Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in Brazil

BACKGROUND: The prevalence and consequences of occult HBV infection in patients with chronic liver disease by HCV remain unknown. AIMS: To evaluate the prevalence of occult HBV infection in a population of HCV-infected patients with hepatocellular carcinoma. METHODS: The serum samples were tested for HBV DNA by nested PCR and liver tissue analysis was carried out using the immunohistochemical technique of 66 HBsAg-negative patients: 26 patients with chronic hepatitis by HCV (group 1), 20 with hepatocellular carcinoma related to chronic infection by HCV (group 2) and 20 with negative viral markers for hepatitis B and C (control group). RESULTS: Occult HBV infection was diagnosed in the liver tissue of 9/46 (19.5%) HCV-infected patients. Prevalence of occult B infection was evaluated in the HCV-infected patients with and without hepatocellular carcinoma, and there were seven (77.7%) of whom from group 2, conferring a 35% prevalence of this group. No serum sample was positive for HBV DNA in the three groups. CONCLUSION: Occult infection B is frequently detected in liver tissue of HCV-infected patients, especially in cases of hepatocellular carcinoma. However large studies are needed to confirm that co-infection could determine a worse progress of chronic liver disease in this population.     

Expression of hepatitis B virus (HBV) markers in chronic liver disease positive for antibody to hepatitis C virus (HCV)

We investigated expression of HBV markers in chronic liver disease positive for antibody to HCV (anti-HCV). Sera from 107 patients with chronic non-A, non-B liver disease, 65 HBs antigen carriers with chronic liver disease and 14 asymptomatic HBV carriers were tested for the presence of anti-HCV. Anti-HCV was detected in 83 (78%) patients with chronic non-A, non-B liver disease, irrespective of the past history of blood transfusion, and anti-HCV prevalence was similar in each category of chronic liver disease. Fifty-three (64%) out of these 83 sera positive for anti-HCV has also antibodies to HBV. Anti-HBc antibody was detected frequently in liver cirrhotics with hepatocellular carcinoma than in chronic persistent hepatitis, chronic active hepatitis and cirrhotics without hepatocellular carcinoma. In addition, titers of anti-HBc antibody were significantly higher in cirrhotics with hepatocellular carcinoma than in the other groups. On the other hand, anti-HCV was detected in 7 out of 65 patients with HBV-related liver disease. Four out of these 7 were patients with HBV-related hepatocellular carcinoma. Anti-HCV was detected in none of asymptomatic HBV carriers. These findings suggest that infection with both HBV and HCV is likely to cause more serious liver disease than infection with a single agent.     

Prevalence of hepatitis C virus antibodies in chronic liver disease and hepatocellular carcinoma patients in India

The prevalence of antibodies to hepatitis C virus (HCV) was investigated in 129 patients with chronic liver disease (85 with chronic active hepatitis and 44 with cirrhosis) and 53 patients with hepatocellular carcinoma. The commercially available second generation anti-HCV enzyme immunoassay kit was used. Antibodies to hepatitis C virus were detected in 16.2% of the patients with chronic liver disease and in 15.1% with hepatocellular carcinoma. Of the HCV positive patients in all groups 51.7% were positive for hepatitis B virus (HBV) markers indicating present or past infection. Prevalence of HBV markers in all the three groups (CAH, cirrhosis and HCC) was higher as compared with anti-HCV prevalence. These results suggest that HCV infection may not be a major cause of chronic liver disease and hepatocellular carcinoma in India and indicate the presence of other aetiological agents.     

Clinical significance of“anti-HBc alone” in human immunodeficiency virus-positive patients

AIM: To determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection ("anti-HBc alone") among human immunodeficiency virus (HIV) type-1 infected patients. Occult hepatitis B infection frequency was also evaluated.METHODS: Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus (HBV) infection were classified into three groups: past hepatitis, "anti-HBc alone" and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus (HCV) were performed on "anti-HBc alone" patients.RESULTS: One hundred and eighty seven (53.7%) HIV-positive patients had markers of HBV infection: 118 past infection (63.1%), 14 chronic hepatitis (7.5%) and 55 "anti-HBc alone" (29.4%). Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals (CI) 1.33-4.00] and antibodies to HCV infection [odds ratio (OR) 2.87; 95% CI 1.10-7.48] were factors independently associated with the "anti-HBc alone" pattern. No differences in liver disease frequency were detected between both groups.Serum levels of anti-HBs were not associated with HCV infection (nor viral replication or HCV genotype), or with HIV replication or CD4 level. No "anti-HBc alone" patient tested positive for HBV DNA.CONCLUSION: "Anti-HBc alone" prevalence in HIVpositive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury.     

Viral hepatitis prevalence in patients with active and latent tuberculosis

AIM: To assess the prevalence of hepatitis B virus(HBV) and hepatitis C virus(HCV) infection and association with drug induced liver injury(DILI) in patients undergoing anti-tuberculosis(TB) therapy.METHODS: Four hundred and twenty nine patients with newly diagnosed TB- either active disease or latent infection- who were due to commence antiTB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus(HIV) infections- hepatitis B core antigen(HBc Ag), hepatitis B surface antigen(HBs Ag), hepatitis B e antigen, Ig G and Ig M antibody to HBc Ag(anti-HBc), HCV Ig G antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of antiTB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher's exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant.RESULTS: Of the 429 patients, 270(62.9%) had active TB disease and 159(37.1%) had latent TB infection. 61(14.2%) patients had isolated anti-HBc positivity, 11(2.6%) were also HBs Ag positive and 7(1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis(HBs Ag or HCV antibody positive; P = 0.023). Similarly the proportion of HBs Ag positive patients were significantly greater in the active vs latent TB infection group(10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association between DILI and presence of serological markers of HBV or HCV. Three(5.3%) patients with serological markers of HBV or HCV infection had DILI compared to 25(9.5%) patients without; P = 0.04.CONCLUSION: Viral hepatitis screening should be considered in TB patients. DILI risk was not increased in patients with HBV/HCV.     

Prevalence of antibodies to hepatitis C virus among Saudi patients with chronic liver diseases.

The prevalence of antibodies against hepatitis C virus (anti-HCV) was determined in 55 patients with chronic liver diseases including liver cirrhosis (42 patients), liver cirrhosis and hepatocellular carcinoma (8 patients), and chronic active hepatitis (4 patients). A total of 63.6% of these patients were positive for anti-HCV, a significantly higher prevalence than the rate of 3.9% observed in 488 asymptomatic volunteers. Of the 42 patients with liver cirrhosis 16 (38.1%) had positive anti-HCV without any markers of hepatitis B virus (HBV), while 12 (28.6%) had markers of neither HCV nor HBV infection. Our findings suggest that HCV infection may play a significant role in the pathogenesis of chronic liver disease in Saudi Arabia, which is an area of endemic HBV infection. Screening for anti HCV should be considered mandatory in patients with chronic liver disease (CLD) especially where the etiology appears obscure.     

Clinical features of HBsAg-negative but anti-HBc-positive hepatocellular carcinoma in a hepatitis B virus endemic area

BACKGROUND: The presence of antibody to the hepatitis B core antigen (anti-HBc) IgG in serum usually means a past infection of the hepatitis B virus (HBV). The clinical characteristics of patients with hepatocellular carcinoma (HCC), who have only a marker for past HBV infection, were investigated. METHODS: A total of 565 HCC patients were classified according to their markers for HBV and the hepatitis C virus (HCV). The clinical features and the survival rate of hepatitis B surface antigen (HBsAg)(-)/anti-HBc(+) patients were compared to those of HBsAg(+) patients. RESULTS: Four hundred and three patients were positive for HBsAg (B group, 71.3%), 64 were positive for anti-HCV (11.3%), and 90 were negative for both HBsAg and anti-HCV (N group, 15.9%). In the N group, 71 were positive for anti-HBc (PB group, 12.6% of total patients). The clinical characteristics of the PB group were different from those of the B group: age at diagnosis (60.6 +/- 9.6 vs 53.3 +/- 10.6 years, P < 0.001), habitual drinking (59.2% vs 23.6%, P < 0.001), family history of liver disease (9.9% vs 38.9%, P < 0.005), detection with periodic screening (28.2% vs 50.4%, P < 0.001), and elevated alpha-fetoprotein (53.5% vs 76.2%, P < 0.001). In both the PB group and the B group, liver cirrhosis was accompanied by a similar high prevalence (74.6% vs 89.1%). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS: The prevalence of HBsAg(-)/anti-HBc(+) HCC is not rare or more common than that of anti-HCV(+) HCC in Korea, a high HBV endemic area. Although some differences in clinical characteristics may imply a different pathogenesis, chronic HBV infection or habitual drinking may be major contributing factors in the development of HCC in these patients.     

Hepatitis B and C virus infection in Ujung Pandang, Indonesia

A survey was performed to investigate HBV and HCV infection in Ujung Pandang. The total number of subjects was 406; 196 blood donors, 78 cases of acute hepatitis, 43 of chronic hepatitis, 58 of liver cirrhosis and 31 of hepatocellular carcinoma cases. HBsAg, anti-HBs and anti-HBc as HBV markers and anti-HCV (ELISA, Ortho) as an HCV marker were tested. Positive rates of HBsAg and anti HCV among blood donors were 7.1% and 3.1% respectively, and there was no significant difference among age groups. Donors negative for all viral markers accounted for 21.4%. Of acute hepatitis cases, 18 (23.1%) cases were hepatitis A and 8 (10.3%) cases were hepatitis B, one case of which was considered to be double infection. Acute exacerbation cases of HBV carriers were 16 (20.5%), of which 6 cases were potitive for HCV antibody. Those diagnosed non-A, non-B hepatitis were 37 (47.4%), of which 3 cases where positive for HCV antibody. Blood samples from all of acute hepatitis cases were obtained within 1 week after onset of the disease, thus, it was not possible to accurately assess prevalence of hepatitis C. Positive rates on HBsAg among chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 25.4%, 32.8% and 35.5% respectively, while those for HCV antibody were 16.3%, 43.1% and 35.5% respectively. Positive rates of HBsAg and HCV antibody for overall chronic liver diseases were 31.1% and 32.6%, and 14 (10.6% ) were positive for both markers. This study was supported by a grant from The Japan Society for the Promotion of Science.     

Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection

AIM: To evaluate the prevalence of isolated anti-HBc in patients with chronic hepatitis C virus (HCV) infection, and its relation to disease severity. METHODS: We screened all patients with chronic HCV infection referred to King Faisal Specialist Hospital and Research Center for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and anti-HBc. One hundred and sixty nine patients who tested negative for both HBsAg and anti-HBs were included in this study. RESULTS: Pathologically, 59 had biopsy-proven cirrhosis and 110 had chronic active hepatitis (CAH). Of these 169 patients, 85 (50.3%) tested positive for anti-HBc. Patients with CAH had significantly higher prevalence of isolated anti-HBc than patients with cirrhosis, 71 (64.5%) and 14 (23.7%) respectively (P < 0.001). Twenty-five patients were tested for HBV DNA by qualitative PCR. The test was positive in 3 of them (12%; occult HBV infection). CONCLUSION: Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.     

Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in United States patients with chronic hepatitis C

Previous studies have suggested that prior exposure to hepatitis B virus (HBV) infection may increase the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The aim of this study was to compare the prevalence of previous or occult HBV infection in a cohort of hepatitis B surface antigen-negative patients with histologically advanced chronic hepatitis C in the United States who did or did not develop HCC. Stored sera from 91 patients with HCC and 182 matched controls who participated in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial were tested for hepatitis B core antibody (anti-HBc), hepatitis B surface antibody, and HBV DNA. Frozen liver samples from 28 HCC cases and 55 controls were tested for HBV DNA by way of real-time polymerase chain reaction. Anti-HBc (as a marker of previous HBV infection) was present in the serum of 41.8% HCC cases and 45.6% controls (P=0.54); anti-HBc alone was present in 16.5% of HCC cases and 24.7% of controls. HBV DNA was detected in the serum of only one control subject and no patients with HCC. HBV DNA (as a marker of occult HBV infection) was detected in the livers of 10.7% of HCC cases and 23.6% of controls (P=0.18). CONCLUSION: Although almost half the patients in the HALT-C Trial had serological evidence of previous HBV infection, there was no difference in prevalence of anti-HBc in serum or HBV DNA in liver between patients who did or did not develop HCC. In the United States, neither previous nor occult HBV infection is an important factor in HCC development among patients with advanced chronic hepatitis C.     

Hepatocellular carcinoma in the U.S.A., etiologic considerations. Localization of hepatitis B antigens.

The serologic and tissue markers of hepatitis B virus (HBV) were studied in 50 patients in whom hepatocellular carcinoma (HCC) was confirmed at autopsy. Serologic and tissue markers included serum hepatitis B surface antigen (HBsAg), tissue HBsAg, tissue hepatitis core antigen (HBcAg), and serum antibody to HBcAg (anti-HBc). Twenty-two patients had HCC arising in alcoholic cirrhosis; 2 of the 22 (9.1%) had one or more of the HBV tissue and serologic markers. This infection rate is similar to the rate of 7.9% observed in 63 control alcoholic cirrhotic patients without HCC. In contrast, 15 of 20 (75.0%) patients with HCC in nonalcoholic chronic active liver disease showed evidence of active HBV infection. One of 8 patients with HCC in normal liver had serum HBV markers. This result indicates that there is an extremely high prevalence of HBV infection among HCC patients with nonalcoholic chronic liver disease in the U.S.A. The prevalence of HBV infection in these patients is as high as that observed in Asia and Africa. Thus, it can be concluded that the lower prevalence rate of active HBV infection in HCC patients in the U.S.A. is the result of statistical dilution of HCC-B-viral disease by the large numbers of the alcoholic cirrhotic patients with HCC, and that if chronic active hepatitis type B were as common in the United States as it is in Africa and Asia, the frequency of occurrence of HCC might also be as high.     

Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis

BACKGROUND: There is little information about the effect of infliximab on the clinical course of liver disease in Crohn's disease patients with concomitant hepatitis B virus (HBV) infection. Theoretically, immunosuppression induced by infliximab will facilitate viral replication which could be followed by a flare or exacerbation of disease when therapy is discontinued. There are no specific recommendations on surveillance and treatment of HBV before infliximab infusion. Two cases of severe hepatic failure related to infliximab infusions have been described in patients with rheumatic diseases. PATIENTS AND METHODS: Hepatitis markers (C and B) and liver function tests were prospectively determined to 80 Crohn's disease patients requiring infliximab infusion in three hospitals in Spain. RESULTS: Three Crohn's disease patients with chronic HBV infection were identified. Two of the three patients with chronic HBV infection suffered severe reactivation of chronic hepatitis B after withdrawal of infliximab therapy and one died. A third patient, who was treated with lamivudine at the time of infliximab therapy, had no clinical or biochemical worsening of liver disease during or after therapy. From the remaining 80 patients, six received the hepatitis B vaccine. Three patients had antibodies to both hepatitis B surface antigen (anti-HBs) and hepatitis B core protein (anti-HBc) with normal aminotransferase levels, and one patient had positive anti-hepatitis C virus (HCV) antibodies, negative HCV RNA, and normal aminotransferase levels. Except for the patients with chronic HBV infection, no significant changes in hepatic function were detected. CONCLUSIONS: Patients with Crohn's disease who are candidates for infliximab therapy should be tested for hepatitis B serological markers before treatment and considered for prophylaxis of reactivation using antiviral therapy if positive.     

Prevalence of hepatitis C antibody in patients with chronic liver disease and hepatocellular carcinoma in Korea

Summary. To investigate the contribution of hepatitis C virus (HCV) to chronic liver disease and hepatocellular carcinoma (HCC) in Korea, antibodies to HCV (anti-HCV) were tested by enzyme immunoassay in 1759 patients with chronic liver disease and HCC, and in 808 healthy adults. The prevalence of anti-HCV was 1.6% in 808 controls. Anti-HCV was present in 32 (7.7%) of 418 hepatitis B surface antigen (HBsAg)-positive and 128 (53.1%) of 241 HBsAg-negative patients with chronic hepatitis, 16 (6.0%) of 265 HBsAg-positive and 90 (30.5%) of 295 HBsAg-negative patients with liver cirrhosis, and 16 (4.8%) of 330 HBsAg-positive and 61 (29.0%) of 210 HBsAg-negative patients with HCC. Antibodies to hepatitis B core antigen (anti-HBc) were present in 80–88% of patients who were seropositive for anti-HCV and seronegative for HBsAg. Among the sera from 114 patients with HBsAg-negative and anti-HCV-positive chronic liver diseases, HBV DNA and HCV RNA were detected by polymerase chain reaction (PCR) in 54 (47.4%) and 61 (53.3%), respectively. Both HBV DNA and HCV RNA were detected in 4 (4.4%) samples. The mean age of the patients with both HBsAg and anti-HCV was not different from that of patients who were seropositive for HBsAg alone. These findings indicate that current and/or past HBV infection is still the main cause of chronic liver disease in Korea. Although multivariate analysis showed that anti-HCV is a risk factor for chronic hepatitis, cirrhosis of the liver and HCC, PCR data for HBV DNA and HCV RNA indicate that HCV infection plays only a minor role in HBsAg-positive as well as in HBsAg-negative liver disease and does not accelerate the development of HCC in HBV carriers.     

隐匿性乙型肝炎病毒感染者临床特点和肝组织病理学检查

目的了解血清肝炎病毒标志物阴性、肝功能反复异常患者中HBV隐匿性感染的比例及其临床和病理学特点。方法对27例血清肝炎病毒标志物阴性、肝功能反复异常患者采用免疫组化法检测肝组织HBsAg、HBcAg和HCVAg，并进行常规的病理学检查。结果肝组织HBsAg和（或）HBcAg阳性9例（33．3％）；HBsAg和（或）HBcAg及HCVAg阳性10例（37．0％）；全阴性8例（29．6％）。在HBV隐匿性感染的19例患者中，慢性肝炎8例，肝硬化11例。结论HBV和HCV感染为血清肝炎病毒标志物阴性患者肝功能反复异常的主要原因之一，尤其是HBV感染。这种HBV隐匿性感染与慢性肝炎、肝硬化的发生关系密切，应引起重视。     

Seroepidemiology of hepatitis C virus infection in the Philippines: A preliminary study and comparison with hepatitis B virus infection among blood donors, medical personnel, and patient groups in Davao, Philippines

To determine the seroprevalence of hepatitis C virus in the Philippines and compare it with the seroprevalence of hepatitis B virus infection, HBV and HCV markers in 594 serum samples collected from 392 blood donors, 123 medical and paramedical personnel, and 80 patients (45 liver diseases: 25 acute hepatitis, 9 liver cirrhosis, and 11 hepatocellular carcinoma; 28 hepatitis B carriers, and 7 chronic renal failure patients undergoing dialysis) in Davao, Mindanao Island, Philippines, were examined. HBsAg was determined by RPHA, anti-HBc by HI, anti-HBs by PHA, and HBsAg subtypes, HBeAg, and anti-HBe by EIA. HCV markers determined were anti-HCV (anti-C100-3) by ELISA (Ortho Diagnostic Systems), and anti-HCV core (anti-CP9 and/ or anti-CPIO) also by ELISA. Results showed that 9 (2.2%) blood donors were anti HCV positive; 69 (15.4%) were anti-HCV core positive Nine (2.2%) were HBsAg carriers; 240 (61.3%) were anti-HBs and/or anti-HBc positive (HBsAg carriers excluded from this group). Two of 123 medical and paramedical staff (1.6% ) were anti-HCV positive; 11 (8.1%) were anti-HCV core positive; Eight (6.5%) were HBsAg carriers and 81 (65.8%) anti-HBs and/or anti-HBc positive. Five of 11 (45.4%) hepatocellular carcinoma patients were HBsAg carriers; 2 were anti-HCV core positive. Two of 9 liver cirrhosis patients were antiHCV positive (1 to anti-HCV and the other to anti-HCV core). If anti-HCV positivity means carrier state, then the HCV carrier rate of blood donors in Davao, Philippines is the same as the HBV carrier rate and prospective blood donors should be screened not only for HBV but also for HCV to prevent transfusion-associated hepatitis. Less than 50% of liver cirrhosis and hepatoHCV carcinoma cases have HBV markers and HCV markers but, when present, these markers appear at almost the same frequency; the role of HCV and HBV in the pathogenesis of these 2 diseases in Mindanao should be further investigated.     

Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients

Purpose  The presence of hepatitis B virus (HBV) DNA in liver tissue and/or in serum in the absence of detectable hepatitis B surface antigen (HBsAg) is called occult HBV infection. This pattern was identified in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the role of antibodies to hepatitis B core antigen (anti-HBc) as a screening test for occult HBV infection in Egyptian chronic HCV patients. Methods  One hundred chronic HCV patients negative for HBsAg were included and subdivided into two groups according to anti-HBc-IgG seroreactivity. Group A included 71 patients positive for anti-HBc (53 men and 18 women, mean age ± SD 48.8 ± 9.6 years), and group B included 29 patients negative for anti-HBc (18 men and 11 women, mean age ± SD 46.6 ± 11.7 years). All patients were subjected to full clinical assessment, routine laboratory investigations, abdominal ultrasonography and quantification of HBV-DNA by real-time PCR. Results  Chronic HCV patients positive for anti-HBc have more severe liver disease compared with anti-HBc negative patients. Although HBV-DNA in the serum was detected in 22.5% of anti-HBc-positive chronic HCV patients, it was not detected in any of anti-HBc-negative chronic HCV patients. There was no significant difference in any of the clinical and laboratory data tested between anti-HBc-positive patients with and without HBV-DNA in the serum. Conclusion  A significant number of patients with anti-HBc had detectable levels of HBV-DNA in the serum. Egyptian chronic HCV patients have a high prevalence of occult HBV infection.     

Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study.

OBJECTIVE: To determine whether chronic hepatitis C virus (HCV) infection is an independent risk factor for hepatocellular carcinoma and whether it increases the cirrhosis-related risk for hepatocellular carcinoma. DESIGN: Two pair-matched case-control studies. SETTING: A referral-based hospital. PATIENTS: In study I, 212 patients with hepatocellular carcinoma (197 of whom had known underlying cirrhosis) were compared with controls who had chronic nonhepatic diseases. In study II, the 197 patients with hepatocellular carcinoma and cirrhosis were compared with 197 pair-matched controls who had cirrhosis but not hepatocellular carcinoma. MEASUREMENTS: Levels of antibody to HCV (anti-HCV), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B core antigen (anti-HBc) were assayed, and alcohol abuse was assessed by history. MAIN RESULTS: In study I, 151 patients (71%) with hepatocellular carcinoma were anti-HCV positive compared with 11 controls (5%) with chronic nonhepatic diseases (odds ratio, 42; 95% CI, 22 to 95). Multivariate analysis showed that anti-HCV was an independent risk factor for hepatocellular carcinoma (odds ratio, 69; CI, 15 to 308). The analysis also showed that HBsAg (odds ratio, 8.7; CI, 1.5 to 50) and anti-HBc (odds ratio, 4.2 (CI, 1.7 to 11) were risk factors for hepatocellular carcinoma. No statistically significant interaction was found between anti-HCV and the markers of HBV infection. In study II, 146 patients (74%) with hepatocellular carcinoma and cirrhosis were anti-HCV positive compared with 122 patients (62%) with cirrhosis alone (odds ratio, 1.8; CI, 1.1 to 2.8). Multivariate analysis confirmed that anti-HCV (odds ratio, 2.0; CI, 1.3 to 32) and HBsAg (odds ratio, 2.0; CI, 1.0 to 4.2) were independent risk factors for hepatocellular carcinoma. CONCLUSIONS: Hepatitis C virus infection is a risk factor for hepatocellular carcinoma, apparently by inducing cirrhosis and, to a lesser extent, by enhancing the risk in patients with cirrhosis. Hepatitis C virus infection acts independently of HBV infection (another risk factor) and of alcohol abuse, age, or gender.     

Occult Hepatitis B Infection and its Possible Impact on Chronic Hepatitis C Virus Infection

As a well-recognized clinical phenomenon, persistent detectable viral genome in liver or sera in the absence of other serological markers for active hepatitis B virus (HBV) replication is called occult HBV infection. The main mechanism through which occult infection occurs is not completely understood and several possible explanations, such as integration into human genome and maintenance in peripheral mononuclear cells, exist. Occult HBV infection has been reported in different populations, especially among patients with Hepatitis C (HCV) related liver disease. The probable impact of occult HBV in patients with chronic HCV infection has been previously investigated and the evidence suggests a possible correlation with lower response to anti-viral treatment, higher grades of liver histological changes, and also developing hepatocellular carcinoma. However, in the absence of conclusive results, further studies should be conducted to absolutely assess the impact of occult HBV contamination on the HCV related liver disease.     

Primary hepatocellular carcinoma following nonspecific non-B hepatitis with tumor DNA negative for HBV DNA

Summary An association between non-A, non-B hepatitis and hepatocellular carcinoma has been made on the basis of negative serological markers for hepatitis B virus (HBV); however, hepatocellular carcinomas have been found to contain hepatitis B virus deoxyribonucleic acid (HBV DNA) in individuals who lack serological markers of HBV infection. Therefore, reports which ascribed a hepatocellular carcinoma to non-A, non-B hepatitis but did not examine the tumor for HBV DNA are open to question. We describe a case of chronic active hepatitis with primary hepatocellular carcinoma that lacked HBV DNA in the tumor, the nontumorous liver tissue, and serum. The individual lacked all serological markers for HBV infection. This report more fairly supports the association between hepatocellular carcinoma, and chronic hepatitis not due to hepatitis B. Whether this is related specifically to a non-A, non-B hepatitis agent requires identification of the viral agents that cause non-A, non-B hepatitis.     

Hepatitis B and human immunodeficiency virus co-infection

Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy.