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Liver Diseases: Hepatitis B

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Hepatitis B is a viral infection that affects the liver. It is transmitted through blood or bodily fluids, and can range from a mild illness lasting only a few weeks to a lifelong condition. There's a vaccine for this disease, so most people won't suffer complications, which include cirrhosis or even liver cancer. However, having as much information as possible at hand won't hurt, so prepare an informative slideshow about hepatitis B with this editable template. Its palette revolves around dark red tones, and the text included in the different sections has been generated by AI. While it's not specificaly about hepatitis B, it will give you some tips when it comes to structuring a presentation.

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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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NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Hepatitis b.

Nishant Tripathi ; Omar Y. Mousa .

Affiliations

Last Update: July 9, 2023 .

• Continuing Education Activity

Hepatitis B infection is a serious global healthcare problem. Often transmitted via body fluids like blood, semen, and vaginal secretions, the hepatitis B virus can cause liver injury. After infection with the hepatitis B virus, the majority of adults are able to clear the infection. Patients can present with acute symptomatic disease or have an asymptomatic disease that is identified during screening for the hepatitis B virus. This article focuses on identifying who is at risk of hepatitis B, and clinical evaluation and management of patients with hepatitis B by an interdisciplinary team. It also focuses on preventive measures.

• Describe the epidemiology of hepatitis B.
• Outline the common blood tests for the diagnosis of hepatitis B infection.
• Review the complications of hepatitis B infection.
• Explain the importance of collaboration and communication amongst the interdisciplinary teams to enhance the delivery of care for patients affected by hepatitis B.
• Introduction

Hepatitis B viral infection is a serious global healthcare problem. It is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). It is often transmitted via body fluids like blood, semen, and vaginal secretions. The majority (more than 95%) of immunocompetent adults infected with HBV can clear the infection spontaneously. Patients can present with acute symptomatic disease or have an asymptomatic infection that is identified during screening for HBV. The clinical manifestations of HBV infection vary in both acute and chronic diseases. During the acute infection, patients can have subclinical or anicteric hepatitis, icteric hepatitis, or less commonly fulminant hepatitis. In chronic infection, patients can have an asymptomatic carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Initial symptoms are nonspecific and may include anorexia, nausea, vomiting, abdominal pain, and jaundice. In cases of severe liver damage, patients can develop jaundice, hepatic encephalopathy, ascites, gastrointestinal bleeding secondary to esophageal varices, coagulopathy, or infections. Diagnosis is based on serologic blood tests in patients with suspected signs and symptoms and associated risk factors for viral hepatitis. This will be discussed in more detail below.

Transmission of hepatitis B involves the transfer of the virus from infected people to non-immune people in various ways. Major modes of transmission for hepatitis B are as follows:

1. Horizontal transmission: It involves the transmission of hepatitis B through sexual contact or mucosal surface contact. Unprotected sex and injection drug use are major modes of transmission in low to intermediate prevalence areas. [1]  

2. Vertical transmission: Vertical transmission involves the maternal-to-newborn perinatal transmission of the virus. [2]  It is the predominant mode of transmission in high-prevalence areas. 

Sexual contact includes unprotected intercourse (vaginal, oral, or anal) and mucosal contact involves any contact involving an infected patient’s saliva, vaginal secretion, semen, and blood.

Prevalence areas are based on the percentage of the population with hepatitis B surface antigen (HBsAg) positivity with greater than or equal to 8% representing high prevalence areas, 2-7% representing low to intermediate prevalence areas, and less than 2% representing low prevalence areas. [3]

• Epidemiology

HBV infection has the potential for progression to a chronic state and thus presents as a global public health threat for its associated morbidity and mortality. While hepatitis B vaccines are available, limited access to healthcare and lack of proper health education contributes to the increasing global prevalence of hepatitis B. Lower incidence of hepatitis B in the United States compared to Asia and Africa is due to better access to healthcare and better use of vaccinations and other preventive measures. 

 U.S. Statistics 

• Around 60,000 new cases of HBV infection annually [4]
• 2 million or more people with chronic hepatitis B infection [4]
• Prevalence is higher in black, Hispanic, and Asian populations compared to whites [5]  
• Prevalence is lower in people less than 12 years of age born in the U.S. 
• Accounts for 5% to 10% of chronic end-stage liver disease, and 10% to 15% of cases of hepatocellular cancer
• Causes 5000 deaths annually 

Worldwide Statistics

• 350-400 million of the world population has chronic hepatitis B. [6]
• The following population is known to have a higher prevalence: Asian Pacific Islanders, Alaskan Eskimos, and Australian aborigines. [6]
• The following geographic regions have higher prevalence: the Indian sub-continent, sub-Saharan Africa, and central Asia.
• The prevalence of hepatitis B is reduced after the initiation of the hepatitis B vaccination program.
• 10 genotypes (A-J) of hepatitis B have been identified. [7]

High-risk groups for HBV infection include intravenous drug users, infants born to infected mothers, males who have sexual intercourse with other males, hemodialysis patients (and workers), healthcare workers, household contacts of known patients with chronic HBV. A majority of the global HBV disease burden is primarily through vertical transmission.

• Pathophysiology

Hepatitis B virus is transmitted via percutaneous inoculation or through mucosal exposure with infectious bodily fluids. Oral-fecal transmission is possible but considerably rare. The incubation period of HBV infection is typically between 30 and 180 days, and while recovery is common in immunocompetent patients, a small percentage can progress to a chronic state, serologically defined as the presence of HBsAg for greater than six months. HBsAg is transmitted via blood contact or body secretions, and the risk of acquiring hepatitis B is considerably higher in individuals with close contact with HBsAg-positive patients.

The pathogenesis of liver disease in HBV infection is mainly immune-mediated, and in some circumstances, HBV can cause direct cytotoxic injury to the liver. HBsAg and other nucleocapsid proteins that are present on cell membranes promote T cells-induced cellular lysis of HBV-infected cells. Cytotoxic T cell response to HBV-infected hepatocytes is relatively ineffective; a significant majority of HBV DNA is cleared from the hepatic system prior to maximal T cell infiltration, suggesting that the immune response is likely more robust in the early stages of infection. The immune response may not be the sole etiology behind hepatic injury in hepatitis B patients. Hepatitis B-associated injury is also seen in post-liver transplant patients with hepatitis B that are on immunosuppressant therapy. The histological pattern that follows from this infection is termed fibrosing cholestatic hepatitis and is thought to be associated with an overwhelming exposure to HBsAg. This lends credence to the idea that hepatitis B may possess pathogenicity regardless of the immune system’s response. [8]

• Histopathology

Acute Hepatitis B Infection: Histologic findings include "lobular disarray, ballooning degeneration, multiple apoptotic bodies, Kupffer cell activation, and lymphocyte-predominant lobular and portal inflammation. [9]

Chronic Hepatitis B Infection:  Lymphocyte-predominant portal inflammation with interface hepatitis and spotty lobular inflammation. [9]

• History and Physical

Patients infected with HBV could be asymptomatic initially and, depending on the particular genotype, might not be symptomatic throughout the infected state. In these particular cases, careful history taking is important to establish a diagnosis. However, when symptomatic from acute HBV infection, patients can present with serum sickness-like syndrome manifested as fever, skin rash, arthralgia, and arthritis. This syndrome usually subsides with the onset of jaundice. Patients may also have fatigue, abdominal pain, nausea, and anorexia.

History taking should emphasize the social history, including sexual practices (e.g., unprotected, same-sex, etc.), illicit drug use, profession (e.g., healthcare worker, sex worker), and living arrangements (i.e., within the same household as a patient with HBV infection). Patients in high-risk groups (i.e., healthcare workers, IV substance abuse patients, etc.) or those from highly endemic areas may warrant testing. Those with certain mental illnesses like bipolar disorder, schizophrenia, or manic disorder are at an increased risk for contracting HBV infection during manic states within which one may participate in risky sexual behaviors, including unprotected sex.

Physical examination should also assess for stigmata of chronic liver disease, including jaundice, ascites, hepatomegaly, splenomegaly, palmar erythema, Dupuytren contractures, spider nevi, gynecomastia, caput medusa, and hepatic encephalopathy which suggests portal hypertension and cirrhosis.

Extrahepatic manifestations include polyarteritis nodosa and glomerular disease (membranous nephropathy and, less often, membranoproliferative glomerulonephritis). Aplastic anemia has also been described.

Diagnosis of Hepatitis B is based on proper history taking, physical examination, laboratory works, and imaging. 

Initial symptoms are nonspecific and can include anorexia, nausea, vomiting, abdominal pain, dark urine, clay-colored stool, and jaundice. In cases of severe liver damage, advanced findings specific to liver damage are common and can include hepatic encephalopathy, confusion, coma, ascites, gastrointestinal bleeding, coagulopathy, or infections. In cases of chronic hepatitis B, patients can have a chronic inactive infection, or they can develop findings of acute hepatitis known as chronic active hepatitis. 

The diagnosis of hepatitis B relies on the appropriate history/physical and evaluation of serum or viral biomarkers. Viral serology of hepatitis B is usually detectable 1-12 weeks after initial infection with the primary viral marker being hepatitis B surface antigen (HBsAg). The presence of HBsAg rarely persists beyond 6 months after infection and typically precedes detectable quantities of the corresponding antibody to surface antigen (Anti-HBsAg). The period of time between the disappearance of HBsAg and the appearance of Anti-HBsAg is termed “the window period” or “serological gap.” During the window period, other viral serology could also be undetectable. HBsAg is the first virological marker to be detected thanks to its exposure on the viral surface and is indicative of an acute infection. Immune-mediated destruction of the nucleocapsid allows exposure of core antigen (HBcAg) or e antigen (HBeAg) with subsequent antibody development. Liver enzymes are typically elevated within the latter part of the replicative phase on infection thanks to active inflammatory processes, otherwise, liver transaminases could also be within their reference ranges. Hence, liver transaminases should not be a sole guide to diagnosing suspected hepatitis B infection.

The presence of antibodies to HBsAg indicates immunized status while the presence of antibodies to HBeAg refers to a possible chronic infection state. Seroconversion refers to the transition between an acute, immune-active phase to an inactive carrier state and is marked by the spontaneous development of antibodies to HBeAg. Earlier seroconversion has been related to more favorable outcomes while later seroconversion, in conjunction with recurrent bouts of reactivation and remission, is more liable to complications like liver cirrhosis, thus resulting in poorer outcomes. [10] The persistence of serum HBsAg for a duration of 6 months or greater delineates acute hepatitis B infection from chronic hepatitis B infection. Following groups of people should be screened for hepatitis B: [3]

• Persons born in high or intermediate endemic areas (HBsAg prevalence of greater than or equal to 2%). African countries, countries from North, Southeast, and East Asia. All countries from Australia and South Pacific (except for Australia and New Zealand). All countries from the Middle East (except for Israel and Cyprus). All countries from Eastern Europe (except for Hungary), Western Europe (Spain, Malta, and the indigenous population of Greenland), North America (Alaskan natives and indigenous populations of Northern Canada), Mexico, Guatemala, and Honduras. South America (Ecuador, Guyana, Suriname, Venezuela, and Amazonian areas). Caribbean (Antigua, Barbuda, Dominica, Grenada, Haiti, Jamaica, Saint Kitts and Nevis, Saint Lucia, and Turks and Caicos Islands).
• The unvaccinated U.S. citizens whose parents were born in high prevalence areas.
• History of illicit intravenous drug use.
• Men who have sex with men.
• Persons on immunosuppressive therapy.
• Persons with elevated ALT or AST of unknown origin.
• Blood, plasma, organ, tissues, or semen donors.
• Persons with end-stage renal disease.
• All pregnant women and infants born to HBsAg-positive mothers.
• Persons with chronic liver disease and HIV.
• Close contacts of HBsAg-positive persons, such as household, sexual, or needle-sharing.
• Persons with more than one sexual partner in the last six months.
• Persons requesting evaluation or treatment for sexually transmitted infections.
• Health care workers or public safety workers who are at risk for occupational exposure to blood or blood-contaminated body fluids.
• Residents and staff at facilities for developmentally disabled persons.
• Travelers to countries with an intermediate or high prevalence of Hepatitis B virus infection.
• Correctional facilities inmates.
• 19-59-year-old persons with diabetes who have not been vaccinated for Hepatitis B.
• Persons who are the source of blood or body fluid exposures that might require post-exposure prophylaxis.

Interpretation of Serologic Markers

Following serologic markers are often tested: Hepatitis B surface antigen (HBsAg), antibody to Hepatitis B surface antigen (anti-HBs), Hepatitis B core Ab (Anti-HBc) IgM, Hepatitis B core Ab (Anti-HBc) IgG, Hepatitis B e antigen (HBeAg), and Hepatitis B e antibody (anti-HBe). [10]

HBsAg: Acute infection (less than 6 months) or chronic infection (more than 6 months).

Anti-HBs: Recovery from acute infection or immunity from vaccination.

HBeAg: Mostly associated with high viral load.

Anti-HBe: Low replicative phase.

Anti-HBc IgM: Acute infection, an only marker present in the window period, can be present during exacerbation of chronic infection.

Anti-HBc IgG: Exposure to infection, chronic infection (if present along with HBsAg), recovery from acute infection (if present with anti-HBs), if isolated presence, may represent occult infection.

Other markers are: Hepatitis B viral DNA is for detection of viral load. Hepatitis B genotype provides input about disease progression and response to interferons. [11]

• Treatment / Management

Preventive measures constitute a major component of the management of hepatitis B. As of 2019, hepatitis B vaccines available in the United States are categorized into either single-antigen hepatitis B vaccines or combination vaccines.

Acute hepatitis B infection is self cleared in 95% of healthy adults. Management is supportive in a majority of patients. Patients with severe acute disease (2 of the 3: bilirubin more than 10 mg/dl, INR more than 1.6 and hepatic encephalopathy) and protracted acute severe disease (total bilirubin more than 3 mg/dl or direct bilirubin more than 1.5 mg/dl, INR more than 1.5, hepatic encephalopathy, or ascites) need antiviral treatment.

Management of chronic hepatitis B should include identification of HIV, hepatitis C, and hepatitis D coinfection, hepatitis B virus replication status, and severity of the disease. [10]  The severity of the disease is based on clinical assessment, blood counts, liver enzymes, and liver histology. [10]  While non-invasive tests are useful (blood test, imaging to measure liver stiffness) for chronic hepatitis B with normal alanine transferase, for patients with elevated or fluctuating alanine transferase, liver biopsy is necessary to identify if they need antiviral treatment. [10]

FDA-approved medications for chronic hepatitis B include interferons (peginterferon alfa-2a, interferon alfa-2b), nucleoside analogs (entecavir, lamivudine, telbivudine), and nucleotide analogs (adefovir, tenofovir). Entecavir and tenofovir are preferred for acute HBV infection if treatment is warranted, due to their relatively higher barrier to resistance. Entecavir combination drugs have been developed. However, a 2018 meta-analysis based on 24 studies involved with entecavir polytherapy vs entecavir monotherapy determined that entecavir combination drugs were no more effective than entecavir monotherapy. [12]  Vertical transmission of hepatitis B remains a significant cause of the global HBV burden. In a 2015 prospective, multicenter trial, administration of tenofovir in HBsAg-positive and/or HBeAg-positive mothers demonstrated a benefit in reducing ALT levels in mothers and decreasing infant HBsAg levels at 6 months postpartum. [13]  Major drawbacks for this study, however, include a relatively small sample size (n=118) and the lack of a placebo-based control group.  Oral nucleos(t)ide therapy has been shown to suppress viral replication and thus decrease the viral burden. Lamivudine was the first effective agent to successfully used to suppress viral counts but was associated with high drug resistance. [14]  A 2014 clinical trial comparing entecavir vs lamivudine in chronic B hepatitis reported better virological response in the entecavir group compared to the lamivudine group. [15]  The 2013 GAHB trial was a placebo-controlled, double-blind study that compared lamivudine with a placebo. HBsAg clearance was achieved in a majority of patients with lamivudine therapy but the overall strength of the study was weakened by low recruitment numbers (n = 35). [16] For patients in the immune-tolerant phase of hepatitis B infection, a stage marked by normal liver transaminases and HBV DNA, antiviral medications were not recommended. A randomized controlled study showed suboptimal control of viral burden, likely secondary to high circulating levels of HBV DNA. [17]  Regarding monotherapy versus combined therapy, there have been several limited studies addressing this issue. In the 2018 POTENT study, there was no demonstrated difference between monotherapy versus sequential therapy although there was insufficient data for statistical significance for HBsAg seroconversion. [18]

The counseling of patients on the prevention of transmission is extremely valuable. Lifestyle modifications include reducing intake of agents with potential for liver damage such as alcohol, hepatotoxic medications, herbal medications, and herbal supplements. 

The goals of antiviral therapy are: [10]

• Suppression of hepatitis B virus replication
• Reduction of liver inflammation
• Prevention of progression to liver cirrhosis and hepatocellular carcinoma

Appropriate treatment response is indicated by the following findings: [10]

• Blood tests: normalization of ALT
• Undetectable hepatitis B viral DNA
• Loss of HBsAg and HBeAg with seroconversion to anti-HBs and anti-HBe
• Reduced inflammation on liver biopsy with no worsening of fibrosis

Surgical intervention for hepatitis B is only indicated for fulminant liver disease requiring transplantation.

• Differential Diagnosis

The differential diagnosis for hepatitis B infection is broad due to the presence of non-specific symptoms such as fatigue, abdominal pain, nausea, and vomiting. Other etiologies of hepatitis (i.e., hepatitis A, hepatitis C, hepatitis E, alcoholic hepatitis, and autoimmune hepatitis) should be considered in conjunction with appropriate history taking and pertinent laboratory investigation.

Iron overload (hemochromatosis) can be associated with abdominal tenderness and abnormal liver transaminase levels. Pertinent findings that favor a diagnosis of hemochromatosis compared to hepatitis B include diffuse skin discoloration (bronze diabetes) and impaired glucose tolerance.

Wilson disease is a disease of excessive copper accumulation. It is associated with psychiatric disturbances due to copper accumulation in the basal ganglia. Kayser-Fleischer rings are pathognomonic for Wilson disease but are not completely sensitive (requires an expert ophthalmologist to confirm this finding). Laboratory evaluation that favors a diagnosis of Wilson disease includes low serum ceruloplasmin levels and elevated urinary copper, and if abnormal, requires further evaluation by a hepatologist.

• Alcoholic hepatitis
• Autoimmune hepatitis
• Drug-induced liver injury
• Hemochromatosis
• Hepatitis A
• Hepatitis C
• Hepatitis D
• Hepatitis E
• Hepatocellular carcinoma
• Human immunodeficiency virus
• Wilson disease

Acute HBV infection can be treated symptomatically and in immunocompetent patients, can spontaneously resolve. Those that progress to the chronic state, however, are at increased risk for the development of hepatocellular carcinoma, cirrhosis, or fulminant liver failure. The likelihood of risk is dependent on the particular genotype, and the method of transmission as vertical transmission has a higher risk of long-term complications compared to horizontal transmission cases.

• Complications

Unlike hepatitis A and hepatitis E, in which there is no chronic state, HBV infection has the potential for the development of a chronic state. Chronic hepatitis B predisposes a patient to the development of portal hypertension, cirrhosis, and its complications or hepatocellular carcinoma (HCC). As such, patients with HBV infection should be monitored closely, and a referral to a specialist is highly recommended.Fulminant liver failure from HBV infection requires an emergent liver transplant evaluation at a liver transplant center.

• Consultations

Hepatitis B management ideally involves interprofessional collaboration. Primary care, gastroenterology, hepatology, infectious disease, liver transplant, and palliative care services are among the different services involved.

• Deterrence and Patient Education

Patient education remains one of the most important components in preventative measures regarding HBV infection.

Education should be provided to expecting parents (particularly those from highly endemic regions) about the importance of vaccination and to clarify erroneous beliefs about vaccinations.Patient education should also include counseling about the avoidance of risky behaviors that predispose an individual to be infected, including promiscuous sexual activity or intravenous drug abuse. They should also be advised not to share items such as shaving razors, toothbrushes, or hair combs due to possible transmission via mucosal contact or through microtrauma to protective barriers.

• Pearls and Other Issues

Hepatitis D (a member of the delta virus family) has been long associated with HBV infections and cannot exert pathological influence without the presence of HBV infection. Two forms of infection exist; coinfection (acquired at the same time) and superinfection (hepatitis D infection in a patient with chronic hepatitis B infection). Superinfection tends to be more severe than coinfection. Due to the preexisting hepatitis B infection, anti-HBcAg IgM is undetectable in superinfection states but can be noted in coinfection.

• Enhancing Healthcare Team Outcomes

As hepatitis B infection is highly transmissible via accidental needlesticks, healthcare providers involved in taking care of a patient with HBV should exercise caution and practice proper preventative measures such as vaccination. Patient education should also include counseling about HBV transmission. The interprofessional team's role is crucial in ensuring the best patient outcomes.

The vaccination rate is low in many developing countries, and the majority of patients are undiagnosed. Educational programs and improved awareness among the general public and healthcare providers are necessary to improve the identification of the patients, reduce transmission of the disease, and reduce the complications of hepatitis B infection.

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Disclosure: Nishant Tripathi declares no relevant financial relationships with ineligible companies.

Disclosure: Omar Mousa declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Tripathi N, Mousa OY. Hepatitis B. [Updated 2023 Jul 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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Hepatitis B Training Presentation for Health Workers

• 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
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• 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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• Case Report
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• 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

Bekker L-G, Beyrer C, Mgodi N, Lewin SR, Delany-Moretlwe S, Taiwo B, et al. HIV infection. Nat Rev Dis Primer. 2023;9:1–21.

Google Scholar  

Data on the size of the HIV epidemic. https://www.who.int/data/gho/data/themes/topics/topic-details/GHO/data-on-the-size-of-the-hiv-aids-epidemic?lang=en . Accessed 3 May 2023.

Leumi S, Bigna JJ, Amougou MA, Ngouo A, Nyaga UF, Noubiap JJ. Global burden of hepatitis B infection in people living with human immunodeficiency virus: a systematic review and meta-analysis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71:2799–806.

Article   Google Scholar  

McGovern BH. The epidemiology, natural history and prevention of hepatitis B: implications of HIV coinfection. Antivir Ther. 2007;12(Suppl 3):H3-13.

Article   CAS   PubMed   Google Scholar  

Kaplan JE, Masur H, Holmes KK, Wilfert CM, Sperling R, Baker SA, et al. USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: an overview. USPHS/IDSA Prevention of Opportunistic Infections Working Group. Clin Infect Dis Off Publ Infect Dis Soc Am. 1995;21 Suppl 1:S12-31.

Article   CAS   Google Scholar  

Bamba S, Lortholary O, Sawadogo A, Millogo A, Guiguemdé RT, Bretagne S. Decreasing incidence of cryptococcal meningitis in West Africa in the era of highly active antiretroviral therapy. AIDS Lond Engl. 2012;26:1039–41.

Müller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M, et al. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10:251–61.

Article   PubMed   PubMed Central   Google Scholar  

Haddow LJ, Easterbrook PJ, Mosam A, Khanyile NG, Parboosing R, Moodley P, et al. Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort. Clin Infect Dis Off Publ Infect Dis Soc Am. 2009;49:1424–32.

Obeagu E, Onuoha E. Tuberculosis among HIV patients: a review of Prevalence and Associated Factors. Int J Adv Res Biol Sci. 2023;10:128–34.

Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, et al. The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect Dis. 2022;22:1748–55.

Manegold C, Hannoun C, Wywiol A, Dietrich M, Polywka S, Chiwakata CB, et al. Reactivation of hepatitis B virus replication accompanied by acute hepatitis in patients receiving highly active antiretroviral therapy. Clin Infect Dis Off Publ Infect Dis Soc Am. 2001;32:144–8.

EACS Guidelines | EACSociety. https://www.eacsociety.org/guidelines/eacs-guidelines/ . Accessed 7 May 2023.

Cryptococcosis | NIH. 2021. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/cryptococcosis . Accessed 6 May 2023.

Chang CC, Harrison TS, Bicanic TA, Chayakulkeeree M, Sorrell TC, Warris A, et al. Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM. Lancet Infect Dis. 2024;10:S1473-3099(23)00731-4.

Deeks ED. Bictegravir/emtricitabine/tenofovir alafenamide: a review in HIV-1 infection. Drugs. 2018;78:1817–28.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Bellmann R, Smuszkiewicz P. Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients. Infection. 2017;45:737–79.

Shelburne SA, Darcourt J, White AC, Greenberg SB, Hamill RJ, Atmar RL, et al. The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis Off Publ Infect Dis Soc Am. 2005;40:1049–52.

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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.

Author information

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

Authors and Affiliations

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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Contributions

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.

Corresponding author

Correspondence to Hong Ying Yu .

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The study was approved by the Ethics Committee of the Hunan University of Medicine General Hospital (HYZY-EC-202306-C1), and with the informed consent of the patient.

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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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Received : 30 June 2023

Accepted : 24 May 2024

Published : 27 May 2024

DOI : https://doi.org/10.1186/s12879-024-09431-9

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