Asad Javaid

Recent advances in micro/nanotechnologies for global control of hepatitis B infection

The control of hepatitis B virus (HBV) infection is a challenging task, specifically in developing countries there is limited access to diagnostics and antiviral treatment mainly due to high costs and insufficient healthcare infrastructure. Although the current diagnostic technologies can reliably detect HBV, they are relatively laborious, impractical and require expensive resources that are not suitable for resource-limited settings. Advances in micro/nanotechnology are pioneering the development of new generation methodologies in diagnosis and screening of HBV. Owing to combination of nanomaterials (metal/inorganic nanoparticles, carbon nanotubes, etc.) with microfabrication technologies, utilization of miniaturized sensors detecting HBV and other viruses from ultra-low volume of blood, serum and plasma is realized. The state-of-the-art microfluidic devices with integrated nanotechnologies potentially allow for inexpensive HBV screening at low cost. This review aims to highlight recent advances in nanotechnology and microfabrication processes that are employed for developing point-of-care (POC) HBV assays.

Serum Alanine Aminotransferase and Hepatitis B DNA Flares in Pregnant and Postpartum Women with Chronic Hepatitis B.

OBJECTIVES:Alterations in the immune system during pregnancy have been associated with reactivation of hepatitis B virus (HBV) in chronic hepatitis B (CHB) women. However, the effects of pregnancy on CHB remain not well understood. The goal of this study was to examine flares in HBV DNA and serum alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women untreated prior to pregnancy.METHODS:This was a multicenter retrospective study of 113 pregnancies in 101 CHB women who presented during pregnancy at two community gastroenterology clinics and two tertiary medical centers in the United States during 1997–2015. Outcomes analyzed included onset, severity, and resolution of flares in HBV and ALT that occurred prior to starting antiviral therapy, if antiviral therapy was subsequently initiated. Women who initiated antiviral therapy during pregnancy were not included in the analysis of postpartum flares.RESULTS:HBV DNA flares were observed in 9% (8/90) of women during pregnancy and 4% (2/48) of women during postpartum. Flares in ALT (99–2522 U/l) were observed in 6% (7/112) of women during pregnancy and 10% (5/51) of women within the first 3 months of delivery. Age, HBeAg positivity, baseline HBV DNA, baseline ALT, gravida, and parity were not found to be significant predictors of flare.CONCLUSIONS:Flares in HBV DNA and ALT can occur during late pregnancy and early postpartum in CHB women, and can be severe. Women with CHB should therefore be closely monitored during pregnancy and early postpartum.

Serum Aminotransferase Flares in Pregnant and Postpartum Women With Current or Prior Treatment for Chronic Hepatitis B

Background and Aims: Antiviral therapy is recommended for pregnant women with chronic hepatitis B (CHB) and hepatitis B virus (HBV) DNA>200,000 IU/mL, but there is less consensus on management of women who discontinue therapy in anticipation of pregnancy or who become pregnant while on therapy. The goal of this study was to describe flares in alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women with current and/or prior treatment. Methods: This was a multicenter, retrospective study of 67 pregnancies in 56 CHB women treated before and/or during pregnancy. Main outcomes were frequency, severity, and resolution of ALT flare (≥5× upper limit of normal or ≥3× baseline, whichever was higher). Results: During pregnancy, ALT flares (95 to 1064 U/L) were observed in 16% (7/43) of women who stopped treatment before pregnancy and 31% (4/13) of women who discontinued treatment during first trimester, many of whom had high HBV DNA levels (4.9 to 8.0 log IU/mL). No flares (0/11) were observed in women who continued treatment. Postpartum ALT flares (104 to 1584 U/L) were observed in 0% (0/15) of women who were completely untreated during pregnancy, 29% (2/7) of women who discontinued treatment in first trimester, 33% (3/9) of women who stopped treatment at delivery, and 22% (4/18) of women who continued treatment postpartum. Conclusions: In previously treated women with CHB, ALT flares were common during pregnancy and postpartum, especially if antiviral therapy was discontinued shortly before pregnancy, during first trimester, or at delivery. Thus, these pregnant women should be monitored closely throughout pregnancy and the early postpartum period; larger studies are needed to further characterize the natural history of HBV infection during pregnancy and postpartum.

Subtle presentation of active primary biliary cirrhosis in chronic hepatitis B: a case report

Abstract We are describing an interesting case of two chronic liver diseases in a 48-year-old Chinese woman. While chronic hepatitis B is a common entity in Asia, the patient was later found to have active, asymptomatic primary biliary cirrhosis due to a persistently elevated alkaline phosphatase level after optimal hepatitis B virus DNA suppression on antiviral therapy. This report emphasizes the importance of keeping a high index of suspicion for another potential liver disease process even after a patient has been successfully treated for a primary liver condition. Clinical vigilance, especially in atypical clinical presentations, can result in early accurate diagnosis and prompt treatment.

Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma

Background We previously developed a logistic regression algorithm that uses AFP, age, gender, ALK and ALT levels to improve the detection of hepatocellular carcinoma (HCC). In 3,158 patients from 5 independent sites, this algorithm, referred to as the “Doylestown” algorithm, increased the AUROC of AFP 4% to 12% and had equal benefit regardless of tumor size or the etiology of liver disease. Aims Analysis of the Doylestown algorithm using samples from individuals taken before their diagnosis of HCC. Methods Here, the algorithm was tested using samples at multiple time points from (a) patients with established chronic liver disease, without HCC (120 patients) and (b) 116 patients with HCC diagnosis (85 patients with early stage HCC and 31 patients with recurrent HCC), taken at the time of, and up to 12 months prior to cancer diagnosis. Results Among patients who developed HCC, comparing the Doylestown algorithm at a fixed cut-off to AFP at 20 ng/mL, the Doylestown algorithm increased the True Positive Rate (TPR) in identification of HCC from 36 to 50%, at a time point of 12 months prior to the conventional HCC detection. Similar results were obtained in those patients with recurrent HCC, where the Doylestown algorithm increased TPR in detection of HCC from 18% to 59%, at 12 months prior to detection of recurrence. Conclusions This algorithm significantly improves the prediction of HCC by AFP alone and may have value in the early detection of HCC.

A Review on Therapeutic Management of Chronic Hepatitis B Infection

The current therapeutic goal in the management of chronic hepatitis B (CHB) infection is to persistently suppress hepatitis B virus (HBV) replication and prevent its progression to liver failure and the development of hepatocellular carcinoma (HCC). At present, the therapeutic strategies for CHB includes either a short course of pegylated-interferon-alfa (PEG-IFNa) and/or a long term course of nucleos(t)ide analogues (NA’s). NA’s are more preferable to PEG-IFNa, majorly for its easier route of administration and excellent tolerance and safety profiles. Entecavir (ETV) and tenofovir (TDF) are the current first line options for its potency to maintain sustained virological response (SVR) in almost 100% of the adherent individuals along with minimal to no long-term resistance. These sustained inhibitions of HBV replication have been shown to be associated with histological improvement, modifying the long-term outcomes. However, HBsAg seroconversion, the best surrogate marker for viral clearance is still unachievable with the current first line agents and hence the risk for hepatocellular carcinoma (HCC) still exists among them. This makes us to still consider, a finite duration of PEG-IFN a that has shown considerable results with regards to HBsAg loss, as an attractive add-on or monotherapy option despite its adverse events profile. Existing evidences do not recommends its usage. However, numerous studies are ongoing and also further studies to evaluate the reliable baseline predictors of response to PEG-IFNa and early on-treatment stopping rules based on age, alanine aminotransferase levels (ALT), HBV DNA levels and HBsAg kinetics would be ideal. existing practice guidelines such as that of American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL) assist physicians in the diagnosis and optimal management of CHB; they are still expected to individualize the management considering various factors like cost-effectiveness, compliance, efficacy and duration of anti-viral agents, existence of coinfections etc. [1,3,4]. This article reviews the basis for those guideline recommendations, the natural history of the disease, treatment options and what we do in our practice to illustrate factors that may influence the management of CHB. Natural history of chronic hepatitis B infection

Sa1053 High Hepatic Iron and Low Serum Betaine Levels Are Associated With Hepatic Steatosis Among Males With Chronic Hepatitis B

Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver disease. The prevalence of hepatic steatosis in chronic hepatitis B (CHB) is not well understood. There are reports that low betaine level contributes to hepatic steatosis by increasing oxidative stress. Our aims are to determine the prevalence and impact of hepatic steatosis on CHB and the role of betaine in this disease state. In a single center, CHB patients with pretreatment liver biopsy between 1998 and 2013 were reviewed. The analysis excluded patients with alcoholism (>50g/day), HCV, HDV or HIV coinfection, other liver diseases and liver transplantation. To date, 231 patients (75% Asians) met the inclusion criteria. Serum betaine levels were measured in 40 randomly selected serum samples from patients with and without steatosis in both genders. Results: Total 127 (55%) pts had hepatic steatosis in biopsied tissue. Steatosis was more common in males (91/136, 67%) than females (36/95, 38%) [p=0.0001]. Among those with steatosis, males (mean 41.5 yrs) were younger than females (mean 48.5 yrs) [p=0.02]. For both genders, those with steatosis had higher rate of severe hepatic inflammation (M 63%, F 30%) compared to those without (M 5%, F 3%) [p=0.0001]. Advanced fibrosis (Stage 3+4) was more frequent in males (14%) than females (8%). Hepatic iron was present in 47 of 91 (52%) males with steatosis but in only 7 of 36 (19%) females with steatosis [p=0.0001]. Females with steatosis had higher rates of elevated LDL cholesterol (64% vs. 41%) [p=0.04], triglyceride (31% vs.13%) [p=0.02] and increased body weight (150lbs vs. 126lbs) [p=0.001] compared to those without. The lipid profiles and weight, however, were similar in males with and without steatosis. Interestingly, males with steatosis (N=10) had lower serum level of betaine compared those without steatosis (N=10) [28.3 vs. 43.3 umol/L; p=0.056]. In contrast, females with (N=10) or without steatosis (N=10) had similar betaine levels [42.9 vs. 39.3umol/L; p=0.3]. Viral factors such as serum HBV DNA levels, HBeAg status were not different between those with and without steatosis. Conclusions: High prevalence of hepatic steatosis is identified in this predominantly Asian cohort of patients with chronic hepatitis B. Steatosis is more common in males. For both genders, steatosis is associated with more severe hepatic inflammation. There appears to be a gender difference in predisposition to steatosis. In females, metabolic syndrome is a major contributing factor. In males, presence of hepatic iron and lower betaine levels correlate with steatosis and inflammation. It is possible that betaine attenuates iron-iduced oxidative stress in the liver. The gender differences in steatosis predisposition in CHB warrant further evaluation. Its understanding likely will contribute to better preventive and therapeutic strategies.