Characterization of HBV surface antigen isoforms in the natural history and treatment of HBV infection.

BACKGROUND: The loss of HBV HBsAg or functional cure is a desirable goal of hepatitis B management. The relative abundances of HBsAg isoforms may offer additional diagnostic and predicting values. To evaluate the clinical utility of HBsAg isoforms, we developed novel prototype assays on the ARCHITECT automated serology platform that specifically detects total-HBsAg (T-HBsAg), large (L-HBsAg), and middle (M-HBsAg) products of the S gene to determine the isoform composition of human specimens from acute and chronic HBV infection and during long-term nucleos(t)ide analog therapy. RESULTS: In the early phase of acute HBV infection, L-HBsAg and M-HBsAg emerged within days and were in parallel to T-HBsAg during the entire course of infection. M-HBsAg levels were consistently higher than L-HBsAg levels. Patients with HBeAg(+) chronic hepatitis B had higher T-HBsAg, M-HBsAg, and L-HBsAg levels compared with HBeAg(-) patients. Correlations of M-HBsAg and L-HBsAg to T-HBsAg were similar in both. In contrast, there was no strong correlation between L-HBsAg or M-HBsAg with HBV DNA levels. During long-term nucleos(t)ide analog treatment, changes in HBsAg isoform abundance were proportional to T-HBsAg regardless of treatment responses for both HBeAg(+) and HBeAg(-) chronic hepatitis B. A larger sample size may be necessary to detect a significant difference. CONCLUSION: HBsAg isoform compositions parallel T-HBsAg levels in both acute and chronic hepatitis B infection. L-HBsAg and M-HBsAg individual biomarkers do not appear to provide an additional diagnostic benefit for staging chronic disease or monitoring response to treatment with current therapies.

Derivation and Validation of a Diagnostic Prediction Tool for Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) results in high morbidity and health-care utilization. Diagnostic delays remain common and often occur in nonpulmonology settings. Screening for ILD in these settings has the potential to reduce diagnostic delays and improve patient outcomes. RESEARCH QUESTION: This study sought to determine whether a pulmonary function test (PFT)-derived diagnostic prediction tool (ILD-Screen) could accurately identify incident ILD cases in patients undergoing PFT in nonpulmonology settings. STUDY DESIGN AND METHODS: Clinical and physiologic PFT variables predictive of ILD were identified by using iterative multivariable logistic regression models. ILD status was determined by using a multi-reader approach. An ILD-Screen score was generated by using final regression model coefficients, with a score ≥ 8 considered positive. ILD-Screen test performance was validated in an independent external cohort and applied prospectively to PFTs over 1 year to identify incident ILD cases at our institution. RESULTS: Variables comprising the ILD-Screen were age, height, total lung capacity, FEV1, diffusion capacity, and PFT indication. The ILD-Screen showed consistent test performance across cohorts, with a sensitivity of 0.79 and a specificity of 0.83 when applied prospectively. A positive ILD-Screen strongly predicted ILD (OR, 18.6; 95% CI, 9.4-36.9) and outperformed common ILD clinical features, including cough, dyspnea, lung crackles, and restrictive lung physiology. Prospective ILD-Screen application resulted in a higher proportion of patients undergoing chest CT imaging compared with a historical control cohort (74% vs 56%, respectively; P = .003), with a significantly shorter median time to chest CT imaging (5.6 vs 21.1 months; P < .001). INTERPRETATION: The ILD-Screen showed good test performance in predicting ILD across diverse geographic settings and when applied prospectively. Systematic ILD-Screen application has the potential to reduce diagnostic delays and facilitate earlier intervention in patients with ILD.

Liver Cancer-Specific Serine Protease Inhibitor Kazal Is a Potentially Novel Biomarker for the Early Detection of Hepatocellular Carcinoma.

INTRODUCTION: Liver cancer-secreted serine protease inhibitor Kazal (LC-SPIK) is a protein that is specifically elevated in cases of hepatocellular carcinoma (HCC). We assessed the performance of LC-SPIK in detecting HCC, including its early stages, in patients with cirrhosis, hepatitis B virus (HBV), and hepatitis C virus (HCV). METHODS: We enrolled 488 patients, including 164 HCC patients (81 early HCC) and 324 controls in a blinded, prospective, case-control study. Serum LC-SPIK levels were determined by an enzyme-linked immunosorbent assay-based assay. The performance of serum LC-SPIK and α-fetoprotein (AFP), including area under the curve (AUC), sensitivity, and specificity, are compared. The performance of LC-SPIK was evaluated in an independent validation cohort with 102 patients. RESULTS: In distinguishing all HCC patients from those with cirrhosis and chronic HBV/HCV, LC-SPIK had an AUC of 0.87, with 80% sensitivity and 90% specificity using a cutoff of 21.5 ng/mL. This is significantly higher than AFP, which had an AUC of 0.70 and 52% sensitivity and 86% specificity using a standard cutoff value of 20.0 ng/mL. For early-stage HCC (Barcelona Clinic Liver Cancer stage 0 and A), LC-SPIK had an AUC of 0.85, with 72% sensitivity and 90% specificity, compared with AFP, which had an AUC of 0.61, with 42% sensitivity and 86% specificity. In addition, LC-SPIK accurately detected the presence of HCC in more than 70% of HCC patients with false-negative AFP results. DISCUSSION: The study provided strong evidence that LC-SPIK detects HCC, including early-stage HCC, with high sensitivity and specificity, and might be useful for surveillance in cirrhotic and chronic HBV/HCV patients, who are at an elevated risk of developing HCC.

An update on the management of chronic hepatitis D.

Hepatitis D virus (HDV) infection is associated with severe liver-related morbidity and mortality. The prevalence of HDV is rising especially among people who abuse drugs and immigrants from endemic areas. Reliable diagnostic assays with enhanced sensitivity and specificity are essential for screening at-risk populations. Until recently, interferon has been the only treatment for hepatitis D. Its efficacy is, however, limited and it is associated with significant side effects. A number of novel antiviral agents that target various stages of the HDV life cycle show promising results. They are currently in different phases of clinical development. This review focuses on the changing epidemiology, novel therapeutic agents, and updated management of chronic hepatitis delta.

Foodborne Botulism, I Only Had Nacho Cheese: A Case Report.

A 32-year-old female presented to the emergency department with complaints of diplopia, followed by dyspnea, chest tightness, congestion, and dysphagia. The patient was resuscitated and initial investigations were done. Within a few hours of the admission, she started developing signs of respiratory failure and was intubated and placed on the mechanical ventilator. The patient denied any ingestion of exotic food, shellfish, raw meat, or raw fish. The patient also denied traveling to any exotic place or recent camping trips. The edrophonium tensilon test and lumbar puncture came out to be negative. The botulinum toxin test was positive, the patient was started on botulinum antitoxin, and the rest of symptomatic treatment was continued. The Centre for Disease Control (CDC) tracked the events related to the presentation and found she had eaten nacho cheese from a gas station the day before the appearance of the symptoms. A total of 10 cases were associated with this source within days and one death was reported.

Idiopathic Acquired Dacryocystocele Presenting Only with Epiphora: A Very Rare Case Report.

A 42-years-old male presented with left medial canthal swelling, accompanied with only mild epiphora. There was no history of dacryocystitis, mid-facial trauma, surgery, or bloody tears. On examination, there was an immobile, subcutaneous, non-inflammatory mass below the medial canthal tendon. Lacrimal irrigation showed blockade at the nasolacrimal duct. A computerized axial tomography (CAT) scan revealed a non-enhancing, low-density, cystic lesion at the inferomedial margin of the orbit. There were no signs of bony erosion, consistent with idiopathic acquired dacryocystocele. The patient underwent external dacryocystorhinostomy (DCR) with silicone tube intubation. The patient's symptoms of epiphora resolved after surgery. Idiopathic acquired dacryocystocele with only epiphora, although rare, should be considered in differential diagnosis of medial canthal, non-inflammatory swellings. In areas with insufficient endoscopic facilities, external dacryocystorhinostomy gives similar promising results.