Hepatitis B Virus DNA Measurement Research Articles

Large spontaneous HBV DNA fluctuations and potential usefulness of a single-point measurement of combined HBV DNA and quantitative HBsAg for the exclusion of HBeAg-negative chronic hepatitis B: A prospective Tunisian cohort study

Background and study aimDuring the natural course of HBeAg-negative chronic hepatitis B (CHB), fluctuations in hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) levels are often observed, making the classification of patients difficult. We aimed to describe spontaneous short-term HBV DNA level fluctuations and to assess the usefulness of qHBsAg in Tunisian patients with HBeAg-negative chronic HBV infection. Patients and methodsWe included 174 treatment-naive Tunisian patients with HBeAg-negative chronic HBeAg-negative HBV infection. A prospective 1-year follow-up was conducted with serial determinations of HBV DNA, ALT levels, and qHBsAg. The patients were classified into three groups: inactive carriers (G1), patients with negative HBeAg CHB (G2), and patients with an “indeterminate state” (G3). For the latter group, a liver biopsy was indicated. ResultsOnly genotype D was detected. During follow-up, 21.6% and 19.5% of patients with a low initial (<2,000 IU/ml) and intermediate viral load (2,000–20,000 IU/ml) experienced a subsequent increase in their HBV DNA levels above 2,000 and 20,000 IU/ml, respectively. Significant variations in viral load were observed in 61.1% of patients at 6-month intervals. Among the 174 patients, 89 (51.1%) belonged to G1, 33 (19%) to G2, and 52 (29.9%) to G3. Fourteen patients have undergone a liver biopsy, of whom seven showed moderate to severe liver disease. Combination of HBV DNA < 2,000 IU/ml and qHBsAg < 832 IU/ml excluded CHB in 98.4% of cases. A cutoff point for qHBsAg < 100 IU/ml associated with an annual decline of > 0.5 log 10 IU/ml is a good predictor marker of functional cure for hepatitis B. ConclusionsThis study highlights the large short-term fluctuations in HBV DNA in patients with HBeAg-negative chronic HBeAg-negative HBV infection with genotype D. Thus, using the cutoff value of 832 for qHBsAg combined with that of 2,000 for HBV DNA makes it possible to exclude CHB for most patients.

Hepatitis B care cascade among people with HIV/HBV coinfection in the North American AIDS Cohort Collaboration on Research and Design, 2012-2016.

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

Alinity m, a Random-Access System, for Hepatitis B Virus DNA Quantification in Plasma and Whole Blood Collected on Dried Blood Spots.

ABSTRACTThe International Liver Association recommends the use of accurate and sensitive molecular methods for determination of hepatitis B virus (HBV) DNA levels in plasma or serum of chronic HBsAg carriers. The level of HBV replication represents the strongest predictive biomarker associated with disease progression and long-term outcome of chronic HBV infection. The purpose of this study was to evaluate the ability to the new Alinity m System to detect and quantify HBV DNA in plasma and whole blood collected on dried blood spots (DBS). Paired plasma and DBS samples from patients chronically infected with various HBV genotypes were tested in parallel for HBV DNA detection and quantification. There is a linear relationship between HBV DNA levels measured in plasma samples using the Alinity m HBV assay and the Xpert HBV viral load assay, used for comparison. A slight deviation (0.03 ± 0.31 log IU/mL) was observed within the quantitative range. In DBS, HBV DNA levels closely correlated with levels measured in plasma. All patients had detectable and quantifiable HBV DNA by DBS testing, except for one patient with a plasma HBV DNA level above 2,000 IU/mL. In conclusion, the newly developed real-time PCR-based assay Alinity m HBV assay can correctly detect HBV DNA in DBS, especially for patients with blood HBV DNA levels above 2,000 IU/mL, and also accurately quantify HBV DNA in plasma samples.IMPORTANCE Hepatitis B virus is one of the most prevalent blood-borne viruses affecting the liver and causing acute and chronic hepatitis. Only a small proportion of people with HBV infection are diagnosed. HBV DNA measurement is critical in clinical practice for the diagnosis and treatment decisions of patients requiring antiviral therapy. Dried blood spot (DBS) collection provides a simple, practical, and acceptable alternative to venous blood collection, especially in community settings. We have demonstrated high sensitivity and specificity for HBV DNA detection in DBS compared to plasma samples, especially when using clinically relevant cutoffs of 2,000 and 20,000 IU/mL. Results support the use of DBS in community-based settings.

Risk factors for de novo hepatitis B during solid cancer treatment.

BACKGROUNDReactivation of hepatitis B virus (HBV) during anticancer treatment is a critical issue. When treating patients with solid tumors, it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive patients, so-called de novo hepatitis B patients. The risk of de novo hepatitis B may vary based on different background factors.AIMTo determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODSThis retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies (HBsAbs). The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements. Patient characteristics and disease and treatment information were investigated. HBV DNA measurements were performed using TaqMan polymerase chain reaction (PCR). To identify the risk factors associated with HBV DNA expression, the age, sex, original disease, pathology, treatment method, presence or absence of hepatitis C virus (HCV), and HBsAb and/or HBcAb titers of all subjects were investigated. In patients with HBV DNA, the time of appearance, presence of HBsAgs and HBsAbs at the time of appearance, and course of the subsequent fluctuations in virus levels were also investigated.RESULTSAmong the 1040 patients, 938 were HBcAb positive, and 102 were HBcAb negative and HBsAb positive. HBV DNA expression was observed before the onset of treatment in nine patients (0.9%) and after treatment in 35 patients (3.7%), all of whom were HBcAb positive. The HBV reactivation group showed significantly higher median HBcAb values [9.00 (8.12-9.89) vs 7.22 (7.02-7.43), P = 0.0001] and significantly lower HBsAb values (14 vs 46, P = 0.0342) than the group without reactivation. Notably, the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption (79.0% vs 58.7%, P = 0.0051). A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation (multivariate analysis, P = 0.0002 and P = 0.0095). The group without HBsAbs tended to have a shorter time to reactivation (day 43 vs day 193), and the frequency of reactivation within 6 mo was significantly higher in this group (P = 0.0459) than in the other group.CONCLUSIONA high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.

Prognostic value of neutrophil-to-lymphocyte ratio associated with prognosis in HBV-infected patients.

Chronic severe hepatitis B (CSHB) is a critical clinical syndrome with a high mortality rate in China. The prognostic value of neutrophil to lymphocyte ratio (NLR) which is simple, low-cost, and useful inflammatory marker for hepatitis B virus (HBV)-infected patients is largely overlooked and without further exploration. This study assesses the association of NLR with prognosis of chronic hepatitis B (CHB) and CSHB patients. Two hundred and eighty subjects, including 79 with chronic hepatitis B (CHB) and 67 with chronic severe hepatitis B (CSHB), and 134 healthy individuals were retrospectively recruited into this study. Blood samples were collected to conduct liver function, prothrombin time activity (PTA), international normalized ratio (INR), HBV DNA measurement, and routine hematological testing. All patients were followed up for at least 3 months. NLR values in patients with CSHB (4.984 ± 3.608) and CHB (2.020 ± 1.182) were significantly higher than those in healthy control (1.638 ± 0.601) and patients with CSHB had the highest NLR values than CHB and healthy control. Increased NLR values were clinically associated with severe liver disease and higher mortality rate. NLR was found to be an independent predictor of mortality in multivariable Cox Regression models (HR = 3.912, 95%CI: 1.587-9.640, P = 0.003). NLR values are significantly increased in CHB and CSHB patients with the severity of liver disease. Moreover, NLR value is an independent predicting factor for the mortality rate in HBV-infected patients.

Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients.

BackgroundThe efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear.MethodsIn this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96.ResultsPatients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84–5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m2, p = 0.000)ConclusionsStable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function.Trial registrationClinicalTrials.gov NCT01732367

Frequency of, and factors associated with, hepatitis B virus reactivation in hepatitis C patients treated with all-oral direct-acting antivirals: Analysis of a Japanese prospective cohort.

Several case reports have shown that hepatitis B virus (HBV) reactivation developed in hepatitis C patients with a current or previous HBV infection during direct-acting antiviral (DAA) treatment, which led to severe hepatitis or death in some cases. However, its precise frequency and risk factors are not entirely clear. We analyzed a prospective cohort. We analyzed HBV reactivation in 461 consecutive hepatitis C patients who received 12weeks of ledipasvir/sofosbuvir for genotype 1 or sofosbuvir plus ribavirin for genotype 2 at multiple centers. By the examination of the preserved sera at baseline, 159 patients (34%) were identified as seropositive for HBV core antibody (anti-HBc) and were included in the subsequent analysis; 4 patients were positive for HBV surface antigen (HBsAg), and the others were negative. Serum HBV DNA was undetectable or was detectable but <20IU/mL at baseline for all patients. Serial measurement of HBV DNA at 4weeks and 12weeks in the preserved serum samples was available in 147 patients and identified HBV reactivation (defined as the appearance of serum HBV DNA ≥20IU/mL) in 2 HBsAg-positive and 3 HBsAg-negative patients. No patient developed HBV-associated hepatitis. Patients who developed HBV reactivation had significantly lower anti-HBs titers and higher serum alanine transferase levels before treatment. Hepatitis B virus reactivation during direct-acting antiviral therapies occurs in 3.4% (5/147) of patients who are positive for anti-HBc. A low titer of anti-HBs and a high serum alanine transferase level prior to treatment are associated with reactivation in this patient group.

The relationship between HBcrAg and HBV reinfection in HBV related post-liver transplantation patients.

Post-transplant hepatitis B virus (HBV) reinfection is one of the major problems facing patients who undergo HBV-related liver transplantation (LT). We analyzed the clinical impact of serum hepatitis B core-related antigen (HBcrAg) on HBV reinfection in post-LT patients with HBV-related liver diseases. Serum hepatitis B surface antigen (HBsAg), HBV DNA, and HBcrAg were measured over time in 32 post-LT patients. Twenty-one out of 32 patients had HCC at LT. The effects of HBcrAg, hepatocellular carcinoma (HCC) recurrence, and HBs gene mutation on HBV reinfection and withdrawal from hepatitis B immune globulin (HBIG) were analyzed. Sixteen out of 32 patients (50%) were positive for HBcrAg even though only six patients were thought to have experienced HBV reinfection based on reappearance of either HBV DNA or HBsAg during a median follow-up time of 75months. Three of these six patients who became re-infected with HBV experienced HCC recurrence after LT. The HBV DNA reappearance rate was significantly higher in patients with HCC recurrence after LT (p<0.001). Two HBV re-infected patients without HCC recurrence had HBs gene mutations G145R and G145A, respectively. Anti-HBs antibody development rate by HB vaccination was similar between HBcrAg-positive and negative patients (p=0.325). HBV reinfection is more common than is usually considered based on conventional measurement of HBsAg and HBV DNA. HCC recurrence and mutations in the HBV S gene were associated with HBV reinfection after LT.

Serum Levels of Hepatitis B Surface Antigen and DNA Can Predict Inactive Carriers With Low Risk of Disease Progression.

Serum levels of hepatitis B virus (HBV) DNA (≤2000 IU/mL) and hepatitis B surface antigen (HBsAg) (<1000 IU/mL) have been shown to distinguish inactive carriers with high accuracy. The goal of this study was to validate the predictability of one-time measurement of quantitative HBsAg and HBV DNA levels for inactive carrier status and chronic hepatitis B (CHB) progression in a community-based cohort. This study included 1529 participants chronically infected with HBV genotype B or C from the REVEAL-HBV cohort. They were ascertained as inactive or active CHB after 18 months of follow-up. Validity of the one-time measurement was assessed by sensitivity, specificity, and receiver operating characteristic curves, while associations with clinical outcomes were calculated with Cox proportional hazards regressions. The one-time baseline measurement of HBsAg <1000 IU/mL and HBV DNA <2000 IU/mL distinguished inactive carriers from active CHB with a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 71%, 85%, 83%, 74%, and 78%, respectively. Those identified as inactive carriers using the one-time baseline measurement had multivariate adjusted hazard ratios of 0.36 (95% confidence interval [CI], 0.20-0.63) and 0.36 (0.23-0.56) for hepatocellular carcinoma and liver cirrhosis, respectively, and an adjusted rate ratio of 6.97 (95% CI, 5.21-9.33) for HBsAg seroclearance. Areas under the receiver operating characteristic curve of predicting these outcomes using the one-time definition were similar to those obtained when using long-term follow-up defined carrier status for prediction. This study confirms the predictability of a one-time combined HBsAg and HBV DNA measurement for future inactive carriers. This single-point strategy provides new and complementary information useful for management of patients with chronic hepatitis B infection. (Hepatology 2016;64:381-389).

Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc-positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study.

Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc-positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis. Thirty-three HBsAg-negative/anti-HBc-positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1-8) over 34 months (range 0-80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated. None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs-negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0-70) after RTX discontinuation, no HBV reactivation was observed. The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.

HBV: Do I treat my immunotolerant patients?

Immunotolerant patients with chronic hepatitis B virus (HBV) infection are characterized by positive HBeAg, high viral replication, persistently normal ALT and no or minimal liver damage. Since the risk of the progression of liver disease and the chance of a sustained response with existing anti-HBV agents are low, current guidelines do not recommend treatment but close monitoring with serial alanine aminotransferase (ALT) and HBV DNA measurements instead. However, not treating all these patients is a concern because advanced histological lesions have been reported in certain cases who are usually older (>30-40 years old), and continued high HBV replication could increase the risk of hepatocellular carcinoma (HCC). Thus, the optimal management of immunotolerant patients is often individualised according to age, which is associated with histological severity and patient outcome. In particular, immunotolerant patients <30 years old can be monitored for ALT and HBV DNA, while treatment is often recommended in the few patients over 40. A liver biopsy and/or non-invasive assessment of fibrosis may be helpful to determine the therapeutic strategy in patients between 30 and 40 years old. Moreover, there are three specific subgroups of immunotolerant patients who often require treatment with oral anti-HBV agents: patients who will receive immunosuppressive treatment or chemotherapy, women with serum HBV DNA >10(6-7) IU/ml during the last trimester of pregnancy and certain healthcare professionals with high viraemia levels. More studies are needed to further clarify the natural history for the optimal timing of treatment in this setting.

The prognosis and management of inactive HBV carriers.

Patients with chronic hepatitis B virus (HBV) infection lacking the serum hepatitis B e antigen (HBeAg) and with antibodies against HBeAg (anti-HBe), are the prevalent subgroup of HBV carriers worldwide. The prognosis of these patients is different from inactive carriers (ICs), who are characterized by persistently normal serum alanine aminotransferase (ALT) and low (<2000 IU/ml) serum HBV DNA levels, a serological profile that may also be intermittently observed in patients with HBeAg-negative chronic hepatitis. This is why a confirmed diagnosis of IC requires quarterly ALT and HBV DNA measurements for at least 1 year, while a single-point detection of combined HBsAg <1000 IU/ml and HBV DNA <2000 IU/ml has a robust predictive value for the diagnosis of IC. Characteristically, ICs have minimal or no histological lesions of the liver corresponding to liver stiffness values on Fibroscan of <5 kPa. Antiviral treatment is not indicated in ICs since the prognosis for the progression of liver disease is favourable if there are no cofactors of liver damage such as alcohol abuse, excess weight or co-infection with the hepatitis C virus or delta virus. Moreover, spontaneous HBsAg loss frequently occurs (1-1.9% per year) in these patients while the development of hepatocellular carcinoma (HCC) is rare, at least in Caucasian patients. However, an emerging issue reinforcing the need for clinical surveillance of ICs is the risk of HBV reactivation in patients who undergo immunosuppressive therapy without receiving appropriate antiviral prophylaxis. After diagnosis, management of ICs includes monitoring of ALT and HBV DNA every 12 months with periodic measurement of serum HBsAg levels to identify viral clearance.

Chronic hepatitis B in pregnant women: is hepatitis B surface antigen quantification useful for viral load prediction?

New cases of hepatitis B virus (HBV) infection continue to occur worldwide. Most of these are due to mother-to-child transmission (MTCT), with maternal viraemia as the most important contributing factor. The hepatitis B surface antigen (HBsAg) level, which correlates positively with viral load, has been used for treatment monitoring in chronic hepatitis B. This study evaluated the usefulness of quantitative HBsAg for viral load prediction in HBsAg-positive pregnant women. A total of 943 pregnant women in Makassar, Indonesia, were screened for HBsAg. Sixty-four women were HBsAg-positive and investigated. HBsAg level and hepatitis B e antigen (HBeAg)/hepatitis B e antibody (anti-HBe) status were determined serologically. Viral load was measured by real-time PCR. HBV DNA was sequenced and analysed for identification of genotype and basal core promoter (BCP)/precore (PC) mutations. Of 64 subjects, 12 (18.8%) were HBeAg-positive and 52 (81.3%) were HBeAg-negative. HBsAg and HBV DNA levels were significantly higher in the HBeAg-positive group (p<0.001). HBsAg and HBV DNA levels were positively correlated in the HBeAg-positive group (r = 0.659; p=0.02), but not in the HBeAg-negative group (r=0.194; p=0.168). Low HBsAg levels (<3.0 log10 IU/ml) corresponded with HBV DNA levels<6.0 log10 IU/ml (r=0.404; p=0.001), a recognized threshold for MTCT. Genotype C was more prevalent than genotype B, but not associated with HBsAg level, viral load, or HBeAg status. Two-thirds of HBeAg-negative subjects with high HBV DNA levels harboured BCP (A1762T/G1764A) and/or PC (G1896A) variants. HBsAg levels provide a good viral load predictor in HBeAg-positive but not HBeAg-negative pregnant women. The HBeAg-negative group had a frequent occurrence of BCP/PC variants, which may have contributed to the lack of correlation observed. Samples with a low HBsAg level, which is associated with a low risk of MTCT, do not require HBV DNA measurement.

Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe

The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1–5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries.

Can Viral Load Predict Liver Histology in Patients With Chronic Hepatitis B?

Introduction: Hepatitis B virus (HBV) infection is a global public health problem. Serum HBV DNA measurement is a non-invasive test that predicts the liver disease progression. The aim of this study was to determine the HBV DNA level and look for a relation between the HBV DNA level and liver histology. Methods: This was a cross sectional study on chronic hepatitis B infected patients in Tehran Hepatitis Center from 2006 to 2010. Percutaneus liver biopsy was performed in all patients. Patients with a history of any treatment and co-infection of HCV, HDV and HIV were excluded. Results: 301 patients were included in this study. The mean age was 34.63±13.25 years. Mean serum HBV DNA level was 1.35* 108 ± 10.5*109 copies/ml. Mean inflammatory score (grade) was 5.54±3.26 and fibrosis (stage) was 1.93±1.56. There wasn’t any significant relation between age and sex with liver histology. No significant relation was seen between liver histology and the HBV DNA level. HBe Ag positive patients had a higher serum HBV DNA level. Conclusion: There wasn’t any significant relation between liver histology and the HBV DNA level. We suggest using liver biopsy as a Golden Standard. In addition we need more studies in this field. Keywords: Chronic Hepatitis B, Liver Histology, Serum HBV DNA

Inhibition of placental mTORC1 signalling may explain decreased placental nutrient transport and contribute to restricted fetal growth in placental malaria

Inhibition of placental mTORC1 signalling may explain decreased placental nutrient transport and contribute to restricted fetal growth in placental malaria

Factors Associated With Delayed Hepatitis B Viral Suppression on Tenofovir Among Patients Coinfected With HBV-HIV in the CNICS Cohort

Despite widespread use in HIV and hepatitis B virus (HBV) infection, the effectiveness of tenofovir (TDF) has not been studied extensively outside of small cohorts of coinfected patients with HBV-HIV. We examined the effect of prior lamivudine (3TC) treatment and other factors on HBV DNA suppression with TDF in a multisite clinical cohort of coinfected patients. We studied all patients enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort from 1996 to 2011 who had chronic HBV and HIV infection, initiated a TDF-based regimen continued for ≥ 3 months and had on-treatment HBV DNA measurements. We used Kaplan-Meier curves and Cox-proportional hazards to estimate time to suppression (HBV DNA level <200 IU/mL or <1000 copies/mL) by selected covariates. Among 397 coinfected patients on TDF, 91% were also on emtricitabine or 3TC concurrently, 92% of those tested were hepatitis B e antigen positive, 196 (49%) had prior 3TC exposure; 192 (48%) achieved HBV DNA suppression over a median of 28 months (interquartile range: 13-71). Median time to HBV DNA suppression was 17 months for those who were 3TC-naive and 50 months for those who were 3TC exposed. After controlling for other factors, prior 3TC exposure, baseline HBV DNA level >10,000 IU/mL, and lower nadir CD4 count were independently associated with decreased likelihood of HBV DNA suppression on TDF. These results emphasize the role of prior 3TC exposure and immune response on delayed HBV suppression on TDF.

Serum levels of interleukin‐22 and hepatitis B core‐related antigen are associated with treatment response to entecavir therapy in chronic hepatitis B

We sought to clarify the associations between serum cytokines and chemokines, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and hepatitis B virus (HBV) DNA and response to entecavir therapy in chronic hepatitis B. We analyzed six cytokines (interleukin [IL]-2, IL-6, IL-10, IL-12p70, IL-21 and IL-22) and five chemokines (CCL2, CCL3, CXCL9, CXCL10 and CXCL11) before and at 6, 12 and 24 months during entecavir therapy in 48 chronic hepatitis B patients. Quantitative measurement of HBsAg, HBcrAg and HBV DNA was performed. A virological response (VR) was defined as serum HBV DNA of less than 2.1 log copies/mL by treatment month 24. Thirty-nine patients (81%) achieved a VR. Serum IL-6 (P = 0.031), CXCL-9 (P = 0.002), and CXCL-10 (P = 0.001) were high in chronic HBV and correlated positively with transaminases and bilirubin. Before treatment, elevated IL-22 (P = 0.031) and lower HBsAg (P = 0.001) and HBcrAg (P < 0.001), but not HBV DNA, were associated with a favorable treatment outcome. In multivariate analysis, high IL-22 (hazard ratio = 13.67, P = 0.046) and low HBcrAg (hazard ratio = 10.88, P = 0.048) were independently associated with a VR. The levels of IL-22 (P < 0.001), HBsAg (P < 0.001), and HBcrAg (P < 0.001) all decreased from baseline to 24 months of treatment in virological responders. Serum IL-22 and HBcrAg are predictive markers of a VR to entecavir therapy in patients with chronic hepatitis B.

PWE-145 Restrospective Review of Hepatitis B Database

IntroductionChronic Hepatitis B Virus (HBV) affects 350 million people worldwide with potential serious consequences. The aim of this study was to measure adherence at Sandwell and West Birmingham Hospitals (SWBH)...

Hepatitis B inactive carriers: Clinical course and outcomes

Hepatitis B virus (HBV) inactive carriers are HBV e antigen (HBeAg)-negative patients with normal alanine aminotransferase (ALT) levels and HBV DNA of ≤ 10000 copies/mL. We aimed to determine the clinical impact of ALT and HBV DNA elevations during the course of HBV infection. From January 1989 to January 2012, 146 inactive carriers were prospectively followed every 6-12 months with ALT and HBV DNA measurements and with hepatocellular carcinoma (HCC) surveillance. During the follow-up of 8 ± 6.3 years, 56 of the 146 patients maintained ALT ≤ 40 U/L and HBV DNA ≤ 10000 copies/mL. However, 39 had rises of ALT > 40-80 U/L and 4 had ALT > 80 U/L; all except one reverted to baseline values. Also, during follow up, 69 (47.3%) inactive carriers had increases in HBV DNA of > 10000-999999 copies/mL; 38 of these patients' HBV DNA returned to baseline levels, while the remaining 31 patients maintained elevated HBV DNA values but had corresponding ALT of ≤ 40 U/L. There were four liver-related outcomes: 129 (88.4%) remained "inactive carriers", 13 (8.9%) had loss of hepatitis B surface antigen (HBsAg), one (0.7%) had a spontaneous reactivation to HBeAg-negative chronic hepatitis, and two (1.4%) developed HCC. Although the prognosis of inactive carrier is favorable, transient ALT and HBV DNA elevations may be observed but have minimal clinical significance. Moreover, continuous HCC surveillance remains necessary since the risk of development still exists.