it should be tested for in all patients with CLD as patients with isolated antiHBc IgG positivity can develop liver disease. Furthermore, patients showing isolated anti-HBc IgG with anti-HBs negativity should be monitored closely for liver function. These patients are also more likely to have evidence for HCV infection, which should be investigated.
References [1] EASL International consensus conference on hepatitis B 13–14 September, 2002 Geneva, Switzerland. Consensus statement (Short version). J Hepatol 2003;38(4):533–40. [2] Alter MJ. Epidemiology of hepatitis B in Europe and worldwide. J Hepatol 2003;39(Suppl. 1):S64–9. [3] Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005;5(9):558–67. [4] Shim J, Kim BH, Kim NH, et al. Clinical features of HBsAg-negative but antiHBc-positive hepatocellular carcinoma in a hepatitis B virus endemic area. J Gastroenterol Hepatol 2005;20(5):746–51. [5] Berger A, Doerr HW, Rabenau HF, et al. High frequency of HCV infection in individuals with isolated antibody to hepatitis B core antigen. Intervirology 2000;43(2):71–6.
S.A.B. Selm / Arab Journal of Gastroenterology 11 (2010) 105–107 [6] Bukhtiari N, Hussain T, Iqbal M, et al. Hepatitis B and C single and co-infection in chronic liver disease and their effect on the disease pattern. J Pak Med Assoc 2003;53(4):136–40. [7] Xess A, Kumar M, Minz S, et al. Prevalence of hepatitis B and hepatitis C virus coinfection in chronic liver disease. Indian J Pathol Microbiol 2001;44(3):253–5. [8] Kazemi Shirazi L, Petermann D, Muller C. Hepatitis B virus DNA in sera and liver tissue of HBsAg negative patients with chronic hepatitis C. J Hepatol 2000;33(5):785–90. [9] Fukuda R, Ishimura N, Niigaki M, et al. Serologically silent hepatitis B virus coinfection in patients with hepatitis C virus-associated chronic liver disease: clinical and virological significance. J Med Virol 1999;58(3):201–7. [10] Lee DS, Huh K, Lee EH, et al. HCV and HBV coexist in HBsAg-negative patients with HCV viraemia: possibility of coinfection in these patients must be considered in HBV-high endemic area. J Gastroenterol Hepatol 1997;12(12):855–61. [11] Marusawa H, Osaki Y, Kimura T, et al. High prevalence of anti-hepatitis B virus serological markers in patients with hepatitis C virus related chronic liver disease in Japan. Gut 1999;45(2):284–8.
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[12] Uetake S, Yamauchi M, Itoh S, et al. Analysis of risk factors for hepatocellular carcinoma in patients with HBs antigen- and anti-HCV antibody-negative alcoholic cirrhosis: clinical significance of prior hepatitis B virus infection. Alcohol Clin Exp Res 2003;27(Suppl. 8):47S–51S. [13] Sood A, Sidhu SS, Midha V, et al. High seroprevalence of hepatitis C virus and dual infection (hepatitis B and C virus) in non-alcoholic chronic liver disease in North India. J Assoc Physicians India 1999;47(2):205–8. [14] Chakravarti A, Verma V, Kumaria R, et al. Anti-HCV seropositivity among multiple transfused patients with beta thalassaemia. J Indian Med Assoc 2005;103(2):64–6. [15] Weir RP, Brunton CR, Blakely TA. Chronic liver disease mortality attributable to hepatitis B and C in New Zealand. J Gastroenterol Hepatol 2002;17(5):582–8. [16] Berry N, Chakravarti A, Kar P, et al. Association of hepatitis C virus & hepatitis B virus in chronic liver disease. Indian J Med Res 1998;108:255–9. [17] Fan CL, Wei L, Jiang D, et al. Clinical and virological course of dual infection by hepatitis B and C viruses in China. Zhonghua Yi Xue Za Zhi 2003;83(14):1214–8. [18] Fan CL, Wei L, Jiang D, et al. Spontaneous viral clearance after 6–21 years of hepatitis B and C viruses coinfection in high HBV endemic area. World J Gastroenterol 2003;9(9):2012–6.
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Gastroenterology in Arab Countries
Prevalence of hepatitis B and C viral markers in chronic liver disease patients: A single center experience from Yemen Salem A. Bin Selm * Gastroenterology Unit, Medical Department, Al-Gamhourea Teaching Hospital, Faculty of Medicine, Aden University, P.O. Box 5184, Alden, Yemen
a r t i c l e
i n f o
Article history: Received 11 November 2009 Accepted 9 April 2010
a b s t r a c t Background and study aims: Presence of hepatitis B virus (HBV) anti-core antibodies (anti-HBc) of immunoglobulin G (IgG) type in the absence of surface antigen (HBsAg) in a patient is usually indicative of a past self-limiting HBV infection. This may be associated with hepatitic C virus (HCV) co-infection that can worsen the existing status of a chronic liver disease (CLD). This study evaluates the significance of isolated HBc IgG positivity in CLD patients and also examines the presence of anti-HCV antibodies (anti-HCV Ab) in these patients. Patients and methods: Clinical and biochemical data were collected from all the 67 cases of CLD (which were exposed to B and/or C viral infections) included in this study. Blood samples were taken from these patients and tested using the commercially available enzyme immune assay for the presence of HBsAg, anti-HBc IgG, HBeAg, anti-HBs antibodies (anti-HBsAb), anti-HBe antibodies (anti-HBeAb) anti-HCV Ab. Results: Out of the 67 patients with CLD, anti-HBc IgG positivity in the absence of any other serological markers of HBV infection was detected in 28 patients, whereas 27 had HBV markers, either HBsAg or HBeAb alone or in combination. There was a significant association between isolated anti-HBc IgG positivity and HCV co-infection. Conclusion: All patients with CLD should be tested for anti-HBc IgG, as it is often the only marker of HBV infection in these patients. Patients with anti-HBc IgG positivity should be monitored closely as they can further develop CLD. Co-infection with HCV should be actively investigated in such patients. Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Worldwide, about 350 million persons have chronic hepatitis B virus (HBV) infection, and about 125 million have been infected with hepatitis C virus (HCV), placing viral hepatitis B and C amongst the world’s greatest infectious disease health problems [1–3]. Screening for HBV infection depends in many countries on the presence of surface antigen of HBV (HBsAg), but in 10–20% of patients only anti-HBc IgG can be detected, which is usually indicative of past self-limiting HBV infection [3,4]. The clinical significance of such finding is being recognised and it is seen that, even in HBsAg- and anti-HBs-negative patients, CLD can develop and such patients show anti-HBc IgG positivity as the only marker [4]. Isolated anti-HBc IgG with negative HBs antibodies (HBsAb) is also frequently observed in intravenous drug abusers, human immunodeficiency virus (HIV)-infected individuals, HBV and HCV co-infected patients and pregnant females [3,4]. In cases of co-infection with both HBV and HCV, serious consequences are seen with more severe and aggressive liver disease [5].
* Tel.: +967 2 241482; mobile: +967 777241482. E-mail address: [email protected]
Prevalence of HCC is higher in patients with co-infection than in patients with a single infection [6]. High prevalence of HBV markers such as HBc IgG is seen in patients with HCV-related CLD, particularly those with HCC, suggesting that HBV infection, probably including latent infection, may play an important role in carcinogenesis in these patients [6–8]. Epidemiologic results have also shown that prior exposure to HBV infection is a risk factor for the development of HCC [9]. Hence, in HBV-endemic areas, the possibility of co-infection of HBV in HBsAb- and HBsAg-negative patients with HCV infection should be considered [10]. This study thus evaluates the significance of isolated HBc IgG positivity and investigates the presence of concomitant anti-HCV antibodies (anti-HCV Ab) in a single center in Aden, Yemen where PCR testing is not available.
Patients and methods The present study was conducted in the Department of Internal Medicine, Al-Gamhourea Teaching Hospital (ATH) in Aden, from January 2007 to December 2007. The study group included a total of 67 cases of CLD (all exposed to B and/or C viral infections). Cases with chronic hepatitis, cirrhosis and HCC were included and diagnosed on the basis of clinical,
1687-1979/$ - see front matter Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ajg.2010.04.006
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S.A.B. Selm / Arab Journal of Gastroenterology 11 (2010) 105–107
biochemical, serological, imaging and/or histopathological study. Informed consent was taken from all patients before their inclusion in the study. The patients were evaluated on the basis of a detailed history and detailed physical examination. Autoimmune hepatitis, Wilson’s disease, haemachromatosis and other infective causes were excluded. Serological tests including HBsAg, HBsAb, anti-HBc IgG and anti HCV Ab (anti-HCV Ab) were performed using commercially available enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer’s instructions. The results were statistically analysed using the chi-square test. A p value of <0.05 was considered as statistically significant. Results A total of 67 cases of CLD were found to have evidence of HBV and/or HCV infection. The cases were classified as having chronic hepatitis (21 cases), cirrhosis (43 cases) and HCC (3 cases). Evidence for HBV infection was the most commonly found, which could (55 cases, 82%); none of them had been subjected to HBV vaccination. HBsAg could be detected in only 27 cases (40%), whereas 28 cases (42%) had only HBc IgG and seven of them (12.7%) had both HBc IgG and anti-HBe antibodies. Ten patients with isolated anti-HBc IgG had anti-HCV Ab. The prevalence of HCV infection on the basis of anti-HCV positivity alone was 17.9% (12/67 cases). Anti-HCV could not be detected in any of the HBsAg-positive patients. All the three cases of HCC had evidence of HBV infection, two of whom had HCV Ab (Table 1). Patients showing isolated anti-HBc IgG were further grouped into those with (10 cases) or without (18 cases) anti-HCV Ab. Clinical parameters and the biochemical profile did not show a statistically significant difference between the groups (Table 2).
Table 1 Demographic profile and viral markers in patients with CLD. Variables
CLD (n = 21)
Cirrhosis (n = 43)
HCC (n = 3)
Total (%)
Age Sex M:F (52/15) HBsAg Anti-HBc IgG Anti-HCV Ab
46.5 ± 12.15 16:5 06 12 03
46.4 ± 14.8 33:10 20 13 07
49.3 ± 14.4 3:0 1 3 02
67 67 27 (40%) 28 (42%) 12 (17.9%)
CLD: chronic liver disease and HCC: hepatocellular carcinoma.
Table 2 Clinical and biochemical profile of patients with anti-HBc IgG.a
Abdominal discomfort Jaundice Nausea Vomiting Haematemesis Pruritus AST (normal range: 20–40 U ml 1) ALT (normal range: 20–40 U ml 1) Total bilirubin (normal range: 0.5–1.0 mg/dL) Albumin (normal range: 3.5–5.5 g/dL)
Anti HCV Ab +ve (n = 10)
Anti HCV Ab ve (n = 18)
8 6 6 6 3 3 46 56 3.9 3.12
12 11 08 07 07 05 65 95 4.2 3.1
a Statistical analysis done using the chi-square test. No statistically significant difference was found between the groups.
Discussion HBsAg is still used as the only marker to diagnose the prevalence of HBV infection in some parts of the world, but this can miss a substantial number of cases. Additional tests like anti-HBc IgG and HBV DNA can help to identify further cases of hepatitis B [10,11]. Unfortunately, HBV DNA was not tested for in our study because PCR is still not available in Aden. In our study, HBsAg could be detected in only 27 (40%) out of 67 cases, whereas using additional tests like anti-HBc IgG could be detected in a further 28 cases (42%). This increased the prevalence rate HBV markers from 40% to 82% in CLD patients in our study, approaching, thus, rates reported from other HBV-endemic areas [4]. The prevalence of HCV infection in CLD patients has been reported to be between 10% and 40% [12,13], whereas in a high-risk group like in thalassemias the prevalence can be as high as 60% [14]. In the present study, anti-HCV Ab were detected in 12 cases, that is, in 17.9%; a figure similar to that reported from other regions in Asia [12,13]. Anti-HCV Ab were detected in these 12 patients in isolation, whereas 10 further cases were found to be associated with evidence of past exposure to HBV. These results support the observation that HCV infection occurs more often in association with HBV infection [15–18], and are in agreement with other studies that have reported the presence of HCV in serologically silent HBV infection, with the prevalence ranging between 50% and 87% [3–6]. However, in our study, 10 (35.7%) of the 28 cases with isolated anti-HBc Ab were associated serologically with anti-HCV and may be considered as cases of silent HBV infection. The clinical significance of the silent HBV infection in HCV-associated CLD has not been fully understood. A few studies have reported that the clinical course is generally more severe in patients with HBV/HCV co-infection [6–8], whereas a few have reported decreased severity [16]. However, in our study, the presence of anti-HCV Ab in association with HBV markers did not alter the course of CLD as no significant change in the clinical presentation and biochemical parameters was observed in patients. Isolated anti-HBc IgG positivity is highly prevalent in HCV-infected individuals, raising the possibility of potential interference between HBV and HCV replication [17]. Since HBsAg could not be detected in patients tested positively both for anti-HCV Ab and HBc IgG, it can be hypothesized that HCV reduces HBV replication; a finding that has been documented in other reports [17,18]. The elevated transaminases in patients having isolated HBc IgG positivity confirm the presence of liver disease in such patients. Thus, it can be concluded from the present study that anti-HBc IgG could be the only marker for past HBV infection and it should be tested for in all patients with CLD as patients with isolated antiHBc IgG positivity can develop liver disease. Furthermore, patients showing isolated anti-HBc IgG with anti-HBs negativity should be monitored closely for liver function. These patients are also more likely to have evidence for HCV infection, which should be investigated.
References [1] EASL International consensus conference on hepatitis B 13–14 September, 2002 Geneva, Switzerland. Consensus statement (Short version). J Hepatol 2003;38(4):533–40. [2] Alter MJ. Epidemiology of hepatitis B in Europe and worldwide. J Hepatol 2003;39(Suppl. 1):S64–9. [3] Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005;5(9):558–67. [4] Shim J, Kim BH, Kim NH, et al. Clinical features of HBsAg-negative but antiHBc-positive hepatocellular carcinoma in a hepatitis B virus endemic area. J Gastroenterol Hepatol 2005;20(5):746–51. [5] Berger A, Doerr HW, Rabenau HF, et al. High frequency of HCV infection in individuals with isolated antibody to hepatitis B core antigen. Intervirology 2000;43(2):71–6.
S.A.B. Selm / Arab Journal of Gastroenterology 11 (2010) 105–107 [6] Bukhtiari N, Hussain T, Iqbal M, et al. Hepatitis B and C single and co-infection in chronic liver disease and their effect on the disease pattern. J Pak Med Assoc 2003;53(4):136–40. [7] Xess A, Kumar M, Minz S, et al. Prevalence of hepatitis B and hepatitis C virus coinfection in chronic liver disease. Indian J Pathol Microbiol 2001;44(3):253–5. [8] Kazemi Shirazi L, Petermann D, Muller C. Hepatitis B virus DNA in sera and liver tissue of HBsAg negative patients with chronic hepatitis C. J Hepatol 2000;33(5):785–90. [9] Fukuda R, Ishimura N, Niigaki M, et al. Serologically silent hepatitis B virus coinfection in patients with hepatitis C virus-associated chronic liver disease: clinical and virological significance. J Med Virol 1999;58(3):201–7. [10] Lee DS, Huh K, Lee EH, et al. HCV and HBV coexist in HBsAg-negative patients with HCV viraemia: possibility of coinfection in these patients must be considered in HBV-high endemic area. J Gastroenterol Hepatol 1997;12(12):855–61. [11] Marusawa H, Osaki Y, Kimura T, et al. High prevalence of anti-hepatitis B virus serological markers in patients with hepatitis C virus related chronic liver disease in Japan. Gut 1999;45(2):284–8.
107
[12] Uetake S, Yamauchi M, Itoh S, et al. Analysis of risk factors for hepatocellular carcinoma in patients with HBs antigen- and anti-HCV antibody-negative alcoholic cirrhosis: clinical significance of prior hepatitis B virus infection. Alcohol Clin Exp Res 2003;27(Suppl. 8):47S–51S. [13] Sood A, Sidhu SS, Midha V, et al. High seroprevalence of hepatitis C virus and dual infection (hepatitis B and C virus) in non-alcoholic chronic liver disease in North India. J Assoc Physicians India 1999;47(2):205–8. [14] Chakravarti A, Verma V, Kumaria R, et al. Anti-HCV seropositivity among multiple transfused patients with beta thalassaemia. J Indian Med Assoc 2005;103(2):64–6. [15] Weir RP, Brunton CR, Blakely TA. Chronic liver disease mortality attributable to hepatitis B and C in New Zealand. J Gastroenterol Hepatol 2002;17(5):582–8. [16] Berry N, Chakravarti A, Kar P, et al. Association of hepatitis C virus & hepatitis B virus in chronic liver disease. Indian J Med Res 1998;108:255–9. [17] Fan CL, Wei L, Jiang D, et al. Clinical and virological course of dual infection by hepatitis B and C viruses in China. Zhonghua Yi Xue Za Zhi 2003;83(14):1214–8. [18] Fan CL, Wei L, Jiang D, et al. Spontaneous viral clearance after 6–21 years of hepatitis B and C viruses coinfection in high HBV endemic area. World J Gastroenterol 2003;9(9):2012–6.