Fulminant Hepatitis Research Articles

The Amazon Basin was historically hyperendemic for HBV and HDV, associated with severe outcomes like fulminant hepatitis. Brazil initiated its hepatitis B vaccination in 1989. This study assessed the current prevalence in this endemic region to evaluate the impact of vaccination. A cross-sectional population-based survey enrolled 1100 urban and rural residents. HBsAg prevalence was 1.5%, with no cases in individuals under 20 years, demonstrating interrupted vertical and horizontal transmission. Anti-HBc positivity (30.9%) indicated past exposure, predominantly in those over 30 years. Isolated anti-HBc (10.3%) included two occult HBV infections. HDV coinfection occurred in 25% of HBsAg-positive cases, with HDV RNA detected in two. Anti-HDV positivity was exclusive to adults over 30. Vaccination coverage was poorly documented, but 23.7% had protective anti-HBs titers. HBV vaccination has reduced HBsAg prevalence from high to low endemicity in the region, eliminating chronic infections in younger generations. Persistent HDV in older age groups underscores the need for targeted screening. Despite vaccination record gaps, the findings highlight the program’s success in interrupting transmission and support continued efforts toward HBV/HDV elimination.

Background: Hepatitis E virus (HEV) is a major global cause of acute viral hepatitis, with significant morbidity and mortality in high-risk populations. It is a non-enveloped, single-stranded RNA virus transmitted primarily via the fecal-oral route, though zoonotic transmission is increasingly recognized. Aim: This review provides a comprehensive update on HEV for clinical and research specialists, covering its virology, diagnostic strategies, and laboratory management to improve detection and patient care. Methods: The synthesis is based on a detailed analysis of HEV's virological characteristics, including its genotypes and their distinct epidemiological patterns. Diagnostic approaches are evaluated, comparing serological assays (anti-HEV IgM/IgG) and molecular methods (PCR for HEV RNA) for acute and chronic infection. Results: HEV genotypes 1 and 2 cause waterborne outbreaks in developing regions, while genotypes 3 and 4 are zoonotic and responsible for sporadic cases in developed countries. Infection is often self-limiting but can lead to fulminant hepatitis in pregnant women and chronic infection in immunocompromised individuals. Diagnosis relies on a combination of serology and PCR, with the latter being essential for confirming chronic infection in immunosuppressed patients where antibody responses may be blunted. Conclusion: HEV is a complex pathogen with a variable clinical presentation. Accurate diagnosis requires an understanding of its virology and the strategic use of laboratory tests. Enhanced surveillance, targeted testing in high-risk groups, and a multidisciplinary approach are crucial for effective management and prevention.

Syphilis is a sexually transmitted infection of ongoing public health concern due to its systemic complications, which necessitate early detection and management. As a non-hepatotropic pathogen, syphilis can also cause unexplained hepatitis, a condition that is often overlooked. A retrospective review of 62 patients with neurosyphilis at a metropolitan Australian hospital found that nine (15%) had abnormal liver biochemistry, which improved with antibiotic therapy, consistent with syphilitic hepatitis. This improvement was statistically significant across all liver markers, and the liver pattern of injury was predominantly cholestatic (67%). This study aims to alert clinicians to the incidence and patterns of liver biochemistry abnormalities in syphilis and advise clinicians to perform liver function testing in all patients with neurosyphilis, particularly in high-risk groups. Early detection and diagnosis can prevent unnecessary tests, enable prompt treatment and avoid progression to fulminant hepatitis.

Hepatitis E virus (HEV) is an under-recognized cause of viral hepatitis, with rising incidence in high-income countries largely driven by zoonotic transmission. Patients with multiple myeloma (MM) are especially vulnerable to HEV, yet recommendations for antiviral treatment and impact on the management of myeloma treatment are missing. Here, we describe seven patients (five males, two females) with MM who were diagnosed with HEV infection at a tertiary care center in Western Europe within less than one year. All cases were confirmed by positive HEV RNA PCR in peripheral blood. Although no instances of fulminant hepatitis were observed, HEV prompted clinically relevant interruptions: autologous stem cell transplantation was postponed, lymphocyte apheresis for CAR T-cell manufacturing was delayed, and bispecific antibody regimens were suspended for up to five months. Ribavirin was initiated in four cases. The three patients undergoing T-cell-redirecting therapies, including one with prior ciltacabtagene autoleucel and two on bispecific antibodies, progressed to chronic infection despite ribavirin treatment. One patient, despite clearing HEV from peripheral blood, developed persistent vertigo and tested positive for HEV RNA in cerebrospinal fluid, indicating neuroinvasion. As the largest reported cohort of MM patients with HEV infections and the first to document chronic infection during treatment with T-cell-redirecting therapies, this study emphasizes the urgent need to increase awareness of HEV as an emerging threat, refine screening protocols at baseline or during unexplained aminotransferase flares, and to establish standardized therapeutic strategies in the era of novel immunotherapeutic approaches.

A limited number of studies on human subjects with type-A hepatitis have found a positive correlation between activated natural killer (NK) cell frequencies in blood and the severity of liver injury. However, without knowledge of differences in viral burdens, it remains unclear whether NK cells are elevated due to hepatitis A virus (HAV) replication and ongoing associated injury, or if NK cell responses directly cause pathogenesis. To gain insight into how NK cells respond during the early stages of hepatitis A virus infection, we generated mice that are permissive for HAV infection in the liver but are otherwise immunocompetent. HAV readily infected the liver of these hepatocyte-specific type-I interferon receptor knockout mice (Ifnar1ΔHep), resulting in fecal virus shedding, elevated serum alanine aminotransferase levels, and immune cell infiltrates in the liver. Single-cell RNA sequencing analyses of liver leukocytes from infected Ifnar1ΔHep mice revealed a rapid accumulation of activated NK cells in the liver within 2 days. HAV infection and liver inflammation were brief and substantially reduced in magnitude in these mice compared to global Ifnar1-/- knockout mice that failed to induce substantial antiviral NK cell responses. NK cells were the principal source of interferon (IFN)-γ in Ifnar1ΔHep mice. Ifnar1ΔHep mice that were experimentally depleted of NK cells or IFN-γ showed greatly increased viral replication and liver damage. Moreover, IFN-γ alone was sufficient to suppress HAV replication in primary mouse hepatocytes. Collectively, these findings establish a critical role for type-I IFN induction of NK cells, their expression of IFN-γ, and protection against hepatitis A.IMPORTANCEHepatitis A virus remains a leading cause of foodborne illness among unvaccinated individuals. Infection can result in severe liver injury that can progress to fatal fulminant viral hepatitis. Despite its clinical significance, the molecular, genetic, and cellular factors influencing infection severity remain poorly understood. Previous studies of patient blood have suggested that natural killer (NK) cells cause liver injury during infection. In this study, we used mouse models of infection to characterize early cellular defenses to infection and identified a critical role for NK cells and interferon-γ in conferring rapid immune protection rather than pathogenesis.

Acute or chronic exposure to drugs or herbal and dietary supplements (HDS) can cause drug-induced autoimmune-like hepatitis (DI-ALH), a self-limiting condition resembling autoimmune hepatitis (AIH). We investigated the prevalence of drug exposure among AIH patients at diagnosis to recognise cases of DI-ALH and discern features predicting AIH development. We retrospectively included 705 patients diagnosed with AIH. DI-ALH was defined using published criteria. The clinical, biochemical, serological, and histological data of DI-ALH and AIH were analysed to identify predictors of the evolution of each phenotype. Most patients were female (n = 496, 70%), with a median age of 57 years and a median follow-up of 55 months. A 59% (n = 417) reported exposure to drugs or HDS, and 8% (n = 58) fulfilled the criteria for DI-ALH. Statins and HDS were the most common culprits. Patients with DI-ALH more frequently had acute severe or fulminant hepatitis (22% vs. 12%, p = 0.013) and higher transaminase levels (ALT: 966 vs. 591, p = 0.001) at diagnosis. In total, 97% of the patients received immunosuppression. DI-ALH patients had a faster biochemical response than i-AIH patients (4 vs. 5, p = 0.031), while treatment withdrawal was attempted in only 29% (n = 17). Approximately 30% (n = 17) of DI-ALH cases presented a flare during follow-up. Neither clinical, histological, nor serological findings nor RUCAM and RECAM could predict a DI-ALH flare. DI-ALH is often under-recognised in clinical practice, leading to unnecessary long-term immunosuppression. A causal relationship between drugs and AIH, along with an attempt to withdraw treatment and long-term follow-up, is essential to prevent overtreatment-associated risks.

Liver Transplantation in Childhood: A 2-Year Single Center Experience.

Acute hepatitis E virus infection in adults, Cayenne, French Guiana, 2015-2022.

Background: Measles is a common viral infection in children that is self-limiting, but the fulminant hepatitis induced by measles is a very rare case. And we present the case of fulminant hepatitis induced by measles in an 8-month-old female. Case presentation: we have a patient of an 8-month-old female who presented to pediatric OPD with a complaint of fever for 8 days. Clinically, she was diagnosed as a case of measles with complications (pneumonia). After 2 days of admission, she developed seizures, irritable movement, bruises, and abdominal swelling. Emergency management was started for resuscitation and ultrasound abdomen, and ALT was advised on ultrasound. Minimal ascites, gall bladder edema, and hepatomegaly were reported, and LFTs were advised by the radiologist, and ALT was 1582 U/L. At that time, she was suspected of a case of fulminant hepatitis. We put her on symptomatic treatment for liver and coagulation issues. Her symptoms improved. As far as our literature search is concerned, this is the first case to be submitted for case report in Khyber Pakhtunkhwa.

Therapeutic determinants of melatonin in hepatitis caused by coxsackievirus B3 infection.

Tuberous sclerosis complex (TSC) is a rare genetic neurocutaneous syndrome characterized by glial tumors in the brain and retina, fibromas in various organs, and a classic triad of epilepsy, intellectual disability, and adenoma sebaceum. However, nearly 50% of affected individuals have normal intelligence, and 15% do not experience seizures. Neurological symptoms typically appear in childhood, while skin manifestations often emerge later. We present the case of a 31 year-old woman diagnosed with TSC, who initially sought medical attention for vasamol consumption. The patient developed rhabdomyolysis, acute fulminant hepatitis, and acute kidney injury (AKI) following the ingestion. Her hepatitis was managed with N-acetylcysteine infusion, steroids, and glutathione. Due to worsening renal function, she underwent two dialysis sessions. On examination, multiple small, yellow papules consistent with adenoma sebaceum were noted on her face and neck. She also had hypopigmented ash-leaf macules, confetti lesions on her arms and legs, and shagreen patches on her back, which she had since childhood. The patient had no history of seizures or neurological symptoms, and a significant family history of TSC was noted. Brain MRI revealed cortical tubers, and ultrasonography showed a hyperechoic renal angiomyolipoma in her left kidney. Despite the absence of typical neurological symptoms, the clinical and radiological findings led to the diagnosis of TSC.

The hepatitis E virus (HEV; species Paslahepevirus balayani) is a common human pathogenic and zoonotic virus that can cause both acute fulminant and chronic hepatitis. Despite its reputation as a hepatotropic virus, HEV infection is also associated with a number of extrahepatic diseases, including kidney disorders. However, the extent to which HEV replicates in kidney cells remains unclear. The present study aims to investigate the capacity of HEV to propagate in kidney cells invitro and to assess whether HEV displays mutational signatures that correlate with compartmentalisation invivo. We use HEV cell culture models to study the replication cycle and the effect of antivirals in human kidney cell lines and primary cells. In addition, we identified patients with chronic HEV infection (n = 9) from which we then sequenced the viral RNA of urine, stools and plasma to analyse the viral sequence composition, to assess intra-host diversity and compartmentalisation (n = 2). A wide range of human kidney cell lines as well as primary cells supports viral entry, replication and propagation of HEV invitro. Interestingly, the broad-spectrum antiviral ribavirin was less effective in inhibiting HEV replication in some kidney cells. Sequencing of HEV RNA-directed RNA polymerase coding region from plasma, stool and urine and subsequent phylogenetic analysis revealed diversification of HEV into tissue-specific viral subpopulations. In particular, the viruses derived from urine were found to be distinct from those derived from plasma and stool. In conclusion, kidney cells support the propagation of HEV invitro and exhibit reduced sensitivity to antiviral treatment. Furthermore, HEV patient-derived sequences demonstrated compartmentalisation into distinct clusters that correlated with sample source. Collectively, these data indicate the potential for extrahepatic replication of HEV, which may result in clinically significant disease or serve as a reservoir for patient relapse. HepNet-SofE study (NCT03282474).

A male neonate was born to a mother with a history of scant prenatal care and suspected Herpes lesions in the birth canal. The infant presented after birth with severe anemia, thrombocytopenia, and acute liver failure along with multiple organ involvement. He received multiple transfusions and was treated empirically for potential sepsis and viral infection. Differential diagnoses considered included neonatal HSV infection, enterovirus infection, gestational alloimmune liver disease (GALD), hemophagocytic lymphohistiocytosis (HLH), and inborn errors of metabolism. The case underscores the complexity of diagnosing fulminant hepatitis in neonates and emphasizes the necessity of maintaining a broad differential diagnostic approach. This case report highlights the diagnostic challenges and the need for a systematic approach in managing neonates with fulminant hepatitis.

Arboviruses are a heterogeneous group of vector-borne viruses from various viral families. The clinical manifestations associated with these viruses can vary from self-limiting conditions to life-threatening complications with haemorrhagic disorders. As a class of viruses with systemic infections, arboviruses can either directly or indirectly affect different parts of the body causing systemic complications such as cardiovascular diseases, coagulation dysfunctions, and various liver complications. The present review presents clinical, epidemiological, and mechanistic evidence describing liver involvement during acute arboviral infections, including those caused by Dengue Virus (DENV), Yellow Fever Virus (YFV), Zika Virus (ZIKV), and Chikungunya Virus (CHIKV). While much of the available data pertains to acute liver damage, such as H, hepatomegaly, or fulminant hepatitis, it also discusses the possibility that such acute injuries may, in certain cases, predispose to chronic liver inflammation and fibrosis. Although current direct evidence for long-term hepatic sequelae is limited, this underexplored area may hold important clinical relevance in endemic settings. Therefore, this review emphasises the need for longitudinal research to establish whether arboviral infections pose a significant risk for chronic liver disease. Furthermore, it discusses the potential underlying mechanisms by which these viruses can induce hepatic disorders, including direct viral effects, immune-caused complications, and interactions with various hepatic cells and components. Finally, this review addresses several future research directions to improve clinical outcomes of arbovirus-caused liver complications.

Surgical site infections (SSIs) are common after liver transplantation (LT), with perioperative antibiotic strategies varying across centers. This study compared the incidence of SSIs in patients receiving perioperative antibiotic prophylaxis (PAP) versus preemptive antibiotic therapy (PAT). This retrospective multicenter study included adult LT patients from 5 French hospitals (2019-2022). Exclusion criteria were prior antibiotic use at LT, prophylaxis extended beyond 24 h postoperatively, antibiotic allergies, fulminant hepatitis, and multiorgan transplants. The PAP group received narrow-spectrum antibiotics without extension beyond 24 h, whereas the PAT group received broad-spectrum antibiotics extended postoperatively. Propensity score-based overlap weighting was used for comparisons. Among 595 patients, 271 received PAP and 324 received PAT for a median of 5 (2-7) d (P < 0.001). Cefoxitin (24%) and amoxicillin-clavulanic acid (21%) were most used in the PAP group, whereas piperacillin (19%) and piperacillin-tazobactam (33%) dominated in the PAT group. SSIs occurred in 19% of PAP and 15% of PAT patients (odds ratio [OR] 0.81; 95% confidence interval [CI], 0.29-2.30; P = 0.7). PAT was associated with reduced postoperative infections (OR 0.27; 95% CI, 0.12-0.63; P = 0.002), shorter intensive care unit (-5.2 d; P < 0.0001) and hospital stays (-5.5 d; P = 0.002), and lower early allograft dysfunction (OR 0.12; 95% CI, 0.02-0.87; P = 0.04) but with increased extended-spectrum beta-lactamase SSIs (47% versus 6%; P = 0.006). PAP effectively prevents SSIs and antimicrobial resistance. Broad-spectrum antibiotics should be reserved for early treatment of suspected infections or prophylaxis for carefully selected high-risk patients.

e14587 Background: Despite the fact that the majority of immune-mediated liver injuries caused by immune checkpoint inhibitors (ILICI) clinically present as mild-to-moderate elevations in transaminase levels, severe symptoms of ILICI such as fulminant hepatitis and acute liver failure have been reported. Consequently, the effective identification of risk factors for the occurrence of ILICI will help screen individuals at high risk of ILICI before treatment, thereby assisting clinicians in evaluating the benefit/risk ratio of immunotherapy for cancer patients effectively. This study was to construct a clinical prediction model for ILICI. Methods: A retrospective analysis was performed on the clinical data of 1432 pan-cancers Chinese patients treated with immune checkpoint inhibitors (ICIs) from January 2019 to December 2021. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for the occurrence of ILICI, and a nomogram model for predicting the risk of ILICI was constructed subsequently. The discrimination, calibration, and clinical utility of the nomogram model were comprehensively evaluated by the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Results: Multivariate logistic regression analysis showed that the use of imported PD-1 inhibitors (OR, 6.45, 95% CI 3.60-11.57; p &lt; 0.001), baseline aspartate aminotransferase (AST) level ≥ 26.04 U/L (OR, 2.27; 95% CI 1.33-3.87; p = 0.003), and baseline prognostic nutritional index (PNI) &lt; 38.75 (OR, 2.21; 95% CI 1.22-4.02; p = 0.009) were independent risk factors for the development of ILICI. Based on these identified variables, a nomogram model was developed and underwent validation through diverse analytical methods. The results demonstrated that this nomogram model could serve as a reliable and valid predictive tool for ILICI. Conclusions: In this study, we found that the use of imported PD-1 inhibitor, high baseline AST level (AST ≥ 26.04U/L) and low baseline PNI level (PNI &lt; 38.75) were independent risk factors for the occurrence of ILICI. By integrating these three identified factors, an effective and convenient nomogram model was developed for accurate ILICI risk prediction, which is expected to enable early identification of individuals with increased risk of ILICI and early intervention, thereby potentially improving the prognosis of patients receiving ICIs therapy.

Liver fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM), primarily produced by activated hepatic stellate cells (HSCs). The activation of HSCs is influenced by paracrine signaling interactions among various liver cell types, but molecular mechanisms remain to be elucidated. Secretory Meteorin-like (Metrnl) can effectively ameliorate fulminant hepatitis. However, little is known about its role in liver fibrosis. In our study, we found that hepatic Metrnl mRNA transcripts and protein expression were significantly downregulated in patients and mouse models of hepatic fibrosis. Hepatocyte-specific and global knockout of Metrnl exacerbated CCl4-induced liver fibrosis. In contrast, the administration recombinant Metrnl or AAV-Metrnl overexpression markedly ameliorated CCl4-induced liver fibrosis in mice, suggesting a protective role for Metrnl. Mechanistically, hepatocyte-derived Metrnl not only influences the activation of HSCs through paracrine signaling but also modulates the release of the fibrogenic cytokine PDGFB via the transcription factor EGR1, thereby regulating PDGFB/PDGFRβ signaling to affect HSC activation. Furthermore, Metrnl absence in hepatocytes and HSCs leads to the downregulation of the E3 ubiquitin ligase HECW2, inhibiting K48-linked ubiquitination of FN and preventing its proteasomal degradation, thus promoting FN secretion from HSCs. These effects contribute to ECM deposition and the activation of HSCs, ultimately exacerbating liver fibrosis. Collectively, our study reveals Metrnl as a novel regulator of liver fibrosis that mediates communication between hepatocytes and HSCs, indicating its potential as a therapeutic target for liver fibrosis. The identification of Metrnl as a critical player in the pathogenesis of hepatic fibrosis underscores the importance of understanding cellular crosstalk in the progression of liver disease.

Background: Inflammation is a key driver of various liver diseases. NLRP3 inflammasome in hepatic macrophages is a key mediator of inflammation and has emerged as a promising target. Genome editing presents a powerful approach to modulate inflammation by directly disrupting genes such as NLRP3 directly. However, efficient and cell-specific delivery of CRISPR/Cas9 ribonucleoproteins (RNPs) remains challenging. Methods: We developed a novel delivery system by encapsulating CRISPR/Cas9 RNPs within mannosylated neutrophil membranes vesicles (Cas9/gNLRP3@M-N) to enhance targeting hepatic macrophages. Results: Cas9/gNLRP3@M-N selectively accumulated in hepatic macrophages, effectively disrupted the NLRP3 gene, attenuated inflammation in acute fulminant hepatitis, and improved disease outcomes in chronic steatohepatitis model. Conclusions: Cas9/gNLRP3@M-N represents a promising targeted gene-editing approach for the treatment of inflammatory liver diseases.

Chronic hepatitis B infection is a common condition encountered in clinical practice, with nearly 2 billion people worldwide showing 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. This case highlights a 45-year-old male patient from Burie, Ethiopia, who presented with signs of decompensated liver disease, yet tested negative for Hepatitis B surface Antigen (HBsAg). Further investigation revealed low-level hepatitis B virus (HBV) viremia, confirming occult HBV infection. This underscores the importance of HBV-deoxyribonucleic acid (DNA) testing in HBsAg-negative patients with unexplained cirrhosis. Broader access to hepatitis testing panels and heightened clinical suspicion are essential to ensure timely diagnosis and treatment of OHB, especially in resource-limited settings.

Budd-Chiari syndrome (SBC), defined by obstruction of the suprahepatic veins or the suprahepatic inferior vena cava, presents with an acute, subacute or chronic picture, but exceptionally as fulminant hepatitis. We report the case of a 24-year-old patient, without any particular pathological history, admitted in a picture of fulminant hepatitis, whose etiological assessment was in favor of SBC. The course was marked by the aggravation of his hepatic encephalopathy and death two days later by a major digestive hemorrhage. The therapeutic management of fulminant SBC is poorly codified, with a high mortality rate. Keywords: Budd-Chiari syndrome, suprahepatic veins, fulminant hepatitis, mortality.