Association between adverse outcomes of hepatitis A and acetaminophen use: A population-based cohort study.

BACKGROUND: Acetaminophen (APAP) may cause acute liver injury with therapeutic doses in high-risk conditions such as chronic alcohol consumption or malnutrition. In acute hepatitis A (AHA), however, the safety of APAP has not been fully established. This study examined the potential association between APAP use and clinical outcomes of AHA in a nationwide and hospital-based cohort. METHODS: Adult patients with AHA were identified from claims data of South Korean national healthcare insurance between 2008 and 2016 (n = 43,500). Logistic regression models were used to compare the risk of adverse outcomes (renal replacement therapy, hepatic encephalopathy and/or brain edema, mechanical ventilation, and liver transplantation) in patients exposed to APAP against control and patients exposed to NSAIDs. A propensity score (PS)-matched hospital-based AHA cohort (n = 146) was assessed for biochemical profiles after exposure to APAP or NSAIDs. RESULTS: AHA patients were exposed to APAP or NSAIDs in 26.4% and 11.5% of cases, respectively. Compared to NSAID treatment, APAP exposure was associated with a higher incidence of hospitalization (98.8% vs. 92.4%; p < 0.0001). APAP exposure was independently associated with increased adverse outcomes (odds ratio [OR] = 5.66, p < 0.0001 against control; OR =1.67, p = 0.0015 against NSAIDs). PS-matched hospital cohort showed higher peak serum bilirubin levels (7.0 vs. 5.3 mg/dL; p = 0.03) and a longer time to recovery of jaundice after APAP use than with NSAID use. CONCLUSION: APAP exposure was associated with increased adverse outcomes in a nationwide AHA cohort.

Factors associated with incomplete vaccination and negative antibody test results for measles, mumps, and hepatitis A among children followed in the MINA-BRAZIL cohort.

Vaccination coverage has been dropping in Brazil and other countries. In addition, immune responses after vaccination may not be homogeneous, varying according to sociodemographic and clinical factors. Understanding the determinants of incomplete vaccination and negative antibody test results may contribute to the development of strategies to improve vaccination effectiveness. In this study, we aimed to investigate the frequency of vaccine adherence, factors associated with incomplete vaccination for measles, mumps, rubella (MMR) and hepatitis A, and factors associated with the seronegative test results for measles, mumps and hepatitis A at 2 years of age. This was a population-based cohort that addressed health conditions and mother/infant nutrition in Cruzeiro do Sul city, Brazil. Vaccination data were obtained from official certificates of immunization. The children underwent blood collection at the two-year-old follow-up visit; the samples were analyzed using commercially available kits to measure seropositivity for measles, mumps, and hepatitis A. We used modified Poisson regression models adjusted for covariates to identify factors associated with incomplete vaccination and negative serology after vaccination. Out of the 825 children included in the study, adherence to the vaccine was 90.6% for MMR, 76.7% for the MMRV (MMR + varicella), and 74.9% for the hepatitis A vaccine. For MMR, after the adjustment for covariates, factors associated with incomplete vaccination included: white-skinned mother; paid maternity leave; raising more than one child; lower number of antenatal consultations; and attending childcare. For hepatitis A, the factors included: white-skinned mother and not having a cohabiting partner. The factors with statistically significant association with a negative antibody test result included: receiving Bolsa Familia allowance for measles and mumps; incomplete vaccination for measles; and vitamin A deficiency for mumps. Strategies to improve the efficiency of vaccine programs are urgently needed. These include improvements in communication about vaccine safety and efficacy, and amplification of access to primary care facilities, prioritizing children exposed to the sociodemographic factors identified in this study. Additionally, sociodemographic factors and vitamin A deficiency may impact the immune responses to vaccines, leading to an increased risk of potentially severe and preventable diseases.

Immune-related adverse events in hepatitis treated with thiopurine-based immunosuppressants: A case report.

An 82-year-old man was treated with ipilimumab and nivolumab for malignant pleural mesothelioma. Although he was previously treated with prednisolone (1 mg/kg/day) for immune-related adverse event (irAE) hepatitis by a previous doctor, he still had worsening liver function and was transferred to our hospital. Blood tests and imaging findings were negative for autoimmune and infectious hepatitis, and liver biopsy results were consistent with irAE hepatitis. Steroid pulse therapy improved liver function, but tapering to prednisolone (1 mg/kg/day) again worsened his liver function. Concomitant use of mycophenolate mofetil was initiated, but no improvement in liver function was observed, therefore azathioprine, a thiopurine immunosuppressant, was administered in combination with steroids. During the course of treatment, hepatic dysfunction due to azathioprine was suspected, and the concomitant use of mercaptopurine and prednisolone was started. Afterward, the liver function improved, and the prednisolone dose was gradually reduced to 10 mg/day. This is a rare case in which a thiopurine-based immunosuppressant was effective against irAE hepatitis, therefore thiopurine-based immunosuppressants may be effective against steroid-refractory hepatitis.

Treatment and prevention of viral hepatitis in pregnancy.

Viral hepatitis in pregnancy may be caused by many types of viruses that cause systemic infection or target hepatocytes in their pathogenesis. Because viral hepatitis during pregnancy may represent acute or chronic infection or the reactivation of a prior infection, a high clinical suspicion, medical history review, and awareness of risk factors for the acquisition of infection are important management principles. The route of infection varies widely and ranges from fecal-oral transmission for the hepatitis A and E viruses to vertical transmission for hepatitis B, blood-borne transmission for hepatitis C, and sexual transmission for the herpes simplex virus. For this reason, the exposure details about travel, food preferences, drug use, and sexual contacts are important to elicit. Although routine prenatal screening is recommended for chronic viral hepatitis caused by hepatitis B and C, most other causes of viral hepatitis in pregnancy are detected in the setting of compatible signs and symptoms (fatigue, abdominal discomfort, jaundice, scleral icterus) or incidentally noted transaminitis on routine labs. Serologic testing is helpful for diagnosis with molecular testing as indicated to guide the management of hepatitis B and C. Preventive vaccines for hepatitis A and B with established safety of use in pregnancy are recommended for women who are at risk of acquisition. Postexposure prophylaxis for hepatitis A is a single dose of immunoglobulin and vaccination can be used if immunoglobulin G is not available. Antiviral therapy with tenofovir disoproxil fumarate is recommended as prophylaxis in pregnant women with active hepatitis B and an elevated viral load (>200,000 IU/mL) during the third trimester to prevent vertical transmission. The neonate exposed to hepatitis B at birth should receive immunoglobulin G and a monovalent birth dose vaccine within 12 hours, followed by completion of the 3-dosage vaccine series. The prevalence of hepatitis C in women of reproductive age has increased in the United States, and the role of antiviral therapy during pregnancy is of great interest. Cesarean delivery is not currently recommended for the sole purpose of reducing vertical transmission risk in pregnant women with viral hepatitis. Breastfeeding is recommended in women with hepatitis A, B, and C. New and promising prevention and treatment options for hepatitis B and C are under investigation. Investigators and regulatory authorities should ensure that these clinical trials for promising antivirals and vaccines are designed to include pregnant and lactating women.

Hepatitis A infections in men who have sex with men using HIV PrEP in Paris.

The current hepatitis A outbreak in Europe is largely involving men having sex with multiple male partners. The objective of the present report was to warn teams dealing against the persistent risk of viral and bacterial sexually transmitted infection (STIs) in patients receiving HIV pre-exposure prophylaxis (PrEP). We have notified and investigated three cases of acute hepatitis A virus (HAV) infection in people receiving HIV PrEP in our clinic between December 2016 and March 2017. The patients were not epidemiologically related, had no recent travel history to HAV endemic areas, reported multiple STIs during this period and had not been vaccinated against HAV. They were all identified as genotype A, strain VRD_521_2016 virus.Large-scale vaccination against viral hepatitis is recommended in men having sex with men, especially in those using PrEP, as PrEP is used by people who have high-risk sexual behaviour.

Monitoring liver macrophages using nanobodies targeting Vsig4: concanavalin A induced acute hepatitis as paradigm.

Kupffer cells (KCs) are liver resident macrophages which are important for tissue homeostasis and have been implicated in immunogenic, tolerogenic and pathogenic immune reactions depending on the insult. These cells and the biomarkers they express thus represent interesting in vivo sensors for monitoring liver inflammation. In the current study, we explored whether KCs can be monitored non-invasively using single-photon-emission computed tomography (SPECT) with (99m)Tc labeled nanobodies (Nbs) targeting selected biomarkers. Nbs targeting V-set and immunoglobulin domain-containing 4 (Vsig4) or macrophage mannose receptor (MMR) accumulated in the liver of untreated mice. The liver targeting of anti-Vsig4 Nbs, but not anti-MMR Nbs, was blunted upon depletion of macrophages, highlighting specificity of anti-Vsig4 Nbs for liver macrophage imaging. Ex vivo flow cytometry and immunohistochemistry analysis confirmed that anti-Vsig4 Nbs specifically targeted KCs but no other cell types in the liver. Upon induction of acute hepatitis using concanavalin A (ConA), down-regulation of the in vivo imaging signal obtained using anti-Vsig4 Nbs reflected reduction in KC numbers and transient modulation of Vsig4 expression on KCs. Overall, these results indicate that Nbs targeting Vsig4 as molecular imaging biomarker enable non-invasive monitoring of KCs during hepatic inflammation.

[Viral Hepatitis A over imposed on chronic hepatic damage due to tamoxifen: report of a case]. / Hepatitis viral A sobreimpuesta a injuria hepática crónica por tamoxifeno.

A case of Hepatitis A is reported in a patient prescribed tamoxifen after surgery for breast cancer and taking tamoxifen 20 mg/day for two and a half years. Documented is the indirect development of Hepatitis A and tamoxifen-induced hepatic damage.

[Health hazards to the anaesthesist]. / Zur Frage des Gesundheitsrisikos für das Anästhesiepersonal

During the past years there has been increasing concern regarding potential hazards to the anaesthetist presented by, e.g., anaesthetic agents, exposure to X-rays, virus hepatitis. Chronic exposure to inhalational anaesthetics, in particular, has been held responsible for a variety of complants and disorders. Investigations at the Technical University, Munich, have shown no appreciable difference in the sick rate between the staff of the Department of Anaesthetics and the Department of Medicine. Whereas exposure to X-radiation cannot be regarded as a health hazard provided the prescribed safety measures are adhered to, virus hepatitis still constitutes a major risk. There is also some evidence of an increased incidence of miscarriages amoung the female anaesthetic personnel. The causes are unknown. Halothane hepatitis is very rare and does not present a major risk.