Acute human parvovirus B19 infection triggers immune-mediated transient bone marrow failure syndrome, extreme direct hyperbilirubinaemia and acute hepatitis in patients with hereditary haemolytic anaemias: multicentre prospective pathophysiological study.

A total of 244 patients with hereditary haemolytic anaemias (HHA) were screened for acute symptomatic human parvovirus B19 infection (HPV-B19) in a prospective study. To assess the risks associated with HPV-B19 infection, patients were classified into Group I and Group II according to presence or absence (symptoms, signs and specific serology) of acute HPV-B19 infection respectively. In all, 131 (53·7%) patients had ß-thalassaemia, 75 (30·7%) hereditary spherocytosis (HS), 27 (11·1%) sickle cell anaemia (SCA) and 11 (4·5%) glucose-6-phosphate dehydrogenase (G6PD) deficiency. Of 33 (13·5%) patients who presented with symptomatic HPV-B19 infection, 19 (57·5%) had HS, nine (27·3%) had ß-thalassaemia and five (15·2%) had SCA. In Group I, there were significant differences in the mean white blood cell, red blood cell and platelet counts, haemoglobin concentration, total bilirubin (TB), alanine aminotransferase, aspartate aminotransferase and serum creatinine (all P < 0·001) compared to Group II. In all, 27 (81·8%) patients had arthropathy and bone marrow failure (BMF); 13 (39·4%) had acute kidney injury (AKI), more in SCA (80%); and 12 (36·4%) patients had hepatitis, more in HS (66·8%). Five (15·2%) patients with HS had BMF, AKI, nervous system involvement and extreme hyperbilirubinaemia (TB range 26·3-84·7 mg/dl). Five (15·2%) patients had haemophagocytic syndrome. Two patients with HS combined with Type-I autoimmune hepatitis presented with transient BMF. Complete recovery or stabilisation was noted at 12 months in every patient except for one patient with SCA who died during the infection. HPV-B19 must be suspected and screened in patients with HHA with typical and atypical presentations with careful follow-up.

The liver in COVID-19: prevalence, patterns, predictors, and impact on outcomes of liver test abnormalities.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century, with ≈35 million cases, and more than 1 million deaths globally. Though predominantly a lower respiratory illness, other organ injuries are well-recognized. Among these, liver injury is of major interest. OBJECTIVE: To define prevalence, pattern, predictors, and impact of liver injury among patients hospitalized with COVID-19. METHODS: Demographic, clinical, and biochemical data were collected retrospectively among patients admitted to St. Luke's University Hospital with COVID-19 between 1 March and 18 April 2020. Association of liver tests (LTs) with mortality and need for mechanical ventilation, adjusted for demographic, clinical and biochemical predictors, was examined. RESULTS: Data were available on 551 patients. Prevalence of any or ≥3 × upper limit of normal transaminase elevation on was 61.2 and 9.4% on admission, and 72.1 and 22.4% at peak. Bilirubin and alkaline phosphatase elevations were less common on admission (11.4 and 12.6%, respectively), and at peak (17.7 and 22%, respectively). All liver test (LT) elevations were consistently predicted by inflammatory markers. Hyperbilirubinemia predicted mortality on admission and at peak. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) had opposite impact on mortality with AST positively, and ALT negatively associated with mortality. Hence, besides hyperbilirubinemia, AST:ALT ratio emerged as the best marker for mortality among the LTs. CONCLUSION: LT elevations among patients presenting with COVID-19 are very common, though majority are mild. Admission and peak bilirubin ≥1 mg/dl, as well as admission and peak AST:ALT ratio were significant predictors of mortality, along with age, myocardial injury, and chronic medical illness.

A case report of glecaprevir/pibrentasvir-induced severe hyperbilirubinemia in a patient with compensated liver cirrhosis.

RATIONALE: Glecaprevir/pibrentasvir, a pan-genotypic and ribavirin-free direct acting antiviral agent regimen, has shown significant efficacy and very few serious complications. However, as the drug metabolizes in the liver, it is not recommended in patients with decompensated liver cirrhosis. Herein, we report the case of a patient with compensated liver cirrhosis who developed severe jaundice after glecaprevir/pibrentasvir medication. PATIENT CONCERNS: A 77-year-old man diagnosed with chronic hepatitis C-related compensated liver cirrhosis visited hospital due to severe jaundice after 12 weeks of glecaprevir/pibrentasvir medication. DIAGNOSES: On the laboratory work-up, the total/direct bilirubin level was markedly elevated to 21.56/11.68 from 1.81 mg/dL; the alanine aminotransferase and aspartate aminotransferase levels were within the normal range. We checked the plasma drug concentration level of glecaprevir, and 18,500 ng/mL was detected, which was more than 15 times higher than the drug concentration level verified in normal healthy adults. INTERVENTIONS: Glecaprevir/pibrentasvir was abruptly stopped and after 6 days, the drug concentration level decreased to 35 ng/mL and the serum total/direct bilirubin decreased to 7.49/4.06 mg/dL. OUTCOMES: Three months after drug cessation, the serum total bilirubin level normalized to 1.21 mg/dL and HCV RNA was not detected. LESSONS: We report what is likely the first known case of severe jaundice after medication with glecaprevir/pibrentasvir in a patient with compensated liver cirrhosis. Clinicians should bear potential hyperbilirubinemia in mind when treating chronic hepatitis C with this regimen and should monitor the patient closely during follow-up laboratory exams, especially in elderly cirrhotic patients.

Association between the UGT1A1*28 allele and hyperbilirubinemia in HIV-positive patients receiving atazanavir: a meta-analysis.

Objectives The uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1)*28 allele in HIV-positive patients receiving atazanavir (ATV) might be associated with the risk of hyperbilirubinemia. Owing to mixed and inconclusive results, a meta-analysis was conducted to systematically summarize and clarify this association.Methods Based on a comprehensive search of PubMed, Embase and Web of Science databases, studies investigating the association between UGT1A1 alleles and hyperbilirubinemia was retrieved. We evaluated the strength of this relationship using odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analysis was performed by removing each study one at a time and calculating the pooled ORs of the remaining studies to test the robustness of the meta-analysis results. The Q statistic and the I2 index statistic were used to assess heterogeneity. Publication bias was evaluated using Orwin's fail-safe N test.Results A total of six individual studies were included in this meta-analysis. A significantly increased risk of hyperbilirubinemia was observed in HIV-positive patients receiving ATV with the UGT1A1*1/*28 or UGT1A1*28/*28 genotype, and the risk was higher with the UGT1A1*28/*28 genotype than with the UGT1A1*1/*28 genotype. (UGT1A1*28/*28 versus UGT1A1*1/*28: OR = 3.69, 95%CI = 1.82-7.49; UGT1A1*1/*28 versus UGT1A1*1/*1: OR = 3.50, 95%CI = 1.35-9.08; UGT1A1*28/*28 versus UGT1A1*1/*1: OR = 10.07, 95%CI = 4.39-23.10). All of the pooled ORs were not significantly affected by the remaining studies and different modeling methods, indicating robust results.Conclusions This meta-analysis suggests that the UGT1A1*28 allele represents a biomarker for an increased risk of hyperbilirubinemia in HIV-positive patients receiving ATV.

Epstein-Barr virus-associated cholestatic hepatitis.

Epstein-Barr virus infection is common in children, usually presenting as infectious mononucleosis, including fever, tonsillitis and lymphadenopathy associated with self-resolving increase in transaminases. Cholestasis is rare in children with only a few cases reported but it was described in up to 55% of the adult population affected. We present a case of a 6-year-old boy with fever, vomiting and choluria. The physical examination showed hepatomegaly and jaundice and was otherwise unremarkable. The laboratory studies revealed increased transaminases (aspartate aminotransferase 97 U/L, alanine aminotransferase 166 U/L), hyperbilirubinaemia (total bilirubin 3.2 mg/dL, direct bilirubin 2.89 mg/dL) and increased γ-glutamyl transpeptidase (114 mg/dL). Urine urobilinogen was increased. The abdominal ultrasound showed hepatomegaly. Epstein-Barr viral capsid antibody IgM was positive and IgG was negative. Serological studies for other viruses were negative. We underline the need to consider Epstein-Barr virus in the cholestatic hepatitis differential diagnosis, in order to avoid unnecessary investigations.

Subacute fulminant hepatic failure with intermittent fever.

BACKGROUND: Viral hepatitis B accounts for over 80% of acute hepatic failures in China and the patients die mainly of its complications. A patient with hepatic failure and fever is not uncommon, whereas repeated fever is rare. METHODS: A 32-year-old female was diagnosed with subacute hepatic failure and hepatitis B viral infection because of hyperbilirubinemia, coagulopathy, hepatic encephalopathy, serum anti-HBs-positive without hepatitis B vaccination, and typical intrahepatic pathological features of chronic hepatitis B. Plasma exchange was administered twice and she awoke with hyperbilirubinemia and discontinuous fever. RESULTS: Urethritis was confirmed and medication-induced fever and/or spontaneous bacterial peritonitis (Gram-negative bacillus infection) was suspected. The patient was treated with antibiotics, steroids and a Chinese herbal medicine, matrine, for three months and she recovered. CONCLUSION: The survival rate of patients with hepatic failure might be improved with comprehensive supporting measures and appropriate, timely management of complications.

Successful plasmapheresis for extreme hyperbilirubinemia caused by acute Epstein-Barr virus.

Epstein-Barr virus (EBV) infection can be complicated by cholestatic jaundice and hemolytic anemia, although both complications rarely occur simultaneously. An 18-year-old female developed acute EBV infection complicated by cold agglutinin hemolysis and cholestasis. Corticosteroid and ursodeoxycholic acid were initiated but bilirubin peaked at 1297.47 micromol/L (75.7 mg/dL). Plasmapheresis was initiated and with the corticosteroids, resulted in resolution of extreme hyperbilirubinemia. The patient recovered rapidly, is healthy 2 years later and is neurologically intact. The early use of plasmapheresis with corticosteroids and ursodeoxycholic should be considered in EBV infections complicated by extreme hyperbilirubinemia to prevent the rare complication of adult-onset kernicterus.