hepatitis b case study ppt

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Patient Case Presentation

Our patient, Mr. Smith, is a 43 year old caucasian male who came in today with complaints of fatigue, anorexia, malaise, nausea, vomiting, abdominal pain, and low grade fever for the past month, and recently has been alarmed by the discoloration of his skin and sclera turning yellow. He states that his urine has become dark and stool has become clay colored.

Past Medical History:  Blood transfusion in 1992 due to major blood loss in a motor vehicle accident, arthralgia, peripheral neuropathy, hospitalization due to drug overdose in 2010. Patient states that he is fully up to date on vaccination.

Social History : Patient is an injectable drug user for the past 12 years and is currently sexually active with multiple male partners and states he uses protection “sometimes”. His current occupation is a car mechanic.

Family History: Mother: history of hyperlipidemia and diabetes father died of myocardial infarction, no other siblings or family history available .

pictured: jaundice on an individual’s eye; “Jaundice.” Assignment Point , 5 Oct. 2017, www.assignmentpoint.com/science/medical/jaundice.html.

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INTRODUCTION

The following topic will outline issues related to the management of hepatitis B through the use of cases studies that incorporate patient-specific clinical information and test results. Our approach to treatment is generally consistent with guidelines from the European Association for the Study of the Liver guidelines, Asian-Pacific Association for the Study of the Liver guidelines, and American Association for the Study of Liver Diseases Practice Guidelines and Guidance [ 1-5 ].

Additional topic reviews that address the diagnosis and management of HBV include:

● (See "Hepatitis B and pregnancy" .)

● (See "Clinical manifestations and diagnosis of hepatitis B virus infection in children and adolescents" and "Management of hepatitis B virus infection in children and adolescents" .)

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• Volume 2017, Issue
• Acute hepatitis B virus infection and severe non-immune haemolytic anaemia: a rare relationship
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• http://orcid.org/0000-0003-3985-0718 Inês Furtado 1 ,
• Diana Valadares 2 ,
• Filipe Gaio Nery 2
• 1 Internal Medicine Department , Centro Hospitalar do Porto , Porto , Portugal
• 2 Department of Intensive Care , Centro Hospitalar do Porto , Porto , Portugal
• Correspondence to Dr Inês Furtado, inessilvafurtado{at}gmail.com

The clinical presentation of acute hepatitis B virus (HBV) infection is usually related to the onset of liver failure and damage. Anaemia may occur, but it is only rarely attributed to haemolysis. The authors report about the case of a 41-year-old woman with the diagnosis of acute HBV infection and coagulopathy (without encephalopathy) who developed non-immune haemolytic anaemia. Total recovery of the analytical liver profile, coagulopathy and anaemia was achieved through treatment targeting HBV.This case shows that, although rare, non-immune haemolytic anaemia may occur in association with acute HBV infection and that HBV suppression seems to lead to progressive anaemia resolution.

• infectious diseases
• hepatitis and other gi infections
• hepatitis b
• haematology (incl blood transfusion)

https://doi.org/10.1136/bcr-2017-221763

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The association between viral hepatitis and slight haemolysis is relatively frequent. 1 However, the relationship between acute viral hepatitis and non-immune haemolytic anaemia has been rarely described, is still poorly understood and usually occurs in patients with history of erythrocyte abnormalities and/or previous chronic liver disease. 2 In cases of acute hepatitis B virus (HBV) associated with immune haemolytic anaemia—although controversial—treatment with corticosteroids has proven to resolve the haematological dysfunction. 3 4 Notwithstanding, in the setting of non-immune haemolytic anaemia associated with acute HBV infection, corticosteroids do not have a precise role. HBV suppression, with antiviral agents, together with blood support transfusion might be the preferred approach.

Case presentation

A 41-year-old previously healthy woman presented to the emergency department with asthenia, nausea and choluria developing over 1 week. She was afebrile and haemodynamically stable on admission. On physical examination, the patient did not present signs of chronic liver disease. Yet, the patient was jaundiced and had pain on upper abdominal wall palpation, with no signs of peritoneal irritation or ascites. Hepatic encephalopathy was not observed. No family history of liver disease was registered. The patient was married and personal sexual history pretrained no relevance (one sexual partner, who tested negative for previous or chronic HBV infection).

Investigations

On admission, blood analysis revealed aspartate aminotransferase (AST)=3178 U/L, alanine aminotransferase (ALT)=2889 U/L, gamma glutamyltransferase (GGT)=114 U/L, ALP=119 U/L, total bilirubin=22.9 mg/dL and direct bilirubin=19 mg/dL. Table 1 shows the chronic evolution of laboratory parameters. Renal function was normal. Coagulopathy with an INR of 1.7 was documented. Hepatitis A and C virus were negative, as was HIV-1 and −2. HBV serological profile showed positivity for HBsAg, IgM HBc, HBeAg and Anti-Hbe with negativity of Anti-HBs. The patient tested negative for: HDV, HEV, HSV-1 and −2, HZV, CMV. HBV viral load was 18×10 5  IU/mL. Abdominal ultrasound with Doppler showed no signs of portal or suprahepatic veins thrombosis and abdominal CT revealed a homogeneous liver and indirect signs of chronic liver disease were absent. The clinical scenario was interpreted as an acute HBV infection with acute liver injury (as documented by coagulopathy without hepatic encephalopathy). Furthermore, the patient presented with non-immune haemolytic anaemia (Hb=6 g/dL, normocytic and normochromic; reticulocytes=185.68×10 9 /L) characterised by low haptoglobin levels (<0.24 g/L; normal range 0.25–1.90 g/L), high lactate dehydrogenase (1163 U/L) and negative direct and indirect Coombs test—cold agglutinin titre was normal. The patient did not have a mechanic heart valve, glucose-6-phosphate dehydrogenase deficit was excluded and there was no evidence of acanthocytosis. The peripheral blood smear was normal and other red blood cell (RBC) defects were excluded (such as haemoglobin disorders, RBC enzyme dysfunction, thrombotic microangiopathies, drugs or metal toxicities, thalassemias and paroxysmal nocturnal haemolytic anaemia).

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Evolution of laboratory parameters

The patient was admitted in the intermediate care unit for treatment, follow-up and further investigation.

Treatment with entecavir (1 mg/day) and a 5-day N-acetylcystein protocol was initiated.

The patient was also started on folic acid and vitamin K (administered for 3 days).

Outcome and follow-up

During the hospital stay, bilirubin levels and INR normalised progressively. Encephalopathy was not documented throughout. Haemoglobin levels increased and stabilised. Blood transfusions were not required. The patient was discharged home with total bilirubin of 6.7 mg/dL, INR of 1.1 and Hb of 11 g/dL; she maintained treatment with entecavir. At 4 months of follow-up, the patient had the following analytic profile (see table 1 ):

AST=23 U/L, ALT=13 U/L, GGT=14 U/L, ALP=63 U/L, Hb=12,6 g/dL, INR=1, total bilirubin=0.68 mg/dL, direct bilirubin=0.18 mg/dL, HBV viral load <20 IU/mL, negative HBsAg and positive anti-HBs (156.1 UI/L) and anti-HBc.

The association of acute hepatitis—specifically hepatitis B—and non-immune haemolytic anaemia is rare. 5 It occurs usually in young patients without a significant medical history and presents with haemoglobin levels usually below 8 g/dL, as depicted in the case described above. Only a few cases of this severe association have been described so far, and there is usually an associated erythrocyte disorder. The development of anaemia generally occurs in the recovery phase of hepatitis, which was not reflected in this case—it was coincidental with liver dysfunction. 5 In the majority of described cases (6/8), treatment with corticosteroids and/or blood transfusion was required. However, in this case, supportive treatment did not play an essential role, as after initiation of treatment targeting HBV suppression, a progressive and sustained resolution of dysfunctions was observed. In all patients described in literature, the association of acute HBV and non-immune haemolytic anaemia led to a prolonged hospital stay and increased rate of complications (organ dysfunction in 7/8 patients and death in 2). 6 The pathophysiology of this association remains unknown, which may be virus related, linked to host susceptibility factors or due to liver failure itself. An accurate and prompt diagnostic work-up of anaemia is of uttermost importance to exclude other confounding aetiologies (such as RBC abnormalities), which may imply a different treatment approach. From our point of view, treating the cause (HBV infection) should equally be the mainstay treatment of associated non-immune haemolytic anaemia. In this particular case, entecavir was initiated due to high total bilirubin values (>10 mg/dL) and evidence of coagulation dysfunction (INR >1.6). 7 The association of N-acetylcystein (5-day protocol) followed current recommendations for treatment of acute liver failure irrespective of aetiology.

Learning points

Non-immune haemolytic anaemia related to acute hepatitis B virus (HBV) infection is a rare entity.

Its recognition is of major importance as it is related to increased hospital stay and vulnerability to complications.

Non-immune haemolytic anaemia treatment, in this setting, is based on HBV suppression.

• Lai JY , et al
• Raffensperger EC
• ↵ European Association for the Study of the Liver . EASL clinical practice guidelines: management of cholestatic liver diseases . J Hepatol 2009 ; 51 : 237 – 67 . doi:10.1016/j.jhep.2009.04.009 OpenUrl CrossRef PubMed Web of Science
• Vanderhoof JA ,

Contributors FGN and DV contributed to the conception or design of the work. IF was responsible for data collection, analysis and interpretation. IF drafted the initial version of the article which was critically revised by FGN and DV. FGN, DV and IF approved the final version of the article to be published.

Competing interests None declared.

Patient consent Obtained.

Provenance and peer review Not commissioned; externally peer reviewed.

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Hepatitis A and B Case Study

Jon and Laura Green are siblings sharing similar symptoms. Both have a yellow tinge to their skin and the whites of their eyes. Both have flu-like symptoms. Jon, however, has been living in Brazil while Laura has been in San Francisco. Is this a weird sibling connection? Find out what’s causing their unusual symptoms in Case #5.

Mudule 10: Hepatitis

This case is actually two separate cases that address viral hepatitis. This format was selected...

Hepatitis - Page 1

When Jon arrived home, Jon and Laura’s father arranged for both of his children to see Dr. Lyon...

Hepatitis - Page 2

Dr. Lyon ordered the following laboratory tests on both Jon and Laura Green...

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Since Jon's diagnosis was confirmed by his immune response to the presence of the virus, the physicians agreed...

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Summary of the Case

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• Vaccination
• Tools and Resources
• Clinical Overview
• Perinatal Provider Clinical Overview
• Clinical Signs and Symptoms
• Clinical Testing and Diagnosis
• Clinical Care and Treatment
• Responding to HBV Exposures in Health Care Settings
• Vaccine Administration
• Viral Hepatitis
• Hepatitis A
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• Viral Hepatitis Statistics & Surveillance

Clinical Testing and Diagnosis for Hepatitis B

• CDC published updated recommendations among adults for hepatitis B screening and testing in 2023 that are complementary to the 2022 Advisory Committee on Immunization Practices (ACIP) vaccine recommendations for hepatitis B.
• The recommendations consider a simpler and less stigmatizing implementation strategy than previous risk-based hepatitis B virus (HBV) screening recommendations among adults.

Why it’s important

More than half of people with hepatitis B are unaware of their infection status, and approximately 50%–70% of people with acute hepatitis B are asymptomatic 1 . Without testing, people with hepatitis B virus (HBV) infection can unknowingly transmit the virus to others.

Chronic HBV infection can lead to substantial morbidity and mortality but is detectable before the development of severe liver disease using reliable and inexpensive screening tests. Routine monitoring and treatment for chronic HBV infection can reduce morbidity and mortality, supporting the importance of early detection of HBV infection.

In addition, although not quantifiable, management of chronic infection through prevention efforts can prevent further transmission to others.

Read more on the rationale for the new recommendations .

For the public‎

How to make decisions on whether to test or screen.

Screening generally refers to serologic testing of asymptomatic people not known to be at increased risk for exposure to HBV.

Testing generally refers to serologic testing of people with symptoms or those who are at increased risk for exposure to HBV.

CDC recommends screening all adults aged 18 and older for hepatitis B at least once in their lifetime using a triple panel test. To ensure increased access to testing, anyone who requests HBV testing should receive it regardless of disclosure of risk. Many people might be reluctant to disclose stigmatizing risks.

CDC recommends testing all infants born to HBsAg-positive people for HBsAg and antibody to hepatitis B surface antigen (anti-HBs) seromarkers.

Pregnant people

CDC recommends HBV screening for HBsAg for all pregnant people during each pregnancy, preferably in the first trimester, regardless of vaccination status or history of testing. Pregnant people with a history of appropriately timed triple panel screening without subsequent risk for exposure to HBV (no new HBV exposures since triple panel screening) only need HBsAg screening.

People at increased risk

CDC recommends testing susceptible people periodically, regardless of age, with ongoing risk for exposures while risk for exposures persists. This includes:

• People with a history of sexually transmitted infections or multiple sex partners.
• People with history of past or current HCV infection.
• People incarcerated or formerly incarcerated in a jail, prison, or other detention setting.
• Infants born to HBsAg-positive people.
• People born in regions  with HBV infection prevalence of 2% or more.
• US-born people not vaccinated as infants whose parents were born in  geographic regions  with HBsAg prevalence of 8% or more.
• People who inject drugs or have a history of injection drug use.
• People with human immunodeficiency virus (HIV) infection.
• Men who have sex with men.
• Household contacts or former household contacts of people with known HBV infection.
• People who have shared needles with or engaged in sexual contact with people with known HBV infection.
• People on maintenance dialysis, including in-center or home hemodialysis and peritoneal dialysis.
• People with elevated liver enzymes.

Susceptible people include those who have never been infected with HBV and either did not complete a hepatitis B vaccine (HepB) series per ACIP recommendations or who are known to be vaccine nonresponders.

Recommended tests

CDC now* recommends use of the triple panel test, which includes testing for:

• Total antibody to hepatitis B core antigen (total anti-HBc)

Any periodic follow-up testing can use tests as appropriate based on the results of the triple panel.

*Prior guidance recommended a single test of HBsAg.

Other resources

• Medscape: Driving Hepatitis B Management: Universal Screening and Vaccination in Primary Care

How to interpret test results

Different serologic markers or combinations of markers are used to identify different phases of HBV infection. They determine whether a patient has acute or chronic HBV infection, is immune to HBV as a result of prior infection or vaccination, or is susceptible to infection. Markers include:

• HBsAg : HBsAg is a protein on the surface of HBV that can be detected in high levels in serum during acute or chronic HBV infection. The presence of HBsAg indicates that the person is infectious, except when it might be transiently positive within 30 days after a dose of HepB vaccine. The body normally produces antibodies to HBsAg as part of the normal immune response to infection. HBsAg is the antigen used to make HepB vaccine.
• Anti-HBs : The presence of anti-HBs is generally interpreted as indicating recovery and immunity from HBV infection. Anti-HBs also develops in a person who has been successfully vaccinated against hepatitis B. Among vaccine responders who complete a vaccine series, anti-HBs levels can decline over time; however, the majority remain immune and will mount a response when exposed to HBV.
• Anti-HBc : Anti-HBc appears at the onset of symptoms in acute hepatitis B, is a measure of both immunoglobulin M (IgM) and immunoglobulin G (IgG), and persists for life. The presence of total anti-HBc indicates previous or ongoing infection with HBV in an undefined time frame. People who have immunity to hepatitis B from a vaccine do not develop anti-HBc.
• IgM anti-HBc : IgM anti-HBc positivity indicates recent infection with HBV (within less than 6 months). Its presence indicates acute infection. IgM anti-HBc should be ordered only when acute HBV infection is a concern.
• Hepatitis B Serology Training

How to diagnose hepatitis B

The presence of the total anti-HBc antigen is needed to diagnose a patient with a hepatitis B infection. The results of the HBsAg, anti-HBs, and IgM anti-HBc tests indicate a patient’s type of hepatitis B and if they have developed immunity.

• University of Washington:  Core Concepts — HBV Screening, Testing, and Diagnosis

What to do next

CDC recommends that people who are diagnosed with hepatitis B be provided with:

• Medical evaluation (by either a primary care clinician or specialist for chronic liver diseases) including treatment and monitoring.
• Supportive care for their symptoms as needed.

For more CDC information on recommendations for testing, management, and treatment of hepatitis B, see Hepatitis B Clinical Care & Treatment .

Reporting cases

The National Notifiable Diseases Surveillance System (NNDSS) lists acute, chronic, and perinatal hepatitis B as nationally notifiable conditions.

You should report cases of suspected health care-associated HBV infection to state and local public health authorities for prompt investigation and response.

When you report a case, you will need an event code corresponding to the hepatitis B condition. You can reclassify cases if needed, as long as the changes occur before surveillance data are finalized each year.

National event codes:

• Acute hepatitis B: 10100
• Perinatal hepatitis B : 10104
• Chronic hepatitis B: 10105

In 2024, The Council of State and Territorial Epidemiologists updated the surveillance case definitions for acute and chronic hepatitis B (HBV). These definitions are used to determine how to classify and report cases to the CDC. Surveillance data is in turn used to monitor trends in disease incidence, understand the burden of hepatitis B in the community, determine risk behaviors or exposures, identify outbreaks, and assess opportunities for prevention. For the most current guidance, see: Viral Hepatitis Surveillance and Case Management Guidance for State, Territorial, and Local Health Departments

• University of Washington Infectious Diseases & Assessment (IDEA) program – HBV Screening, Testing, and Diagnosis
• Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations — United States, 2023
• Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices | MMWR | CDC
• Kodani M, Schillie SF. Chapter 4: Hepatitis B. In: Roush S, Baldy LM, Kirkconnell Hall MA, eds. Manual for the Surveillance of Vaccine-Preventable Diseases, 2020 .
• * IgM anti-HBc also might be positive in persons with chronic infection during severe HBV infection flares or reactivation.
• † Immune if anti-HBs concentration is >10 mIU/mL after vaccine series completion.
• ‡ Anti-HBs concentrations might wane over time among vaccine responders. People with a documented, complete HepB vaccine series typically do not need to be revaccinated, except for special populations like patients on  hemodialysis or health care personnel .

Hepatitis B

Hepatitis B is a vaccine-preventable liver infection caused by the hepatitis B virus (HBV). HBV information for both the public and health professionals.

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• Case Report
• Open access
• Published: 27 May 2024

A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient

• Wei Fu 1 , 2   na1 ,
• Zi Wei Deng 3   na1 ,
• Pei Wang 1 ,
• Zhen Wang Zhu 1 ,
• Zhi Bing Xie 1 ,
• Yong Zhong Li 1 &
• Hong Ying Yu 1  

BMC Infectious Diseases volume  24 , Article number:  533 ( 2024 ) Cite this article

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Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates.

Case presentation

The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management.

Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Peer Review reports

HIV infection remains a significant global public health concern, with a cumulative death toll of 40 million individuals [ 1 ]. In 2021 alone, there were 650,000 deaths worldwide attributed to AIDS-related causes. As of the end of 2021, approximately 38 million individuals were living with HIV, and there were 1.5 million new HIV infections reported annually on a global scale [ 2 ]. Co-infection with HBV and HIV is prevalent due to their similar transmission routes, affecting around 8% of HIV-infected individuals worldwide who also have chronic HBV infection [ 3 ]. Compared to those with HBV infection alone, individuals co-infected with HIV/HBV exhibit higher HBV DNA levels and a greater risk of reactivation [ 4 ]. Opportunistic infections, such as Pneumocystis jirovecii pneumonia, Toxoplasma encephalitis, cytomegalovirus retinitis, cryptococcal meningitis (CM), tuberculosis, disseminated Mycobacterium avium complex disease, pneumococcal pneumonia, Kaposi’s sarcoma, and central nervous system lymphoma, are commonly observed due to HIV-induced immunodeficiency [ 5 ]. Tuberculosis not only contributes to the overall mortality rate in HIV-infected individuals but also leads to a rise in the number of drug-resistant tuberculosis cases and transmission of drug-resistant strains. Disseminated cryptococcal infection is a severe opportunistic infection in AIDS patients [ 6 ], and compared to other opportunistic infections, there is a higher incidence of IRIS in patients with cryptococcal infection following antiviral and antifungal therapy [ 7 ]. This article presents a rare case of an HIV/HBV co-infected patient who presented with MDR-PTB and discontinued all medications during the initial treatment for HIV, HBV, and tuberculosis. During the subsequent re-anti-HBV/HIV treatment, the patient experienced two episodes of IRIS associated with cryptococcal infection. One episode was classified as “unmasking” IRIS, where previously subclinical cryptococcal infection became apparent with immune improvement. The other episode was categorized as “paradoxical” IRIS, characterized by the worsening of pre-existing cryptococcal infection despite immune restoration [ 8 ]. Fortunately, both episodes were effectively treated.

A 50-year-old male patient, who is self-employed, presented to our hospital in January 2022 with a chief complaint of a persistent cough for the past 2 months, without significant shortness of breath, palpitations, or fever. His medical history revealed a previous hepatitis B infection, which resulted in hepatic failure 10 years ago. Additionally, he was diagnosed with HIV infection. However, he ceased taking antiviral treatment with the medications provided free of charge by the Chinese government for a period of three years. During this hospital visit, his CD4 + T-cell count was found to be 26/μL (normal range: 500–1612/μL), HIV-1 RNA was 1.1 × 10 5 copies/ml, and HBV-DNA was negative. Chest computed tomography (CT) scan revealed nodular and patchy lung lesions (Fig.  1 ). The BALF shows positive acid-fast staining. Further assessment of the BALF using XpertMTB/RIF PCR revealed resistance to rifampicin, and the tuberculosis drug susceptibility test of the BALF (liquid culture, medium MGIT 960) indicated resistance to rifampicin, isoniazid, and streptomycin. Considering the World Health Organization (WHO) guidelines for drug-resistant tuberculosis, the patient’s drug susceptibility results, and the co-infection of HIV and HBV, an individualized treatment plan was tailored for him. The treatment plan included BIC/TAF/FTC (50 mg/25 mg/200 mg per day) for HBV and HIV antiviral therapy, as well as linezolid (0.6 g/day), cycloserine (0.5 g/day), moxifloxacin (0.4 g/day), pyrazinamide (1.5 g/day), and ethambutol (0.75 g/day) for anti-tuberculosis treatment, along with supportive care.

The patient’s pulmonary CT scan shows patchy and nodular lesions accompanied by a small amount of pleural effusion, later confirmed to be MDR-PTB

Unfortunately, after 3 months of follow-up, the patient discontinued all medications due to inaccessibility of the drugs. He returned to our hospital (Nov 12, 2022, day 0) after discontinuing medication for six months, with a complaint of poor appetite for the past 10 days. Elevated liver enzymes were observed, with an alanine aminotransferase level of 295 IU/L (normal range: 0–40 IU/L) and a total bilirubin(TBIL) level of 1.8 mg/dL (normal range: 0–1 mg/dL). His HBV viral load increased to 5.5 × 10 9 copies/ml. Considering the liver impairment, elevated HBV-DNA and the incomplete anti-tuberculosis treatment regimen (Fig.  2 A), we discontinued pyrazinamide and initiated treatment with linezolid, cycloserine, levofloxacin, and ethambutol for anti-tuberculosis therapy, along with BIC/TAF/FTC for HIV and HBV antiviral treatment. Additionally, enhanced liver protection and supportive management were provided, involving hepatoprotective effects of medications such as glutathione, magnesium isoglycyrrhizinate, and bicyclol. However, the patient’s TBIL levels continued to rise progressively, reaching 4.4 mg/dL on day 10 (Fig.  3 B). Suspecting drug-related factors, we discontinued all anti-tuberculosis medications while maintaining BIC/TAF/FTC for antiviral therapy, the patient’s TBIL levels continued to rise persistently. We ruled out other viral hepatitis and found no significant evidence of obstructive lesions on magnetic resonance cholangiopancreatography. Starting from the day 19, due to the patient’s elevated TBIL levels of 12.5 mg/dL, a decrease in prothrombin activity (PTA) to 52% (Fig.  3 D), and the emergence of evident symptoms such as abdominal distension and poor appetite, we initiated aggressive treatment methods. Unfortunately, on day 38, his hemoglobin level dropped to 65 g/L (normal range: 120–170 g/L, Fig.  3 A), and his platelet count decreased to 23 × 10 9 /L (normal range: 125–300 × 10 9 /L, Fig.  3 C). Based on a score of 7 on the Naranjo Scale, it was highly suspected that “Linezolid” was the cause of these hematological abnormalities. Therefore, we had to discontinue Linezolid for the anti-tuberculosis treatment. Subsequently, on day 50, the patient developed recurrent fever, a follow-up chest CT scan revealed enlarged nodules in the lungs (Fig.  2 B). The patient also reported mild dizziness and a worsening cough. On day 61, the previous blood culture results reported the growth of Cryptococcus. A lumbar puncture was performed on the same day, and the cerebrospinal fluid (CSF) opening pressure was measured at 130 mmH 2 O. India ink staining of the CSF showed typical encapsulated yeast cells suggestive of Cryptococcus. Other CSF results indicated mild leukocytosis and mildly elevated protein levels, while chloride and glucose levels were within normal limits. Subsequently, the patient received a fungal treatment regimen consisting of liposomal amphotericin B (3 mg/kg·d −1 ) in combination with fluconazole(600 mg/d). After 5 days of antifungal therapy, the patient’s fever symptoms were well controlled. Despite experiencing bone marrow suppression, including thrombocytopenia and worsening anemia, during this period, proactive symptom management, such as the use of erythropoietin, granulocyte colony-stimulating factor, and thrombopoietin, along with high-calorie dietary management, even reducing the dosage of liposomal amphotericin B to 2 mg/kg/day for 10 days at the peak of severity, successfully controlled the bone marrow suppression. However, within the following week, the patient experienced fever again, accompanied by a worsened cough, increased sputum production, and dyspnea. Nevertheless, the bilirubin levels did not show a significant increase. On day 78 the patient’s lung CT revealed patchy infiltrates and an increased amount of pleural effusion (Fig.  2 C). The CD4 + T-cell count was 89/μL (normal range: 500–700/μL), indicating a significant improvement in immune function compared to the previous stage, and C-reactive protein was significantly elevated, reflecting the inflammatory state, other inflammatory markers such as IL-6 and γ-IFN were also significantly elevated. On day 84, Considering the possibility of IRIS, the patient began taking methylprednisolone 30 mg once a day as part of an effort to control his excessive inflammation. Following the administration of methylprednisolone, the man experienced an immediate improvement in his fever. Additionally, symptoms such as cough, sputum production, dyspnea, and poor appetite gradually subsided over time. A follow-up lung CT showed significant improvement, indicating a positive response to the treatment. After 28 days of treatment with liposomal amphotericin B in combination with fluconazole, liposomal amphotericin B was discontinued, and the patient continued with fluconazole to consolidate the antifungal therapy for Cryptococcus. Considering the patient’s ongoing immunodeficiency, the dosage of methylprednisolone was gradually reduced by 4 mg every week. After improvement in liver function, the patient’s anti-tuberculosis treatment regimen was adjusted to include bedaquiline, contezolid, cycloserine, moxifloxacin, and ethambutol. The patient’s condition was well controlled, and a follow-up lung CT on day 117 indicated a significant improvement in lung lesions (Fig.  2 D).

Upon second hospitalization admission ( A ), nodular lesions were already present in the lungs, and their size gradually increased after the initiation of ART ( B , C ). Notably, the lung lesions became more pronounced following the commencement of anti-cryptococcal therapy, coinciding with the occurrence of pleural effusion ( C ). However, with the continuation of antifungal treatment and the addition of glucocorticoids, there was a significant absorption and reduction of both the pleural effusion and pulmonary nodules ( D )

During the patient's second hospitalization, as the anti-tuberculosis treatment progressed and liver failure developed, the patient’s HGB levels gradually decreased ( A ), while TBIL levels increased ( B ). Additionally, there was a gradual decrease in PLT count ( C ) and a reduction in prothrombin activity (PTA) ( D ), indicating impaired clotting function. Moreover, myelosuppression was observed during the anti-cryptococcal treatment ( C )

People living with HIV/AIDS are susceptible to various opportunistic infections, which pose the greatest threat to their survival [ 5 ]. Pulmonary tuberculosis and disseminated cryptococcosis remain opportunistic infections with high mortality rates among AIDS patients [ 9 , 10 ]. These infections occurring on the basis of liver failure not only increase diagnostic difficulty but also present challenges in treatment. Furthermore, as the patient’s immune function and liver function recover, the occurrence of IRIS seems inevitable.

HIV and HBV co-infected patients are at a higher risk of HBV reactivation following the discontinuation of antiviral drugs

In this case, the patient presented with both HIV and HBV infections. Although the HBV DNA test was negative upon admission. However, due to the patient’s self-discontinuation of antiretroviral therapy (ART), HBV virologic and immunologic reactivation occurred six months later, leading to a rapid increase in viral load and subsequent hepatic failure. Charles Hannoun et al. also reported similar cases in 2001, where two HIV-infected patients with positive HBsAg experienced HBV reactivation and a rapid increase in HBV DNA levels after discontinuing antiretroviral and antiviral therapy, ultimately resulting in severe liver failure [ 11 ]. The European AIDS Clinical Society (EACS) also emphasize that abrupt discontinuation of antiviral therapy in patients co-infected with HBV and HIV can trigger HBV reactivation, which, although rare, can potentially result in liver failure [ 12 ].

Diagnosing disseminated Cryptococcus becomes more challenging in AIDS patients with liver failure, and the selection of antifungal medications is significantly restricted

In HIV-infected individuals, cryptococcal disease typically manifests as subacute meningitis or meningoencephalitis, often accompanied by fever, headache, and neck stiffness. The onset of symptoms usually occurs approximately two weeks after infection, with typical signs and symptoms including meningeal signs such as neck stiffness and photophobia. Some patients may also experience encephalopathy symptoms like somnolence, mental changes, personality changes, and memory loss, which are often associated with increased intracranial pressure (ICP) [ 13 ]. The presentation of cryptococcal disease in this patient was atypical, as there were no prominent symptoms such as high fever or rigors, nor were there any signs of increased ICP such as somnolence, headache, or vomiting. The presence of pre-existing pulmonary tuberculosis further complicated the early diagnosis, potentially leading to the clinical oversight of recognizing the presence of cryptococcus. In addition to the diagnostic challenges, treating a patient with underlying liver disease, multidrug-resistant tuberculosis, and concurrent cryptococcal infection poses significant challenges. It requires considering both the hepatotoxicity of antifungal agents and potential drug interactions. EACS and global guideline for the diagnosis and management of cryptococcosis suggest that liposomal amphotericin B (3 mg/kg·d −1 ) in combination with flucytosine (100 mg/kg·d −1 ) or fluconazole (800 mg/d) is the preferred induction therapy for CM for 14 days [ 12 , 14 ]. Flucytosine has hepatotoxicity and myelosuppressive effects, and it is contraindicated in patients with severe liver dysfunction. The antiviral drug bictegravir is a substrate for hepatic metabolism by CYP3A and UGT1A1 enzymes [ 15 ], while fluconazole inhibits hepatic enzymes CYP3A4 and CYP2C9 [ 16 ]. Due to the patient's liver failure and bone marrow suppression, we reduced the dosage of liposomal amphotericin B and fluconazole during the induction period. Considering the hepatotoxicity of fluconazole and its interaction with bictegravir, we decreased the dosage of fluconazole to 600 mg/d, while extending the duration of induction therapy to 28 days.

During re-antiviral treatment, maintaining vigilance for the development of IRIS remains crucial

IRIS refers to a series of inflammatory diseases that occur in HIV-infected individuals after initiating ART. It is associated with the paradoxical worsening of pre-existing infections, which may have been previously diagnosed and treated or may have been subclinical but become apparent due to the host regaining the ability to mount an inflammatory response. Currently, there is no universally accepted definition of IRIS. However, the following conditions are generally considered necessary for diagnosing IRIS: worsening of a diagnosed or previously unrecognized pre-existing infection with immune improvement (referred to as “paradoxical” IRIS) or the unmasking of a previously subclinical infection (referred to as “unmasking” IRIS) [ 8 ]. It is estimated that 10% to 30% of HIV-infected individuals with CM will develop IRIS after initiating or restarting effective ART [ 7 , 17 ]. In the guidelines of the WHO and EACS, it is recommended to delay the initiation of antiviral treatment for patients with CM for a minimum of 4 weeks to reduce the incidence of IRIS. Since we accurately identified the presence of multidrug-resistant pulmonary tuberculosis in the patient during the early stage, we promptly initiated antiretroviral and anti-hepatitis B virus treatment during the second hospitalization. However, subsequent treatment revealed that the patient experienced at least two episodes of IRIS. The first episode was classified as “unmasking” IRIS, as supported by the enlargement of pulmonary nodules observed on the chest CT scan following the initiation of ART (Fig.  2 A). Considering the morphological changes of the nodules on the chest CT before antifungal therapy, the subsequent emergence of disseminated cryptococcal infection, and the subsequent reduction in the size of the lung nodules after antifungal treatment, although there is no definitive microbiological evidence, we believe that the initial enlargement of the lung nodules was caused by cryptococcal pneumonia. As ART treatment progressed, the patient experienced disseminated cryptococcosis involving the blood and central nervous system, representing the first episode. Following the initiation of antifungal therapy for cryptococcosis, the patient encountered a second episode characterized by fever and worsening pulmonary lesions. Given the upward trend in CD4 + T-cell count, we attributed this to the second episode of IRIS, the “paradoxical” type. The patient exhibited a prompt response to low-dose corticosteroids, further supporting our hypothesis. Additionally, the occurrence of cryptococcal IRIS in the lungs, rather than the central nervous system, is relatively uncommon among HIV patients [ 17 ].

Conclusions

From the initial case of AIDS combined with chronic hepatitis B, through the diagnosis and treatment of multidrug-resistant tuberculosis, the development of liver failure and disseminated cryptococcosis, and ultimately the concurrent occurrence of IRIS, the entire process was tortuous but ultimately resulted in a good outcome (Fig.  4 ). Treatment challenges arose due to drug interactions, myelosuppression, and the need to manage both infectious and inflammatory conditions. Despite these hurdles, a tailored treatment regimen involving antifungal and antiretroviral therapies, along with corticosteroids, led to significant clinical improvement. While CM is relatively common among immunocompromised individuals, especially those with acquired immunodeficiency syndrome (AIDS) [ 13 ], reports of disseminated cryptococcal infection on the background of AIDS complicated with liver failure are extremely rare, with a very high mortality rate.

A brief timeline of the patient's medical condition progression and evolution

Through managing this patient, we have also gained valuable insights. (1) Swift and accurate diagnosis, along with timely and effective treatment, can improve prognosis, reduce mortality, and lower disability rates. Whether it's the discovery and early intervention of liver failure, the identification and treatment of disseminated cryptococcosis, or the detection and management of IRIS, all these interventions are crucially timely. They are essential for the successful treatment of such complex and critically ill patients.

(2) Patients who exhibit significant drug reactions, reducing the dosage of relevant medications and prolonging the treatment duration can improve treatment success rates with fewer side effects. In this case, the dosages of liposomal amphotericin B and fluconazole are lower than the recommended dosages by the World Health Organization and EACS guidelines. Fortunately, after 28 days of induction therapy, repeat CSF cultures showed negative results for Cryptococcus, and the improvement of related symptoms also indicates that the patient has achieved satisfactory treatment outcomes. (3) When cryptococcal infection in the bloodstream or lungs is detected, prompt lumbar puncture should be performed to screen for central nervous system cryptococcal infection. Despite the absence of neurological symptoms, the presence of Cryptococcus neoformans in the cerebrospinal fluid detected through lumbar puncture suggests the possibility of subclinical or latent CM, especially in late-stage HIV-infected patients.

We also encountered several challenges and identified certain issues that deserve attention. Limitations: (1) The withdrawal of antiviral drugs is a critical factor in the occurrence and progression of subsequent diseases in patients. Improved medical education is needed to raise awareness and prevent catastrophic consequences. (2) Prior to re-initiating antiviral therapy, a thorough evaluation of possible infections in the patient is necessary. Caution should be exercised, particularly in the case of diseases prone to IRIS, such as cryptococcal infection. (3) There is limited evidence on the use of reduced fluconazole dosage (600 mg daily) during antifungal therapy, and the potential interactions between daily fluconazole (600 mg) and the antiviral drug bictegravir and other tuberculosis medications have not been extensively studied. (4) Further observation is needed to assess the impact of early-stage limitations in the selection of anti-tuberculosis drugs on the treatment outcome of tuberculosis in this patient, considering the presence of liver failure.

In conclusion, managing opportunistic infections in HIV patients remains a complex and challenging task, particularly when multiple opportunistic infections are compounded by underlying liver failure. Further research efforts are needed in this area.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

Hepatitis B virus

Acquired immunodeficiency virus disease

Immune reconstitution inflammatory syndrome

Human immunodeficiency virus

Multi-drug resistant pulmonary tuberculosis

Bronchoalveolar lavage fluid

Bictegravir/tenofovir alafenamide/emtricitabine

Cryptococcal meningitis

World Health Organization

Computed tomography

Total bilirubin

Cerebrospinal fluid

European AIDS Clinical Society

Intracranial pressure

Antiretroviral therapy

Prothrombin activity

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Acknowledgements

We express our sincere gratitude for the unwavering trust bestowed upon our medical team by the patient throughout the entire treatment process.

This work was supported by the Scientific Research Project of Hunan Public Health Alliance with the approval No. ky2022-002.

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Wei Fu and Zi Wei Deng contributed equally to this work.

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Center for Infectious Diseases, Hunan University of Medicine General Hospital, Huaihua, Hunan, China

Wei Fu, Pei Wang, Zhen Wang Zhu, Ye Pu, Zhi Bing Xie, Yong Zhong Li & Hong Ying Yu

Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, XinXiang, Henan, China

Department of Clinical Pharmacy, Hunan University of Medicine General Hospital, Huaihua, Hunan, China

Zi Wei Deng

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WF and ZWD integrated the data and wrote the manuscript, YHY contributed the revision of the manuscript, PW and YP provided necessary assistance and provided key suggestions, ZWZ, YZL and ZBX contributed data acquisition and interpretation for etiological diagnosis. All authors reviewed and approved the final manuscript.

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Correspondence to Hong Ying Yu .

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Fu, W., Deng, Z.W., Wang, P. et al. A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient. BMC Infect Dis 24 , 533 (2024). https://doi.org/10.1186/s12879-024-09431-9

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Arbutus Biopharma to Present Key Findings at EASL Congress 2024

WARMINSTER, PA — Arbutus Biopharma Corporation announced that two of its research abstracts have been accepted for presentation at the European Association for the Study of the Liver (EASL) Congress 2024. The event will take place from June 5 to 8, 2024, in Milan, Italy.

The first abstract, number 2389, will be presented as a poster by Prof. Man-Fung Yuen. Titled “Imdusiran (AB-729) administered every 8 weeks in combination with 24 weeks of pegylated interferon alfa-2a in virally suppressed, HBeAg-negative subjects with chronic HBV infection leads to HBsAg loss in some subjects at end of IFN treatment,” this study shows promising results. At the end of treatment, 28% of subjects receiving imdusiran plus 24 weeks of interferon showed a reduction in hepatitis B surface antigen (HBsAg). However, no subjects receiving shorter treatments showed similar outcomes. This data suggests that longer therapy durations may be critical for achieving significant viral suppression. Further study results and additional data will be shared during the congress.

The second abstract, number 505, will be delivered as an oral presentation by Prof. Kosh Agarwal. The study, titled “Imdusiran (AB-729) administered every 8 weeks for 24 weeks followed by the immunotherapeutic VTP-300 maintains lower HBV surface antigen levels in NA-suppressed CHB subjects than 24 weeks of imdusiran alone,” focuses on a combined treatment regimen. Subjects who received both imdusiran and VTP-300 maintained lower HBsAg levels compared to those treated with imdusiran alone. Impressively, many subjects on the combined treatment were able to stop their nucleos(t)ide analog (NA) therapy and remained off it. This finding could mark a significant step forward in managing chronic hepatitis B (CHB).

Revolutionizing Chronic Hepatitis B Treatment

These presentations are more than just academic exercises. They highlight potential advancements in the treatment of chronic hepatitis B, a persistent and often debilitating disease. Chronic hepatitis B impacts millions worldwide, leading to severe liver complications if untreated.

Arbutus Biopharma’s research offers a glimpse into the future of hepatitis B treatment. Both studies focus on imdusiran, an investigational drug showing promise in reducing the virus’s presence in the body. By potentially enabling patients to discontinue long-term antiviral therapies, these findings could improve quality of life and reduce treatment costs.

For the pharmaceutical industry, these developments could drive new research directions and investment opportunities. If successful, the treatments could reshape how chronic hepatitis B is managed globally.

As the EASL Congress approaches, the medical community will closely watch Arbutus Biopharma’s presentations. The outcomes could influence future treatment protocols and offer hope to millions battling chronic hepatitis B.

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Fatal Post COVID mRNA-Vaccine Associated Cerebral Ischemia

Nadia mcmillan.

1 Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA

Harry J. Rosenberg

2 Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA

Matthew P. Anderson

3 Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA

Kathryn Stephenson

Corey r. fehnel.

Venous thromboses have been linked to several COVID-19 vaccines, but there is limited information on the Moderna vaccine’s effect on the risk of arterial thrombosis. Here we describe a case of post-Moderna COVID-19 vaccination arterial infarct with vaccine-associated diffuse cortical edema that was complicated by refractory intracranial hypertension.

Case Summary

24 hrs after receiving her first dose of the Moderna COVID-19 vaccine, a 30-year-old female developed severe headache. Three weeks later she was admitted with subacute headache and confusion. Imaging initially showed scattered cortical thrombosis with an elevated opening pressure on lumbar puncture. An external ventricular drain was placed, but she continued to have elevated intracranial pressure. Ultimately, she required a hemicraniectomy, but intractable cerebral edema resulted in her death. Pathology was consistent with thrombosis and associated inflammatory response.

Though correlational, her medical team surmised that the mRNA vaccine may have contributed to this presentation. The side effects of COVID-19 infection and vaccination are still incompletely understood. Though complications are rare, clinicians should be aware of presentations like this one.

Family consent to publish this case was obtained both verbally and written. The conversation was documented in our institutions electronic medical record.

Case Presentation

A 30-year-old woman with prior asymptomatic COVID-19 infection three months earlier developed severe, throbbing bi-frontal headache 24-hours after first dose of the mRNA COVID-19 vaccine (Moderna). The headaches were atypical, prompting evaluation by her primary care provider and three emergency department visits where vital signs and neurologic examinations were normal. She had a history of class I obesity, but no prior headaches. Symptomatic management for presumed migraine did not alleviate the headaches. Three weeks after vaccination, she developed blurred vision and confusion, prompting further emergency evaluation. At this time, imaging of her head was first obtained. Computed tomography (CT) of her head was normal, and lumbar puncture revealed an opening pressure of 27cmH20 with lymphocytosis ( Table 1 ). A brain MRI with contrast showed multiple punctate areas of diffusion restriction in occipital regions but no evidence of large arterial or venous occlusion. There was no evidence of abnormal enhancement ( Figure 1A ). Upon transfer to this hospital, the patient endorsed a bifrontal headache with photophobia. Complete blood count was without leukocytosis, extended chemistry panel, and toxicology screening were normal. Repeat lumbar puncture revealed an opening pressure of 50mmH20 and rising lymphocytic pleocytosis ( Table 1 ). Broad spectrum antimicrobial coverage was started. Her mental status acutely worsened later that evening, and she was noted to have a new left hemiparesis. Vitals were notable for fever and tachycardia. CT/CT angiography with perfusion were without major vessel occlusion and no evidence for low pressure/post-LP herniation. Labs were notable for mild thrombocytopenia (119 K/u) and elevated D-dimer (3457) with a negative platelet factor 4 antibody (PF4). Given elevated ICP, hyperosmolar therapy was given and an external ventricular drain (EVD) was placed. Studies to evaluate for infectious etiology, primary angiitis of the CNS, secondary CNS vasculitis, or one of its mimics were sent ( Table 1 ). CSF cultures and PCR testing returned negative ( Table 1 ), and she was started on high dose intravenous methylprednisolone followed by intravenous immune globulin. Intracranial pressure remained refractory to maximal medical management including deep sedation, paralysis and hypothermia, prompting a right decompressive hemicraniectomy. Subsequent brain MRI showed extensive bilateral subacute infarcts without evidence of infection or cerebral venous sinus thrombosis (CVST) ( Figure 1B ). Upper extremity and bilateral lower extremity ultrasounds to evaluate for systemic thromboses were negative for deep vein thrombosis. The patient expired from refractory cerebral edema. Brain autopsy showed leptomeningeal, perivascular and focal intraparenchymal infiltrates of CD8 and CD4-positive T-cells in association with intravascular thrombi ( Figure 1C and D ). There was no CVST or demyelination. Fungal and bacterial stains were negative.

Lab Test Analysis.

CSF Analysis: TNC indicates Total Nucleated Cells; RBC, Red Blood Cells; LP lumbar puncture; EVD External Ventricular Drain; OP opening pressure; Ab antibody; Ig immune globulin; Arborvirus panel includes: IgG and IgM for Calif Virus (LaCrosse), East Equine Encephalitis (EEE), St. Louis Encephalitis, West Equine Encephalitis; EBV Epstein Barr virus; PCR polymerase chain reaction; Meningitis Encephalitis Panel includes: Escherichia Coli, Haemophilus Influenzae, Listeria monocytogenes, Neisseria Meningitides, Streptococcus Agalactiae, Streptococcus Pneumoniae, Cytomegalovirus, Enterovirus, Herpes Simplex Virus 1, Herpes Simplex Virus 2, Human Herpesvirus 6, Human Parechovirus, Varicella Zoster Virus, Cryptococcus neoformans and gattii. HSV herpes simplex virus; CMV cytomegalovirus; MOG Myelin Oligodendrocyte Glycoprotein antibodies are associated with acute disseminated encephalomyelitis (ADEM). Serum Analysis: ANA antinuclear antibody, ANCA antineutrophil cytoplasmic antibod, C3 complement component 3, C4 complement component 4, CRP c-reactive protein, HBsAg hepatitis B surface antigen, HbsAb antibody to hepatitis b surface antigen, HbcAb hepatitis b core antibody, HCV Ab hepatitis c virus antibody, EBV epstein barr virus, HIV human immunodeficiency virus, VZV varicella zoster virus, dsDNA anti double stranded DNA antibody, anti-RNP anti-ribonucleoprotein antibody.

Imaging A : Representative axial MRI brain images on day of admission. B : Eight days after admission, left panels represent diffusion weighted (DWI) sequences and right apparent diffusion coefficient (ADC) images. C. Hematoxylin and eosin ( H&E)-stained section of leptomeningeal vessel with lymphocytic cuff D. H&E-stained section of leptomeningeal blood vessel with intraluminal organizing thrombus. Scale bars =100um.

The diffuse endothelial damage and vessel wall inflammation seen on pathology suggested an underlying pro-thrombotic state and T cell inflammatory response. A number of case reports have demonstrated cerebral venous sinus thrombosis and systemic thromboses post-COVID-19 vaccination. 1 - 3 While this patient did not have CVST, CVST has been previously associated with COVID-19 vaccination 1 - 3 where thrombocytopenia is frequent and termed ‘vaccine-induced prothrombotic immune thrombocytopenia’ (VIPIT). VIPIT is similar to heparin-induced thrombocytopenia (HIT) with antibodies directed against platelet factor 4 (PF4). 1 , 4 , 5 Mild thrombocytopenia occurred in this case, but PF4 antibodies were negative. The arterial infarct in this case is likely related to a pro-thrombotic state but with a different underlying mechanism to that seen in venous thrombosis. Due to the large volume of infarction, the patient was not started on anticoagulation after extensive discussion of the risks vs potential benefit.

In summary, administration of COVID-19 vaccine was considered a possible cause of the extensive multifocal arterial thromboses with associated inflammatory response and elevated intracranial pressure given the temporal association. The mechanism for initial elevation in intracranial pressure is not known but may relate to cerebral autoregulatory changes in the setting of cortical microvascular thrombosis. Review of the medical literature and vaccine adverse event reporting system (VAERS) produced no similar cases, suggesting the condition is extremely rare, but a potentially fatal vaccine-associated event.

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Nadia McMillan https://orcid.org/0000-0003-0423-0471

Corey R. Fehnel https://orcid.org/0000-0003-1726-5809