Risk of hepatitis B surface antigen seroreversion after corticosteroid treatment in patients with previous hepatitis B virus exposure.

BACKGROUND & AIMS: Systemic corticosteroids may cause HBV reactivation, but the impact on patients with previous HBV exposure is poorly defined. We aimed to study the risk of HBsAg seroreversion and hepatitis flare in patients with previous HBV exposure. METHODS: Patients who were negative for HBsAg and received corticosteroids between 2001-2010 were included. Patients who were positive for antibody to HBsAg (anti-HBs) and/or to HBcAg (anti-HBc) were defined as having previous HBV exposure. The primary endpoint was HBsAg seroreversion; the secondary endpoint was hepatitis flare (alanine aminotransferase >80 U/L) at 1 year. RESULTS: A total of 12,997 patients fulfilled the inclusion criteria: anti-HBs positive only (n = 10,561); anti-HBc positive only (n = 970); anti-HBs & anti-HBc positive (n = 830) and anti-HBs & anti-HBc negative (n = 636). HBsAg seroreversion occurred in 165 patients. Patients who were anti-HBc positive only had a higher risk of HBsAg seroreversion (1-year incidence 1.8%) than those negative for both anti-HBs & anti-HBc (0%; p = 0.014). Patients with previous HBV exposure had a similarly low risk of liver failure as unexposed individuals (1.1% vs. 0.9%). The risk of a hepatitis flare started to increase in those receiving corticosteroids at peak daily doses of 20-40 mg (adjusted hazard ratio [HR] 2.19, p = 0.048) or >40 mg (aHR 2.11, p = 0.015) prednisolone equivalents for <7 days, and was increased at treatment durations of 7-28 days and >28 days (aHR 2.02-3.85; p <0.001-0.012). CONCLUSIONS: In HBsAg-negative patients who were only anti-HBc positive, high peak daily doses of corticosteroids increased the risk of hepatitis flare, but not seroreversion. The rate of liver failure was low and similar in HBV exposed and unexposed individuals; there were no deaths, nor any requirement for liver transplantation. LAY SUMMARY: It is important to know the hepatitis B virus (HBV) status before starting corticosteroid therapy. Patients with resolved HBV infection without detectable immunity are at an increased risk of HBV surface antigen seroreversion after corticosteroid therapy. High peak daily doses of corticosteroids (>40 mg prednisolone equivalents) increase the risk of hepatitis flare, but not seroreversion, in patients with previous exposure to HBV, irrespective of the duration of treatment. Interval monitoring of liver biochemistries is essential for the early detection of hepatitis flares in these patients.

Impact of dose and duration of corticosteroid on the risk of hepatitis flare in patients with chronic hepatitis B.

BACKGROUND: Systemic corticosteroid is used for different medical conditions and may cause hepatitis B virus (HBV) reactivation. AIMS: To study the impact of duration and peak dose of corticosteroid on the risk of hepatitis flare in patients with chronic hepatitis B (CHB). METHODS: All patients who received corticosteroid from January 2001 to December 2004 were retrieved from the Hospital Authority, Hong Kong. We stratified patients by daily dose prednisolone equivalents (<20 mg, 20-40 mg, >40 mg) and durations (<7; 7-28; >28 days). The primary endpoint was hepatitis flare (alanine aminotransferase >2×upper limit of normal, ie 80 IU/L) at 1 year. RESULTS: A total of 85 763 patients fulfilled the inclusion criteria (5254 CHB, 80 509 non-CHB). CHB patients had higher risk of hepatitis flare (388/5254 [7.8%]) than those without CHB (2728/80 509 [4.2%]; P < 0.001 by log-rank test). Among CHB patients, peak daily dose >40 mg compared to <20 mg prednisolone equivalents (adjusted hazard ratio [aHR] 1.64, 95% CI 1.26-2.14; P < 0.001) was an independent risk factor of hepatitis flare. Risk of hepatitis flare started to increase in those receiving corticosteroid of peak daily dose >40 mg prednisolone equivalents even for <7 days (aHR 1.55, P = 0.026), which was also increased for 7-28 days and >28 days (aHR 1.90 and 1.64 respectively, both P < 0.001). CONCLUSION: Even short courses of high-dose corticosteroid increase the risk of hepatitis flare in CHB patients. Patients receiving high-dose corticosteroid should be considered for antiviral prophylaxis regardless of the duration of treatment.

Leptospirosis as Cause of Febrile Icteric Illness, Burkina Faso.

Patients in Burkina Faso who sought medical attention for febrile jaundice were tested for leptospirosis. We confirmed leptospirosis in 27 (3.46%) of 781 patients: 23 (2.94%) tested positive using serologic assays and 4 (0.51%) using LipL32 PCR. We further presumed leptospirosis in 16 (2.82%) IgM-positive specimens.

Discolored blood and blood components: a dilemma for transfusion specialists.

BACKGROUND AND OBJECTIVES: It is not uncommon in transfusion practice to see blood/components with abnormal colored plasma. The present study was conducted to identify and determine the etiology of blood and/or blood components showing altered color. MATERIAL AND METHODS: The present study was conducted in the Department of Transfusion Medicine, Government Medical College and Hospital, Chandigarh over a period of seven months. All the blood units/components having an abnormal appearance were segregated as: 1. Green discoloration. 2. Yellow discoloration. 3. Bright cherry red color. 4. Lipemic plasma. The donor's history was carefully evaluated and relevant investigations were done depending on discoloration. RESULTS: Seventeen units out of 7370 (0.23%) donations showed discoloration. In 3 units the plasma was green, 5 units were yellow, in 3 units PRBC/WB unit was bright cherry red and in the remaining 6 units the plasma was lipemic. Total bilirubin of all the 5 donors with yellowish plasma ranged from 1.6 to 2.3mg/dl. The hemoglobin and hematocrit of two out of three donors with cherry red discoloration of PRBC/WB was low. All the donors with lipemic plasma gave history of intake of fatty meal prior to donating blood. CONCLUSION: The existing rules prohibit issue of blood and blood components if the plasma is abnormal in color. Our study showed that many of the discolored units could have been safely transfused but further larger studies are required to confirm the safety of recipients receiving such units.

Association of Serum Metabolites with Serum Indices and Preanalytical Factors of Biobanked Serum Samples.

Background: Serum indices (hemolysis, icterus, and lipemia; HIL) are known to impact clinical chemistry assay results. This study aimed to investigate the impact of HIL indices on serum metabolite profiles and the association of serum metabolite levels with pre-analytical factors of serum samples. Methods: A cohort of serum samples (n = 12,196) from the Korean Genome and Epidemiology Study (KoGES) was analyzed for HIL indices and the pre-analytical variables (SPRECs) which were generated in the process of serum collection. We further performed targeted metabolomics on a subset comprising hemolyzed (n = 60), icteric (n = 60), lipemic (n = 60) groups, and a common control group of non-HIL samples (n = 60) using the Absolute IDQ p180 kit. Results: We found 22 clinical chemistry analytes significantly associated with hemolysis, 25 with icterus, and 24 with lipemia (p < 0.0001). Serum metabolites (n = 27) were associated with all of hemolysis, icterus, and lipemia (p < 0.05). The PC ae C36 2 had exhibited a significant association with pre-analytical factors corresponding to the third (pre-centrifugation delay between processing) and sixth (post-centrifugation) elements of the SPREC. Conclusions: This study showed the association of the serum index and pre-analytical factors with serum metabolite profiles. In addition, the association of pre-analytical factors with serum metabolite concentrations would corroborate the utility of SPRECs for the quality control of biobanked serum samples.

Resolving icteric interference by a novel photoisomerization device: Bilibox.

Icterus, a phenomenon caused by bilirubin elevation in the blood, is a common endogenous interference in chemistry testing, occurring either spectrally or through chemical reactivity with assay reagents. Often, laboratories have few options other than to dilute or reject samples exceeding icteric thresholds. However, recent studies have optimized in vitro photoisomerization of bilirubin to a 17-minute bilirubin half-life using 500 nm light at 37 °C. Using an enzymatic creatinine assay as a model, due to its prevalence in routine laboratory testing and susceptibility to icteric interference, our study explores the usage of in vitro photoisomerization by replicating these conditions in a device, the Bilibox, as means of resolving icterus in laboratory testing. Left-over icteric and non-icteric clinical samples, collected by lithium heparin vacutainer (n = 10), were analyzed for baseline creatinine, diluted creatinine (1:4 0.9 % NaCl), total bilirubin, direct bilirubin, and hemolysis, icterus and lipemia (HIL) indices. Samples were then placed in the Bilibox in two intervals of 30 min with repeat measurements of the aforementioned analytes. On average, icteric-index, total bilirubin (TBIL), and direct bilirubin (DBIL) decreased by 33.5, 39.1 and 39.9 % respectively following 30 min of Bilibox treatment; and by 47.6 %, 63.7 % and 59.8 % following 60 min. The average percent difference between the pre-exposure diluted and undiluted creatinine was 5.8 %, demonstrating the icterus interference. Following Bilibox treatment, the difference between undiluted (post-exposure) and diluted (pre-exposure) creatinine decreased to 0.02 % (p = 0.0232) and 2.2 % (p = 0.0021) at 30 and 60 min of treatment respectively, demonstrating resolution of interference. Consequently, photoisomerization can be utilized as an additional and reasonably quick method for resolving icterus when dilutional methods cannot be applied.

Retinopathy of Prematurity Screening of Preterm Infants With Icteric Vitreous.

Purpose: To present 2 cases of premature newborns with hyperbilirubinemia and retinopathy of prematurity (ROP) who could not be examined properly to assess for disease progression because of vitreous opacification in the setting of an icteric vitreous and frail health status. Methods: The cases and their findings were analyzed. Results: Given the sickness of the neonates and examination difficulty, intravitreal bevacizumab was administered in both eyes to prevent disease progression. During subsequent examinations, the patients remained stable until discharge from the neonatal intensive care unit and were followed in the outpatient clinic without complication. Conclusions: The ROP and vitreous opacification in our cases were thought to be caused by hyperbilirubinemia. Because of vitreous opacification, these patients could not be properly examined for ROP. Treatment with an intravitreal antivascular endothelial growth factor injection might be considered to delay disease development until the newborn is healthier and able to be examined.

Compound glycyrrhizin injection for improving liver function in children with acute icteric hepatitis: A systematic review and meta-analysis.

BACKGROUND: Compound glycyrrhizin injection (CGI) is a preparation with glycyrrhizin as the main active ingredient extracted from licorice. As clinical trials suggest that CGI is effective in improving liver function for acute icteric hepatitis in children (AIHC), this systematic review aimed to evaluate and verify its therapeutic effects and safety. METHODS: Six electronic databases were searched from their inception to 15 May 2021. Randomized controlled trials (RCTs) assessing therapeutic effects and safety of CGI for AIHC were included. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. Primary outcomes were indexes related to liver function, including total bilirubin (TBiL), alanine aminotransferase (ALT) and aspartate transaminase (AST). RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Six RCTs involving 608 children were included. The overall bias was assessed as having "high risk of bias" in all trials. All trials compared the combination of CGI and conventional western medicine (CWM) with CWM alone. Regarding the effects of CGI for AIHC, results showed that CGI plus CWM was superior to CWM alone in reducing the levels of TBiL (mean difference (MD) = -8.19 mmol/L, 95% CI -9.86 to -6.53), ALT (MD = -24.09 U/L, 95% CI -30.83 to -17.34) and AST (MD = -18.67 U/L, 95% CI -21.88 to -15.45). No trial reported adverse events. The certainty of the evidence for outcomes were all evaluated as low or very low. CONCLUSION: CGI may have adjuvant therapeutic effects on improving the liver function of children with AIHC. There is no evidence to determine the safety of CGI for AIHC. As current evidence is weak, further well-designed RCTs are required for verification of the therapeutic effects of CGI.

The Uncommons: A Case of Pancreatitis and Hepatitis Complicating Salmonella Infection.

Salmonella typhi infection can be associated with serious complications, ranging from self-limited to fulminant organ damage. In particular, liver and pancreatic damage may complicate the course of infection resulting in devastating outcomes. Enteric fever encompasses a tropical disease caused by Salmonellaspecies and can be associated with high morbidity and mortality. Invasive infection rarely presents with acute hepatitis and pancreatitis. Early recognition of associated clinical conundrums can improve prognosis in affected patients. Here, we present a case of acute hepatitis and pancreatitis in an otherwise healthy child.

Proton Beam Therapy in Managing Unresectable Hepatocellular Carcinoma with Bile Duct Invasion.

Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.

Evaluation of Visual Serum Indices Measurements and Potential False Result Risks in Routine Clinical Chemistry Tests in Addis Ababa, Ethiopia.

BACKGROUND: Serum indices (SI) including hemolyzed, lipemic, and icteric samples, affects the accuracy of test result. The aim of this study was to evaluate SI values done by visual inspections and potential false result risks by comparing with actual measurements done by Cobas 6000 Chemistry analyzer at Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia. METHODS: An observational, cross-sectional study was conducted from April to May 2017 on samples referred to Clinical Chemistry laboratory of EPHI, Ethiopia. These samples SI values, after visual inspection by three trained observers, was analyzed again on Roche Cobas 6000 analyzer (RCA). The generated data was analyzed by using weighted kappa methods on STAT statistical software version 20. RESULTS: From a total of 1509 samples, SI values identified by the RCA as hemolysis, icteric, and lipemic were 933 (62%), 74(5%) and 59(4%) respectively. The SI average weighted kappa between RCA and visual inspection were: 0.1870, 0.3421, and 0.1259 for hemolysis, icteric, and lipemic samples, respectively. Combined inter-observers variability among observers for hemolysis, Icterus, and lipemic samples were 0.4758, 0.3258, and 0.3628 respectively. The best agreement among observers was in the case of hemolysis (0 grades), while the lowest agreement was observed in the case of icterus (+3 grades). In addition, test parameters, such as CK-MB (22%), and LDH (20%) were falsely accepted, whereas Cl- and Na+ (up to 25%) were falsely rejected tests by observers. On the other hand, results rejected by Cobas SI assessments included CK-MB (22%), LDH (20%), and BIL-D (4%). CONCLUSION: Visual inspection of SI showed poorly agreement with automated system. Thus, there is genuine need for more training of Laboratory professionals on identification of SI, and as much as possible SI should be done by automated system to improve quality of test results.

Serogroups and genotypes of Leptospira spp. strains from bovine aborted foetuses.

Leptospirosis is a global disease of animals, with potential major economic impact on livestock industry and important zoonotic capacities. The disease represents a major challenge in the developing countries as humans and animals frequently live in close association. The serovar Hardjo of Leptospira whose primary host is cattle has been studied extensively, but few data exist on other current circulating or emerging serotypes. To better understand the disease in cattle and how to prevent and/or control it, it is necessary to identify the genotype and the serotype of circulating Leptospira. This study presents results of several investigations performed on a historical Belgian collection of congenital jaundice in bovine aborted foetuses coming from the leptospirosis emerging episode of 2014 (Delooz et al., Transboundary and Emerging Diseases, 62, 2015, 124). The results revealed that L. Grippotyphosa and L. Australis were the most prevalent serogroups with, respectively, 17/42 and 13/42 positive microscopic agglutination test (MAT) during this emerging event associated with the same clinical pattern. The study also confirms that congenital jaundice is associated with L. kirscheneri and L. interrogans and provides the genotyping of DNA obtained from these two species.

Acute Viral Hepatitis: Beyond A, B, and C.

From the standpoint of the surgical pathologist "hepatitis" is defined as the set of histologic patterns of lesions found in livers infected by hepatotropic viruses, by non-hepatotrophic viruses leading to liver inflammation in the context of systemic infection, or due to an autoimmune disease, drug, or toxin involving the liver. This article is centered on the histologic patterns of injury in acute viral hepatitis, encompassing the hepatotropic viruses A, B, C, D, and E and the "icteric hemorrhagic fevers" (dengue, hantavirus, yellow fever). A brief mention of viruses causing hepatitis in immunosuppressed patients also is presented.

A patient who made an impact on how I practice: Severe leptospirosis presenting as ARDS in the ICU.

Severe leptospirosis can be a rare cause of acute respiratory distress syndrome (ARDS) and multiorgan failure. A patient who made an impact on how I practice was a case of severe leptospirosis (Weil's disease) that presented as ARDS in the ICU. Leptospirosis is an under-reported infectious disease worldwide and should be considered as a cause of ARDS especially in patients with exposure history complicated with diffuse alveolar bleeding (DAH), icteric hepatitis and renal deterioration. Empiric treatment should be recommended before confirmation of laboratory tests as serological diagnosis is time consuming.

Congenital jaundice in bovine aborted foetuses: an emerging syndrome in southern Belgium.

Southern Belgium faces an unusual recent increase of icteric bovine aborted foetuses. In the necropsy room, the majority of foetuses presented jaundice and splenomegaly. Despite a wide range of analyses, no definitive cause of abortion has yet been established but some analysis results support the leptospirosis hypothesis. This first description of cases will help veterinary practitioners to recognize more cases and to conduct those to the laboratory for future investigations.

An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh.

A total of 45 patients with acute hepatitis were detected in a medical facility of Bangladesh over a period of 6 months. All of them were physicians, nurses, students or employees of the hospital. About 50% of these patients suffered from acute hepatitis within a period of 2 months. All of them had clinical and biochemical evidences of acute hepatitis. All of them shared common working places as well as common dining and cooking facilities. Although the disease was supposed to be caused by hepatitis viruses, none of them were expressing IgM type antibody to hepatitis B core antigen (IgM anti-HBc) or hepatitis C virus (IgM anti-HCV). IgM type antibody to hepatitis A virus (IgM HAV) was detected in one patient and IgM type antibody to hepatitis E virus (anti-HEV IgM) were found in 14 patients. In conclusion, diagnosis of etiological agent of viral acute hepatitis constitutes a formidable challenge to the existing health care delivery system in developing countries as available serological and routine screening fails to find the proper etiological agent. How to cite this article: Mahtab MA, Akbar SMF, Podder DC, Saha PK, Jahan M, Begum L, Afrose T, Chowdhury F, Rahman S. An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(1):66-67.