Hepatitis D virus infection,cirrhosis and hepatocellular carcinoma in The Gambia

Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q‐MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case‐control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha‐foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q‐MAC, western blot and RNA assays. We evaluated separate cut‐offs of the Q‐MAC assay for predicting anti‐HDV and RNA positivity. Q‐MAC correctly identified 29/29 subjects who were western blot‐positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA‐positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA?; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV‐HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti‐HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74‐11.98) and HBV‐HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97‐134.95). In this Gambian population, HDV Q‐MAC had high sensitivity and specificity for both anti‐HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia.     

Analysis of the efficacy of treatment with peginterferon α‐2a and ribavirin in patients coinfected with hepatitis B virus and hepatitis C virus

Objective: To study the virological features of patients coinfected with hepatitis B virus (HBV) and hepatitis C virus (HCV) and the efficacy of combination therapy with peginterferon α‐2a and ribavirin in these patients. Methods: The epidemiological and virological data of 50 patients coinfected with HBV and HCV were analysed. The virological response rates of patients treated with peginterferon α‐2a and ribavirin between the HBV and HCV coinfection group and the HCV monoinfection group were compared. Results: HCV‐dominant virus strains accounted for 92.0% of the 50 coinfected individuals, and HCV‐ and HBV‐dominant virus strains accounted for the remaining 8.0%. The HBV DNA level of the patients coinfected with HBV and HCV was 4.6±0.9 log₁₀ copies/ml, which was significantly lower than that in the HBV monoinfection group (5.9±1.2 log₁₀ copies/ml) (t=5.964, P<0.01). The HBeAg‐positive rate (12.0%, 6/50) of the coinfection group was significantly lower than (45.3%, 19/42) that of the HBV monoinfection group (χ²=12.743, P<0.01). The partial early virological response (pEVR) rate and the end‐of‐treatment virological response (ETVR) rate (50.0%, 15/30; 90.0%, 27/30) of patients with genotype 1 in the coinfection group were significantly higher than those (16.0%, 4/25; 56.0%, 14/25) in the HCV monoinfection group (χ²=6.971, P=0.008; χ²=8.307, P=0.004). The relapse rate (55.6%, 15/27) of patients with genotype 1 in the coinfection group was significantly higher than that (21.4%, 3/14) in the HCV monoinfection group (χ²=4.360, P=0.037). The sustained virological response (SVR) rate (40.0%, 12/30) of patients with genotype 1 in the coinfection group was compared with that of the HCV monoinfection group (44.0%, 11/25) (χ²=0.090, P=0.765). There was no significant difference in the on‐treatment virological response, ETVR, SVR and relapse rates between two groups for patients with genotype 2. The incidence of side effects (30%, 15/50) of patients in the coinfection group was significantly higher than that (13%, 6/46) in the HCV monoinfection group (χ²=4.031, P=0.045). The reactivation rate of HBV DNA (33.3%, 9/27) with HCV SVR was significantly higher than that of patients without SVR (8.7%, 2/23) (χ²=4.393, P=0.036). Conclusions: The replication of HBV was suppressed, and HCV was the dominant virus strain. Compared with HCV‐monoinfected patients, pEVR, ETVR and relapse rates of patients with genotype 1 in the coinfection group were high, while they shared similar SVR rates. HBV and HCV coinfection had no impact on the rate of virological response for genotype 2.     

Maternal ABO and rhesus blood group phenotypes and hepatitis B surface antigen carriage

In view of a persistently high prevalence of hepatitis B surface antigen (HBsAg) carriage in our obstetric population, we examined the association between HBsAg carriage with maternal ABO and rhesus (Rh) blood group phenotypes determined at routine antenatal screening. In a retrospective study, the antenatal screening results of women booked for confinement between 1998 and 2011 in our hospital were examined for the relationship between HBsAg carriage with the ABO and rhesus blood groups, taking into account also the effects of advanced maternal age (≥35 years) and parity status (nulliparous or multiparous), and year of birth before or following the availability of the hepatitis B vaccine (1984). HBsAg carriage was found in 9.9%, 9.6%, 9.1% and 10.2% (P = 0.037) for group‐A (n = 20 581 or 26.1%), ‐B (n = 20 744 or 26.4%), ‐AB (n = 5138 or 6.5%) and ‐O (n = 32 242 or 41.0%) among the 78 705 women in the study cohort. Rhesus negativity was found in 0.6%, and HBsAg carriage was 12.3% and 9.8%, respectively, for the Rh‐negative and Rh‐positive women (P = 0.071). Carriage rate between group‐O and non‐O was influenced by nulliparity, age ≥35 years and Rh‐positive status. Regression analysis indicated that group‐B (P = 0.044, aOR = 1.062, 95% CI 1.002–1.127) and group‐AB (P = 0.016, aOR = 1.134, 95% CI 1.024–1.256) were associated with HBsAg carriage. Blood groups‐B and ‐AB are associated with increased hepatitis B virus (HBV) infection in our population, and further studies are warranted to elucidate the implications of this on the sequelae of HBV infection.     

Low prevalences of HBV and HCV infection in patients with primary biliary cirrhosis in Taiwan: A case control study

To study the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with primary biliary cirrhosis (PBC) against the background of HBV and HCV infection in the general population, serum specimens from a consecutive series of 27 patients with PBC and 108 age/sex matched ‘healthy subjects’ as control group were submitted to assays for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis B surface antigen (anti-HBs) and antibodies to hepatitis C virus (anti-HCV). None of the patients with PBC were HBsAg or anti-HCV positive while 17 (15.7%) and 6 (5.6%) of ‘healthy’ controls were HBsAg positive and anti-HCV positive (P= 0.017 and 0.26). Patients with PBC also had a significantly lower prevalence of HBV infection than matched controls (70.4%vs 88.9%, P= 0.022). The results suggest that neither HBV nor HCV plays any significant role in the pathogenesis of PBC, and that PBC would not develop or be masked in patients with HBV or HCV infection.     

Long‐term entecavir therapy results in falls in serum hepatitis B surface antigen levels and seroclearance in nucleos(t)ide‐naïve chronic hepatitis B patients

Entecavir (ETV) is reported to result in suppression of hepatitis B virus DNA (HBV DNA) replication with minimal drug resistance. However, information on the long‐term effect of such therapy on serum hepatitis B surface antigen (HBsAg) level and elimination of HBsAg is not available. ETV therapy was started in 553 nucleos(t)ide‐naïve patients with chronic hepatitis B infection (HBeAg positive: 45%) in our hospital. Serum HBsAg levels were measured serially by the Architect assay. The median baseline HBsAg was 2180 IU/mL (0.12–243 000 IU/mL), and median follow‐up period was 3.0 years, with 529, 475, 355, 247 and 163 patients followed‐up for 1, 2, 3, 4 and 5 years, respectively. At year 5, the mean log HBsAg decline from baseline was −0.48 log IU/mL, and the cumulative HBsAg clearance rate was 3.5%. Multivariate analysis identified HBV DNA level at baseline (<3.0 log copies IU/mL, odd ratio = 10.2; 95% confidence interval = 1.87–55.5, P = 0.007) and HBsAg level (<500 IU/mL, odd ratio = 29.4; 95% confidence interval = 2.80–333, P = 0.005) as independent predictors of HBsAg seroclearance. These results indicate that although serum HBsAg level declines gradually during ETV therapy, HBsAg seroclearance remains a rare event.     

Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct‐acting antiviral therapy

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon‐free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co‐infected patients and 765 patients with resolved HBV infection during and after treatment with direct‐acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000 IU/mL were treated with entecavir before anti‐HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)‐positive patients with an HBV DNA level <2000 IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti‐HBs titres at baseline with those at post‐DAA therapy in 123 patients without HBsAg. There was no significant difference in anti‐HBs levels between the two points (P = .79). In conclusion, HBV reactivation was rare in HBsAg‐negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV‐reactivated patients with a baseline HBV DNA level <2000 IU/mL before DAA therapy.     

Quantification of hepatic FOXP3+ T‐lymphocytes in HIV/hepatitis C coinfection

Coinfection with HIV adversely impacts every stage of hepatitis C (HCV) infection. Liver damage in HCV infection results from host antiviral responses rather than direct viral pathogenesis. Despite depressed cellular immunity, coinfected patients show accelerated hepatic fibrosis compared with HCV monoinfected patients. This paradox is poorly understood. T‐regulatory (Treg) cells (CD4+ and FOXP3+) are hypothesized to limit hepatic damage in HCV. Our hypothesis was that reduced frequency of hepatic Treg in HIV/HCV coinfection compared with HCV monoinfection may explain poorer outcomes. We quantified FOXP3+, CD4+, CD8+ and CD20+ cells in liver biopsies of 35 male subjects matched by age and ISHAK fibrosis score, 12 HIV monoinfected, 11 HCV monoinfected and 12 HIV/HCV coinfected. Cell counts were performed using indirect immunohistochemical staining and light microscopy. HIV/HCV coinfected subjects had fewer hepatic FOXP3+ (P = 0.031) and CD4+ cells (P = 0.001) than HCV monoinfected subjects. Coinfected subjects had more hepatic CD8+ cells compared with HCV monoinfected (P = 0.023), and a lower ratio of FOXP3+ to CD8+ cells (0.08 vs 0.27, P < 0.001). Multivariate analysis showed number of CD4+ cells controlled for differences in number of FOXP3+ cells. Fewer hepatic FOXP3+ and CD4+ cells in HIV/HCV coinfection compared with HCV monoinfection suggests lower Treg activity, driven by an overall loss of CD4+ cells. Higher number of CD8+ cells in HIV/HCV coinfection suggests higher cytotoxic activity. This may explain poorer outcomes in HIV/HCV coinfected patients and suggests a potential mechanism by which highly active antiretroviral therapy may benefit these patients.     

Anti‐envelope antibody responses in highly exposed seronegative individuals may be associated with protection from HCV infection

In rare cases, individuals with a history of long‐term injecting drug use remain seronegative and aviraemic, despite prolonged and likely repeated exposure to Hepatitis C virus (HCV) through high‐risk behaviour. We describe anti‐HCV Envelope (E) antibody responses in a prospective cohort of carefully defined highly exposed but uninfected subjects (HESN) and comparison subjects who were also high risk and uninfected, but rapidly became HCV infected (Incident). Longitudinally collected samples from HESN cases (n = 22) were compared to Incident controls (n = 22). IgG, IgM and IgA from sera were tested by ELISA to genotype 1a and 3a E glycoproteins, and recombinant genotype 1a E2 antigen. IgG subclass isotyping was performed for those positive for IgG. Virus‐neutralizing activity was assessed on HCV pseudoparticles, and HCV E–specific B cells analysed using flow cytometry. A significant minority of HESN cases (n = 10; 45%) had anti‐E, predominantly in the IgG2 subclass, which was not found in the pre‐infection time point of the Incident cases (n = 1; 5%). A subset of the HESN subjects also had neutralizing activity and HCV‐specific B cells detected significantly more than Incident cases pre‐infection. In conclusion, the HESN phenotype is associated with IgG2 anti‐E antibodies, neutralization activity and HCV E–specific memory B cells. These findings suggest that HESN subjects may be resistant to HCV infection through humoral immune‐mediated mechanisms.     

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.     

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

The correlation between serum HBcrAg and HBV RNA is unclear, and correlations of intrahepatic cccDNA with HBcrAg, HBV RNA and HBsAg are rarely reported in the same cohort. This study aimed to assess the correlation of HBcrAg with HBV RNA and HBsAg, and investigate whether serum HBcrAg is superior to serum HBV RNA and HBsAg in reflecting intrahepatic HBV cccDNA in HBeAg‐positive and HBeAg‐negative CHB patients. In this study, 85 HBeAg‐positive and 25 HBeAg‐negative patients who have never received antiviral therapy were included. Among HBeAg‐positive patients, HBcrAg was correlated positively with HBsAg (r = 0.564, P < 0.001) and HBV RNA (r = 0.445, P < 0.001), and HBV RNA was also correlated positively with HBsAg (r = 0.323, P = 0.003). Among HBeAg‐negative patients, no significant correlation was observed between HBcrAg, HBsAg and HBV RNA. By multivariable linear regression, HBcrAg (β = ?0.563, P < 0.001), HBsAg (β = ?0.328, P < 0.001) and HBV RNA (β = 0.180, P = 0.003) were all associated with cccDNA levels among HBeAg‐positive patients, but only serum HBcrAg was associated with cccDNA level (β = 0.774, P = 0.000) among HBeAg‐negative patients. HBcrAg was better correlated with cccDNA as compared to HBsAg and HBV RNA, irrespective of HBeAg status. Among HBeAg‐positive patients, though HBcrAg level was influenced by hepatic inflammatory activity and HBV DNA levels, the good correlations of HBcrAg with cccDNA persisted after stratification by inflammatory activity and HBV DNA levels. In conclusion, correlations of serum HBcrAg, HBV RNA and HBsAg levels differ significantly between HBeAg‐positive and HBeAg‐negative patients, but serum HbcrAg correlates with cccDNA levels better than HBV RNA and HBsAg, irrespective of HBeAg status.     

Seroprevalence of HBV/HCV coinfection among patients with HCV screened during the national campaign for HCV eradication in Egypt

Background and study aimsLittle is known about the true prevalence of hepatitis B virus (HBV) coinfection in patients with hepatitis C virus (HCV). This multicenter nationwide study aimed to assess the seroprevalence of HBV among Egyptian patients with HCV and its possible risk factors.Patients and methodsThis is a cross-sectional, multicenter, nationwide study. Data were extracted from the National Network of Viral Hepatitis Treatment Centers database. Baseline data of patients proved to be viremic during the national campaign for HCV eradication (October 2018–April 2019) were retrieved. Data included demographics, laboratory tests (HBsAg, CBC, liver biochemical profile, creatinine, AFP, HbA1c, and viral load), FIB-4 score calculation, and abdominal ultrasound results.ResultsResults of 297,965 patients showed that HBsAg was positive in 2,347 (0.8%) patients. Patients with HBV/HCV were 57% females and had a mean age of 51 ± 13 years. Patients with positive HBsAg showed significantly more tobacco consumption, intravenous drug abuse, hypertension, and diabetes. No significant difference was noted in HCV viremia between patients with HCV and those with HBV/HCV. Only 14% of patients with HBV/HCV had cirrhosis compared with the 9% of those with HCV; two of them had HCC.ConclusionAlthough Egypt has a heavy HCV burden, the overall prevalence of HBV is low among patients with HCV infection. Comorbid conditions seem to favor coinfection.     

T‐ and B‐cell responses and previous exposure to hepatitis B virus in ‘anti‐HBc alone’ patients

A serologic response to hepatitis B virus (HBV) defined as ‘anti‐HBc alone’ is commonly observed, but its significance remains unclear. This study aimed to define the relationship between ‘anti‐HBc alone’ serostatus and HBV infection, including HBV‐specific T‐ and B‐cell memory responses. We enrolled 31 ‘anti‐HBc alone’ patients. Total HBV DNA and cccDNA were tested by nested polymerase chain reaction (PCR) analysis in liver samples from 22 ‘anti‐HBc alone’ patients vs controls (chronic or resolved HBV infection), followed by HBsAg/HBcAg immunohistochemical (IHC) staining. IFN‐γ secretion by HBV‐specific T cells was compared in individuals who were ‘anti‐HBc alone’ (n = 27), resolved HBV (n = 21), chronic HBV (n = 24) and 12 healthy controls using enzyme‐linked immunospot (ELISpot) assays. An HBsAg‐IgG B‐cell ELISpot assay was performed in ‘anti‐HBc alone’ patients before and after one dose of recombinant HBsAg vaccine. The majority (23/31, 74.2%) of the ‘anti‐HBc alone’ individuals were co‐infected with HCV. Infrequent intrahepatic total HBV DNA (2/22, 9.1%) and cccDNA (1/22, 4.5%) were detected in biopsies; HBsAg and HBcAg IHC staining was negative. HBV‐specific T‐cell responses were similar between ‘anti‐HBc alone’ individuals and HBV resolvers. Circulating HBV‐memory B‐cell responses were detected in all ‘anti‐HBc alone’ individuals, consistent with an HBsAg‐specific memory pool. After one HBV vaccine dose, increased anti‐HBs antibody levels were observed, accompanied by an expansion of HBsAg‐specific memory B cells (P = 0.0226). ‘Anti‐HBc alone’ individuals showed HBV‐specific T‐cell and memory B‐cell responses typical of previous viral exposure and protective memory, suggesting a resolved infection.     

The inverse relationship between chronic HBV and HCV infections among injection drug users is associated with decades of age and drug use

Summary.  Infection with hepatitis C virus (HCV) may suppress co-infection with hepatitis B virus (HBV) during acute or chronic HBV infection. We examined relationships between HBV infection, HCV infection and other factors among injection drug users (IDUs) with antibodies to both viruses. Participants enrolled in a cross-sectional study during 1998–2000 were considered to have been infected with HBV if they had core antibody, to be chronically infected if they had hepatitis B surface antigen (HBsAg), to have been infected with HCV if they had HCV antibody and to be chronically infected if they had HCV RNA. Among 1694 participants with antibody to both viruses, HBsAg prevalence decreased with increasing age among those positive for HCV RNA [from 4.55% in those 18–29 years to 1.03% in those ≥50 years old ( P _trend = 0.02)], but not among those who were negative for HCV RNA. Chronic HBV infection was less common overall among those with chronic HCV infection (odds ratio [OR], 0.25; P  < 0.0001), but this inverse relationship was much stronger in the oldest (>50 years; OR = 0.15) than the youngest (18–29 years; OR = 0.81) participants ( P _trend = 0.03). Similar results were obtained when duration of injection drug use was substituted for age ( P _trend = 0.05). Among IDUs who have acquired both HBV and HCV, chronic HBV infection is much less common among those with chronic HCV infection, but this inverse relationship increases markedly with increasing years of age and injection drug use. Co-infection with HCV may enhance the resolution of HBsAg during the chronic phases of these infections.     

The infection rates of HBV and HCV decreased significantly in Zhejiang Province,China: A comparative study based on the data of two sero-epidemiological surveys in 1992 and 2020

In 2020, China conducted a nationwide, sero-epidemiological, cross-sectional survey of viral hepatitis. The stratified multi-stage cluster random sampling method was used to select the permanent population aged 1–69 years, followed by questionnaire survey and sample collection and detection of the serological markers of hepatitis B (HBV) and hepatitis C viruses (HCV). A total of 4747 individuals aged 1–69 years were investigated in Zhejiang Province. The positive rates of hepatitis B surface antigen and anti-HCV were 4.3% and 0%, respectively. Compared to a similar sero-epidemiological survey in 1992, the 2020 survey showed that the HBV infection rate in Zhejiang Province decreased by 56.5%. In both surveys, HBV infection rate increased with age (in 1992, χ² = 185.866, p = .000; in 2020, χ² = 1383.836, p = .000). Compared with 1992, the positive anti-HCV rate in those aged 1–69 years in 2020 decreased by 100.0%. This result showed that the HBV vaccine and blood screening to prevent HBV and HCV infection significantly decreased the infection rate of HBV and HCV in the younger generation of Zhejiang province. However, the rate of HBV carriers aged 30–69 years was still high, which underscores the need to strengthen the management and treatment of chronic HBV infection. Hence, Zhejiang province can eliminate the public health threat of viral hepatitis.     

Stronger hepatitis C virus‐specific CD8+ T‐cell responses in HIV coinfection

Summary. Hepatitis C virus (HCV) is a widespread chronic infection that shares routes of transmission with human immunodeficiency virus (HIV). Thus, coinfection with these viruses is a relatively common and growing problem. In general, liver disease develops over years with HIV coinfection, when compared to decades in HCV monoinfection. The role of the immune system in the accelerated pathogenesis of liver disease in HIV/HCV coinfection is not clear. In this study, we compared the frequency, magnitude, breadth and specificity of peripheral blood CD4⁺ and CD8⁺ T‐cell responses between HCV‐monoinfected and HCV/HIV‐coinfected individuals and between HIV/HCV‐coinfected subgroups distinguished by anti‐HCV antibody and HCV RNA status. While HIV coinfection tended to reduce the frequency and breadth of anti‐HCV CD8⁺ T‐cell responses in general, responses that were present were substantially stronger than in monoinfection. In all groups, HCV‐specific CD4⁺ T‐cell responses were rare and weak, independent of either nadir or concurrent CD4⁺ T‐cell counts of HIV‐infected individuals. Subgroup analysis demonstrated restricted breadth of CD8⁺ HCV‐specific T‐cell responses and lower B‐cell counts in HIV/HCV‐coinfected individuals without anti‐HCV antibodies. The greatest difference between HIV/HCV‐coinfected and HCV‐monoinfected groups was substantially stronger HCV‐specific CD8⁺ T‐cell responses in the HIV‐coinfected group, which may relate to accelerated liver disease in this setting.     

Loss of intrahepatic HBsAg expression predicts sustained response to peginterferon and is reflected by pronounced serum HBsAg decline

There is a lack of knowledge regarding the effect of peginterferon (PEG‐IFN) on the expression of intrahepatic hepatitis B core and surface antigen (HBcAg and HBsAg) in chronic hepatitis B (CHB) and its relation with response to therapy. Fifty‐two HBeAg‐positive and 67 HBeAg‐negative CHB patients with paired liver biopsies taken at baseline and after 1 year of PEG‐IFN therapy were studied. After PEG‐IFN therapy, HBeAg‐negative patients showed a significant reduction in both intrahepatic HBcAg (P = 0.04) and HBsAg expression (P < 0.001). In contrast, a reduction in intrahepatic HBcAg expression was not observed in HBeAg‐positive patients, while a trend in reduction of intrahepatic HBsAg staining was found (P = 0.09). Post‐treatment, 7 (13%) HBeAg‐positive and 9 (14%) HBeAg‐negative patients had no expression of intrahepatic HBsAg. Patients without any intrahepatic HBsAg expression post‐treatment were more likely to achieve a combined response (HBeAg loss with hepatitis B virus (HBV) DNA <2000 IU/mL for HBeAg ‐positive and HBV DNA <2000 IU/mL and normal alanine aminotransferase for HBeAg‐negative CHB): 71% vs 5% for HBeAg‐positive (P < 0.001) and 60% vs 16% for HBeAg‐negative patients (P = 0.004), respectively. Moreover, a more profound decline of serum HBsAg was observed in patients with absence of intrahepatic HBsAg staining (3.1 vs 0.4 log IU/mL, P < 0.001 and 1.7 vs 0.4 log IU/mL, P = 0.005 for HBeAg‐positive and HBeAg‐negative CHB, respectively). In conclusion, PEG‐IFN reduces expression of intrahepatic HBsAg. Loss of HBsAg as assessed by immunohistochemistry from the liver predicts a sustained response and is reflected in a pronounced serum HBsAg decline.     

HIV/HBV and HIV/HCV coinfection,and outcomes following highly active antiretroviral therapy

Objectives

To assess the prevalence and risk factors for HBV and HCV coinfection in the Australia HIV Observational Database (AHOD), and examine outcomes of HIV disease following initiation of highly active antiretroviral therapy (HAART).

Methods

Analyses were based on 2086 participants recruited to AHOD by September 2002. Of these, 1605 (77%) had been tested for HBV surface antigen, 1704 (82%) for anti‐HCV antibody and 1453 (70%) for both. Demographic and clinical predictors of HBV and HCV coinfection were examined. The impact of HBV and HCV coinfection on HIV disease progression was assessed by Kaplan‐Meier survival curves and Cox proportional hazard model of time to AIDS events and death.

Results

Among those tested, prevalence of HBV surface antigen and HCV antibody were 6.3% and 13.1%, respectively (4.8% and 10.7%, respectively, among the entire cohort). In multivariate analyses, the only independent risk factor for HIV/HBV coinfection was coinfection with HCV. Independent risk factors for HIV/HCV coinfection were HIV exposure category (with people who reported injecting drug use [MSM & IDU, IDU only] or receipt of blood or blood products at markedly increased risk) and HBV coinfection. HIV disease outcomes following first initiation of a HAART regimen were similar for HIV/HBV and HIV/HCV coinfected patients compared with HIV‐only patients in terms of AIDS‐free survival and detectable HIV virus during the first 12 months. However, patients coinfected with HIV/HCV appeared to have a poorer response to HAART in terms of CD4 count changes, with a CD4 count increase of 32 cells/μL (95% CI 1–67) less than HIV‐only patients.

Conclusions

Coinfection with HBV or HCV is relatively common among HIV‐infected participants in AHOD. HIV disease outcomes following HAART do not appear to be adversely affected by HBV/HCV coinfection, except for slightly poorer CD4 count responses in HIV/HCV coinfected patients.

     

HBV/HIV coinfection is associated with poorer outcomes in hospitalized patients with HBV or HIV

We examined the impact of HBV/HIV coinfection on outcomes in hospitalized patients compared to those with HBV or HIV monoinfection. Using the 2011 US Nationwide Inpatient Sample, we identified patients who had been hospitalized with HBV or HIV monoinfection or HBV/HIV coinfection using ICD‐9‐CM codes. We compared liver‐related admissions between the three groups. Multivariable logistic regression was performed to identify independent predictors of in‐hospital mortality, length of stay and total charges. A total of 72 584 discharges with HBV monoinfection, 133 880 discharges with HIV monoinfection and 8156 discharges with HBV/HIV coinfection were included. HBV/HIV coinfection was associated with higher mortality compared to HBV monoinfection (OR 1.67, 95% CI 1.30–2.15) but not when compared to HIV monoinfection (OR 1.22, 95% CI 0.96–1.54). However, the presence of HBV along with cirrhosis or complications of portal hypertension was associated with three times greater in‐hospital mortality in patients with HIV compared to those without these complications (OR 3.00, 95% CI 1.80–5.02). Length of stay and total hospitalization charges were greater in the HBV‐/HIV‐coinfected group compared to the HBV monoinfection group (+1.53 days, P < 0.001; $17595, P < 0.001) and the HIV monoinfection group (+0.62 days, P = 0.034; $8840, P = 0.005). In conclusion, HBV/HIV coinfection is a risk factor for in‐hospital mortality, particularly in liver‐related admissions, compared to HBV monoinfection. Overall healthcare utilization from HBV/HIV coinfection is also higher than for either infection alone and higher than the national average for all hospitalizations, thus emphasizing the healthcare burden from these illnesses.     

Novel hepatitis B virus surface antigen mutations associated with occult genotype B hepatitis B virus infection affect HBsAg detection

The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infection were investigated. Fifty‐seven hepatitis B surface antigen (HBsAg)‐positive/HBV DNA‐positive blood donors served as control group for comparison. Occult HBV‐related mutations with a high incidence (P < .05) in the S gene were identified. To further verify these occult infection‐related mutations, a conservative full‐gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection‐related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P < .05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P < .05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P < .05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P < .0001). Hence, ten mutations were associated with genotype B occult HBV infection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion.     

Antibody screening tests variably overestimate the prevalence of hepatitis C virus infection among HIV‐infected adults in Ghana

HIV coinfection with HCV has been poorly studied in sub‐Saharan Africa, and the reliability of available seroprevalence estimates remains uncertain. The study aim was to determine HCV RNA prevalence in HIV‐infected subjects receiving care in Kumasi, Ghana, and relate the findings to HCV antibody detection. From a population of 1520 HIV‐infected adults, all HBsAg‐positive subjects (n = 236) and a random subset of HBsAg‐negative subject (n = 172) were screened for HCV RNA using pooled plasma; positive samples were genotyped by core and NS5B sequencing. HCV antibodies were detected by three commercial screening assays and confirmed by the line immunoassay. HCV RNA was detected in 4/408 subjects (1.0%, 95% confidence interval 0.0–1.9%), comprising 3/236 (1.3%; 0.0–2.8%) HBsAg‐positive and 1/172 (0.6%; 0.0–1.8%) HBsAg‐negative subjects. HCV RNA‐positive subjects showed reactivity in all three antibody screening assays. Among HCV RNA‐negative subjects, 5/67 (7.5%), 5/67 (7.5%) and 19/67 (28.4%) showed antibody reactivity by each screening assay, respectively, including two (3.0%) with reactivity by all three assays. Only one sample (1.5%) had confirmed antibody reactivity by line immunoassay indicating past HCV infection. HCV‐positive subjects (three males, two females) were aged 30–46 years, by questionnaire‐based interview reported surgical procedures and blood transfusion as risk factors for infection. HCV genotypes were 2 (subtypes 2j, 2l, 2k/unassigned) and 1 (subtype unassigned). Without further testing, HCV antibody screening assays variably overestimated HCV prevalence among HIV‐infected subjects in Ghana. These findings inform the interpretation of previous seroprevalence estimates based upon screening assays alone.