ABSTRACT
Objectives
Hepatitis B virus (HBV) is a DNA virus that can cause acute and chronic hepatitis, liver failure, and liver cancer. It is a widespread public health problem that can be prevented by vaccination. This study aimed to evaluate the demographic, clinical, and laboratory data of patients with acute hepatitis B who were hospitalized in our clinic.
Materials and Methods
Twenty-three patients diagnosed with acute hepatitis B who were hospitalized and followed up in the infectious disease service between 2021 and 2023 were included in the study. Our study was designed as a retrospective cohort study.
Results
The patients had an average age of 51.3±12.6 years, with 21 (91.3%) being male. Twelve (52.1%) of 23 patients had chronic diseases, which prolonged hospital stays. All patients involved in the study were not vaccinated for HBV. An examination of the transmission routes showed that 3 (13%) patients were infected through intravenous drug use or tattooing, 6 (36%) through dental procedures, and 14 (61%) through sexual contact. Patients who contracted the virus sexually stayed longer in the hospital. Antiviral treatment was started in 7 out of 23 patients (30.4%) because of international normalized ratio elevation (above 1.5) during hospitalization. One patient was referred to a liver transplantation clinic. Other patients were recovered and discharged. All 14 patients who regularly attended outpatient follow-ups had negative hepatitis B surface antigen.
Conclusion
This study demonstrated that acute HBV infection continues to be observed in individuals over 50 years of age who were not routinely vaccinated in our country. The findings underscore the importance of adult vaccination and the implementation of methods to prevent sexually transmitted infections.
Introduction
Hepatitis B virus (HBV) is a DNA virus that causes infection through parenteral, sexual, and vertical (from mother to baby) transmission routes (1). In our country, HBV infection is a common public health issue worldwide, and it is preventable with vaccination. According to World Health Organization 2019 data, there are 296 million HBV carriers worldwide and approximately 1 million deaths per year (2). In addition to causing severe liver damage, it is considered a leading cause of liver cancer.
The incubation period for acute hepatitis B infection ranges from 28 to 180 days, with most infections typically showing symptoms within a period of 60 to 110 days (3). During the incubation period, patients are generally asymptomatic, which increases the risk of transmission (4). Most cases are subclinical, and the course of the disease varies significantly. Although acute hepatitis B usually resolves in immunocompetent individuals, it becomes chronic in 90% of newborns, 30-50% of children under 5 years old, and 5-10% of adults (5).
Hepatitis B surface antigen (HBsAg) and anti-HBs, HBeAg and anti-HBe, and anti-HBc immunoglobulin M (IgM) and IgG are virological biomarkers of hepatitis B infection (6). Biochemical parameters indicating liver damage include aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), total and direct bilirubin, serum albumin, gamma globulin, complete blood count, and prothrombin time (PT). Increased AST and ALT levels indicate the degree of liver fibrosis. When biochemical parameters are insufficient, invasive and non-invasive methods are preferred to determine the degree of liver damage.
Acute hepatitis B infection is usually managed with supportive therapy, whereas direct antiviral therapy is recommended in the presence of severe liver disease, coagulopathy, and prolonged jaundice (7). The hepatitis B vaccine is a safe and effective vaccine that has been in use worldwide since 1981 (8). In our country, the hepatitis B vaccine has been included in the routine vaccination schedule since 1998 (9).
Materials and Methods
Our study was designed as a retrospective cohort study. Patients diagnosed with acute hepatitis B who were hospitalized and followed up in the infectious disease department between 2021 and 2023 were included in the study. The demographic data of the patients, routes of transmission, accompanying comorbidities, clinical data, biochemical, microbiological, and serological laboratory parameters, medical imaging, and treatment management were examined. The patient data were scanned retrospectively from the hospital information database. Our study was reviewed and approved by the Clinical Research Ethics Committee of İstanbul Medeniyet University, Göztepe Prof. Dr. Süleyman Yalçın City Hospital (approval number: 2022/0719, date: 21.12.2022).
Statistical Analysis
In the case of categorical variables, descriptive characteristics are presented along with frequencies, percentages, means, and standard deviations (SDs). Several statistical techniques, including the t-test, analysis of variance (One-Way ANOVA), and Pearson correlation analysis, were utilized. A p-value 0.05 was considered statistically significant.
Results
The study included 23 patients. The gender distribution of the patients was as follows: 21 males (91.3%) and 2 females (8.7%). The patients’ ages were found to have a mean of 51.3±12.6 years. In total, 12 (52.1%) of the 23 patients had accompanying chronic diseases, while 11 patients (47.9%) did not have any accompanying chronic diseases. All patients were unvaccinated against HBV. Analysis of the transmission routes revealed that 14 patients (61%) acquired the virus through sexual contact, 6 patients (36%) through dental procedures, and 3 patients (13%) through intravenous (IV) drug use or tattooing.
The symptoms at the time of the patients’ emergency department admissions were fatigue (61%), jaundice (57%), nausea (43%), dark urine (35%), light-colored stool (17%), and fever (9%) (Table 1).
Regarding the distribution of symptoms, fatigue was the predominant symptom, representing 27% of the cases. The percentage distribution of symptoms at admission is shown in Figure 1.
The average HBV-DNA level of the patients at initial admission was determined to be 2719165-3187990 IU/mL. The average AST level was 1664-829 U/L, ALT level was 2332-1151 U/L, ALP level was 289-145 U/L, and GGT level was 272-100 U/L. The mean total bilirubin level is 11.2-6.3 mg/dL; direct bilirubin level is 8.7-5.1 mg/dL. The international normalized ratio (INR) was 1.27 with a SD of 0.1.
Patients’ AST and ALT values peaked on the first day of hospitalization. The peak AST value was determined to be an average of 1861-827 SD U/L, and the peak ALT value was an average of 2480-1192 SD U/L. While total bilirubin reached its peak value on the 4th day of hospitalization, with a peak value average of 14.7-6.5 SD mg/dL, INR reached its peak value on the 3rd day of hospitalization, with an average peak value of 1.38 SD ±0.2.
When patients’ age, initial ALT, and HBV-DNA data were examined using descriptive statistical methods, younger patients generally had higher ALT values but lower average HBV-DNA values. Conversely, older patients had higher HBV-DNA levels but lower ALT levels. The correlation between age, HBV-DNA, and ALT levels upon admission is shown in Figure 2.
When examining the correlation between the initial AST-ALT values and the hospitalization duration, we observed that as the liver function test values increased, the hospitalization duration also increased. The correlation between AST, ALT, and length of hospital stay is shown in Figure 3.
All patients had positive anti-Hbc-IgM and anti-IgG antibodies. Five out of 23 patients (21.7%) had positive anti-HBs values. Sixteen patients (70%) had positive HbAg values, whereas 14 patients (61%) had positive anti-Hb values. All patients tested positive for anti-Hbc-IgM and anti-Hbc-IgG (Table 2).
Ultrasonographic examination revealed hepatomegaly in 10 patients (43.4%), grade 1-2 hepatosteatosis in 8 patients (34.7%), and thickening of the gallbladder wall in 11 patients (47.8%). During hospitalization, 30.4% (7 out of 23) of the patients were prescribed antiviral therapy. Specifically, 3 patients were given entecavir and 4 patients were given tenofovir disoproxil fumarate. This treatment was initiated due to an increase in INR levels above 1.5.
The average length of hospital stay was 9.48-4.4 SD days. The number of patients with and without chronic diseases and the average length of hospital stay is presented in Table 3. The t-test indicated that the hospital stay duration was significantly longer for patients with chronic diseases than for those without chronic diseases (p=0.014).
The correlation between patient age and length of hospital stay is presented in Table 4. Pearson correlation analysis showed a significant increase in hospital stay duration with increasing age (p=0.013).
The correlation between hepatitis B transmission routes and length of hospital stay is presented in Table 5. Statistical analysis using the One-Way ANOVA test showed that the mode of transmission had a significant effect on the length of hospital stay, with sexually transmitted infections having the most significant impact (p=0.004).
One patient was referred to a liver transplantation center due to the development of severe liver disease and progression to hepatic failure. The remaining patients recovered and were discharged. During follow-up, 15 patients attended control visits within 1 to 6 months. Among these patients, 6 continued to have positive HbsAg levels, while 9 were found to be HbsAg-negative. During the 6-12 month follow-up, seroconversion to negative HbsAg was detected in 5 out of 6 patients who were initially found to be HbsAg-positive at the first outpatient visit, while the HbsAg status of 1 patient could not be determined due to a loss of follow-up. In 6 patients, HBV-DNA was negative during the 1- to 6-month follow-up, while 1 patient continued to have positive HBV-DNA. For the patient with positive HBV-DNA, the 6-12 months data showed that HBV-DNA had become negative.
Discussion
This study examined the demographic characteristics, clinical findings, transmission routes, laboratory parameters, treatment, and follow-up outcomes of patients with acute hepatitis B infection. In studies conducted in different regions of Turkey, the prevalence of HbsAg positivity is higher in males (10). The majority of the 23 patients included herein were male, suggesting that HBV transmission may be associated with gender and age.
Since 1998, routine vaccination against hepatitis B has been implemented in Turkey. Vaccination coverage has been increasing in recent years, with vaccination rates rising from 64% in 1999 to 98% in 2016. As a result, the incidence of acute HBV infections in the young population has significantly decreased (11). In a study on the epidemiology of acute viral hepatitis conducted by Karacaer et al. (12) in 2018, it was observed that the ages of patients with acute HBV were mostly between 20 and 40. Considering that hepatitis B vaccination was included in the routine vaccination program in Turkey in 1998, the average age of patients indicates that most of them were not included in Turkey’s national vaccination program, suggesting that unvaccinated individuals are at high risk (12).
In a study conducted by Miao et al. (13), a 57.31% decrease in the incidence of acute hepatitis B was observed between 2005 and 2019 in China following the widespread adoption of hepatitis B vaccination. In our study, the high mean age of the patients supported the effectiveness of hepatitis B vaccination in Turkey. The absence of HBV vaccination among the patients we followed also underscores the importance of adult immunization.
When examining transmission routes, we found that most patients acquired the virus through sexual contact and had longer hospitalization periods. These data confirm that unprotected sexual intercourse is a significant risk factor for HBV transmission. In addition, dental procedures and IV drug use/tattooing were identified as contributing factors to transmission routes. In a study conducted by Wu et al. (14) in China, out of 164 patients diagnosed with acute hepatitis B, 33 (20.12%) acquired the virus through sexual transmission and 21 (12.80%) acquired it after dental procedures. The hepatitis B vaccination rate among these patients was only 5.49%.
The most common symptoms of acute viral hepatitis are abdominal pain, nausea, and/or vomiting; dark urine or clay-colored stools; fatigue; fever; jaundice; joint pain; and loss of appetite (15). In our study, when symptoms were examined, patients commonly experienced typical hepatitis symptoms, such as fatigue and jaundice, upon presentation. Looking at the correlation between liver function tests and HBV-DNA according to the age groups of patients at admission, it is observed that liver function tests are high in the younger age group, while HBV-DNA was low, whereas the opposite was true in the older age group. This suggests that inflammation and hepatocyte damage are predominant in young patients, whereas the viral replication burden is higher in older individuals.
Chronicity occurs in 5-10% of individuals who have had acute hepatitis B infection in adulthood, but it is observed in 90% of cases in the newborn period and in 20-50% of cases in childhood (16). In our study, all 14 patients who attended follow-up visits had negative HbsAg values. For patients with severe acute HBV clinical and laboratory findings (INR≥1.5 and/or PT longer than 4 seconds above the upper limit of normal and jaundice period >4 weeks), oral antiviral therapy (OAT) is recommended (17). Fulminant hepatitis occurs in less than 1% of jaundiced cases of acute infections. (18).
A meta-analysis to determine the efficacy of nucleoside analogs (NA) compared with placebo or no intervention to treat acute primary HBV infection revealed that there is insufficient evidence to suggest that NA has superior efficacy compared with placebo/standard care in patients with acute viral hepatitis (19). In our study, OAT was preferred for patients with severe liver disease and elevated INR. Among the 7 patients who received OAT, one progressed to liver failure despite antiviral treatment and was referred to a liver transplantation center. The remaining patients were discharged, and follow-up revealed negative HBsAg levels. When examining the relationship between hospitalization duration and liver function, patients with high liver function values had longer hospital stays.
Upon reviewing the medical histories and vaccination records of the patients, it was found that none had been vaccinated against HBV, highlighting the importance of vaccination for preventing HBV infection. Unprotected sexual contact was the most common route of transmission for acute hepatitis B, emphasizing the importance of safe sexual practices.
Study Limitations
The limitations of this study include a small number of patients, irregular attendance at follow-up visits, and data obtained from a single center. Future studies with larger sample sizes and data from different centers may provide more comprehensive results.
Conclusion
In conclusion, this study demonstrated that acute hepatitis B infection continues to occur in individuals over 50 years of age in our country, where routine vaccination is not implemented, emphasizing the importance of adult vaccination and prevention methods against sexually transmitted infections.
