Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients

Background and Aims: Although hepatic steatosis (HS) has an association with hepatitis C virus (HCV) infection, an association with hepatitis B virus (HBV) is controversial. We performed a meta‐analysis to evaluate HS prevalence and risk factors, in HBV infection. Methods: Standard guidelines for performance of meta‐analyses were followed. Studies with HS assessed by histology were included. Pooled odd ratios (OR) and standardized mean differences (SMD) were obtained with the random‐effects model and DerSimonian‐Laid method. Results: Seventeen out of 21 studies were included, comprising 4100 HBV infected patients. Overall HS prevalence was 29.6%. Eight studies also included 945 HCV infected patients, showing decreased risk of HS in HBV versus HCV patients (OR 0.55, 95%CI [0.45–0.67], P < 0.001). In HBV, HS positively associated with male gender (OR 1.74, 95%CI [1.28–2.38], P < 0.001), body mass index (SMD 2.17, 95%CI [1.23, 3.11], P < 0.001), obesity (OR 6.59, 95%CI [3.51–12.257], P = 0.003), diabetes (OR 2.62, 95%CI [1.37–4.00], P = 0.004), glycemia (SMD 0.84, 95%CI [0.00, 1.67], P = 0.049), triglycerides (SMD 1.18, 95%CI [0.48, 1.89], P = 0.001), cholesterol (SMD 0.88, 95%CI [0.31, 1.45], P = 0.003), moderate alcohol consumption (OR 1.54, 95%CI [1.10–2.15], P = 0.011) and negatively with HBV DNA (SMD ?74.12, 95%CI [?82.93, ?65.31], P < 0.001). HS had no association with aminotransferases, HBeAg, genotype or hepatic histology, necroinflammation or fibrosis. Conclusion: HS in HBV seems to be as frequent as in the general population, and lower than in HCV infected patients, relating to metabolic factors but not with hepatic histology severity. A puzzling strong negative association between viral load and HS, may even suggest a protective effect of the virus on HS.     

Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from India

AIM: To assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol intake as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis in Indian population. METHODS: A total of 213 patients with HCC and 254 control subjects not affected with hepatic diseases or neoplasm were recruited. Odds ratios (ORs) were estimated for each risk factor and synergism among various risk factors was also studied. RESULTS: The ORs and 95% confidence intervals (CI) of HCC were 48.02 (25.06-91.98) for any HBV marker, 38.98 (19.55-77.71) for HBsAg positivity, 12.34 (2.84-53.61) for HBsAg negative and antibody positive (either of anti-HBe or total anti-HBc), 5.45 (2.02-14.71) for anti-HCV positive and HCV RNA positive, and 2.83 (1.51-5.28) for heavy alcohol use. No significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA negative. Synergism between alcohol and HCV infection in causing HCC was found, but not between alcohol and HBV. Overall, conclusive evidence of the presence or absence of cirrhosis was reached in 189 (88.73%) HCC patients; cirrhosis was present in 137 (72.48%) of them. ORs with 95% CI of HCC in the presence and absence of cirrhosis, respectively, for HBV were as follows: (i) 48.90 (24.61-97.19) and 35.03 (15.59-78.66) for any HBV marker; (ii) 39.88 (19.41-81.97) and 24.40 (10.60-56.18) for HBsAg positivity; and (iii) 12.10 (2.67-54.88) and 19.60 (3.94-97.39) for HBsAg negativity and antibody positivity. Significantly increased risk was found among cirrhotic patients for anti-HCV positivity and HCV RNA positivity [OR = 7.53 (2.73-20.78)] and for heavy alcohol use [OR = 3.32 (1.70-6.47)]; however, in the absence of cirrhosis, no significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA positive [OR = 0.97 (0.11-8.54)], or who had history of heavy alcohol use [OR = 1.58 (0.55-4.53)]. CONCLUSIONS: Infection with HBV and HCV are the major risk factors for the development of HCC in Indian patients. Presence of HBV antibodies even in the absence of HBsAg conferred increased risk for HCC in the presence or absence of cirrhosis. Anti-HCV positivity in the absence of HCV RNA conferred no increased risk. HCV RNA positivity and heavy alcohol use significantly increased the risk of HCC among cirrhotic patients, but not non-cirrhotic patients.     

A case-control study on a novel DNA virus (TT virus) infection and hepatocellular carcinoma. The Brescia HCC Study.

We performed a case-control study to evaluate the association of a new human DNA virus named TT virus (TTV) with hepatocellular carcinoma (HCC). We recruited 174 subjects hospitalized for HCC (84% males; mean age: 64 years) and 118 patients hospitalized for non-liver diseases in Brescia, northern Italy, as controls (94% males; mean age: 66 years). TTV DNA was found in serum by polymerase chain reaction (PCR) in 26 cases (15%) and 11 controls (9.3%) (P >. 1). TTV group 2 infection was identified in 16 cases (61.5%) and 4 controls (36.4%) (P >.1) using a type-specific PCR method. Sequence analysis of 222 nt of TTV DNA demonstrated that the remaining 10 cases and 7 controls were all infected by group 1. The odds ratio (OR) for TTV-DNA positivity, adjusted for demographic variables, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, and heavy alcohol intake was 1.8 (95% CI: 0.7-4.8; P >.1). The OR did not change when the analysis was restricted to 14 HCC cases and 56 controls who were negative for each known risk factor for HCC (OR = 1.7; 95% CI: 0.8-4.0). TTV-DNA positivity was not associated with transfusion history. The prevalence of TTV DNA was higher among HCC cases positive for HBsAg (10 of 38 [26.3%]) than among those positive for HCV RNA (8 of 62 [12.9%]) or negative for hepatitis B virus (HBV), HCV, and hepatitis G virus (HGV) infections (5 of 62 [8. 1%]) (P =.02). This study does not support the hypothesis of an association between TTV infection and HCC.     

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.     

GB virus C/hepatitis G virus infection among patients with hepatocellular carcinoma in the inshore area of the Yangtze river, China

To investigate the association between GB virus C/hepatitis G virus (GBV-C/HGV) infection and the development of hepatocellular carcinoma (HCC) in H city, in the inshore area of the Yangtze River, where high prevalence of HCC has been reported, we determined hepatitis B virus (HBV) and hepatitis C virus (HCV) markers, GBV-C/HGV-RNA and GBV-C/HGV E₂ antibody (anti-HG E₂) among 114 HCC patients and the same number of age- and sex-matched controls. There were no significant differences in the clinical and demographic characteristics between them, except for serum alanine aminotransferase level and history of liver diseases. There was a significant difference of hepatitis B virus surface antigen (HBsAg) prevalence between the HCC patients (75.4%) and the controls (20.2%; P < 0.01). Hepatitis C virus antibody was detected in 4.4% of the HCC patients, compared with 1.7% of the controls. GB virus-C/HGV-RNA and anti-HG E₂ were detected in 14.9 and 1.7% of the HCC patients, respectively, compared with 7.0 and 1.7% of the controls, respectively. Nucleotide sequences and molecular evolutionary analysis showed the strains of GBV-C/HGV-RNA were classified into genotype 2 and 3 (HG and ASIA type). An effect analysis showed an odds ratio (OR) for developing HCC from GBV-C/HGV infection among HBsAg-positive subjects was 14.9, with a 95% CI of 4.9–45.4. HBsAg infection alone was 13.83 (95% CI 7.4–25.9) and GBV-C/HGV infection alone, 3.74 (95% CI 1.1–13.1), respectively. These data indicate that HBV infection is considered to be one of the major risk factors in patients with HCC and although GBV-C/HGV infection was observed in both the HCC and the control groups, it might not play an important role in the development of HCC in this area.     

Hepatitis B and C virus infection in Crohn's disease.

Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-alpha (IFN-alpha) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00-2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04-11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61-3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37-3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37-3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06-1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-alpha for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.     

Hepatitis B or C viral infection and risk of pancreatic cancer: A meta-analysis of observational studies

AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found.     

Highly endemic hepatitis B infection in rural Vietnam

BACKGROUND AND AIM: Hepatitis B is a major public health problem in Vietnam; however, estimates of the prevalence of hepatitis B virus (HBV) and hepatitis delta virus (HDV), and risk factors in rural Vietnam are limited. The aim of this study was to determine HBV and HDV prevalence, and identify risk factors for HBV infection. METHODS: A cross-sectional seroprevalence study was undertaken in two rural districts in Thai Binh province. The study population was randomly selected using multistage sampling. Demographic and behavioral risk information and serological samples were obtained from 837 participants. RESULTS: Mean age was 42.3 years +/- 15.8 (range, 16-82 years), and 50.8% were female. Prevalence of anti-HBV core antibody (anti-HBc) and hepatitis B virus surface antigen (HBsAg) was 68.2% and 19.0%, respectively, and hepatitis B e antigen HBeAg was detected in 16.4% of the HBsAg-positive group. Prevalence of HDV was 1.3% in the HBsAg-positive group. Factors associated with HBV infection (anti-HBc or HBsAg positive) were age 60 years or older (OR, 3.82; 95% CI, 1.35-10.80; P = 0.01), residence in Vu Thu district (OR, 3.00; 95% CI, 2.16-4.17; P < 0.0001), hospital admission (OR, 2.34; 95% CI, 1.33-4.13; P = 0.003) and history of acupuncture (OR, 2.01; 95% CI, 1.29-3.13; P = 0.002). Household contact with a person with liver disease (OR, 2.13; 95% CI, 1.29-3.52; P = 0.003), reuse of syringes (OR, 1.81; 95% CI, 1.25-2.62; P = 0.002) and sharing of razors (OR, 1.69; 95% CI, 1.03-2.79; P = 0.04) were independent predictors of HBsAg positivity. Alanine aminotransferase (ALT) level was elevated (>40 IU/L) in 43% of the HBsAg-positive group; proportion elevated was higher in HBeAg-positive (65%) compared with HBeAg-negative (39%) individuals in this group (P = 0.02). CONCLUSION: Hepatitis B virus infection is highly endemic in rural Vietnam. Poor infection control activities in health-care settings contribute to high HBV prevalence in this region. Universal HBV infant vaccination and improved infection control procedures are required for improved HBV control in Vietnam.     

Ethnicity, socioeconomic status, transfusions and risk of hepatitis B and hepatitis C infection

This study identifies the risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) and measures the prevalence of hepatitis B surface antigen (HBsAg) and antibody to hepatitis C (anti-HCV) in the general population of Jakarta. A population-based sample of 985 people aged 15 and above was surveyed. Risk factors were identified through questionnaires and home visits. Serum was analysed for HBsAg, antibody to hepatitis B surface antigen (anti-HBs), anti-HCV, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The seroprevalence was: 4.0% (39/985) for HBsAg, 17.2% (170/985) for anti-HBs, and 3.9% (38/985) for anti-HCV. The risk factors for hepatitis B and hepatitis C infection had little in common. Low socioeconomic status was a strong risk factor for HBsAg (adjusted odds ratio (OR) 18.09; 95% confidence interval (CI) 2.35–139.50). In addition, the Chinese group has 2.97 higher risk of having HBV infection compared with the Malayan ethnic group (adjusted OR 2.97; 95% CI 1.22–7.83). There was moderate positive trend between family size and risk of HBsAg positivity (P= 0.130). Age over 50 (adjusted OR 14.72; 95% CI 4.35–49.89) and history of transfusion were significant risk factors for hepatitis C (adjusted OR 3.03; 95% CI 1.25–7.33). Hepatitis B and hepatitis C infections have different risk factors in Jakarta, a high risk in population for both diseases. Hepatitis B transmission is associated with low socioeconomic status, Chinese ethnic group and large family size, while hepatitis C is associated with an older age and a history of transfusions.     

Impact of comorbidities on the severity of chronic hepatitis B at presentation

AIM: To evaluate the clinical relevance of each cofactor on clinical presentation of chronic hepatitis B.METHODS: Out of 1366 hepatitis B surface antigen (HBsAg) positive subjects consecutively observed in 79 Italian hospitals, 53 (4.3%) showed as the only cofactor hepatitis D virus (HDV) infection [hepatitis B virus (HBV)/HDV group], 130 (9.5%) hepatitis C virus (HCV) (group HBV/HCV), 6 (0.4%) human immunodeficiency virus (HIV) (group HBV/HIV), 138 (10.2%) alcohol abuse (group HBV/alcohol); 109 (8.0%) subjects had at least two cofactors and 924 were in the cofactor-free (CF) group.RESULTS: Compared with patients in group CF those in group HBV/alcohol were older and more frequently had cirrhosis (P < 0.001), those in group HBV/HDV were younger (P < 0.001), more frequently resided in the south of the country and had cirrhosis (P <0.001), those in group HBV/HCV were older (P < 0.001) and more frequently had cirrhosis (P < 0.001). These cofactors were all independent predictors of liver cirrhosis in HBsAg positive patients. Multivariate analysis showed that an older age [odds ratio (OR) 1.06, 95% CI: 1.05-1.08], alcohol abuse with more than 8 drinks daily (OR 2.89, 95% CI: 1.81-4.62) and anti-HDV positivity (OR 3.48, 95% CI: 2.16-5.58) are all independently associated with liver cirrhosis. This association was found also for anti-HCV positivity in univariate analysis, but it was no longer associated (OR 1.23, 95% CI: 0.84-1.80) at multivariate analysis.CONCLUSION: Older age, HDV infection and alcohol abuse are the major determinants of severe liver disease in chronic HBV infection, while HCV replication plays a lesser role in the severity of hepatic damage.     

Excess mortality of hepatocellular carcinoma and morbidity of liver cirrhosis and hepatitis in HCV-endemic areas in an HBV-endemic country: geographic variations among 502 villages in southern Taiwan

AIMS: The aim of this study was to investigate excess mortality for hepatocellular carcinoma (HCC) and prevalence of hepatitis and liver cirrhosis (LC) in hepatitis C virus (HCV)-endemic areas in Taiwan, which is a hepatitis B virus (HBV)-endemic country. METHODS: Tainan County, located in southern Taiwan, consists of 533 villages in 31 townships. A total of 56 702 subjects >or= 40 years old (mean age, 60.9 +/- 11.8 years) were enrolled from 502 of the 533 villages between April and November 2004 (n >or= 20/village). Serum blood HBV surface antigen (HBsAg), antibody to HCV (anti-HCV) and alanine transaminase (ALT) levels and platelet counts were measured. Township-specific mortality for liver cancer (ICD = 155) for both sexes between 1992 and 2001 were obtained from official publications. RESULTS: The prevalence of anti-HCV in Tainan County was 10.2% (township range, 2.6-30.9%; village range, 0-90.5%). The prevalence of HBsAg was 10.9% (township range, 5.5-17.2%; village range, 0-30.8%). The prevalence of hypertransaminemia (serum ALT > 40 IU/L) was 12.8%. At township levels, prevalence of anti-HCV (r2 = 0.92, P < 0.001), HBsAg and anti-HCV (multiple r2 = 0.94) were correlated with hypertransaminemia prevalence by single and multiple linear analysis, respectively. At village levels, prevalence of anti-HCV (r2 = 0.52, P < 0.001), HBsAg and anti-HCV (multiple r2 = 0.53) were each correlated with prevalence of hypertransaminemia, respectively. The prevalence of thrombocytopenia (<150,000 platelets/microL) was 5.5%, and adopted as a surrogate prevalence for LC. At township levels, prevalence of anti-HCV (r2 = 0.58) was the only factor correlated by multivariate analysis with prevalence of thrombocytopenia. At village levels, prevalence of anti-HCV and female-to-male ratio (multiple r2 = 0.43) were each independently associated with prevalence of thrombocytopenia. At township levels, HBsAg prevalence (r2 = 0.42) was more correlated with HCC mortality than anti-HCV prevalence (r2 = 0.28) for male subjects, while anti-HCV prevalence (r2 = 0.45) was more correlated with HCC mortality than HBsAg prevalence (r2 = 0.14) for female subjects. Prevalence of HBV and HCV infection were associated by multivariate analysis with both male (multiple r2 = 0.62) and female (multiple r2 = 0.53) HCC mortality. CONCLUSIONS: Prevalence of anti-HCV showed significant correlations with prevalence of hypertransaminemia, thrombocytopenia and liver cancer mortality. The findings indicate excessive mortality due to HCC, and LC and hepatitis prevalence in HCV-endemic areas in Taiwan, an HBV-endemic country.     

Hepatitis B and C virus infection as risk factors for liver cirrhosis and cirrhotic hepatocellular carcinoma: a case-control study

To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are risk factors for liver cirrhosis and hepatocellular carcinoma (HCC), a case-control study of 102 cirrhotic HCC patients, 102 sex-matched and age-matched patients with liver cirrhosis, and 102 matched patients with non-hepatic disease controls was performed. The prevalences of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) in HCC (70.5%, 39.2%) and liver cirrhosis (74.5%, 27.4%) were higher than controls (16.6%, 10.5%) (P = 0.0001). In HBsAg-negative patients, the prevalence of anti-HCV in cirrhotic HCC (66.6%) and liver cirrhosis (46.1%) was higher than in controls (10.5%; P = 0.0001). There was no such difference in HBsAg-positive patients. Multivariate analysis revealed that both HBsAg and anti-HCV were important risk factors for HCC (odds ratio, 6.52 and 4.59, respectively) and liver cirrhosis (odds ratio, 4.22 and 2.29, respectively). There was no difference in odds ratio when HCC and liver cirrhosis were compared. Our result implies that both HBV and HCV are independent risk factors for cirrhotic HCC and liver cirrhosis in Taiwan.     

Trends in incidence of hepatocellular carcinoma after diagnosis of hepatitis B or C infection: a population-based cohort study, 1992-2007

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major risk factors for hepatocellular carcinoma (HCC). We examined trends in the incidence of HCC among a population-based cohort of people infected with HBV or HCV. HBV and HCV cases notified to the New South Wales Health Department between 1992 and 2007 were linked to the Central Cancer Registry, Registry of Births, Deaths and Marriages, and National HIV/AIDS Registries. Crude HCC incidence rates were estimated using person-time methodology. Age-standardized incidence rates were calculated using the 2001 Australian population. Trends in incidence were examined using join point regression models. Between 1992 and 2007, 1201 people had a linked HCC record: 556 of those with HBV; 592 with HCV; 45 with HBV/HCV co-infection; and 8 with HIV co-infection. The overall age-standardized HCC incidence rates declined non-significantly from 148.0 (95% confidence intervals (CI) 63.7, 287.4) per 100,000 population in 1995 to 101.2 (95% CI 67.3, 144.6) in 2007 among the HBV monoinfected group and significantly from 151.8 (95% CI 62.4, 299.8) per 100,000 population to 75.3 (95% CI 50.8, 105.5) among the HCV monoinfected group. However, incidence rates in the HCV monoinfected group progressively increased from the period 1992-1997 to 2004-2007 when adjusted for age, sex, and birth cohort, and the total number of cases per annum continued to increase. Despite declines in the age-adjusted incidence rates of HCC over time, the absolute number of cases increased likely due to the ageing cohort and an increasing prevalence of both hepatitis B and C in Australia.     

Serum alanine aminotransferase level in relation to hepatitis B and C virus infections among blood donors

Abstract: To assess the serum alanine aminotransferase (ALT) activity in relation to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among blood donors, antibodies to HCV (anti-HCV) and hepatitis B surface antigen (HBsAg) were detected in 400 blood donors with normal ALT level (≤750 μmol/s per liter), and 76 blood donors with raised ALT level. The prevalence of anti-HCV (10.5%) and HBsAg (28.9%) in the latter was higher than that (2.0% and 17.5%, respectively) in the former (p<0.001 and p<0.03, respectively). There was a trend that indicated that the risk of anti-HCV positivity increased with increasing age (p<0.001). Thirty of 76 (39.5%) donors with raised ALT level were positive for anti-HCV or HBsAg. Compared with HBsAg-positive donors, donors with anti-HCV had higher serum ALT levels (p<0.01) and greater mean age (p<0.01). Multivariate analysis indicated that both anti-HCV (odds ratio: 6.2; 95% confidence interval: 2.2–17.8) and HBsAg (odds ratio: 2.2; 95% confidence interval: 1.3–3.9) were significantly associated with raised serum ALT activity. The estimated population-attributable risk was 8.6% for anti-HCV, and 13.8% for HBsAg. In conclusion, although HBV and HCV infections are independent risk factors of raised ALT activity among blood donors, they play a minor role in the etiology of raised ALT activity.     

The role of hepatitis C in hepatocellular carcinoma: a case control study among Egyptian patients

BACKGROUND: Egypt has one of the highest prevalence rates of hepatitis C virus (HCV) infection in the world; however, the risk and attribution related to HCV in Egyptian patients with hepatocellular carcinoma (HCC) remains unknown. GOALS: The current study was undertaken to estimate the risk of HCC in relation to HCV in Egypt. STUDY: Thirty-three patients with HCC and 35 healthy controls who had a similar socioeconomic status were prospectively enrolled at the University of Cairo National Cancer Institute. RESULTS: Anti-HCV antibodies were present in 75.8% of the patients and in 42.9% of the controls (p = 0.01); hepatitis B surface antigen (HBsAg) was present in 15.2% of the patients and in 2.9% of the controls (p = 0.03). In addition, the sex-and age-adjusted odds ratio (OR) for anti-HCV antibodies was 5.1 (95% CI = 1.5-17.4) and for HBsAg was 13.2 (95% CI = 1.2-148.2). Concurrent Schistosoma mansoni and anti-HCV was associated with an OR of 10.3 (95% CI = 1.3-79.8), which was higher than that for anti-HCV (6.5; 95% CI = 1.6-26.6) and S. mansoni infection (0.2; 95% CI = 0.1-6.2) alone. Finally, we estimated the attributable fraction of HCC to HCV to be 64% in this study population and 48% in the general Egyptian population. CONCLUSIONS: Both HCV and hepatitis B virus infection increase the risk of HCC in Egyptian patients, whereas isolated Schistosoma infection does not. Because of the very high prevalence rate of HCV in the general Egyptian population, it accounts for most HCC cases in Egypt.     

Association of pre-S deletion mutant of hepatitis B virus with risk of hepatocellular carcinoma

BACKGROUND: Pre-S deletion mutant of hepatitis B virus (HBV) affects the expression of middle and small surface proteins, resulting in intracellular accumulation of large surface protein. The correlation between pre-S deletion mutant and risk of hepatocellular carcinoma (HCC) in hepatitis B virus carriers remains unclear. METHODS: Using molecular assays, pre-S deletion mutant of HBV were determined in 266 patients with chronic HBV genotype B or C infection. They included 202 asymptomatic carriers and 64 HCC patients. RESULTS: The overall prevalence of pre-S deletion mutant was 16.5%. Hepatocellular carcinoma (odds ratio [OR], 3.23; 95% confidence interval [CI], 1.23-8.48, P = 0.02) and genotype C (OR, 3.19; 95%CI, 1.54-6.62, P = 0.002) were independently associated with the presence of pre-S deletion mutant. The prevalence of pre-S deletion mutant was comparable between HCC patients with genotype B and C infection. Nevertheless, in asymptomatic carriers, patients with genotype C infection were significantly associated with the presence of pre-S deletion mutant compared to those with genotype B infection (20.8% vs 7.2%, P = 0.007). Compared with age- and genotype B-matched asymptomatic carriers, young HCC patients (<50 years of age) had a significantly higher frequency of pre-S deletion (3.4% vs 20%, P = 0.04). CONCLUSIONS: Pre-S deletion mutant is more frequent in HBV carriers with genotype C infection, and those with pre-S deletion mutant may be associated with the development of HCC, irrespective of HBV genotype.     

Prevalence and etiology of elevated serum alanine aminotransferase level in an adult population in Taiwan

BACKGROUND: The prevalence and etiologies of elevated alanine aminotransferase (ALT) have geographic variations and they are rarely reported in Taiwan. Through a population-based screening study, the prevalence and etiologies of elevated ALT in an adult population of Taiwan were assessed. METHODS: A cross-sectional community study in a rural village of Taiwan was conducted in 3260 Chinese adults (age >or=18 years) undergoing ultrasonography (US), blood tests, and interviews with a structured questionnaire. The diagnostic criteria of non-alcoholic fatty liver disease (NAFLD) included alcohol intake <20 g/week for women or <30 g/week for men, negative hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, no known etiologies of liver disease, and US consistent with fatty liver. RESULTS: The prevalence of elevated ALT was 11.4% (372/3260). The probable cause of this elevation was excess alcohol consumption in 0.8%, HBV in 28.5%, HCV in 13.2%, both HBV and HCV in 2.2%, NAFLD in 33.6%, and unexplained cause in 21.8%. The etiologic distribution of elevated ALT was similar in both genders, although elevation was more common in men compared to women (17.3%vs 6.1%, P < 0.05). The prevalence of elevated ALT in NAFLD was 18.1% (125/691), and the positive predictive value was 33.6% (125/372). The development of NAFLD was related to increasing age (age between 40 years and 64 years, odds ratio [OR] 1.59, 95% confidence interval [CI]: 1.25-2.01; age >or= 65 years, OR 1.46, 95%CI: 1.08-1.96), fasting plasma glucose (FPG) >or= 126 mg/dL (OR 1.54, 95%CI: 1.11-2.14), body mass index (BMI) >or= 25 kg/m(2) (OR 5.01, 95%CI: 4.13-6.26), triglyceridemia >or= 150 mg/dL (OR 1.96, 95%CI: 1.58-2.42), and hyperuricemia (OR 1.50, 95%CI: 1.22-1.84). Elevated ALT was related to male gender, BMI >or= 25 kg/m(2), and triglyceridemia >or= 150 mg/dL in subjects without known etiologies of liver disease (all P < 0.05). CONCLUSIONS: Non-alcoholic fatty liver disease appears to be the commonest cause of elevated ALT and presumed liver injury in Taiwan. The development of NAFLD is closely associated with many metabolic disorders. Metabolic disorders are also related to elevated ALT in subjects without known etiologies of liver disease.     

Epidemiology of viral hepatitis in Somalia: Systematic review and meta-analysis study

AIM To provide a clear understanding of viral hepatitis epidemiology and their clinical burdens in Somalia.METHODS A systematic review and meta-analysis was conducted as Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search of published studies on viral hepatitis was performed from 1977-2016 in Pub Med, Google Scholar, Science Direct, World Health Organization African Index Medicus and the Africa Journals Online databases, as well as on the Ministry of Health website. We also captured unpublished articles that were not available on online systems.RESULTS Twenty-nine studies from Somalia and Somali immigrants(United Kingdom,United States,Italy,Libya)with a combined sample size for each type of viral hepatitis[hepatitis A virus(HAV):1564,hepatitis B virus(HBV):8756,hepatitis C virus(HCV):6257,hepatitis D virus(HDV):375 and hepatitis E virus(HEV):278]were analyzed.The overall pooled prevalence rate of HAV was 90.2%(95%CI:77.8%to 96%).The HAV prevalence among different age groups was as follows:1 year old,61.54%(95%CI:40.14%to79.24%);1-10 years old,91.91%(95%CI:87.76%to94.73%);11-19 years old,96.31%(95%CI:92.84%to 98.14%);20-39 years old,91.3%(95%CI:83.07%to 95.73%);and40 years old,86.96%(95%CI:75.68%to 93.47%).The overall pooled prevalence of HBV was 18.9%(95%CI:14%to 29%).The overall pooled prevalence among subgroups of HBV was20.5%(95%CI:5.1%to 55.4%)in pregnant women;5.7%(95%CI:2.7%to 11.5%)in children;39.2%(95%CI:33.4%to 45.4%)in patients with chronic liver disease,including hepatocellular carcinoma(HCC);7.7%(95%CI:4.2%to 13.6%),12.4%(95%CI:6.3%to 23.0%)and 11.8%(95%CI:5.3%to 24.5%)in age groups20 years old,20-39 years old and40years old,respectively.The HBV prevalence among risk groups was 20%(95%CI:7.19%to 44.64%)in female prostitutes,21.28%(95%CI:7.15%to48.69%)in hospitalized adults,5.56%(95%CI:0.99%to 25.62%)in hospitalized children,60%(95%CI:31.66%to 82.92%)in patients with acute hepatitis,33.55%(95%CI:14.44%to 60.16%)in patients with ancylostomiasis,12.34%(95%CI:7.24%to 20.26%)in patients with leprosy and 20.19%(95%CI:11.28%to33.49%)in schistosomiasis patients.The overall pooled prevalence of HCV was estimated as 4.84%(95%CI:3.02%to 7.67%).The prevalence rates among blood donors,risk groups,children and patients chronic liver disease(including HCC)was 0.87%(95%CI:0.33%to 2.30%),2.43%(95%CI:1.21%to 4.8%),1.37%(95%CI:0.76%to 2.46%)and 29.82%(95%CI:15.84%to 48.98%),respectively.The prevalence among genotypes of HCV was 21.9%(95%CI:15.36%to 30.23%)in genotype 1,0.87%(95%CI:0.12%to 5.9%)in genotype 2,25.21%(95%CI:18.23%to 33.77%)in genotype 3,46.24%(95%CI:37.48%to 55.25%)in genotype 4,2.52%(95%CI:0.82%to7.53%)in genotype 5,and 1.19%(95%CI:0.07%to16.38%)in genotype 6.The overall pooled prevalence of HDV was 28.99%(95%CI:16.38%to 45.96%).The HDV prevalence rate among patients with chronic liver disease,including HCC,was 43.77%(95%CI:35.09%to 52.84%).The overall pooled prevalence of HEV was46.86%(95%CI:5.31%to 93.28%).CONCLUSION Our study demonstrates a high prevalence of all forms of viral hepatitis in Somalia and it also indicates that chronic HBV was the commonest cause of chronic liver disease.This highlights needs for urgent public health interventions and strategic policy directions to controlling the burden of the disease.     

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.     

SEN virus infection in patients with hepatocellular carcinoma

Although most cases of hepatocellular carcinoma (HCC) are associated with either the hepatitis B or C viruses (HBV, HCV), about 10-20% of HCCs occur in patients with chronic hepatitis that is aetiologically undefined. The aim of the present study was to determine the prevalence of the transfusion-transmitted SEN virus (SEN-V) in patients with HCC, including those patients who do not otherwise appear to be infected with HBV or HCV. Fragments of SEN-V subtypes D and H were amplified separately by PCR from the sera of 50 patients with HCC (31 from Canada and 19 from Japan) as well as from HCC and adjacent nontumourous liver tissues from eight of the Canadian patients. SEN-V DNA was found in the serum of 10 of 31 (32%) Canadian patients and eight of 19 (42%) Japanese patients [overall, 18 of 50 (36%) HCC patients]. SEN-V DNA was detected in the serum of 10 of 23 (43%) HCC patients with antibody to HCV (anti-HCV), six of 11 (55%) with hepatitis B surface antigen (HBsAg), and two of 16 (12%) without detectable anti-HCV or HBsAg. Twenty-three HCC patients in this study had 'silent HBV,' characterized by the detection of HBV DNA in the absence of HBsAg; eight of these (35%) also had SEN-V infections. SEN-V DNA was detected in HCC patients most typically in those with coexistent HBV or HCV infection. SEN-V was found in only one of seven HCC patients without HBV (without HBsAg or HBV DNA) or HCV and thus does not appear to be an important cause of 'cryptogenic' HCC.