A case of simultaneous hepatitis B reactivation in a married couple

Introduction

Chronic hepatitis B virus (HBV) infection is a dynamic state involving interactions between the HBV virus, the infected hepatocytes, and the host immune system. It is therefore possible that hepatitis activity with alanine aminotransferase (ALT) elevation, known as acute exacerbations or hepatitis flares, may occur spontaneously. Hepatitis B flare defined as an abrupt rise in ALT levels to more than five times the upper limit of normal in chronic HBV infection. It is considered to be the result of cytotoxic T lymphocyte-mediated immune response against HBV. ¹ Generally, it occurs in the setting of immunosuppression and/or chemotherapy.

Case report

A married couple was admitted to our hospital with complaints of malaise, jaundice, dark urine, white stool, and acute onset abdominal pain for ten days. Both patients appeared fatigued and jaundice was more prominent in the female. The medical history revealed that the female patient (35 years old) had chronic Hepatitis BAg-negative infection (formerly being an inactive HBsAg carrier) and the male patient had HBeAg-positive chronic HBV infection (formerly immune-tolerant). Both presented to our emergency department with elevated liver enzymes. The patients were admitted to our unit for further investigation. Laboratory tests for the female revealed aspartate aminotransferase (AST) of 1003 IU/L (normal 0–50), ALT of 1418 IU/L (normal 0–50), gamma-glutamyl transferase (GGT) of 235 IU/L (normal 0–38), alkaline phosphatase (ALP) of 104IU/L (normal 30–120), alpha fetoprotein (AFP) level 29 µg/L, total bilirubin: 109.40 µ/l, with a direct fraction of 46.2 µ/l and International normalized ratio (INR): 1.1. The serum HBV-DNA level was 4382 UI/mL. HBeAg was negative but anti-HBe and anti-HBcIgM were positive.

For the male (32 years old), results were: AST of 253 IU/L, ALT of 458 IU/L, GGT of 82 IU/L, ALP of 66 IU/L, total bilirubin: 119.7 µ/l, with a direct fraction of 34.2 µ/l and INR 1.1. The serum HBV-DNA level was 3177x 10⁵ UI/mL. AFP level was 3 µg/L. Both patients reported no use of alcohol, herbal medicines, nor drugs. Anti-HBe was negative but HBeAg and anti-HBcIgM were positive. Serological tests for Epstein-Barr virus, HIV, syphilis, hepatitis A, C, E and D, cytomegalovirus, and toxoplasmosis were negative in both patients. ANA, ASMA, Anti-LKM, Alpha 1 anti-trypsin, and ceruloplasmin levels were likewise negative. The female was discharged from the hospital subsequent to clinical and biochemical improvement. She ultimately developed anti-HBs antibodies and cleared the viral infection. For the male, a liver biopsy was performed and antiviral treatment administered. Both patients have exhibited favourable clinical progress for a period of 6 months.

Discussion

Both wife and husband had previously been infected with HBV. The female is originally from Morocco and had moved to Turkey 2 years earlier. During the period of preparation for their wedding, both individuals experienced considerable stress and encountered numerous challenges. In their first month of marriage, both patients simultaneously exhibited elevated levels of liver enzymes concurrently and were diagnosed with HBV reactivation. Eventually, the female patient developed antibodies, and the infection itself was resolved. The male patient was diagnosed with HBeAg-positive chronic hepatitis B and commenced antiviral therapy. It is plausible that the reactivations were triggered by emotional stress related to the wedding

Spontaneous reactivation (flare or exacerbation) of HBV infection is likely explained by changes in the immunological control of viral replication. ¹ It appears to be more prevalent in male homosexuals and in the setting of emotional or physical distress. ² Pregnancy and postpartum period may also be a risk factor. ³ In a study investigating the impact of stress on the reactivation of HBV, the incidence of hepatitis B flares was higher in the depression/anxiety cohort than in the control group. ⁴ These psychiatric conditions are independent risk factors for hepatitis B flares. These findings suggest that patients with chronic hepatitis B and concomitant depression or anxiety may be at an increased risk of hepatitis B reactivation. Also, the presence of positive anti-HBc IgM in both patients makes other primary causes less likely, as this antibody typically indicates recent or reactivated HBV infection.

The exact mechanism by which stress impairs the immune system is not known. Nevertheless, a number of hypotheses have been proposed. There is evidence to suggest that markers of impairment of cellular immunity (such as decreased natural killer cell cytotoxicity) are associated with depression. ⁵ Depression-induced immune dysregulation exerts a pronounced effect on the peripheral immune system, primarily due to its impact on the function and number of immune cells, particularly lymphocytes, and monocytes/macrophages. ⁶ Immune dysregulation may play a key role in the link between depression and medical disorders such as infection. Furthermore, stress and anxiety have an influence on the immune system, specifically affecting the B- and T-cell-mediated immune response. Also, there is evidence that depression and anxiety increase the risk of developing infectious diseases and reactivation of latent viral infections.^7,8

In conclusion, hepatitis B reactivation is a complex condition that can occur at any point in an individual's life. The primary cause is immunosuppression, although the underlying cause is frequently undetermined. In the absence of an identified aetiology, the condition is attributed to spontaneous occurrence. In such cases, stress may serve as a potential trigger.