Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: comparison with hepatitis B virus‐infected and hepatitis C virus‐cleared patients

Background/Aims: Our aim was to evaluate the relationship between hepatitis C virus (HCV) infection and development of diabetes mellitus (DM) or insulin resistance (IR) in comparison with hepatitis B virus (HBV) infection and eradication of HCV infection by interferon treatment. Methods: This study consisted of 952 outpatients, including 544 HCV‐infected (HCV+chronic), 286 HBV‐infected (HBV+chronic) and 122 patients whose HCV was cleared by interferon treatment (HCV+cleared) (diabetes study). Among 849 without overt DM, IR was assessed in 423 patients, including 232 HCV‐infected (HCV+chronic), 135 HBV‐infected (HBV+chronic) and 56 HCV‐eradicated patients (HCV+cleared) (IR substudy). Results: The prevalence of DM in the HBV+chronic, HCV+chronic and HCV+cleared groups was 6.3, 13.6 and 9.0%, respectively (HBV+chronic vs HCV+chronic, P<0.005), in the diabetes study, and the prevalence of IR in the HCV+chronic group (54.3%) was also higher than that in the HBV+chronic (36.3%) (P<0.005) and HCV+cleared groups (35.7%) (P<0.05) in the IR substudy. However, HCV infection was not shown to be independently associated with DM development [odds ratio (OR) 1.669; P=0.0936] and with IR (OR 1.531; P=0.2154) by multivariate analysis in comparison with HBV infection as control. Conclusions: HCV‐infected patients showed a higher prevalence of DM and IR than those with HBV infection. However, in Japan, other confounding factors appeared to be more important risk factors for the development of disturbance in glucose metabolism.     

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.     

Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C

Background: Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV‐DNA detection. Aims: We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection. Methods: This cross‐sectional study included hepatitis B surface antigen‐ and human immunodeficiency virus‐negative subjects with positive HCV‐RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV‐DNA using a commercial assay. The METAVIR system was used for histological analysis. Results: One‐hundred and eleven patients were evaluated. Thirty‐one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti‐HBc). HBV‐DNA was not detected in any sample. Anti‐HBc‐positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti‐HBc‐positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532; P=0.032] and significant hepatic fibrosis (OR=3.364; P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti‐HBc‐negative subjects who acquired HCV before the age of 30 and in 57% of those anti‐HBc‐positive patients who were infected by HCV after 30 years of age (P<0.001). Conclusion: Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.     

Hepatocellular carcinoma in Saudi Arabia: role of hepatitis B and C infection

BACKGROUND AND AIM: To estimate the risk of hepatocellular carcinoma (HCC) in non-alcoholic patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, 118 patients who were admitted to a regional hospital in Saudi Arabia were compared with 118 age- and sex-matched healthy individuals. RESULTS: The prevalence of HBsAg in HCC patients (67%; 95% confidence interval (CI): 57.7-75.3) was significantly higher than the rate (6.7%; 95%CI: 3.0-12.9) in the controls (OR: 28.4; 95%CI: 12.6-63.9; P < 0.001). There was a high risk of HCC in the presence of HBsAg alone (OR: 34.3; 95%CI: 14.8-79.1, P < 0.001) and anti-HCV alone (OR: 12.2; 95%CI: 3.2-47.2; P < 0.001). Although HBV and HCV were independent risk factors in the development of HCC, there was no interactive relationship between the two viruses. Dual infections occurred in only 3.4% and were associated with only a moderate increase in the risk of HCC (OR: 14.6; 95%CI: 1.57-135.9). In 24.6% of the cases no virus was identified as the etiologic factor. CONCLUSION: Hepatitis B virus constitutes a major risk factor and HCV contributes a less significant role in the development of HCC. The ongoing program of HBV vaccination may significantly decrease the prevalence of HBV-associated HCC in this population.     

Association between occult hepatitis B infection and the risk of hepatocellular carcinoma: a meta‐analysis

Background: The association between occult hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) remains controversial. Aims: We conducted a meta‐analysis of prospective studies and retrospective studies to examine whether occult HBV infection increases the risk of HCC. Methods: Two independent reviewers searched databases for eligible studies published in English or Chinese dated from 1966 to 6 April 2010. The odds ratios or the relative risks (RRs) of each study were considered respectively. Results: We identified 16 eligible studies. A significantly increased risk of HCC was found in subjects with occult HBV infection in comparison with non‐infected controls in both retrospective [OR_unadjusted=6.08, 95% confidence interval (CI)=3.45–10.72] and prospective studies (RR_adjusted=2.86, 95% CI=1.59–4.13), and occult HBV increased the risk for HCC in both hepatitis C virus (HCV)‐infected populations (summary RR=2.83, 95% CI=1.56–4.10) and in non‐infected populations (OR_unadjusted=10.65, 95% CI=5.94–19.08). A higher prevalence of occult HBV was observed in individuals who were positive for anti‐HBs and anti‐HBc (OR_unadjusted=1.81, 95% CI=1.06, 3.09). Conclusion: Our findings suggest that occult HBV infection was associated with an increased risk of HCC. Occult HBV may serve as a cofactor in the development of HCV‐related HCC, and it may also play a direct role in promoting Non‐B and Non‐C HCC growth. Suggestive evidence indicates that individuals with a concomitant presence of anti‐HBs and anti‐HBc had an increased risk of occult HBV infection. However, further studies are needed to clarify these observations.     

Effect of hepatitis B virus on steatosis in hepatitis C virus co‐infected subjects: A multi‐centre study and systematic review

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi‐centre cohort of HBV‐HCV subjects, and by performing a systematic review and meta‐analysis of the literature. We centrally and blindly assessed steatosis prevalence and severity in a cohort of HBV‐HCV coinfected subjects compared to HCV and HBV monoinfected controls and we performed a systematic review of studies addressing the prevalence of steatosis in HBV‐HCV subjects compared to HCV controls. In the clinical cohort, we included 85 HBV‐HCV, 69 HBV and 112 HCV subjects from 16 international centres. There was no significant difference in steatosis prevalence between the HBV‐HCV and the HCV groups (33% vs 45%, P = .11). In subgroup analysis, lean HBV‐HCV subjects with detectable HBV DNA had less steatosis than lean HCV subjects matched for HCV viremia (15% vs 45%, P = .02). Our literature search identified 5 additional studies included in a systematic review. Overall, prevalence of steatosis > 5% was similar in HBV‐HCV infection compared to HCV (pooled odds ratio [OR] 0.91, 95% CI 0.53‐1.6) although there was significant heterogeneity (I² 69%, P = .007). In conclusion, although the prevalence of steatosis is similar in HBV‐HCV compared to HCV subjects, our analysis suggests that there may be an inhibitory effect of HCV‐induced steatogenesis by HBV in certain subgroups of patients.     

High rates of active hepatitis B and C co-infections in HIV-1 infected Cameroonian adults initiating antiretroviral therapy

Objectives

To investigate the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA in HIV‐infected patients initiating antiretroviral therapy in Cameroon.

Methods

Baseline blood samples from 169 patients were tested retrospectively for hepatitis B surface antigens (HBsAg), anti‐hepatitis B core (anti‐HBc), anti‐HCV and – if HBsAg or anti‐HCV result was positive or indeterminate – for HBV DNA or HCV RNA, respectively, using the Cobas Ampliprep/Cobas TaqMan quantitative assay (Roche Diagnostics GmbH, Mannheim, Germany).

Results

HBV DNA was detected in 14 of the 18 patients with positive or indeterminate HBsAg results [8.3% of the total study population, 95% confidence interval (CI) 4.6–13.5]. The median HBV viral load was 2.47 × 10⁷ IU/mL [interquartile range (IQR) 3680–1.59 × 10⁸; range 270 to >2.2 × 10⁸]. Twenty‐one patients (12.4%, 95% CI 7.9–18.4) were found with HCV RNA (all with positive HCV serology). The median HCV viral load was 928 000 IU/mL (IQR 178 400–2.06 × 10⁶; range 640–5.5 × 10⁶). No patient was co‐infected with HBV and HCV. In multivariate analysis, HCV co‐infection was associated with greater age [≥45 years vs. <45 years, odds ratio (OR) 11.89, 95% CI 3.49–40.55, P<0.001] and abnormal serum alanine aminotransferase level [≥1.25 × upper limit of normal (ULN) vs. <1.25 × ULN, OR 7.81, 95% CI 1.54–39.66, P=0.01]; HBV co‐infection was associated with abnormal serum aspartate aminotransferase level (OR 4.33, 95% CI 1.32–14.17, P=0.02).

Conclusions

These high rates of active HBV and HCV co‐infections in HIV‐positive Cameroonian patients requiring antiretroviral therapy underline the need to promote: (i) screening for HBV and HCV before treatment initiation; (ii) accessibility to tenofovir (especially in HBV‐endemic African countries); and (iii) accessibility to treatment for HBV and HCV infections.     

Effects of interferon therapy on development of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis: A meta-analysis of randomized controlled trials

Aim: The role of interferon (IFN) therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)‐related cirrhosis remains controversial. This meta‐analysis aimed to determine whether IFN therapy reduced the incidence of HCC in HCV‐related cirrhotic patients. Methods: We performed a meta‐analysis including eight randomized controlled trials (RCT) (a total of 1505 patients) to assess the effect of IFN therapy on prevention of HCC in patients with HCV‐related cirrhosis. The pooled odds ratios (OR) were calculated using a random or fixed effects model. Results: Our results showed that IFN therapy significantly decreased the overall HCC incidence in HCV‐related cirrhotic patients (OR, 0.29; 95% confidence interval [CI], 0.10–0.80; P = 0.02). HCC risk in patients who failed to achieve sustained virological response (SVR) in the initial IFN‐based treatment was also reduced by maintenance IFN therapy (OR, 0.54; 95% CI, 0.32–0.90; P = 0.02). Subgroup analysis indicated that IFN therapy decreased HCC incidence in HCV‐related cirrhotic patients during long‐term follow up (>48 months) evidently (OR, 0.25; 95% CI, 0.09–0.67; P = 0.006). However, subgroup analysis of four RCT with short‐term follow up (≤48 months) did not demonstrate the significant difference in HCC incidence between IFN‐treated cirrhotic patients and controls (OR, 0.78; 95% CI, 0.39–1.55; P = 0.48). Conclusion: The present study suggested that IFN therapy could efficiently reduce HCC development in patients with HCV‐related cirrhosis; this effect was more evident in the subgroup of patients with long‐term follow up (>48 months). Patients who received maintenance IFN therapy had a lower risk of HCC than controls.     

HIV/hepatitis C virus and HIV/hepatitis B virus coinfections protect against antiretroviral-related hyperlipidaemia

Introduction

Hyperlipidaemia is a recognized complication of HIV antiretroviral therapy. The interactions among HIV, viral hepatitis, antiretroviral therapies and lipids are poorly understood.

Methods

Ontario HIV Treatment Network Cohort Study participants with at least one lipid level after highly active antiretroviral therapy (HAART) initiation were assessed. Hepatitis B virus (HBV)‐ and hepatitis C virus (HCV)‐coinfected patients were identified by serology or chart review. HCV antiviral recipients, diabetics and those on lipid‐lowering drugs at baseline were excluded from the study. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use were assessed by multivariate logistic regression.

Results

A total of 1587 HIV‐monoinfected, 190 HIV/HBV‐coinfected and 255 HIV/HCV‐coinfected patients were evaluated. Most were male (85–92% for the 3 groups evaluated: HIV, HIV/HBV, HIV/HCV). The median [interquartile range (IQR)] age at HAART initiation was 48 (44–56) years and was similar between groups. The median (IQR) CD4 count at HAART initiation was 245 (120–370) cells/μL in HIV‐monoinfected participants, 195 (110–330) cells/μL in HIV/HBV‐coinfected participants and 268 (140–409) cells/μL in HIV/HCV‐coinfected participants. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use included HIV/HCV coinfection [odds ratio (OR) 0.46; 95% confidence interval (CI) 0.34, 0.61; P<0.0001], HIV/HBV coinfection (OR 0.74; 95% CI 0.55, 0.99; P=0.04), year of starting HAART after 2004 vs. 1997 or earlier (OR 0.37; 95% CI 0.29, 0.48; P<0.0001) and year of starting HAART between 1998 and 2003 vs. 1997 or earlier (OR 0.75; 95% CI 0.61, 0.92; P<0.01). Factors associated with increased risk included age (OR 1.55; 95% CI 1.39, 1.72; per 10 years, P<0.0001) and male gender (OR 1.84; 95% CI 1.36, 2.48; P<0.0001).

Conclusions

HIV/HCV and to a lesser extent HIV/HBV coinfections are protective against HAART‐related hyperlipidaemia.     

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.     

Hepatitis B or hepatitis C coinfection in HIV-infected pregnant women in Europe

Objectives

The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV‐infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use.

Methods

Information on HBV surface antigen (HBsAg) positivity and HCV antibody (anti‐HCV) was collected retrospectively from the antenatal records of HIV‐infected women enrolled in the European Collaborative Study and linked to prospectively collected data.

Results

Of 1050 women, 4.9% [95% confidence interval (CI) 3.6–6.3] were HBsAg positive and 12.3% (95% CI 10.4–14.4) had anti‐HCV antibody. Women with an injecting drug use(r) (IDU) history had the highest HCV‐seropositivity prevalence (28%; 95% CI 22.8–35.7). Risk factors for HCV seropositivity included IDU history [adjusted odds ratio (AOR) 2.92; 95% CI 1.86–4.58], age (for ≥35 years vs. <25 years, AOR 3.45; 95% CI 1.66–7.20) and HBsAg carriage (AOR 5.80; 95% CI 2.78–12.1). HBsAg positivity was associated with African origin (AOR 2.74; 95% CI 1.20–6.26) and HCV seropositivity (AOR 6.44; 95% CI 3.08–13.5). Highly active antiretroviral therapy (HAART) use was less likely in HIV/HCV‐seropositive than in HIV‐monoinfected women (AOR 0.34; 95% CI 0.20–0.58). HCV seropositivity was associated with a higher adjusted HIV RNA level (+0.28log₁₀ HIV‐1 RNA copies/mL vs. HIV‐monoinfected women; P=0.03). HIV/HCV‐seropositive women were twice as likely to have detectable HIV in the third trimester/delivery as HIV‐monoinfected women (AOR 1.95; P=0.049).

Conclusions

Although HCV serostatus impacted on HAART use, the association between HCV seropositivity and uncontrolled HIV viraemia in late pregnancy was independent of HAART.     

Prevalence of hepatitis B virus infection in non‐Hodgkin lymphoma: a systematic review and meta‐analysis

Background and aim: A recent meta‐analysis has demonstrated an association between hepatitis C virus and non‐Hodgkin lymphoma (NHL). There is also evidence on the association between hepatitis B virus (HBV) and NHL. The aim of this study was to evaluate this evidence using a meta‐analytic approach. Methods: We searched the MEDLINE database from 1962 to 2008 for case–control studies that have reported the association of HBV with NHL. We calculated the odds ratio (OR) and 95% confidence intervals (CI) to assess the prevalence of HBV infection and pooled the results using three different statistical models. Results: Our search yielded 12 studies with 11 studies (3262 NHL patients, 1 523 205 controls) evaluating HBV infection in NHL and one study (3888 HBV‐infected individuals, 205 203 controls) that had investigated for NHL in HBV infection. The OR of detecting HBV infection in NHL when compared with the control population was 2.56 (95% CI, 2.24–2.92) by the fixed effects model; 2.61 (95% CI, 2.29–2.98) by the exact method and 2.67 (95% CI, 2.04–3.49) by the random effects model suggesting a high prevalence of HBV carrier state in lymphoma. There was evidence of statistical heterogeneity which disappeared after exclusion of retrospective studies on sensitivity analysis. Conclusions: The results of this study suggest a possible causal relation between HBV infection and NHL which needs to be confirmed by experimental and epidemiological studies. In countries where prevalence of HBV infection is 1% or more, it may be prudent to screen patients with NHL for occult HBV infection.     

Maternal hepatitis B and hepatitis C infection and neonatal neurological outcomes

To examine the associations between maternal hepatitis B (HBV) and hepatitis C (HCV) infection status and selected infant neurological outcomes diagnosed at birth, we conducted a population‐based, retrospective cohort study on singleton live births in Florida from 1998 to 2009. Primary exposures included maternal HBV and HCV monoinfection. The neurological outcomes included brachial plexus injury, cephalhematoma, foetal distress, feeding difficulties, intraventricular h aemorrhage and neonatal seizures. Multivariable logistic regression models were used to generate odds ratios (OR) and 95% confidence intervals (CI) that were adjusted for socio‐demographic characteristics, risky behaviours, pregnancy complications and pre‐existing medical conditions, and timing of delivery. The risk of an adverse neurological outcome was higher in infants born to mothers with hepatitis viral infection (7.2% for HCV, 5.0% for HBV), compared with infants of hepatitis virus‐free mothers (4.2%). After adjusting for potential confounders, women with HBV were twice as likely to have infants who suffered from brachial plexus injury (OR = 2.04, 95% CI = 1.15–3.60), while those with HCV had an elevated odds of having an infant with feeding difficulties (OR: 1.32, 95% CI = 1.06–1.64) and a borderline increased likelihood for neonatal seizures (OR = 1.74, 95% CI = 0.98–3.10). Additionally, HCV+ mothers had a 22% increased odds of having an infant with some type of adverse neurological outcome (OR: 1.22, 95% CI = 1.03–1.44). Our findings add to current understanding of the association between maternal HBV/HCV infections and infant neurological outcomes. Further research evaluating the role of maternal HBV and HCV infections (including viraemia, treatment) on pregnancy outcomes is warranted.     

Predictive value of serum globulin levels for the extent of hepatic fibrosis in patients with chronic hepatitis B infection

The mechanism underlying disease progression in hepatitis B virus (HBV) infection is unknown. Immunoglobulins stimulate the proliferative activity of rat hepatic stellate cells in vitro. A strong association was found between serum immunoglobulin levels and hepatic fibrosis in patients with hepatitis C virus infection. Our objective was to determine if the same index could also be used in patients with chronic HBV infection. The records of 100 patients with biochemical, serological, virological and histological evidence of chronic HBV infection were reviewed for background factors and serum globulin and immunoglobulin levels. Mean (+/-SD) patient age was 44.0 +/- 14.7 years; 80 (80%) were male. Of the factors found to be significant on univariate analysis, the only significant predictors of severe hepatic fibrosis (stage > or = 2) on multivariate analysis were serum globulin level [odds ratio (OR) 5.97, 95% confidence intervals (CI) 1.82-19.53, P = 0.0004], platelet count (OR 0.98, CI 0.97-0.99, P = 0.001), and immunoglobulin G (IgG) level (OR 1.003, CI 1.000-1.007, P < 0.042) but not IgA, alkaline phosphatase, albumin or international normalized ratio. For each increase of 0.33 mg/dL in serum globulin, there was a 0.5 point increase in the stage of hepatic fibrosis. There appears to be a strong association between levels of serum globulin and IgG and extent of hepatic fibrosis in patients with chronic HBV infection. They can serve as noninvasive markers of hepatic fibrosis and, if confirmed, have important implications for the management of patients with chronic HBV infection.     

Feasibility of individualized treatment for hepatitis C patients in the real world

Background and Aim: Individualized treatment with a combination of peg‐interferon and ribavirin for patients with hepatitis C virus (HCV) infection has been validated in randomized controlled clinical trials, but its usefulness in the real world is unknown. The aim of the present study was to assess the feasibility of individualized treatment for HCV patients compared with standard therapy in a real‐life clinical setting. Methods: A total of 253 naïve patients with HCV infection who received peg‐interferon and ribavirin combination treatment were analyzed and grouped into one of three clinical settings: (i) infection with genotype non‐1 (HCV non‐1) and treatment for standard 24 weeks (n = 105; none received an abbreviated therapy); (ii) genotype 1 (HCV‐1) and standard therapy for either 24 weeks (n = 71) or 48 weeks (n = 21); and (iii) HCV‐1 and individualized treatment (n = 56). The individualized therapy used was an abbreviated 24‐week treatment for HCV‐1 patients who achieved a rapid virological response, otherwise patients received a 48‐week course of treatment. Early termination of treatment at week 16 was recommended for non‐responders. Results: A sustained virological response (SVR) was achieved in 83.8% of patients with HCV non‐1 infection. Among the HCV‐1‐infected patients, 53.5% of patients who underwent standard 24‐week treatment, 66.7% of patients who underwent standard 48‐week treatment, and 64.3% of patients treated by individualized therapy achieved SVR. Patients infected with HCV‐1 and treated by individualized therapy had a similar efficacy response compared with the standard 48‐week therapy (adjusted odds ratio [OR] 0.765, 95% confidence interval [CI], 0.220–2.659, P = 0.673). Both individualized therapy (adjusted OR 2.855, 95% CI 1.189–6.855, P = 0.019) or standard 48‐week treatment (adjusted OR 3.733, 95% CI 1.073–12.986, P = 0.038) had significantly higher odds of SVR compared with HCV‐1 patients treated by standard 24‐week course. Conclusion: Individualized therapy is feasible in the real world, especially for patients with HCV‐1 infection.     

Epidemiological survey of Japanese children infected with hepatitis B and C viruses

Aim: The lack of a nationwide survey on hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Japan led us to investigate the epidemiological profiles of these infections among Japanese children. Methods: We conducted a questionnaire survey of children (<20 years of age) infected with either HBV (n = 136) or HCV (n = 114), who visited 636 pediatric institutions in Japan from 2003 through 2005. Most HBV‐infected subjects (94%) were born in 1986 or after when a nationwide immunization program for infants born to HBe antigen‐positive carriers was initiated. The transmission routes were divided into five groups: maternal, horizontal (subdivided into intrafamilial, iatrogenic and other horizontal), and unknown transmission. Results: Comparison of subjects born in 1990 or after and those born in 1989 or before, when anti‐HBc and anti‐HCV (c100‐3) screening tests of blood donors began, showed a shift in the relative proportions of maternal, intrafamilial, iatrogenic, other horizontal, and unknown transmission from 52%, 19%, 4%, 7% and 19% to 70%, 14%, 6%, 1% and 9%, respectively, for HBV, which was statistically insignificant (P = 0.120), and from 14%, 0%, 76%, 4% and 7% to 89%, 2%, 4%, 0% and 5%, respectively, for HCV, which was statistically significant (P < 0.001). HBV horizontal transmission did not decrease in proportion. No transfusion‐acquired HCV infection was reported in subjects born in 1993 or after. Conclusion: Maternal transmission is a prominent source of HCV infection among Japanese children. The implementation of measures to prevent HBV horizontal infection is also essential, and the present system of selective vaccination should be expanded to universal vaccination.     

Association of metabolic profiles with hepatic fibrosis in chronic hepatitis C patients with genotype 1 or 2 infection

Background and Aims: Metabolic profiles are associated with severity of liver histology in chronic hepatitis C (CHC) infection. However, the influence of hepatitis C virus (HCV) genotypes, especially genotype 1 and 2, on the association between metabolic profiles and hepatic fibrosis remains unknown. Methods: We consecutively enrolled 528 CHC patients infected by HCV genotype 1 or 2, and used univariate and multivariate approaches to determine the influence of HCV genotype on the association of metabolic characteristics with severity of liver histology. Results: In univariate analysis, diabetes mellitus, obesity, higher grades of hepatic steatosis, homeostasis model assessment–insulin resistance index and alanine aminotransferase level, but lower serum total cholesterol and low‐density lipoprotein level, were associated with advanced hepatic fibrosis. Advanced hepatic fibrosis was associated with an adjusted odds ratio of 13.72 (95% confidence interval, 2.15–87.7) for serum fasting blood glucose, 1.07 (1.01 to 1.13) for body mass index (BMI), and 0.03 (0.00–0.32) for total cholesterol level. Older age, lower serum total cholesterol level and more necro‐inflammatory activity were associated with advanced hepatic fibrosis in both genotype 1 and 2 patients (P < 0.05). Advanced hepatic fibrosis was associated with an adjusted odds ratio of 31.18 (2.31–421.4) for fasting blood glucose level in genotype 1 infection, whereas 1.16 (1.05–1.28) for BMI in genotype 2 infection. Conclusions: Age, serum total cholesterol, and hepatic necro‐inflammation have important associations with severity of hepatic fibrosis in CHC patients. Moreover, these associations are different between HCV genotype: the effects of fasting blood glucose level and BMI are increased on genotype 1 and genotype 2 patients, respectively.     

Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C

Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients underwent antiviral therapy with PEG-IFN alfa-2a plus ribavirin. HCV-RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up. Mean serum values of homocysteine were higher in patients than in controls (15.8 ± 5.8 μg/L vs 12.5 ± 5.8 μg/L; P < 0.001), with a similar CC, CT and TT MTHFR distribution (23.6%, 48.7% and 27.7% in G1-CHC vs 34%, 48.5% and 17.5% in controls; P = 0.14). In genotype 1, HCV MTHFR TT homozygosis was independently linked to higher LDL (OR 1.016; CI 1.002-1.031; P = 0.03), but not to homocysteine. No association were found between homocysteine, MTHFR and histological features or both rapid virological response (RVR) and SVR. Low cholesterol (OR 0.988, 95%CI 0.975-0.999, P = 0.04) was independently linked to severe fibrosis, and high LDL was the only independent positive predictors of both RVR and SVR (OR 1.036; 95%CI 1.017-1.055; P < 0.001; and OR 1.016; 95%CI 1.001-1.031; P = 0.04 respectively). In patients with genotype 1 hepatitis C, showing higher homocysteine serum levels than controls, MTHFR C677T homozygosis, via modulating cholesterol levels, could interfere with liver fibrosis and response to antiviral therapy.     

Effect of hepatitis C virus on immunological and virological responses in HIV‐infected patients initiating highly active antiretroviral therapy: a meta‐analysis

Co‐infection of human immunodeficiency virus (HIV) with hepatitis C virus (HCV) is rather common. In the era of highly active antiretroviral therapy (HAART), viral hepatitis could result in adverse outcomes in HIV+ patients. The current meta‐analysis aims to evaluate the impact of HCV on immunological and virological responses after HAART initiation in HIV/HCV co‐infected individuals by synthesizing the existing scientific evidence. A comprehensive search of electronic databases was performed. Eligible studies were analysed using univariate and multivariate meta‐analytic methods. Totally, 21 studies involving 22533 individuals were eligible. The estimated summary difference in CD4 cell counts increase between HIV and HIV/HCV co‐infected subjects after 3–12 months on HAART was 34.86 cells/mm³ [95% confidence interval (CI): 16.82–52.89]. The difference was more prominent in patients with baseline CD4 counts below 350 cells/mm³ (38.97, 95% CI: 20.00–57.93) and attenuated 2 years later (13.43, 95% CI: 0.83–26.04). The analysis of ratio measures yielded similar findings. The virological control remained unaffected by the presence of HCV (adjusted Hazard Ratio for co‐infected patients vs those with HIV alone: 0.99, 95% CI: 0.91–1.07). The bivariate meta‐analytic method confirmed the results of the univariate approaches. This meta‐analysis supports the adverse effect of HCV on immune recovery of HIV+ patients initiating HAART, especially of those with initially impaired immunologic status. Although this effect diminishes over time, early administration of HAART in the setting of co‐infection seems to be justified.     

Association of on‐treatment serum hepatitis B surface antigen level with sustained virological response to nucleos(t)ide analog in patients with hepatitis B e‐antigen positive chronic hepatitis B

Aim: This study evaluated the on‐treatment serum hepatitis B surface antigen (HBsAg) level during nucleos(t)ide analog (NUC) therapy and the correlation with off‐treatment sustained virological response (SVR). Methods: Fifty‐one consecutive patients with hepatitis B e‐antigen (HBeAg) positive chronic hepatitis B who achieved HBeAg loss/seroconversion after NUC therapy and completed 12 months or more of additional therapy were included. Serum HBsAg and hepatitis B virus (HBV) DNA levels were determined at baseline, 3, 6, 9 and 12 months, and at the end of treatment. SVR was defined as HBV DNA levels of less than 10 000 copies/mL until 6 or 12 months off‐treatment without reappearance of HBeAg. Results: Twenty‐two (43.1%) and 13 (25.5%) patients maintained SVR at 6 and 12 months off‐treatment, respectively. In univariate analyses, a decline of HBsAg of 0.5 log₁₀ IU/mL or less at 6 months (P = 0.006) and 12 months (P = 0.013), the mean change in HBsAg level at 6 months (P = 0.024), and lamivudine or entecavir treatment (P = 0.019) were significant predictive factors for SVR at 6 months off‐treatment. A decline of HBsAg of 0.5 log₁₀ IU/mL or less at 6 months and lamivudine or entecavir treatment were independent factors on multivariate analyses (odds ratio [OR], 16.67; 95% confidence interval [CI], 1.86–142.86 [P = 0.012]; and OR, 14.83; 95% CI, 1.18–185.73 [P = 0.036]; respectively). Conclusion: On‐treatment serum HBsAg level predicted early off‐treatment SVR to NUC therapy in patients infected with genotype C.