European Journal of Cardiovascular Medicine

Acute hepatitis represents a significant clinical entity characterised by the sudden onset of hepatic inflammation, often manifesting with jaundice, anorexia, malaise, abdominal discomfort, and derangements in liver function tests [1-3]. The condition may arise from a wide spectrum of etiologies, including viral infections, drug-induced liver injury, autoimmune hepatitis, ischemic insults, and metabolic or toxic exposures [4-9]. Among these, viral hepatitis remains the most common cause worldwide, with hepatitis A, B, E, and, to a lesser extent, hepatitis C viruses being the principal contributors [10]. The clinical course of acute hepatitis is highly variable, ranging from complete spontaneous recovery to fulminant hepatic failure with high mortality. Understanding the clinical spectrum and outcomes of acute hepatitis is therefore crucial for guiding timely diagnosis, management, and prognostication. In resource-limited settings, the burden of acute hepatitis is compounded by delayed presentation, limited access to advanced diagnostic modalities, and variability in treatment practices. Tertiary care hospitals often serve as referral centres for severe or complicated cases, providing a unique opportunity to study the disease spectrum and outcomes in a real-world, high-burden context. India bears a disproportionate share of the global burden of acute viral hepatitis. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are endemic in many regions, transmitted primarily through the fecal–oral route due to inadequate sanitation and unsafe water supplies. HEV, in particular, is recognized as a leading cause of acute sporadic hepatitis and outbreaks in India, especially among young adults and pregnant women, where it is associated with high maternal and perinatal mortality [11]. Hepatitis B virus (HBV) infection, though more commonly associated with chronic liver disease, also contributes to acute hepatitis presentations, particularly in unvaccinated populations. Hepatitis C virus (HCV) is less frequently implicated in acute symptomatic disease but remains an important consideration [4-10]. Beyond viral causes, drug-induced liver injury (DILI) is increasingly recognised in India, often linked to the widespread use of over-the-counter medications, herbal remedies, and anti-tubercular therapy [12]. Autoimmune hepatitis and ischemic hepatitis, though less common, also contribute to the clinical spectrum. The epidemiological profile of acute hepatitis in India is thus shaped by a complex interplay of infectious, pharmacological, and environmental factors, with significant regional variation. Several studies from India and other developing countries have documented the predominance of HAV and HEV as etiological agents of acute hepatitis. Outbreak investigations have consistently highlighted contaminated water supplies as the source of infection, underscoring the role of public health infrastructure in disease prevention. Hospital-based studies have described the clinical features of acute hepatitis, including jaundice, hepatomegaly, elevated transaminases, and coagulopathy, while also reporting variable rates of complications such as acute liver failure (ALF) and encephalopathy [11]. Outcomes of acute hepatitis are influenced by etiology, host factors, and timely access to supportive care. For instance, HEV-related hepatitis in pregnancy carries a particularly grave prognosis, while HBV-related acute liver failure is associated with high mortality in the absence of liver transplantation. Despite these insights, much of the existing evidence is fragmented, with studies often limited by small sample sizes, single-etiology focus, or lack of systematic follow-up [13]. Although acute hepatitis is a common clinical problem in India, there remains a paucity of comprehensive observational studies that systematically evaluate the full clinical spectrum and outcomes across diverse etiologies in a tertiary care setting. This study seeks to investigate the clinical spectrum and outcomes of acute hepatitis among patients presenting to a tertiary care hospital in India, addressing the heterogeneity of its etiologies and prognoses. The central hypothesis is that viral hepatitis, particularly due to HEV and HAV, constitutes the predominant cause, with outcomes varying according to etiology, demographic factors, and clinical presentation. The objectives are to comprehensively describe the demographic, clinical, and biochemical characteristics of affected patients, determine the distribution of viral and non-viral causes, evaluate short-term outcomes such as recovery, complications, and mortality, and identify associations between etiology, clinical features, and outcomes to highlight predictors of adverse prognosis.

Study Overview: This was a prospective, observational study conducted in the Department of Gastroenterology and Hepatology at a tertiary care teaching hospital in India in a 2-year study period from 2023 to 2025. The study protocol was reviewed and approved by the Institutional Ethics Committee, and all procedures adhered to the principles of the Declaration of Helsinki.

Study Population: The study population comprised patients of all age groups presenting with features suggestive of acute hepatitis, defined as an acute onset of jaundice, anorexia, malaise, or abdominal discomfort, with biochemical evidence of hepatocellular injury (elevated serum aminotransferases more than three times the upper limit of normal) and/or hyperbilirubinemia.

Inclusion criteria: Patients with an acute onset of clinical and biochemical features of hepatitis within the preceding 12 weeks.

Exclusion criteria: Patients with known chronic liver disease or cirrhosis. Patients with acute-on-chronic liver failure. Patients with incomplete clinical or laboratory data.

Sample Size: Consecutive sampling was done to enrol all cases in the study period.

Outcome Parameters

The primary outcome parameters were:

• Etiological distribution of acute hepatitis (viral vs. non-viral causes).
• Clinical spectrum, including demographic profile, presenting symptoms, and biochemical abnormalities.
• Short-term outcomes, including recovery, persistence of symptoms, development of complications (encephalopathy, coagulopathy, acute liver failure), and in-hospital mortality.

Secondary outcomes included:

• Identification of predictors of adverse outcomes (e.g., age, etiology, biochemical markers).
• Comparison of outcomes between viral and non-viral etiologies.

Methodology

All patients underwent a detailed clinical evaluation, including history of presenting illness, risk factors (contaminated water exposure, drug intake, alcohol use, comorbidities), and physical examination. Laboratory investigations included:

• Complete blood count, liver function tests, renal function tests, coagulation profile, and serum electrolytes.
• Viral serology: IgM anti-HAV, IgM anti-HEV, HBsAg, IgM anti-HBc, anti-HCV, and HCV RNA (where indicated).
• Autoimmune markers (ANA, SMA, LKM-1) in selected cases with suspected autoimmune hepatitis.
• Additional tests such as ultrasound abdomen and Doppler studies to assess liver size, echotexture, and vascular flow.

Patients were managed according to standard institutional protocols, with supportive care, monitoring for complications, and referral for liver transplantation evaluation when indicated. Follow-up was maintained until discharge or death.

Statistical Analysis:

Data were entered into a predesigned case record form and subsequently compiled in Microsoft Excel. Statistical analysis was performed using Graph Pad version 8.4.3. Continuous variables were expressed as mean ± standard deviation (SD). Categorical variables were presented as frequencies and percentages. Unpaired t-test was used for continuous variables, and Chi-square or Fisher’s exact test for categorical variables. A p-value <0.05 was considered statistically significant

93 patients with acute viral hepatitis were studied in our study. Viral infections were the predominant etiology (68.8%), with Hepatitis A being the most common single cause (50.5%). Non-viral causes accounted for nearly a third of cases (31.2%), with drug-related injury, Budd-Chiari syndrome, and indeterminate causes being the most frequent within this group [Table 1].

Table 1: Distribution of Patients with Acute Hepatitis with respect to Etiology

Patients with non-viral hepatitis were notably older and had significantly higher average bilirubin levels. In contrast, the viral hepatitis group had higher hemoglobin levels and markedly elevated liver enzymes (AST and ALT). A critical distinguishing feature was the AST/ALT ratio; a ratio greater than 1 was exclusively observed in nearly half of the non-viral patients, a finding with a highly significant p-value, while it was absent in the viral group [Table 2].

Table 2: Comparison of Baseline Variables between Viral Etiology and Non-Viral Etiology

Patients with non-viral hepatitis reported right hypochondrium pain and presented with ascites at significantly higher rates than those with viral hepatitis. Fever and hepatomegaly showed no statistically significant difference in prevalence between the two groups, suggesting they are not reliable indicators for distinguishing the etiology [Table 3].

Table 3: Comparison of Clinical Signs between Viral Etiology and Non-Viral Etiology

The vast majority of patients with viral hepatitis experienced recovery (90.6%), with a smaller proportion developing chronicity and no deaths were recorded. In sharp contrast, the non-viral group had a much less favourable prognosis, with lower recovery rates (62.1%), higher rates of chronicity (27.6%), and a notable mortality rate of 10.3%, indicating that acute hepatitis from non-viral causes is associated with significantly greater morbidity and mortality [Figure 1].

The presented study investigates the etiological spectrum and clinical outcomes of acute hepatitis, a condition characterised by sudden liver inflammation. The scientific premise is that the underlying cause (etiology) dictates the disease's clinical presentation, laboratory profile, and ultimate prognosis. The liver responds to injury in a limited number of ways, primarily through the release of enzymes like AST and ALT, and impaired synthetic function leading to jaundice (elevated bilirubin). However, the pattern of these markers can offer diagnostic clues. For instance, a very high AST/ALT ratio (>1) is classically associated with alcoholic liver disease but is also seen in ischemic or drug-induced injury, as it reflects mitochondrial damage, which is more pronounced in these toxic/metabolic insults than in standard viral hepatitis. The stark difference in outcomes—recovery versus chronicity or death—underscores that acute hepatitis is not a single disease but a syndrome with diverse triggers, each carrying a distinct pathophysiological mechanism and natural history.

The clinical significance of these findings is substantial. Firstly, the demographic and biochemical profile can rapidly narrow the differential diagnosis. A younger patient with extremely high ALT/AST but a low AST/ALT ratio is highly suggestive of viral hepatitis, whereas an older patient with a higher bilirubin and an AST/ALT ratio >1 should urgently raise suspicion for a non-viral cause, particularly drug-induced or autoimmune. Secondly, the dramatically worse outcomes in the non-viral group (higher chronicity and a 10.3% mortality) highlight a critical management imperative: early and accurate etiological diagnosis is not academic but lifesaving. It allows for specific interventions—such as stopping an offending drug, initiating immunosuppression for autoimmune hepatitis, or managing vascular complications like Budd-Chiari syndrome—which can alter the disease course. The zero mortality in the viral group reinforces that in immunocompetent adults, hepatitis A and B are often self-limiting, whereas non-viral causes frequently drive the progression to acute liver failure and death.

Our finding that viral hepatitis (68.8%) is the leading cause, with Hepatitis A predominating, is strongly consistent with the Tunisian cohort by Elleuch et al. (2021), which reported 76.1% viral causes, also led by HAV [14]. Both studies confirm that viral hepatitis typically affects a younger demographic. The presence of Budd-Chiari syndrome and drug-induced liver injury (DILI) as significant non-viral causes is also a common thread. This consistency across different regions underscores the global importance of vaccination (for HAV/HBV) and pharmacovigilance.

The pattern of higher transaminases in the viral group mirrors Elleuch et al.'s results. More importantly, the specific finding of an AST/ALT ratio >1 being exclusive to the non-viral group (48.28%) is a key diagnostic differentiator [14]. This aligns with the pathophysiology of DILI and ischemic injury, as highlighted in studies like Cao et al. (2014) on NSAID-induced toxicity, where direct mitochondrial injury can elevate AST disproportionately [15]. The higher bilirubin and more frequent complications like ascites and right upper quadrant pain in our non-viral group are classic indicators of more severe synthetic dysfunction and a greater likelihood of progressing to acute-on-chronic liver failure or acute liver failure (ALF), a theme echoed in Radha Krishna et al. (2009) and Mori et al. (2012) [16, 17].

The most critical concordance is in the prognosis. Our study found that non-viral etiologies had significantly higher rates of chronicity (27.6%) and mortality (10.3%) compared to the viral group. Elleuch et al. similarly reported more severe forms, greater transition to chronicity, and higher mortality in non-viral cases [14]. Reuben et al. (2010) focused on DILI as a cause of ALF, finding a very low transplant-free survival (27.1%), emphasizing the high mortality of severe non-viral hepatitis without intervention [18]. Bernal et al. (2013) showed that while outcomes for ALF have improved over time (largely due to transplantation and better ICU care), the etiological shift away from viruses to other causes like DILI means these patients now form a core group with high baseline severity [19].

Our study identified AIH in 5.4% of all acute hepatitis cases. The presentations described in Aljumah et al. (2019) and Abu Faddan et al. (2011)—jaundice, high transaminases, and elevated immunoglobulins—are consistent with our cohort [20, 21]. The favourable response to immunosuppression noted by Licata et al. (2014) and Abu Faddan et al. underscores why promptly identifying these patients is crucial, as their disease is highly treatable [21, 22].

The concept from Licata et al. that drug-induced autoimmune hepatitis (DI-AIH) is clinically similar to idiopathic AIH but may have a favorable outcome with treatment is vital. It suggests that some of our "indeterminate" or "autoimmune" cases could have been triggered by drugs, and a detailed drug history is essential [22].

In summary, our study's results are not isolated but fit securely within the global narrative of acute hepatitis. They confirm that etiology is the principal determinant of outcome, with non-viral causes constituting a more severe, prognostically ominous group that demands early recognition and specific management. The comparative analysis validates our findings and reinforces established clinical principles for diagnosing and managing this complex syndrome.

The present study has several key limitations, including its relatively small single-center cohort of 93 patients, which may limit the statistical power and generalizability of the findings, particularly for rare etiologies. The high proportion of cases classified as "indeterminate" (7.5%) suggests potential diagnostic challenges or a lack of comprehensive testing for all possible causes.

In the present study of 93 patients with acute hepatitis, viral etiologies—predominantly Hepatitis A—accounted for the majority of cases, while a substantial proportion were due to non-viral causes such as drug-induced hepatitis, autoimmune hepatitis, and Budd–Chiari syndrome. Patients with viral hepatitis were significantly younger, had higher transaminase levels, and demonstrated a more favourable clinical course with higher recovery rates and no mortality, in contrast to non-viral etiologies, which were associated with older age, higher bilirubin, greater frequency of complications such as ascites and right hypochondrial pain, and poorer outcomes, including chronicity and death. These findings highlight the importance of distinguishing viral from non-viral acute hepatitis at presentation, as the underlying etiology strongly influences clinical profile, disease progression, and prognosis.

1. Cacciola I, Scoglio R, Alibrandi A, Squadrito G, Raimondo G., SIMG-Messina Hypertransaminasemia Study Group. Evaluation of liver enzyme levels and identification of asymptomatic liver disease patients in primary care. Intern Emerg Med. 2017 Mar;12(2):181-186.
2. Agrawal S, Dhiman RK, Limdi JK. Evaluation of abnormal liver function tests. Postgrad Med J. 2016 Apr;92(1086):223-34.
3. Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014 Jan;98(1):1-16.
4. Wilson TR. The ABCs of hepatitis. Nurse Pract. 2005 Jun;30(6):12-21, quiz 22-3.
5. Ryder SD, Beckingham IJ. ABC of diseases of liver, pancreas, and biliary system: Acute hepatitis. BMJ. 2001 Jan 20;322(7279):151-3.
6. Hosseini N, Shor J, Szabo G. Alcoholic Hepatitis: A Review. Alcohol Alcohol. 2019 Jul 01;54(4):408-416.
7. Crabb DW, Im GY, Szabo G, Mellinger JL, Lucey MR. Diagnosis and Treatment of Alcohol-Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology. 2020 Jan;71(1):306-333.
8. Katarey D, Verma S. Drug-induced liver injury. Clin Med (Lond). 2016 Dec;16(Suppl 6):s104-s109.
9. Mikolasevic I, Filipec-Kanizaj T, Jakopcic I, Majurec I, Brncic-Fischer A, Sobocan N, Hrstic I, Stimac T, Stimac D, Milic S. Liver Disease During Pregnancy: A Challenging Clinical Issue. Med Sci Monit. 2018 Jun 15;24:4080-4090.
10. Montrief T, Koyfman A, Long B. Acute liver failure: A review for emergency physicians. Am J Emerg Med. 2019 Feb;37(2):329-337.
11. Satapathy P, Galdane S, Bishoyi AK, Ganesan S, Kavita V, Mishra S, et al. Burden of acute hepatitis E virus in South Asia: Insights from Global Burden of Disease study 2021. Diagn Microbiol Infect Dis. 2025 Jul;112(3):116767. doi: 10.1016/j.diagmicrobio.2025.116767.
12. Tiwari V, Shandily S, Albert J, Mishra V, Dikkatwar M, Singh R, Sah SK, Chand S. Insights into medication-induced liver injury: Understanding and management strategies. Toxicol Rep. 2025 Jun;14:101976. doi:10.1016/j.toxrep.2025.101976
13. Girish V, Royer A, John S. Acute Liver Failure. [Updated 2025 Jul 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482374/
14. Elleuch N, Ben Jazia E, Ben Salem A, Hefaiedh R, Boubaker J, Gharbi L, et al. Spectrum of acute hepatitis and its clinical outcome in a central region in Tunisia. Arab J Gastroenterol. 2021;22(4):317‑22.
15. Cao Z, Liu Y, Xu Y, Zhou J, Liu Y, Liu Y, et al. Characteristics and clinical outcome of nonsteroidal anti-inflammatory drug-induced acute hepato-nephrotoxicity among Chinese patients. Clin Nephrol. 2014;82(4):251‑60.
16. Radha Krishna Y, Saraswat VA, Das K, Himanshu G, Yachha SK, Aggarwal R, et al. Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis. Liver Int. 2009;29(3):392‑8.
17. Mori N, Imamura M, Kawakami Y, Aikata H, Takaki S, Kawakami Y, et al. Determinants of the clinical outcome of patients with severe acute exacerbation of chronic hepatitis B virus infection. J Gastroenterol. 2012;47(9):1022‑32.
18. Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52(6):2065‑76.
19. Bernal W, Auzinger G, Dhawan A, Wendon J. Lessons from look-back in acute liver failure? A single centre experience of 3300 patients. J Hepatol. 2013;59(1):74‑80.
20. Aljumah AA, Alqutub AN, Fallatah HI, Al Hamoudi WK, Al Faleh FZ, Al Ashgar HI, et al. Acute onset autoimmune hepatitis: Clinical presentation and treatment outcomes. Ann Hepatol. 2019;18(2):318‑24.
21. Abu Faddan NH, El-Shabrawi MH, El-Karaksy HM, El-Koofy NM, El-Hennawy AM, El-Sayed R, et al. Clinico-laboratory study on children with auto-immune hepatitis in Upper Egypt. Arab J Gastroenterol. 2011;12(3):133‑7.
22. Licata A, Maida M, Cabibbo G, Butera G, Macaluso FS, Alessi N, et al. Clinical features and outcomes of patients with drug-induced autoimmune hepatitis: a retrospective cohort study. Dig Liver Dis. 2014;46(12):1116‑20.