Chronic hepatitis B infection is a common condition encountered in clinical practice, with nearly 2 billion people worldwide showing past or present serologic evidence of infection. It can lead to a wide range of hepatic manifestations, including acute hepatitis, fulminant hepatitis (though rare), cirrhosis, hepatocellular carcinoma (HCC), and even extra-hepatic manifestations. Occult hepatitis B infection (OHB) is a significant area of concern, as many patients may remain undiagnosed and, consequently, miss out on appropriate management. To address this issue, hepatitis testing panels should be readily available at government hospitals. Additionally, clinicians should maintain a high index of suspicion before diagnosing a patient with cryptogenic cirrhosis.

Occult hepatitis B, Cirrhosis, Viremia, Cryptogenic, Chronic hepatitis B virus infection.

Chronic HBV infection is a major health issue worldwide, with an estimated 1.5 million new infections and 820,000 deaths yearly (predominantly from cirrhosis and hepatocellular carcinoma).[1] It is transmitted at birth or later via person-to-person transmission. Vaccination is an effective prevention strategy for infection. In individuals with chronic infection, elevated serum HBV-DNA concentration is the main risk factor for disease progression, although there are other clinical and viral parameters that influence disease outcomes.[2] Occult HBV infection (OBI), alternatively defined as OHB, is a challenging clinical entity. It is recognized by two main characteristics: absence of HBsAg, and low viral replication.[3] This paper aims to highlight the clinical significance of OHB in patients with cryptogenic cirrhosis and to emphasize the need for routine HBV-DNA testing in HBsAg-negative individuals to improve diagnostic accuracy and optimize management strategies in resource-limited settings.

A 45-year-old male patient from Burie, Ethiopia, presented with a two-month history of progressive abdominal swelling, accompanied by easy fatigability and loss of appetite. He reported no history of sleep disturbances, melena, hematemesis, or changes in the color or quantity of urine. There was also no history of significant alcohol consumption. On physical examination, his vital signs were as follows: blood pressure (BP) 110/70 mmHg, respiratory rate (RR) 18 breaths per minute, pulse rate (PR) 88 beats per minute, and temperature (T) 36.6°C. Notable findings on abdominal examination included ascites and splenomegaly.

Initial laboratory investigations revealed a white blood cell (WBC) count of 2.4 × 10³/µL, hemoglobin (Hb) of 9 g/dL, mean corpuscular volume (MCV) of 97 fL, and platelet count of 78 × 10³/µL. Coagulation studies showed a prothrombin time (PT) of 12 seconds, a partial thromboplastin time (PTT) of 25 seconds, and an international normalized ratio (INR) of 1.2. Liver function tests demonstrated elevated transaminases with aspartate aminotransferase (AST) at 61 IU/L, alanine aminotransferase (ALT) at 52 IU/L, and alkaline phosphatase (ALP) at 125 IU/L. Total bilirubin was 0.9 mg/dL (direct fraction: 0.4 mg/dL), and serum albumin was reduced to 3 g/dL. Renal function was within normal limits with a serum creatinine level of 0.8 mg/dL.

Viral serology was negative for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, and human immunodeficiency virus (HIV). Due to concern for occult hepatitis B infection, HBV DNA testing was performed and revealed low-level viremia (15 IU/mL). Serum alpha-fetoprotein (AFP) was 4.44 IU/mL. Abdominal ultrasonography revealed a coarsely nodular liver with an irregular surface, consistent with cirrhosis, without evidence of focal hepatic lesions or portal vein thrombosis. The portal vein measured 17 mm in diameter, and the spleen was enlarged to 19 cm. Moderate ascites were also noted. Echocardiography showed no abnormalities. Upper gastrointestinal endoscopy revealed grade 3 esophageal varices with red wale signs and mild portal hypertensive gastropathy. Endoscopic variceal band ligation was performed, and the patient was scheduled for a follow-up session in four weeks.

Based on the clinical findings, the patient was started on tenofovir disoproxil fumarate (TDF) 300 mg orally once daily, furosemide 20 mg orally once daily, spironolactone 50 mg orally once daily, and propranolol 20 mg orally twice daily, with planned dose escalation to reach the target heart rate. He is also scheduled for his next esophageal variceal band ligation procedure.

HBV is one of the common causes of cirrhosis globally, along with HCV, alcohol, and non-alcoholic steatohepatitis (NASH), with regional differences in their contribution.[4] OBI is characterized by the presence of HBV-DNA in the liver of individuals who test negative for HBsAg and have low viral load (<200 IU/mL). Diagnosing OBI is challenging due to the intermittent detection of HBV-DNA in blood and the lack of standardized molecular tests for viral load.[5] OBI may have significant clinical implications, including: (a) transmission via blood transfusion or organ transplantation, leading to classic hepatitis B infection; (b) reactivation during conditions of immunosuppression, potentially resulting in fulminant hepatitis; (c) accelerated progression of liver disease and cirrhosis; (d) increased risk of hepatocellular carcinoma.[6] The gold standard for diagnosis of OBI is through highly sensitive molecular techniques like HBV nucleic acid amplification testing (NAT), a polymerase chain reaction (PCR) technique which can detect very low levels of HBV-DNA. While liver specimens can be used for diagnosis, serum samples are typically analyzed due to their easier availability. [7] Even with normal liver enzymes, OBI may still pose a risk for cirrhosis and HCC. In studies of patients considered to have cryptogenic cirrhosis, it has also been found that 4.8–40% of these patients had OBI.[8] To improve the treatment and management of patients with cryptogenic liver disease, HBV-DNA determination by highly sensitive molecular assays is recommended before the patient develops signs of cirrhosis or HCC.[9] A meta-analysis has shown an increased risk of HCC with OBI, with an odds ratio (OR) of 6.1 (95% confidence interval (CI): 3.5–10.7) for retrospective studies and an OR of 2.9 (95% CI: 1.6–4.1) for prospective
studies.[10]

It is important to consider the possibility of occult hepatitis B in patients with negative HBsAg test results who also have cirrhosis. Identifying occult hepatitis B and offering treatment can help reduce the potential risk of hepatocellular carcinoma. As a country from a high-prevalence region, our laboratories and healthcare infrastructure should be equipped to provide hepatitis serologic testing and viral load determination. Further studies are needed nationwide to determine the extent and significance of occult hepatitis B infection in cirrhotic patients.

I would like to thank the patient for their willingness to share information in this case report.

No funding

Zelalem Mulu
Department of Internal Medicine
Debre Markos University, Debre Markos, Ethiopia
Email: zmlaew@gmail.com

The author contributed to the conceptualization, investigation, and data curation by acquiring and critically reviewing the selected articles and was involved in the writing – original draft preparation and writing – review & editing to refine the manuscript.

The case report was approved by the research and ethical committee of Felege Hiwot Comprehensive Specialized Hospital, Ethiopia.

The author declares no conflict of interest.

None

https://doi.org/10.63096/medtigo30623214

Zelalem M. Occult Hepatitis B Infection in a Decompensated Cirrhosis Patient. medtigo J Med. 2025;3(2):e30623214. doi:10.63096/medtigo30623214 Crossref