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Viral Hepatitis: A Case Study

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• Aisha Prioleau-Johnson
• Beth Mengstu
• Matt Kilboy

Our rationale for choosing viral hepatitis

Viral hepatitis is an infection of the liver that comes in several forms. The different forms of hepatitis (A,B,C,D,E) determine how it was contracted, how it is treated and the prognosis. Research has allowed the development of vaccines for hepatitis A and B, however, with the increase in the anti-vaccination movement and IV drug use, the prevalence of Hepatitis has not decreased as one would expect. Professionals in healthcare must remain aware of this preventable disease so we can educate patients about the effective methods in reducing its prevalence.

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Hepatitis A to E: An Overview

Published by Micah Seamons Modified over 9 years ago

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Presentation on theme: "Hepatitis A to E: An Overview"— Presentation transcript:

Module 1 Introduction to rotavirus disease and vaccine

Hepatitis B: Epidemiology and Public Health Issues

Hepatitis B - virology DNA virus class Hepadnaviridae Transmission Sexual contact Injecting drug use or other percutaneous exposure i.e. tatoos Perinatal.

Hepatitis B Virus. Hepatitis B - Clinical Features Incubation period:Average days Range days Clinical illness (jaundice):

Hepatitis B Campaign 28 July.  HEPATITIS B is a liver disease caused by the hepatitis B virus (HBV). WHAT IS HEPATITIS B DISEASE?

A “Infectious” “Serum” Viral hepatitis EntericallytransmittedParenterallytransmitted other other E “NANB” BD C VIRAL HEPATITIS HISTORICAL PERSPECTIVE.

Hepatitis B.

Hepatitis A and Hepatitis A Vaccine Epidemiology and Prevention of Vaccine- Preventable Diseases National Immunization Program Centers for Disease Control.

Hepatitis B and Hepatitis B Vaccine Epidemiology and Prevention of Vaccine- Preventable Diseases National Center for Immunization and Respiratory Diseases.

Hepatitis web study H EPATITIS W EB S TUDY Hepatitis A: Epidemiology Presentation Prepared by: David Spach, MD and Nina Kim, MD Last Updated: May 31, 2011.

Acute Viral Hepatitis. Viral Hepatitis Infectious: Hepatitis A Infectious: Hepatitis A Serum : Hepatitis B, D Serum : Hepatitis B, D NANB : Hepatitis.

Hepatitis E - Clinical Features Incubation period:Average 40 days Range days Case-fatality rate:Overall, 1%-3% Pregnant women, 15%-25% Illness severity:Increased.

FECAL-BORNE HEPATITIS. ETIOLOGY Hepatitis A virus (HAV), Hepatovirus Picornavirus, enterovirus nm 1 serotype only, although there are 4 genotypes.

Iva Pitner Mentor: A. Žmegač Horvat

Viral Hepatitis A “Infectious” “Serum” Viral hepatitis Enterically transmitted Parenterally transmitted F, G, ? other E NANB BD C.

Varicella Zoster Virus Herpesvirus (DNA) Primary infection results in varicella (chickenpox) Recurrent infection results in herpes zoster (shingles) Short.

Childhood Immunization Update for WIC and Clerical Personnel Presented by: Date:

Measles and Measles Vaccine Epidemiology and Prevention of Vaccine- Preventable Diseases National Center for Immunization and Respiratory Diseases Centers.

HEPATITIS A VIRUS Week Response Clinical illness ALT IgM IgG HAV in stool Infection Viremia EVENTS IN HEPATITIS A VIRUS INFECTION.

By: Dr.Malak El-Hazmi Assistant Professor & Consultant Virologist College of Medicine & KKUH.

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Educational Case: Hepatitis B Virus

Caitlin m. nickens.

1 Department of Pathology, Walter Reed National Military Medical Center, Bethesda, MD, USA

Barbara Knollmann-Ritschel

2 Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 .

Primary Objective

Objective M3.1: Hepatotropic Viruses: Describe the laboratory findings that diagnose hepatitis and correlate with the different possible clinical outcomes for each of the major hepatotropic viruses.

Competency 3: Diagnostic Medicine and Therapeutic Pathology; Topic M: Microbiology; Learning Goal 3: Virology.

Patient Presentation

A 28-year-old female presents to the clinic with a 10-day history of flu-like symptoms, including anorexia and malaise. She does not report any pertinent prior medical history or surgeries. She takes no medications. Her family history is noncontributory, and she reports no sick contacts. She is sexually active with multiple partners and has used oral contraceptives regularly for the past 12 years. She has not traveled outside the United States in the past 5 years.

On physical examination, she is alert and oriented, in no acute distress. Her vital signs are temperature of 99.9°F, pulse 78/minute, respirations of 18/minute, and blood pressure of 121/78 mm Hg. Her extraocular muscles are intact; however, mild scleral icterus is noted. Heart sounds are regular rate and rhythm without murmurs, and lungs are clear to auscultation bilaterally. The abdomen is soft and nontender, except the liver is tender when palpated and extends 8 cm below the costal margin, with a smooth edge. Initial laboratory testing is performed and shown in Table 1 . 1

Table 1.

Initial Laboratory Findings. 1

Alanine aminotransferase (ALT)	3817 U/L	7-55 U/L
Aspartate aminotransferase (AST)	2152 U/L	8-48 U/L
Alkaline phosphatase (ALP)	176 U/L	45-115 U/L
Albumin	3.4 g/dL	3.5-5 g/dL
Total protein	6.7 g/dL	6.3-7.9 g/dL
Total bilirubin	8.5 mg/dL	0.1-1.2 g/dL

Diagnostic Findings, Part I

Complete blood count (CBC) and basic metabolic panel (BMP) are within normal limits. Liver function tests are performed, and the findings are reported in Table 1 .

Questions/Discussion Points, Part I

Given the clinical history, what is a broad differential diagnosis.

The differential diagnosis for a patient with flu-like symptoms, an enlarged liver, and scleral icterus is broad and includes hemolytic anemia, hepatotropic viruses, 2 and other sources of liver injury such as autoimmune disorders including Sjögren disease and primary sclerosing cholangitis, drug induced (eg, acetaminophen), and chronic alcohol abuse. HIV must also be considered. The history and viral serology studies will help to narrow this differential. 3

How Does the Initial Hepatic Panel Help Narrow the Differential Diagnosis?

The initial hepatic panel shows very elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT), while the alkaline phosphatase is relatively normal. A low albumin may indicate liver dysfunction (impaired synthesis); however, this patient’s albumin is only slightly low. Elevated total bilirubin may indicate hemolysis or liver dysfunction (impaired metabolism of bilirubin). When AST and ALT are highly elevated, particularly when disproportionately elevated compared to alkaline phosphatase, acute hepatitis must be strongly considered in the differential diagnosis. Classically, AST is significantly higher than ALT in the setting of alcoholic hepatitis. These patients will also likely have a history of chronic alcohol use. When ALT is higher than AST, viral hepatitis is favored. A thorough history and assessment of risk factors can help to determine which of the viral hepatitis types is most likely involved. 3

What Is the Most Likely Diagnosis?

Given the patient’s presentation of flu-like symptoms with jaundice and tender hepatomegaly, acute viral hepatitis must be considered very high on the differential diagnosis. Her history of multiple sexual contacts without barrier protection is a risk factor for hepatitis B in particular, as well as HIV. As indicated in Table 1 , the CBC is normal, ruling out anemia, and the BMP is also within normal limits. The diagnosis can be confirmed with viral serology. Viral serology is ordered.

Diagnostic Findings, Part II

Viral serology can be very helpful to narrow the differential diagnosis. Viral serology results are reported in Table 2 .

Table 2.

Viral Serology for Hepatitis B.

HBsAg	Positive
HBeAg	Positive
IgM Anti-HBc	Positive
IgG Anti-HBe	Negative
IgG Anti-HBs	Negative
HBV-DNA	Positive

Abbreviations: HBc, hepatitis B core; HBeAg, hepatitis B envelope antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; Ig, immunoglobulin.

Questions/Discussion Points, Part II

How does the hepatitis serology help narrow the differential diagnosis.

As seen in Table 2 , the serology is positive for hepatitis B.

What Are the Risk Factors for Hepatitis B Compared to Other Types of Viral Hepatitis?

Hepatitis B is most often transmitted by bodily fluids (blood or semen), via unprotected sexual contact or contaminated needles as in intravenous drug use, or very rarely via blood products. Though rare in the United States, vertical transmission (from mother to child during childbirth) is more common in Asian countries where the prevalence of chronic hepatitis B is higher among the general population. Hepatitis A is more commonly seen with ingestion of infected foods, such as raw oysters or other shellfish, and spreads through fecal–oral contact; it is endemic in developing countries with poor hygienic conditions. Hepatitis C is most commonly transmitted via blood and through contaminated needles in the setting of intravenous drug use, tattoos, or piercings. Hepatitis D is almost exclusively seen as a coinfection with hepatitis B. Hepatitis E is transmitted via the fecal–oral route, and the presentation may be severe in pregnant women. 2

Diagnostic Findings, Part III

The patient’s disease state—active infection versus cleared/immunized, acute versus chronic—can be better characterized using viral serum markers, as given in Table 3 .

Table 3.

Viral Serology Interpretation for Hepatitis B. 2

Marker	Definition	Significance
HBsAg	Surface antigen	Active infection
HBeAg	E-antigen (replication marker)	Active infection
IgM Anti-HBc	Antibody against core antigen	Acute infection
IgG Anti-HBe	Antibody against E-antigen	Prior exposure—cleared or chronic infection
IgG Anti-HBs	Antibody against surface antigen	Prior exposure—cleared or chronic infection History of vaccination (if isolated finding)
HBV-DNA	Viral DNA	Active infection

Abbreviations: HBc; hepatitis B core; HBeAg, hepatitis B envelope antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; Ig, immunoglobulin.

Questions Discussion, Part III

What are the possible clinical outcomes of hepatitis b.

Once exposed, a patient may experience an acute, symptomatic viral hepatitis accompanied by an immune response. A healthy, immunocompetent patient will likely be able to clear the infection (and become subsequently immune), whereas other patients, particularly if they are immunocompromised, are unable to completely clear the acute infection. These patients will either progress rapidly to liver failure (fulminant hepatitis) or slowly to possible cirrhosis (chronic hepatitis). It is also possible for a patient to experience a subclinical hepatitis after exposure and progress to chronic disease without ever manifesting acute hepatitis. 2

Chronic hepatitis B also carries increased risk of developing hepatocellular carcinoma, even before progressing to end-stage cirrhosis. Known patients with chronic hepatitis B from high risk populations should be monitored for this complication via a combination of liver ultrasound and α-fetoprotein levels. 2 , 4

What Are Possible Treatments of Hepatitis B?

Acute hepatitis B requires only supportive treatment while the patient clears the infection. 3 Antiviral medications have not been shown to shorten or improve the course for patients with acute hepatitis with severe presentations. Patients with chronic hepatitis B should be treated with interferons and antivirals and regularly tested for viral loads and liver function markers to monitor for progression (increasing viral load and/or declining liver function). 3

What Are the Typical Clinical Findings and Clinical Course of the Other Types of Hepatitis Infection (A, C, D, and E)?

Hepatitis A presents as acute hepatitis, often without jaundice. The infection usually resolves within 2 months following the acute illness, with rare progression to fulminant hepatitis. Hepatitis C will become chronic in about 80% to 90% of infected patients, some of whom may never manifest an acute hepatitis. These patients are at risk for eventual cirrhosis and hepatocellular carcinoma (rarely without preexisting cirrhosis). Hepatitis D is only able to replicate in the presence of hepatitis B. It presents as an unusually severe hepatitis B infection (acute coinfection with both B and D) or an exacerbation of a preexisting chronic hepatitis B infection (superinfection with hepatitis D). Hepatitis E typically presents like an acute hepatitis, but pregnant patients may experience a severe course with increased risk of fulminant hepatitis and death. 2

Are All the Hepatitis Viruses the Same?

Hepatitis viruses are linked because they all invade hepatocytes. However, they actually come from different virus families and have varying characteristics. Hepatitis A is single-stranded RNA picornavirus. Hepatitis B virus is an enveloped hepadnavirus with partially double-stranded, circular DNA. Hepatitis C is a single-stranded RNA flavivirus. Hepatitis D is a defective circular single-stranded RNA deltavirus that can only replicate in the presence of hepatitis B or as a superinfection with chronic hepatitis B. Hepatitis E is an enterically transmitted single-stranded RNA calicivirus. 2

Teaching Points

• Patient presentation and history can help differentiate among the viral hepatitis etiologies. Suspect hepatitis B in patients presenting with acute hepatitis (flu-like symptoms and jaundice), particularly with a history of either unprotected sexual contact or intravenous drug use. 2
• Hepatitis A is transmitted fecal–orally and typically presents with acute hepatitis. Progression to fulminant hepatitis is rare and supportive care is indicated. 2
• Hepatitis C is transmitted via contaminated needles, as in intravenous drug use, tattoos, or piercings. The course is typically chronic, and patients are at risk of developing cirrhosis and hepatocellular carcinoma. 2
• Hepatitis D is unable to replicate unless in the presence of hepatitis B, and so only presents as either a coinfection (severe initial course) or a superinfection in a patient with known chronic hepatitis B (sudden exacerbation). 2
• Hepatitis E is fecal–orally transmitted and presents as acute hepatitis. Pregnant patients are at increased risk for a severe course, including fulminant hepatitis and death. 2
• Diagnosis can be made with viral serologies. It is important to characterize the infection as acute or chronic to determine the appropriate treatment course. 2
• Infected patients presenting with acute hepatitis B will either clear the infection and recover or progress to either acute liver failure or chronic hepatitis and eventual cirrhosis. Patients may also skip the acute viral illness stage and present much later with a subclinical chronic infection. 2
• Patients with chronic hepatitis B are at increased risk for developing hepatocellular carcinoma, even before reaching end-stage cirrhosis. 2
• Acute hepatitis B is treated with supportive care. Chronic hepatitis B infection will likely require long-term treatment with interferons and antivirals. 4

Authors’ Note: The views expressed in this case are those of the author(s) and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or US Government.

Declaration of Conflicting Interests: 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.

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24:  Hepatitis C

Lindsey Childs-Kean

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Patient presentation.

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Chief Complaint

“I want to get this Hepatitis C cured.”

History of Present Illness

PD is a 45-year-old Caucasian male who presents to the infectious diseases clinic seeking treatment for his chronic hepatitis C infection. He states that he was diagnosed with the disease a few years ago, but he’s not sure when he contracted it. He doesn’t remember having any symptoms related to the infection. He has never received any treatment for his hepatitis C.

Past Medical History

HTN, anxiety, dyslipidemia, GERD

Surgical History

Family history.

Father and mother both alive with HTN and dyslipidemia; sister is alive with no known medical issues.

Social History

Former IV drug user and alcohol drinker, but clean and sober for 7+ years. No tobacco. Works repairing wheelchairs and scooters. Married with 2 children (12 and 4 years). Enjoys playing sports and doing outdoor activities with wife and children.

Home Medications

Amlodipine 10 mg PO daily

Alprazolam 1 mg PO TID PRN for anxiety

Simvastatin 20 mg PO daily

Omeprazole 40 mg PO daily

Multivitamin PO daily

Acetaminophen 325 mg PO PRN for headache

Physical Examination

Vital signs.

Temp 98.8°F, P 82 bpm, RR 18 breaths per minute, BP 127/78 mm Hg, pO 2 99%, Ht 6′, Wt 101 kg

Normal appearing male in no apparent distress, well groomed

Nomocephalic, atraumatic, PERRLA, EOMI, b/l sclera anicteric, moist mucous membranes, poor dentition

Clear to auscultation, no use of accessory muscles, no cracks or wheezes

Cardiovascular

NSR, no m/r/g

Soft, non-distended, non-tender, normal bowel sounds

Genitourinary

Normal male genitalia, no complaints of dysuria or hematuria

Alert and oriented × 3, CN 2-12 grossly intact

Extremities

No edema, cyanosis, or clubbing

Intact, w/o rashes or lesions, or erythema

Laboratory Findings

cells/L

Glucose: 80 mg/dL	Albumin: 3.8 mg/dL
Hgb: 15 g/dL	BUN: 15 mg/dL	T ...

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• Case report
• Open access
• Published: 26 June 2024

Hepatitis A virus infection associated with bilateral pleural effusion, ascites, and acalculous cholecystitis in childhood: a case report

• Fatima Breim   ORCID: orcid.org/0000-0003-2081-3490 1 ,
• Bakri Roumi Jamal   ORCID: orcid.org/0000-0003-0903-0794 1 ,
• Lama Kanaa   ORCID: orcid.org/0000-0003-2871-557X 1 ,
• Saleh Bourghol   ORCID: orcid.org/0000-0003-1342-7073 1 ,
• Besher Jazmati   ORCID: orcid.org/0009-0000-4640-4404 1 &
• Samia Dadah   ORCID: orcid.org/0009-0007-1288-1545 2  

Journal of Medical Case Reports volume  18 , Article number:  304 ( 2024 ) Cite this article

118 Accesses

Metrics details

Acute hepatitis A infection is common among children in developing nations. The clinical presentation in children is usually asymptomatic and anicteric, and it is a self-limiting infection. Rarely, it can be associated with extrahepatic complications such as pleural effusion, acalculous cholecystitis, and ascites.

Case presentation

An 8-year-old middle eastern child presented with abdominal pain, jaundice in the sclera, yellowish color of urine, and poor appetite. In the last two days, abdominal distension developed. After conducting diagnostic investigations, the child was diagnosed with HAV hepatitis associated with bilateral pleural effusion, acalculous cholecystitis, and ascites. He was managed conservatively with vitamin K supplementation and supportive parenteral fluids. After 4 days, clinical improvement was observed.

Hepatitis A infections presented with extrahepatic manifestations like pleural effusion, acalculous cholecystitis, and ascites are very rare, especially in children. There have been some reports of these manifestations occurring in isolation, but for them to co-exist to our knowledge, this has only been reported in two cases in the literature, and this is the third case with all these three rare complications being presented simultaneously in a single child. Although HAV infection is an asymptomatic and self-limiting viral disease in childhood, it can manifest with rare extrahepatic complications, so pediatricians should be aware of this rare association to avoid unnecessary investigations.

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Introduction

Hepatitis A virus (HAV) causes liver inflammation, resulting in a range of symptoms from mild to severe, including fever, severe fatigue, loss of appetite, abdominal discomfort, nausea and vomiting. However, it is usually a self-limiting disease, especially in childhood [ 1 , 2 ]. HAV is transmitted through physical contact and the fecal–oral route when contaminated food or water containing the feces of an infected person is ingested [ 2 ]. It is a widespread illness, especially in developing countries due to poor hygiene and sanitation practices [ 3 ]. It is infrequently accompanied by extrahepatic manifestations in children, such as acalculous cholecystitis, pancreatitis, pleural effusion, ascites, urticarial and maculopapular rash, and acute kidney injury [ 4 ].

Pleural effusion is a rare complication of hepatitis A that typically occurs in children during the early stages of the disease [ 3 , 4 ]. Ascites is also a rare extrahepatic manifestation, tends to be commonly observed in the later stages of the illness [ 5 ].

We presented a case of an 8-year-old boy with hepatitis A virus infection who exhibited all three manifestations of ascites, acalculous cholecystitis, and pleural effusion simultaneously.

To the best of our knowledge, this is only the third reported case in the literature where all three complications have presented concurrently. The case highlights the importance of recognizing these manifestations in primary care settings to avoid unnecessary procedures.

An 8-year-old middle eastern boy presented to the hospital with abdominal pain for the past 5 days and abdominal distention for the last 2 days. The patient remained hemodynamically stable with scleral icterus, yellowish urine, poor appetite, and vital signs showing a heart rate of 116 beats per minute, respiratory rate of 24 breaths per minute, and blood pressure of 120/80 mmHg. There was no fever, diarrhea, constipation, or significant medical or surgical history noted.

On physical examination, dullness in percussion and decreased breath sounds were noted on chest examination. The liver was found to be soft and palpable 3 cm below the costal margin, and the spleen was not palpable. Laboratory studies revealed a hemoglobin level of 9.8 g/dL, hematocrit of 29.0%, white blood cell count of 9.3 × 10 9 cells/L, lymphocyte count of 5.1 × 10 9 cells/L, and platelet count of 221 × 10 9 cells/L. The total protein level was 6.60 g/dL, with an albumin level of 3.13 g/dL, and prothrombin time was 17.20 s. The patient also had hyperbilirubinemia with a total bilirubin level of 6.54 mg/dL and direct bilirubin level of 6.35 mg/dL, transaminitis with aspartate aminotransferase of 741.5 U/L, and alanine aminotransferase of 805.7 U/L (Table  1 ).

The IgM anti-HAV test was positive. Serologic tests for hepatitis B virus, hepatitis C virus, and hepatitis E virus were negative. Serological analysis for cytomegalovirus, parvovirus, leptospira, and Epstein Barr virus were also found to be negative. As a result, the diagnosis of HAV infection was confirmed.

A chest X-ray revealed bilateral pleural effusion, with the left side exhibiting a greater effusion volume than the right side. Thoracic ultrasonography showed mild bilateral pleural effusion. Abdominal ultrasound indicated mild hepatomegaly and a thickened (7 mm), non-calculous gallbladder, suggestive of acalculous cholecystitis, as well as moderate free fluid in the abdomen (Fig.  1 ).

Thickening of the gallbladder wall and edematous pericholecystic area in abdominal ultrasonography

The patient was diagnosed with HAV acute hepatitis associated with bilateral pleural effusion and ascites, confirmed by X-ray imaging and ultrasonography. The patient received conservative management, including vitamin K supplementation and supportive parenteral fluids. Specifically, the patient received 5 mg of vitamin K twice daily for 3 days and was given 70% of the maintenance requirement of potassium chloride dissolved in a solution of 5% dextrose and sodium chloride intravenously for 2 days. He remained hemodynamically stable throughout the duration of illness.

After 4 days, a repeat ultrasound showed resolution of pleural effusion, ascites, and acalculous cholecystitis. Subsequent liver function tests and plain film chest X-ray revealed complete recovery over the course of a month. The patient did not experience any further complications or require additional treatment, and there were no long-term sequelae reported in this case.

HAV infection-induced acute hepatitis typically follows a benign, self-limiting course. The clinical manifestations and severity vary depending on age and are mainly associated with liver inflammation. In children, it is usually asymptomatic and not accompanied by jaundice; 80% of them recover completely in 3 months [ 4 , 5 ].

Acute hepatitis caused by HAV infection may also present with rare extrahepatic manifestations, such as urticarial and maculopapular rash, acute kidney injury, autoimmune hemolytic anemia, aplastic anemia, acute pancreatitis, reactive arthritis, Guillain–Barre syndrome, pleural or pericardial effusion, ascites, glomerulonephritis, polyarteritis nodosa, thrombocytopenia, and cryoglobulinemia [ 4 ]. In childhood, pleural effusion, ascites, and acalculous cholecystitis are rare manifestations due to hepatitis A virus infection [ 3 , 4 ].

Pleural effusion with hepatitis A virus infection was described in 20 case reports; most of them were children [ 4 ]. It has commonly been reported on the right side in patients during the early period of the disease. All cases were resolved spontaneously except one, which progressed to fulminant liver failure and led to death [ 4 ]. The exact mechanism of the effusion in hepatitis A virus infection is unknown; it appears to be multifactorial, potentially involving immune complex deposition or a direct viral invasion of the pleura. Additionally, there may be a secondary mechanism related to the transport of fluid from co-presenting ascites to the pleura cavity through small diaphragmatic defects or diaphragmatic lymphatics [ 3 , 4 , 6 ].

The association between hepatitis A and ascites has rarely been reported in both children and adults, with most cases documented in children at advanced disease stages. Possible mechanisms include venous and lymphatic obstruction due to liver involvement or a decrease in oncotic pressure caused by hypoalbuminemia [ 5 ].

Acalculous cholecystitis is a rare complication of acute viral hepatitis A. In children, it is usually asymptomatic and recovers within 3 weeks. The most common finding is gallbladder wall thickening greater than 3.5 mm. Suggested mechanisms include the direct effect of viral antigens [ 2 , 3 ].

In our case, we reported hepatitis A complicated by pleural effusion, ascites, and acalculous cholecystitis. Pleural effusion due to pneumonia was considered less likely because the child had no history of coughing or tachypnea. Tuberculosis was ruled out due to the short duration of the illness and the absence of a contact history of tuberculosis. Surgical intervention was not required for acalculous cholecystitis because it was transient and gradually disappeared.

All three of these complications spontaneously resolved with supportive treatment in our patient.

To our knowledge, this is the third case with the presence of pleural effusion, ascites, and acalculous cholecystitis, three rare manifestations due to hepatitis A virus infection in a single child (Table  2 ) [ 1 , 3 ].

This case highlights the significance of recognizing extrahepatic manifestations of childhood hepatitis A in primary care settings. It underscores the importance of primary care physicians being knowledgeable about these manifestations to prevent unnecessary procedures like pleural and ascitic taps. When encountering cases with similar presentations, it is crucial to consider hepatitis A in the differential diagnosis. Management of such cases typically involves conservative approaches, including regular clinical assessments and monitoring through biochemical and radiological studies.

This work has been reported in line with the CARE criteria [ 7 ].

The most important educational point of this study is that although HAV infection is an asymptomatic and self-limiting viral disease in childhood, it can manifest with rare extrahepatic complications. Additionally, hepatitis A infection should be considered in the differential diagnosis of pleural effusion, ascites, and acalculous cholecystitis in a patient with features of acute hepatitis, so pediatricians should be aware of this rare association to avoid unnecessary investigations.

Availability of data and materials

Not applicable.

Dalai R, Malhotra S, Gupta A, Mandal M, Kant S. A rare case of childhood Hepatitis A infection with pleural effusion, acalculous cholecystitis, and ascites. J Fam Med Prim Care. 2018;7(6):1581.

Article   Google Scholar  

Salajegheh F, Shafieipour S, Nakhaie M, Jahangiri S. Induced acalculous cholecystitis : a case report and literature review. 2023;(February):1–10.

Erdem E, Urganci N, Ceylan Y, Kara N, Ozcelik G, Gulec SG. Hepatitis a with pleural effusion, ascites and acalculous cholecystitis. Iran J Pediatr. 2010;20(4):479–82.

PubMed   PubMed Central   Google Scholar  

Zalloum JS, Alzughayyar TZ, Abunejma FM, Mayadma I, Tomeh LZ, Abulaila KJ, et al . Acute benign pleural effusion, a rare presentation of hepatitis A virus: a case report and review of the literature. J Med Case Rep. 2022;16(1):1–8. https://doi.org/10.1186/s13256-022-03449-w .

Vinoth PN, Anitha P, Muthamilselvan S, Shuba S, Rajakumar PS, Scott JX, et al . Pleural effusion—an unusual cause. Case details Implications Pract. 2012;113–6.

Dhakal AK, Shakya A, Shrestha D, Shah SC, Shakya H. An unusual association of pleural effusion with acute viral hepatitis A infection. Pediatr Health Med Ther. 2014. https://doi.org/10.2147/PHMT.S70869 .

Agha RA, Franchi T, Sohrabi C, Mathew G, Kerwan A; SCARE Group. The SCARE 2020 Guideline: Updating Consensus Surgical CAse REport (SCARE) Guidelines. Int J Surg. 2020;84:226–230. https://doi.org/10.1016/j.ijsu.2020.10.034

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Fatima Breim, Bakri Roumi Jamal, Lama Kanaa, Saleh Bourghol & Besher Jazmati

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Samia Dadah supervised and helped in writing the manuscript. Fatima Breim, Bakri Roumi Jamal, Lama Kanaa, Saleh Bourghol and Besher Jazmati wrote the manuscript. Fatima Breim critically revised the manuscript. All authors read and approved the final manuscript.

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Breim, F., Roumi Jamal, B., Kanaa, L. et al. Hepatitis A virus infection associated with bilateral pleural effusion, ascites, and acalculous cholecystitis in childhood: a case report. J Med Case Reports 18 , 304 (2024). https://doi.org/10.1186/s13256-024-04627-8

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Genetic variation of TLR3 gene is associated with the outcome of hepatitis b infection in mauritanian patients: case control study

• Tetou Soumbara 1 , 2 ,
• Crystel Bonnet 3 ,
• Cheikh Tijani Hamed 2 ,
• Fatimetou Veten 2 ,
• Mohamed Hemeyine 2 ,
• F-Zahra Fall-Malick 2 ,
• Mohamed Mahmoud El Yezid 2 ,
• Aichetou Diallo 2 ,
• Moustapha Mouhamedou Mounah 2 &
• Ahmed Houmeida 1  

BMC Infectious Diseases volume  24 , Article number:  616 ( 2024 ) Cite this article

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Toll-Like receptors (TLRs) play an important role in the immune response during hepatitis B virus (HBV) infection. In this study, we evaluated the association between two SNP variants (TLR3 rs3775290 and TLR4 rs4986790) and susceptibility to chronic HBV infection in Mauritania.

Subjects and methods

: A total of 188 subjects were recruited for this study: 102 chronically infected patients and 86 individuals with spontaneously resolved HBV infection who were considered controls. Targeted PCR products were sequenced using Sanger sequencing.

We found that TLR3 rs3775290 was significantly more frequent in patients with chronic HBV than in the control population ( p  = 0.03). However, no association was found between the TLR4 rs3775290 polymorphism and chronic infection.

Our results suggest that the TLR3 rs3775290 polymorphism may be a risk factor for susceptibility to chronic HBV infection in the Mauritanian population.

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Introduction

The WHO estimated that approximately 296 million people were affected by chronic hepatitis B virus (HBV) infection in 2019, with one of the highest burdens (81 million) found among African populations [ 1 ]. In Mauritania, although on a decreasing slope since the introduction of the hepatitis B virus (HBV) vaccination for children and newborns in 2000, the prevalence of hepatitis B surface antigen (HBsAg) remained relatively elevated, with more than 10% positivity in blood donors [ 2 , 3 ]. A fraction of these cases, yet precisely undetermined, lead to HBV-related hepatocellular carcinoma (HCC) and cirrhosis [ 4 , 5 , 6 ].

Among the factors that control the course of HBV infection from spontaneous HBsAg seroclearance to long-term illness, the genetic background of the host is considered to be a major determinant of disease progression [ 7 , 8 , 9 ]. Numerous studies have indeed reported a connection between human Toll-Like receptors (TLRs) and HBV infection, for instance, the reduced expression of TLRs in patients with chronic hepatitis B [ 10 , 11 ] or the effect of SNPs in TLRs on the immune control of HBV infection [ 12 , 13 , 14 ]. The main function of these receptors is to discern specific structurally conserved molecules derived from pathogens, called pathogen-associated molecular patterns (PAMPs), as well as endogenous molecules emitted from damaged cells (DAMPs) [ 15 , 16 ]. The proposed mechanisms of their contribution to the outcome of HBV infection range from alteration of the extent of viral replication to activation of the body’s native immunity, leading to the development of an anti-HBV-specific adaptive response [ 17 , 18 , 19 ]. Despite the high prevalence of HBV infection in Mauritania and, globally, in sub-Saharan populations, data on the pathophysiological process of disease outcome and the role of TLRs remain scarce in our region. Data on TLR3 rs3775290 and TLR4 rs4986790 polymorphisms are often controversial with significant variability among different populations [ 13 , 20 , 21 , 22 ]. TLR3 and TLR4 SNPs alter the interaction between the receptor and its ligand [ 23 , 24 ]. A recent report have highlighted the association between TLR3 rs3775290 and TLR4 rs4986790 and chronic HBV infection within North African population [ 13 ]. Mauritania is known for its rich ethnic diversity, which includes multiple racial groups originating from both sub-Saharan Africa and North Africa [ 25 ].

In this study, we explored the relationship between TLR3 rs3775290 and TLR4 rs4986790 polymorphisms and susceptibility to chronic HBV infection in a cohort of Mauritanian HBV patients.

Sample size estimation was performed using an equation developed by Daniel (1999) [ 26 ]. It considered a 95% confidence interval [CI], a 5% margin of error, and an estimated prevalence of HBV at 10% [ 27 ]. The initial estimated sample size was 137 participants. However, to ensure sufficient statistical power for the analysis, the sample size was subsequently increased to 188 subjects previously infected with HBV.

The subjects included 102 patients with chronic HBV infection and 86 controls who had recovered spontaneously from the infection. Patients and controls were recruited at the National Institute of Hepato-Virology and the National Blood Transfusion Center, respectively, between 2020 and 2022. Chronic HBV patients were identified by the presence of HBsAg and HBV DNA for more than six months after their first positive blood test. Spontaneous hepatitis B seroclearance was tested in controls by HBsAg negativity in addition to hepatitis B core (total anti-HBc) and hepatitis B surface (anti-HBs) antibody-positive results. Patients were classified according to HBV viral load, alanine aminotransferase (ALT) levels and HBeAg status, as recommended by the European Association for the Study of the Liver (EASL). HBeAg negative chronic infection (inactive carriers) patients ( N  = 91) were identified by the absence of HBeAg, low levels of HBV DNA in the serum (< 2000 IU/mL) and consistently normal ALT levels. The HBeAg negative chronic hepatitis patients ( N  = 7) were characterized by HBeAg negativity, a high viral load (≥ 2000 IU/mL) and persistently elevated ALT levels. Patients with HBeAg positive chronic infection (immune tolerant) ( N  = 4) were characterized by the presence of HBeAg, high viral load and normal ALT levels.

HBV serological markers and alpha-fetoprotein (AFP) levels were analyzed using a commercial kit (Vidas®; Biomérieux Diagnostics, France). HBV viral load was quantified in patient plasma using the GeneXpert® System. Both patients and controls were negative for HCV and HIV. Blood alanine transaminase (ALT) levels were measured using a Biosystems A25 analyzer (BioSystems S.A., Barcelona, Spain).

The study was conducted in accordance with the Helsinki Declaration and was approved by the ethics committee of the University of Nouakchott (ethics clearance letter No002/2020/CE/UNA). Participants signed an informed consent questionnaire at the time of inclusion.

TLR3 and TLR4 genotyping

Whole blood was collected in EDTA tubes, and genomic DNA was extracted using the QIAamp.

DNA Blood Mini kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions. Agarose 2% electrophoresis and a NanoDrop spectrophotometer (Jenway, USA) were used to assess the purity and DNA concentration in samples.

TLR3 (1377 C > T) (rs3775290) and TLR4 (896 A > G) (rs4986790) polymorphisms were amplified using forward and reverse primers previously used by Cheng et al., 2007 and Pandey et al. [ 28 , 29 ]. , in a final volume of 50 µl. The PCR mix consisted of 25 µl dNTP (200 µM, Invitrogen, Carlsbad, CA, USA), 2 µl of each primer (2 pmol/µl, Sigma‒Aldrich, Germany), 3.2 µl of genomic DNA template (30–100 ng/µl), 17.3 µl of ultrapure H2O, and 0.5 µl of DNA polymerase (0.25 U/µl, GreenTaq DNA Polymerase, GenScript, USA). A 2% agarose gel was used to visualize the PCR products.

PCR products were purified on a membrane before fluorometric quantification using Pico Green reagent (Invitrogen). All validated samples were then sequenced in both directions using an ABI 3730XL DNA sequencer by Genoscreen (Genoscreen, Inc., Lille, France).

Continuous demographic variables were compared by Student’s t test or the Mann‒Whitney test when adequate. We used the χ2 test to evaluate categorical data between patients and controls. Allele and genotype frequencies of TLR3 rs3775290 and TLR4 rs4986790 were evaluated by direct counting. Genotype distributions of SNPs between the expected and observed genotypes were assessed using Hardy-Weinberg equilibrium (HWE). The χ2 test was used to analyze the genotype and allele distributions. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were also calculated. Statistical analyses were performed using SPSS ver.25.0 software (SPSS Inc., Chicago, IL, USA). Statistical significance was set at P  < 0.05.

The demographic characteristics and liver function tests of the participants are summarized in Table  1 . The mean age was 41 ± 1.03 years and 36 ± 0.96 years for the 102 chronic HBV patients and 86 healthy controls enrolled, respectively. Males represented the majority of the recruited subjects (55.9% of chronic HBV patients and 71.3% of healthy controls). Age and sex distributions differed significantly between patients and controls ( p  = 0.001 and p  = 0.03, respectively). The mean viral load recorded here for chronic HBV patients was 2.45 ± 34.23 log10 IU/ml, while the average hepatic alanine transaminase (ATL) level was 26.9 ± 0.97 IU/l.

AFP levels have been shown to be associated with liver fibrosis [ 30 ]. In our chronic HBV patient cohort, the mean AFP level was 1.69 ± 0.99 ng/ml and there was no statistical difference in AFP levels ( p  = 0.14) among chronic HBV patients with different disease stages (Fig.  1 ).

AFP levels in chronic HBV patient at different disease stages (page 9–10

Genotype distribution showed that the chronic HBV and control groups were in Hardy-Weinberg equilibrium for both TLRs: TLR3 (1377 C > T) (rs3775290) and TLR4 (896 A > G) (rs4986790) SNPs ( p  > 0.05) (Table  2 ).

The allele frequencies of TLR3 and TLR4 polymorphisms in patients and healthy controls for each genotype are given in Table  3 .

All three genotypes (CC, CT, and TT) were identified for the TLR3 (1377 C > T) (rs3775290) polymorphism (Fig.  2 ). Both patients and healthy control groups had the highest prevalence of the wild-type CC genotype (51% and 62%, respectively). The prevalence of the homozygous mutant TT genotype in HBV patients (12.7%) was significantly higher than that in controls (2%) ( p  = 0.03) (Table  3 ). This frequency was also higher in the chronic HBV infection group than in the non-TT genotype group. ( P  = 0.009) (Table  3 ).

Sanger sequencing chromatograms of the TLR3 rs3775290 and TLR4 rs4986790 polymorphisms. Arrows in panels A-C (left panel) show CC (wild type), TC (heterozygous) and TT (mutant) genotypes, respectively. The arrows in panels A-C (right panel) show AA (wild type), AG (heterozygous) and GG (mutant) genotypes, respectively. (page 9–10

Looking in allelic distribution, the prevalence of the C allele was 69% and 80% in HBV patients and controls, respectively (Table  4 ). The mutant T allele was significantly more prevalent in patients (31%) than in controls (20%) (OR = 0.57, 95% CI: 0.35–0.92, P  = 0.02) (Table  4 ).

All three genotypes (AA, AG, and GG) were identified for the TLR4 (896 A > G) (rs4986790) polymorphism (Fig.  2 ). However, both genotype and allele analyses showed no significant difference in genotype and allele distribution between chronically infected patients and healthy controls ( p  = 0.11 and p  = 0.57, respectively) (Tables  3 and 4 ).

The links between TLR3 and TLR4 SNPs and chronic HBV disease stages were examined and presented in Table  5 . No statistically significant difference was observed in the frequency of the mutant TT genotype of the TLR3 rs3775290 among the various the HBV patient groups ( p  = 0.4). The homozygous mutant GG genotype of the TLR4 rs s4986790 was not detected in chronic HBV patients. Additionally, the frequency of AA genotype compared to non-AA genotype showed no significant variation among chronic HBV patients groups ( p  = 0.2).

The role of TLRs in the host antiviral immune response during HBV infection has been extensively reviewed, particularly the disease manifestation from spontaneously resolved asymptomatic infection to long lasting chronic HBV infection [ 14 , 31 , 32 ]. In the first study exploring this effect in the Mauritanian population, 102 patients with chronic HBV infection and 86 controls were examined. The patient group mainly consisted of older males with normal ALT and AFP levels. The majority of patients had HBeAg negative chronic infection (inactive carriers), which is commonly seen in patients with chronic HBV infection in African regions [ 33 , 34 ] and other parts of the world [ 35 ]. This HBV profile was generally associated with a positive prognosis and low severity of liver disease [ 36 ].

We showed that the TLR3 rs3775290 polymorphism was significantly associated with an increased probability of developing chronic HBV infection. The frequencies of both the minor T allele and TT homozygous genotype were indeed higher ( p  < 0.05) in chronic HBV infection carriers than in healthy controls. A similar result in our region has been reported for HBV infection in the Tunisian population; with a twofold higher risk of chronic HBV infection in TLR3 rs3775290 (T allele) carriers than in non-mutant controls [ 13 ]. This result is in agreement with previous studies showing a similar prevalence of various biomarkers of disease, reflecting the common ethnicity of the two populations [ 25 ]. Conversely, no overall risk of developing chronic HBV was found in the South China population, where the rs3775290 polymorphism of the TLR3 gene has a protective effect against the development of chronic HBV infection [ 22 ]. Our results were obtained using the reliable Sanger method in a reference sequencing facility (Genoscreen/France). Therefore, this inconsistency in HBV infection outcome between our population and the Chinese cohort may have resulted from differences in TLR3 rs3775290 levels in the respective populations. Worldwide, many studies have reported that variation in the level of genetic polymorphisms in populations of different ethnicities has an important role in disease susceptibility [ 9 , 37 , 38 ]. For instance, activation of the intracellular signaling pathway inducing TLR-mediated INF generation has been shown to play an important role in the natural course of HBV infection [ 19 , 39 ], as revealed by the concomitant reduction in TLR3 expression and alteration of TNF-α in liver cell lines of chronic HBV patients compared to healthy controls [ 40 ]. In addition, restoration of TLR expression levels improved the immune response to HBV infection [ 41 ]. TLR3 deficiency has also been shown to increase the risk of other diseases, such as herpes simplex encephalitis and Coxsackie virus infection [ 42 , 43 ], supporting the role of the TLR3-mediated immune response [ 44 ]. The difference in the prevalence of TLR3 rs3775291, another TLR3 variant, between chronic HBV patients and healthy Caucasian individuals with resolved infection was concluded to contribute to the lower risk of HBV persistence [ 45 ]. This polymorphism (substitution of G for A) changes leucine to phenylalanine at position 412. Its role in reducing antiviral immunity was explained by its action on TLR3 dimerization, resulting in reduced dsRNA binding affinity and, consequently, decreased production of interferon signaling activity. Because the TLR3 rs3775290 SNP (residue 459) was located in the same protein region, a comparable impact on transcriptional activity may be proposed here as also leading to a similar HBV infection in carriers of both SNPs. The TLR3 rs3775290 variant also showed conserved wild-type phenylalanine residues. Because silent mutations do not affect the amino acid sequence, they often have no observable effect on the phenotype. However, recent studies have suggested that these mutations may influence steps in the protein-making process, both in DNA transcription and translation of mRNA into proteins [ 44 ]. This process may be applicable to the impairment of TLR3 binding to dsRNA from pathogens that activate the immune response mentioned above.

Furthermore, the TLR3 rs3775290 polymorphism is a hotspot mutation [ 46 ]. The significantly higher occurrence of these mutations in highly conserved TLR receptors makes them very likely functional, and many examples of their role in various regulatory pathways have been reported [ 47 , 48 ].

In the second Toll-like receptor explored in this study, we found no association between TLR4 (896 A > G) (rs4986790) and susceptibility to chronic HBV infection in the Mauritanian cohort, as no significant differences were observed in the distribution of genotypes ( p  = 0.11) and mutant alleles ( p  = 0.57) between chronic HBV patients and healthy controls. Similar results were reported by Pires-Neto et al., where TLR4 rs4986790 was not associated with chronic carriers of HBV or HCV infections [ 49 ]. Katrinli et al. also found no relationship between TLR4 variants and the persistence of HBV infection [ 20 ].

Conclusions

In this study, the TT mutant genotype of the TLR3 rs3775290 polymorphism was significantly associated with an increased risk of chronic HBV infection, whereas the TLR4 rs4986790 polymorphism was not associated with long-term HBV chronicity in the Mauritanian population. This result supports the key role of this class of receptors in the immune response during HBV infection. No effect of the TLR4 (896 A > G) (rs4986790) polymorphism on the disease outcome was observed in this study. Further studies should include investigating the impact of these SNPs on HBV-related diseases such as liver cirrhosis and hepatocellular carcinoma. Additionally, it is important to examine the role of hepatitis D virus (HDV) as an aggravating factor in these diseases. Implication of TLR variants could also be carried out as part of the action against the spread of HBV infection, which remains prevalent in our region.

Limitations

A limitation of this study is that we did not assess the interaction between TLR3 SNP rs3775290 frequency and the level of known HBV infection biomarkers such as HBeAg and HBsAg both in chronic HBV patients and individuals with spontaneous clearance of HBV. These markers may inhibit TLR-induced antiviral activity, as evidenced by decreased activation of IRF-3, NF-κB and ERK1/2 in hepatic non-parenchymal cell (NPC) supernatants containing HBsAg, HBeAg, and HBV virions.

Data availability

The datasets generated and/or analyzed during the current study are available in the SRA repository, PRJNA1013319.

Web link: http://www.ncbi.nlm.nih.gov/bioproject/1013319 .

Abbreviations

Alanine transaminase

Confidence intervals

Damage-associated molecular patterns

Deoxyribonucleic acid

Hepatitis B surface antigen

Hepatitis B virus

Hepatocellular carcinoma

Hepatitis C virus

Human immunodeficiency virus

Hardy-Weinberg equilibrium

Interferons

Non-parenchymal cell

Odds ratios

Pathogen-associated molecular patterns

Polymerase chain reaction

Ribonucleic acid

• Single-nucleotide polymorphism

Toll-Like receptor

Tumor necrosis factor-alpha

Hepatitis B. data 2019. [cited 2022 Nov 25]. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b .

Mansour W, Bollahi MA, Hamed CT, Brichler S, Le Gal F, Ducancelle A, et al. Virological and epidemiological features of hepatitis delta infection among blood donors in Nouakchott, Mauritania. J Clin Virol. 2012;55(1):12–6.

Article   PubMed   Google Scholar  

Boushab BM, Melaïnine Mohamed Limame OC, Zahra FMF, Mamoudou S, Roseline Darnycka BM, Saliou SM. Estimation of seroprevalence of HIV, hepatitis B and C virus and syphilis among blood donors in the hospital of Aïoun, Mauritania. Pan Afr Med J. 2017 [cited 2023 Jul 1];28. http://www.panafrican-med-journal.com/content/article/28/118/full/ .

Suzuki Y, Maekawa S, Komatsu N, Sato M, Tatsumi A, Miura M, et al. Hepatitis B virus (HBV)-infected patients with low hepatitis B surface antigen and high hepatitis B core‐related antigen titers have a high risk of HBV‐related hepatocellular carcinoma. Hepatol Res. 2019;49(1):51–63.

Article   CAS   PubMed   Google Scholar  

Nguyen VTT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat. 2009;16(7):453–63.

Bixler D, Zhong Y, Ly KN, Moorman AC, Spradling PR, Teshale EH, et al. Mortality among patients with chronic Hepatitis B infection: the chronic Hepatitis Cohort Study (CHeCS). Clin Infect Dis. 2019;68(6):956–63.

Ma Z, Zhang E, Yang D, Lu M. Contribution of toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses. Cell Mol Immunol. 2015;12(3):273–82.

King H, Xing J, Dean HD, Holtzman D. Trends in Prevalence of protective levels of Hepatitis B surface antibody among adults aged 18–49 years with risk factors for Hepatitis B Virus infection—United States, 2003–2014. Clin Infect Dis. 2020;70(9):1907–15.

Zhang Z, Wang C, Liu Z, Zou G, Li J, Lu M. Host genetic determinants of Hepatitis B Virus infection. Front Genet. 2019;10:696.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Chen Z, Cheng Y, Xu Y, Liao J, Zhang X, Hu Y, et al. Expression profiles and function of toll-like receptors 2 and 4 in peripheral blood mononuclear cells of chronic hepatitis B patients. Clin Immunol. 2008;128(3):400–8.

Li N, Li Q, Qian Z, Zhang Y, Chen M, Shi G. Impaired TLR3/IFN-β signaling in monocyte-derived dendritic cells from patients with acute-on-chronic hepatitis B liver failure: relevance to the severity of liver damage. Biochem Biophys Res Commun. 2009;390(3):630–5.

Kayesh MEH, Kohara M, Tsukiyama-Kohara K. Toll-like receptor response to Hepatitis B Virus infection and potential of TLR agonists as Immunomodulators for Treating Chronic Hepatitis B: an overview. Int J Mol Sci. 2021;22(19):10462.

Sghaier I, Zidi S, Mouelhi L, Ghazoueni E, Brochot E, Almawi WY et al. TLR3 and TLR4 SNP variants in the liver disease resulting from hepatitis B virus and hepatitis C virus infection. Br J Biomed Sci. 2018 Dec 3 [cited 2022 Jun 23]; https://www.tandfonline.com/doi/abs/ https://doi.org/10.1080/09674845.2018.1547179 .

Al-Qahtani A, Al-Ahdal M, Abdo A, Sanai F, Al-Anazi M, Khalaf N, et al. Toll-like receptor 3 polymorphism and its association with hepatitis B virus infection in Saudi Arabian patients. J Med Virol. 2012;84(9):1353–9.

El-Zayat SR, Sibaii H, Mannaa FA. Toll-like receptors activation, signaling, and targeting: an overview. Bull Natl Res Cent. 2019;43(1):187.

Article   Google Scholar  

Kawai T, Akira S. Toll-like receptors and their crosstalk with other Innate receptors in infection and immunity. Immunity. 2011;34(5):637–50.

Du Y, Wu J, Liu J, Zheng X, Yang D, Lu M. Toll-like receptor-mediated innate immunity orchestrates adaptive immune responses in HBV infection. Front Immunol. 2022;13:965018.

Ait-goughoulte M, Lucifora J, Zoulim F, Durantel D. Innate antiviral Immune responses to Hepatitis B Virus. Viruses. 2010;2(7):1394–410.

Zhang E, Lu M. Toll-like receptor (TLR)-mediated innate immune responses in the control of hepatitis B virus (HBV) infection. Med Microbiol Immunol (Berl). 2015;204(1):11–20.

Katrinli S, Nigdelioglu A, Ozdil K, Dinler-Doganay G, Doganay L. The association of variations in TLR genes and spontaneous immune control of hepatitis B virus. Clin Res Hepatol Gastroenterol. 2018;42(2):139–44.

Wu JF, Chen CH, Ni YH, Lin YT, Chen HL, Hsu HY, et al. Toll-like receptor and Hepatitis B Virus Clearance in Chronic Infected patients: a long-term prospective cohort study in Taiwan. J Infect Dis. 2012;206(5):662–8.

Huang X, Li H, Wang J, Huang C, Lu Y, Qin X, et al. Genetic polymorphisms in toll-like receptor 3 gene are associated with the risk of hepatitis B virus-related liver diseases in a Chinese population. Gene. 2015;569(2):218–24.

Pandey S, Mittal B, Srivastava M, Singh S, Srivastava K, Lal P, et al. Evaluation of toll-like receptors 3 (c.1377 C/T) and 9 (G2848A) gene polymorphisms in cervical cancer susceptibility. Mol Biol Rep. 2011;38(7):4715–21.

Cussigh A, Fabris C, Fattovich G, Falleti E, Cmet S, Bitetto D, et al. Toll like receptor 4 D299G Associates with Disease Progression in caucasian patients with chronic HBV infection: relationship with gender. J Clin Immunol. 2013;33(2):313–6.

Hamed CT, Meiloud G, Veten F, Hadrami M, Ghaber SM, Boussaty EC, et al. HLA class I (-A, -B, -C) and class II (-DR, -DQ) polymorphism in the Mauritanian population. BMC Med Genet. 2018;19(1):2.

Article   PubMed   PubMed Central   Google Scholar  

Metcalfe C, Biostatistics WW, Daniel. Wiley, 1999. No. of. pages: xiv + 755 + appendices. Price: £28.95. ISBN 0-471-16386-4. Stat Med. 2001;20(2):324–6.

Polaris Observatory Collaborators. Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study. Lancet Gastroenterol Hepatol. 2023;8(10):879–907.

Cheng PL, Eng HL, Chou MH, You HL, Lin TM. Genetic polymorphisms of viral infection-associated toll-like receptors in Chinese population. Transl Res. 2007;150(5):311–8.

Pandey NO, Chauhan AV, Raithatha NS, Patel PK, Khandelwal R, Desai AN, et al. Association of TLR4 and TLR9 polymorphisms and haplotypes with cervical cancer susceptibility. Sci Rep. 2019;9(1):9729.

Yang K, Pan Y, Liu L, Sun B, Shi W. Serum Alpha-Fetoprotein as a predictor of liver fibrosis in HBeAg-Positive chronic Hepatitis B patients. Med (Mex). 2023;59(5):923.

Google Scholar  

Xu Y, Xue W, Gao H, Cui J, Zhao L, You C. Association of toll-like receptors single nucleotide polymorphisms with HBV and HCV infection: research status. PeerJ. 2022;10:e13335.

An P, Xu J, Yu Y, Winkler CA. Host and viral genetic variation in HBV-Related Hepatocellular Carcinoma. Front Genet. 2018;9:261.

Riches N, Vinikoor M, Guingane A, Johannessen A, Lemoine M, Matthews P, et al. Hepatitis B in Africa Collaborative Network: cohort profile and analysis of baseline data. Epidemiol Infect. 2023;151:e65.

Somé EN, Guingané AN, Zongo I, Sané D, Drabo KM, Sombié R. Chronic viral HBeAg-negative hepatitis B: Epidemiological, clinical and biochemical characteristics in an outpatient descriptive cohort in Burkina Faso. Clin Epidemiol Glob Health. 2021;11:100799.

Chevaliez S, Roudot-Thoraval F, Brouard C, Gordien E, Zoulim F, Brichler S, et al. Clinical and virological features of chronic hepatitis B in the French national surveillance program, 2008–2012: a cross-sectional study. JHEP Rep. 2022;4(12):100593.

Manno M, Cammà C, Schepis F, Bassi F, Gelmini R, Giannini F, et al. Natural history of chronic HBV carriers in northern Italy: morbidity and mortality after 30 years. Gastroenterology. 2004;127(3):756–63.

Chiarella P, Capone P, Sisto R. Contribution of genetic polymorphisms in Human Health. Int J Environ Res Public Health. 2023;20(2):912.

Yan ZH, Fan Y, Wang XH, Mao Q, Deng GH, Wang YM. Relationship between HLA-DR gene polymorphisms and outcomes of hepatitis B viral infections: a meta-analysis. World J Gastroenterol WJG. 2012;18(24):3119–28.

Takeuchi O, Akira S. Pattern Recognition Receptors and inflammation. Cell. 2010;140(6):805–20.

Huang YW, Lin SC, Wei SC, Hu JT, Chang HY, Huang SH, et al. Reduced toll-like receptor 3 expression in Chronic Hepatitis B patients and its restoration by Interferon Therapy. Antivir Ther. 2013;18(7):877–84.

Deng G, Ge J, Liu C, Pang J, Huang Z, Peng J, et al. Impaired expression and function of TLR8 in chronic HBV infection and its association with treatment responses during peg-IFN-α-2a antiviral therapy. Clin Res Hepatol Gastroenterol. 2017;41(4):386–98.

Guo Y, Audry M, Ciancanelli M, Alsina L, Azevedo J, Herman M, et al. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J Exp Med. 2011;208(10):2083–98.

Richer MJ, Lavallée DJ, Shanina I, Horwitz MS. Toll-Like Receptor 3 Signaling on Macrophages Is Required for Survival Following Coxsackievirus B4 Infection. Means T, editor. PLoS ONE. 2009;4(1):e4127.

Gosu V, Son S, Shin D, Song KD. Insights into the dynamic nature of the dsRNA-bound TLR3 complex. Sci Rep. 2019;9(1):3652.

Fischer J, Koukoulioti E, Schott E, Fülöp B, Heyne R, Berg T, et al. Polymorphisms in the toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in caucasian population. Sci Rep. 2018;8(1):12737.

Wang BG, Yi DH, Liu YF. TLR3 gene polymorphisms in cancer: a systematic review and meta-analysis. Cancer Commun. 2015;34(3):19.

Miller ML, Reznik E, Gauthier NP, Aksoy BA, Korkut A, Gao J, et al. Pan-cancer analysis of mutation hotspots in protein domains. Cell Syst. 2015;1(3):197–209.

Mitchell AL, Attwood TK, Babbitt PC, Blum M, Bork P, Bridge A, et al. InterPro in 2019: improving coverage, classification and access to protein sequence annotations. Nucleic Acids Res. 2019;47(D1):D351–60.

Pires-Neto O, de Gomes S. STM. Lack of association between polymorphisms of the TLR4 gene and infection with the Hepatitis B and C viruses. Mediators Inflamm: 7.

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Acknowledgements

This work was partially supported by the National Agency for Scientific Research and Innovation.

We thank the director of the National Blood Transfusion Center and all the workers there for their help.

This study was not funded.

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Research Unit on Biomarkers in the Mauritanian Population, Faculty of Sciences and Technology, University of Nouakchott, Nouakchott, Mauritania

Tetou Soumbara & Ahmed Houmeida

National Institute of Hepato- Virology (INHV), Nouakchott, Mauritania

Tetou Soumbara, Cheikh Tijani Hamed, Fatimetou Veten, Mohamed Hemeyine, F-Zahra Fall-Malick, Mohamed Mahmoud El Yezid, Aichetou Diallo & Moustapha Mouhamedou Mounah

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Contributions

TS collected and organized patient files for genotyping and contributed to statistical analysis and manuscript writing. CB analyzed sequencing data; CH, FV, ZM and MY contributed to genotyping and statistical analysis; MH, AD; and MM carried out patient and control clinical assessments; AH carried out manuscript design and writing.

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Correspondence to Ahmed Houmeida .

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The study was conducted in accordance with the Helsinki Declaration and approved by the ethics committee of the University of Nouakchott (ethics clearance letter No002/2020/CE/UNA). Participants signed an informed consent questionnaire at the time of inclusion.

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Informed consent was obtained from all study participants. Informed consent of all patients was also obtained for data publication.

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Soumbara, T., Bonnet, C., Hamed, C.T. et al. Genetic variation of TLR3 gene is associated with the outcome of hepatitis b infection in mauritanian patients: case control study. BMC Infect Dis 24 , 616 (2024). https://doi.org/10.1186/s12879-024-09503-w

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Received : 01 August 2023

Accepted : 12 June 2024

Published : 21 June 2024

DOI : https://doi.org/10.1186/s12879-024-09503-w

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Report of renal allograft tuberculosis a decade after transplant: challenges in diagnosis and management

• Case Report
• Published: 26 June 2024

Cite this article

• Joy Kumar 1 ,
• Shankar Prasad Nagaraju 2 ,
• Kavitha Saravu 3 &
• Dharshan Rangaswamy   ORCID: orcid.org/0000-0002-6152-7493 2  

Post-transplant infections constitute an important cause of morbidity and mortality in renal transplant recipients worldwide. Tuberculosis (TB) contributes significantly to this burden in endemic countries, such as India. We report a case of renal allograft TB, 10 years post-transplantation, diagnosed during a routine outpatient visit. An asymptomatic rise in serum creatinine level and a 6 month history of immunosuppressive drug non-compliance prompted evaluation of graft dysfunction. Biopsy of the renal allograft tissue suggested chronic active antibody mediated rejection with epithelioid granulomas in the interstitium. Guided by kidney biopsy, further testing with urine acid fast bacilli and urinary GeneXpert yielded positive results for TB. Treatment of TB was further complicated by the development of anti-tubercular therapy induced hepatitis and immune reconstitution inflammatory syndrome, which were managed with the reintroduction regimen and escalation of steroid dose, respectively. Our case highlights the atypical presentation and challenges in managing patients with TB in a post-renal transplant setting.

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Data availability

The data that support the findings of this study are available on request from the corresponding author, [DR]. The data are not publicly available due to restrictions, containing information that could compromise the privacy of research participants.

Sundaram M, Adhikary SD, John GT, Kekre NS. Tuberculosis in renal transplant recipients. Indian J Urol. 2008;24(3):396. https://doi.org/10.4103/0970-1591.42625 .

Article   PubMed   PubMed Central   Google Scholar  

Khaira A, Bagchi S, Sharma A, Mukund A, Mahajan S, Bhowmik D, Dinda AK, Agarwal SK. Renal allograft tuberculosis: report of three cases and review of literature. Clin Exp Nephrol. 2009;13:392–6. https://doi.org/10.1007/s10157-009-0158-6 .

Article   PubMed   Google Scholar  

John GT, Shankar V, Mukundan U, Thomas PP, Jacob CK. Risk factors for post-transplant tuberculosis. Kidney Int. 2001;60(3):1148–53. https://doi.org/10.1046/j.1523-1755.2001.0600031148.x .

Article   CAS   PubMed   Google Scholar  

Sasi S, Varghese MK, Nair AP, Hashim S, Al MM. Tuberculosis in an allogeneic transplant kidney: a rare case report and review of literature. Cureus. 2020. https://doi.org/10.7759/cureus.11661 .

Canet E, Dantal J, Blancho G, Hourmant M, Coupel S. Tuberculosis following kidney transplantation: clinical features and outcome a french multicentre experience in the last 20 years. Nephrol Dial Transplant. 2011;26(11):3773–8. https://doi.org/10.1093/ndt/gfr156 .

Krishnamoorthy S, Kumaresan N, Zumla A. Latent tuberculosis infection and renal transplantation–diagnosis and management. Int J Infect Dis. 2019;1(80):S73–6. https://doi.org/10.1016/j.ijid.2019.01.049 .

Article   Google Scholar  

Sathiyamoorthy R, Kalaivani M, Aggarwal P, Gupta SK. Prevalence of pulmonary tuberculosis in India: a systematic review and meta-analysis. Lung India. 2020;37(1):45. https://doi.org/10.4103/lungindia.lungindia_181_19 .

Clinical Spectrum of Extrapulmonary Tuberculosis in a Tertiary Care Center South India (2020) InC53. Global Experiences. In: Tb And Ntm Care American Thoracic Society pp A5442-A5442 https://doi.org/10.1164/ajrccm-conference.2020.201

Torre-Cisneros J, Doblas A, Aguado JM, San Juan R, Blanes M, Montejo M, Cervera C, Len O, Carratala J, Cisneros JM, Bou G. Tuberculosis after solid-organ transplant: incidence, risk factors, and clinical characteristics in the RESITRA (spanish network of infection in transplantation) cohort. Clin Infect Dis. 2009;48(12):1657–65. https://doi.org/10.1086/599035 .

Surendran S, Thirumalvalavan K, MurugeshAnand S, Prasad ND, Fernando ME. Tuberculosis in kidney transplant recipients: a retrospective study from a tertiary care center-an observational study. Indian J Transplant. 2022. https://doi.org/10.4103/ijot.ijot_33_22 .

Sorohan BM, Ismail G, Tacu D, Obrișcă B, Ciolan G, Gîngu C, Sinescu I, Baston C. Mycobacterium tuberculosis infection after kidney transplantation: a comprehensive review. Pathogens. 2022;11(9):1041. https://doi.org/10.3390/pathogens11091041 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Muñoz P, Rodríguez C, Bouza E. Mycobacterium tuberculosis infection in recipients of solid organ transplants. Clin Infect Dis. 2005;40(4):581–7. https://doi.org/10.1086/427692 .

Wang YC, Salvador NG, Lin CC, Wu CC, Lin TL, Lee WF, Chan YC, Chen CL, Co JS, Encarnacion DD. Comparative analysis of the drug-drug interaction between immunosuppressants safety and efficacy of rifabutin from rifampicin-based anti-TB treatment in living donor liver transplant recipients with active tuberculosis. Biomed J. 2021. https://doi.org/10.1016/j.bj.2020.08.010 .

Sun HY, Munoz P, Torre-Cisneros J, Aguado JM, Lattes R, Montejo M, Garcia-Reyne A, Bouza E, Valerio M, Lara R, John GT. Mycobacterium tuberculosis—associated immune reconstitution syndrome in solid-organ transplant recipients. Transplantation. 2013;95(9):1173–81. https://doi.org/10.1097/TP.0b013e31828719c8 .

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Acknowledgements

The authors would like to thank Dr. Kiran K, Consultant Nephropathologist, Manipal Hospitals, Bengaluru, India for renal pathology inputs and providing the renal biopsy image.

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Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India

Department of Nephrology, Kasturba Hospital and Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India

Shankar Prasad Nagaraju & Dharshan Rangaswamy

Department of Infectious Diseases, Kasturba Hospital and Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India

Kavitha Saravu

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Correspondence to Dharshan Rangaswamy .

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Kumar, J., Nagaraju, S.P., Saravu, K. et al. Report of renal allograft tuberculosis a decade after transplant: challenges in diagnosis and management. CEN Case Rep (2024). https://doi.org/10.1007/s13730-024-00904-z

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Received : 19 June 2023

Accepted : 15 June 2024

Published : 26 June 2024

DOI : https://doi.org/10.1007/s13730-024-00904-z

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