Cause Of Fulminant Hepatitis Research Articles

Diagnosis and treatment of viral hepatitisB andD in 2024

Despite the availability of vaccines, hepatitisB remains asignificant cause of fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. The increase in reported hepatitisB cases in Germany is attributed to factors such as immigration and the hepatitisB surface antigen (HBsAg) screening introduced in 2020 as part of health check-ups. The indication for treatment depends on various factors, including the level of hepatitisB virus (HBV) DNA and inflammatory activity. Nucleos(t)ide analogues are the preferred treatment option, but functional cure, defined as HBsAg loss, is rare. In principle, treatment with nucleos(t)ide analogues should usually be discontinued after loss of HBsAg, but can be stopped earlier under certain conditions and is currently the subject of ongoing research. Pregnancy and immunosuppression in the context of hepatitisB require special attention. In addition, apossible hepatitisD virus co-infection must always be taken into account, which is why every HBsAg-positive person should be tested for anti-HDV. Since 2020, the entry inhibitor bulevirtide has become anew treatment option alongside pegylated interferon alfa, which represents asignificant advance in the treatment landscape.

Seroprevalence of Hepatitis E Virus Infection Among Pregnant Women in Ilam, West of Iran.

Hepatitis E infection is commonly known as acute and self-limiting hepatitis, and therefore, less attention is paid to it, whereas hepatitis E virus is a major cause of fulminant hepatitis in pregnant women and its infection during pregnancy is associated with maternal and fetal mortality. The prevalence of anti-HEV antibodies in pregnant women in Ilam city is unknown. The aim of the present study was to investigate the prevalence of anti-HEV total and anti- HEV IgM antibodies among pregnant women in this area. A total of 420 serum samples were collected between March 2018 and September 2019 from pregnant women, with a mean age of 29.61 years, ranging from 19 to 47 years, referred to Ilam health centers, West of Iran. Demographic data, including age and place of residence, were collected from patient records. The titers of anti-HEV total and anti-HEV IgM antibodies were measured by the ELISA method. The association between the prevalence of hepatitis E antibody and age and place of residence variables was evaluated by the chi-square test. Statistical analysis was performed using SPSS version 20. In total, 18 of the 420 participants (4.3%) were positive for anti-HEV total, while 2 (0/47%) tested positive for anti-HEV immunoglobulins M (IgM). Anti-HEV status had no statistically significant association with age and place of residence. The seroprevalence rate of HEV infection among pregnant women in Ilam city is relatively low. Considering that seronegative pregnant women are at risk of acquiring HEV, it is recommended that pregnant women be educated to avoid sources of HEV infection.

Management of Fulminant Hepatitis B

Purpose of ReviewAcute HBV infection and acute exacerbations of chronic HBV infection can cause acute liver injury (ALI) or fulminant hepatitis (FH). At this stage, spontaneous survival is poor, less than 25%. The purpose of this review is to provide an overview of specific management of patients with HBV-ALI/FH.Recent FindingsAcute HBVinfection and acute exacerbations of chronic HBVinfection can cause acute liver injury (ALI) or fulminant hepatitis (FH). Spontaneous survival at this stage is poor. It is urgent to distinguish between these two entities so that antiviral therapy can be initiated rapidly. Although the indications for antiviral therapy are clear for HBV reactivation, there is no true consensus regarding ALI/FH related to acute HBV infection. The global management of HBV-related FH does not differ from that implemented for other causes of FH, i.e. close cardiorespiratory and neurological monitoring, treatment with acetylcysteine, organ support in the event of organ failure (haemodynamic, renal, respiratory) and albumin dialysis. Liver transplantation remains the only alternative when certain criteria for a poor prognosis are met. A recurrence of HBV infection on the graft can be prevented post-transplant by the administration of HBIG and antiviral therapy for HBV, the modalities varying depending on the risk of recurrence.

Fatal Septic Shock Associated with Herpes Simplex Virus Hepatitis: A Case Report.

Herpes simplex viruses are endemic worldwide, with an estimated seroprevalence of approximately 70% in developed countries. However, it is less well known that they are one of the viral causes of fulminant hepatitis (<2%) and constitute <1% of all causes of acute liver failure. We describe the case of an 89-year-old man who developed sepsis caused by a urinary tract infection due to drug-sensitive Escherichia coli. After empirical treatment with piperacillin-tazobactam was initiated, the patient’s condition worsened with shock, acute liver and renal failure, encephalopathy and persistent fever, that led to admission to the intensive care unit. The emergence of an acute abdomen prompted exploratory laparotomy but the patient died soon after surgery from abdominal haemorrhage. Immunohistochemical analysis of a liver biopsy specimen identified herpes simplex virus (HSV) hepatitis. The authors emphasize the need for better understanding of this rare condition in order to more precisely identify patients at risk who need more aggressive evaluation and empirical treatment, especially patients presenting with marked hepatic cytolysis with a rapidly worsening clinical evolution.LEARNING POINTSHerpes simplex virus hepatitis should be considered in patients with acute liver failure.This condition can occur even in immunocompetent individuals.Empirical treatment with aciclovir should be initiated in case of clinical suspicion.

Hepatitis B virus preS/S gene mutations and their clinical implications

Hepatitis B virus (HBV) infection remains a major health problem worldwide. HBV is one of the smallest enveloped DNA viruses, and also one of the principal pathogens causing acute and chronic hepatitis. Hepatitis B surface antigen (HBsAg) is a hallmark for the diagnosis of HBV infection, and the quantification of serum HBsAg is regarded as a reliable marker of disease progression and predictor of the outcome. However, the mutations in the preS/S genomic region can occur in HBV DNA sequences from the patients with chronic HBV infection, including genetic recombination, base pair deletion, and point mutations. These variants carrying the modified surface antigen may induce immune escape or occult HBV infection (OBI). Furthermore, the preS/S variants may be the cause of fulminant hepatitis (FH) and fibrosing cholestatic hepatitis (FCH). The mutations in the preS/S region would increase the difficulty of preventing and treatment of HBV infection. In this review, we summarized the prevalence of the mutations in the preS/S region and their effect for the diagnosis or progression of HBV infection.

Herpes Hepatitis Causing Fulminant Liver Failure in a Crohnʼs Disease Patient

A 24-year old non pregnant white woman with history of Crohn's disease, started on azathioprine and mesalamine, one month prior to admission, presented with a five day history of fever, chills, diarrhea and abdominal pain. Her physical examination revealed temperature of 102.4 F, abdominal distension and epigastric tenderness. Initial labs showed normal CBC, Klebsiella pneumoniae positive urine culture, ALT 104 units/L (U/L), AST 120 U/L, and normal amylase and lipase levels. She was started on levofloxacin for UTI, and methyl prednisone and metronidazole for possible Crohn's flare. On day 2 of hospitalization, she developed vesiculopapular rash on her chest and abdomen which later spread to her extremities. Her ALT and AST increased to 1401 U/L and 2386 U/L respectively. Hepatitis A IgM, hepatitis B surface antigen, hepatitis core IgM antibody, hepatitis C antibody, ANA, chlamydia/gonococcal PCR test, ASMA, AMA and EBV serology were negative. Imaging studies including RUQ ultrasound, CT scan of abdomen/pelvis, and HIDA scan were normal. Her condition declined with fulminant hepatitis, coagulopathy, and pancytopenia. She admitted to having unprotected sex and contracting herpes simplex virus (HSV) in the past. She was empirically started on intravenous acyclovir and subsequently found positive for HSV type 2 IgM antibodies with titer >1:160. Acyclovir was continued for 14 days with near complete normalization of liver enzymes, coagulation studies, and blood counts. HSV viral load decreased from 500 million to 158,000 in 3 weeks. She was discharged on lifelong maintenance dose of acyclovir. HSV is a rare cause of fulminant hepatitis and at risk individuals include neonates, pregnant women, patients like those on steroids, immunosuppressant medications and HIV and cancer patients. Clinical features include fever, nausea, vomiting, abdominal pain, leukopenia, and coagulopathy with or without mucocutaneous lesions. Serum HSV PCR is the diagnostic modality of choice, although liver biopsy remains the gold standard. When HSV hepatitis is suspected or diagnosed, acyclovir should be empirically started, since delay in initiation of antiviral therapy leads to rapid development of sequelae and poor outcomes. To our knowledge, this is the second reported case of HSV hepatitis in a Crohn's disease patient. Hence, HSV hepatitis should be considered in the differential diagnosis of fulminant hepatitis in immunocompromised patients.

Acute liver failure in the setting of herpes simplex virus and coexistent acute fatty liver of pregnancy

Fulminant hepatitis is a rare complication of herpes simplex virus (HSV-1 and HSV-2). Another rare cause of fulminant hepatitis in pregnant women is acute fatty liver of pregnancy (AFLP). Here we present a female with fulminant hepatitis after a cesarean section whose infant clinically decompensated in the early neonatal period. Mother and child were diagnosed with fulminant hepatic failure from HSV, and the mother was found to have coexistent fatty liver of pregnancy on biopsy. Thus, two rare causes of fulminant hepatitis were co-morbid in the same patient. Rapid diagnosis enabled successful treatment, and both mother and infant recovered well.

HEV Related Guillian-Barre' Syndrome: A Case Report

HEV Related Guillian-Barre' Syndrome: A Case Report HEV virus has been known to be a cause of fulminant hepatitis. Recently it has been suggested that HEV may have extra-hepatic manifestations, especially neurological, of which has been an AIDP (Acute Inflammatory Demyelinating Polyneuropathy) like syndrome i.e., Guillian Barre syndrome has been reported. A 19 year old male patient was admitted with fulminant hepatic failure with hepatic encephalopathy. The patient was electively intubated and treated for fulminant liver failure. As the patients encephalopathy improved, an ascending motor weakness that resolved over the next 3 weeks.

Hepatitis A in Children- Clinical Course, Complications and Laboratory Profile: Correspondence

To the Editor: We read with great interest the article by Kumar et al. that reported the clinical course, complications and laboratory profile of Hepatitis A in children [1]. Although, they emphasized the hyperendemicity, fatal complications and cost effectiveness of Hepatitis A infection; and importance of improved sanitation and health education for its prevention, the importance of vaccination for preventing and control of Hepatitis A virus infection was not mentioned in their article. We think that vaccination against Hepatitis A would be significant part of planning for the prevention and control of viral hepatitis. Therefore, we want to make some comments on their article. Hepatitis A infection is a widespread disease, accounting for 1.4 million cases annually worldwide. In high endemic areas, the reported incidence of Hepatitis A infection may reach 150 per 100,000 per year [2]. The clinical spectrum of Hepatitis A infection ranges from asymptomatic infection to fulminant hepatitis. Clinical manifestations depend on the age of host: less than 30 % of infected young children are symptomatic, while approximately 80 % of adults manifest severe hepatitis with remarkably elevated serum aminotransferases [3]. Acute liver failure occurs in less than 1 % of cases. Hepatitis A infection is the most common detected cause of fulminant hepatitis among children in our country as well as worldwide [4]. The application of a routine Hepatitis A virus vaccine among children will reduce the potential for the development of severe complications. Hepatitis A incidence has declined 92 % with universal vaccination of young children in United States [5]. Universal Hepatitis Avirus immunization program has begun in Turkey since October 2012. Nearly 100 % of people develop protective levels of antibodies to the virus within one month after a single dose of the vaccine. Even thougha single dose of the vaccine has protectiveeffects; still, manufacturers recommend two vaccine doses to ensure a longer-term protection of about 5 to 8 y after vaccination. Hepatitis A infection is an important public health problem indevelopingcounties.Vaccinationagainst hepatitisAvirusis necessary for children older than one year. We believe that in addition to improved sanitation and food safety, the universal Hepatitis Avirus immunization programs are the most important means in effort to reduce Hepatitis A virus infection and related severe complications.

Etiology and prognosis of fulminant hepatitis and late‐onset hepatic failure in Japan: Summary of the annual nationwide survey between 2004 and 2009

To summarize the annual nationwide survey on fulminant hepatitis (FH) and late-onset hepatic failure (LOHF) between 2004 and 2009 in Japan. The annual survey was performed in a two-step questionnaire process to detail the clinical profile and prognosis of patients in special hospitals. Four hundred and sixty (n = 227 acute type; n = 233 subacute type) patients had FH and 28 patients had LOHF. The mean age of patients with FH and LOHF were 51.1 ± 17.0 and 58.0 ± 14.4 years, respectively. The causes of FH were hepatitis A virus in 3.0%, hepatitis B virus (HBV) in 40.2%, other viruses in 2.0%, autoimmune hepatitis in 8.3%, drug allergy-induced in 14.6% and indeterminate etiology in 29.6% of patients. HBV reactivation due to immunosuppressive therapy was observed in 6.8% of FH patients. The short-term survival rates of patients without liver transplantation (LT) were 48.7% and 24.2% for the acute and subacute type, respectively, and 13.0% for LOHF. The prognosis was poor in patients with HBV reactivation. The implementation rate for LT in FH patients was equivalent to that in the previous survey. The short-term survival rates of total patients, including LT patients, were 54.2% and 40.8% for the acute and subacute type, respectively, and 28.6% for LOHF. The demographic features and etiology of FH patients has gradually changed. HBV reactivation due to immunosuppressive therapy is problematic. Despite advances in therapeutic approaches, the prognosis of patients without LT has not improved.

Epidemiology of liver failure

The etiology of fulminant hepatitis varies in different countries and at different times. The main causes of fulminant hepatitis are viruses, paracetamol, drugs (other than paracetamol), poisons and 15-30% remained of undetermined origin. The prevalence of these etiologies varies according to the geographic region and has changed over the past 10 years. Paracetamol has now overtaken viruses (particularly hepatitis B virus) as the leading cause of fulminant hepatitis. Establishing the cause of fulminant hepatitis is an important step in the management of acute liver failure, so that specific therapy can be initiated and any contraindications to liver transplantation be eliminated.

Autoimmune fulminant liver failure in adults: Experience in a Japanese center

After the establishment of the international criteria of autoimmune hepatitis (AIH) in 1999 and the recognition of acute onset AIH, the diagnosis of patients with fulminant type of AIH came to be made. We diagnosed autoimmune fulminant liver failure based on the criteria, and discussed the etiology of fulminant hepatitis (FH) and late onset hepatic failure (LOHF), and the characteristics of autoimmune fulminant liver failure. We investigated the etiology of 95 consecutive adult patients with FH or LOHF admitted to our liver unit between 1990 and 2009. Clinical and biochemical features, therapies and outcomes were examined in patients with AIH after 2000. Of 95 patients, 85 were FH and 10 LOHF. The etiology was due to viral infections in 51.6% (hepatitis A virus in 7.4%, hepatitis B virus in 43.2% and hepatitis E virus in 1.1%), AIH in 15.8%, drug allergy-induced in 12.6%, and unknown causes in 20.0%. The rate of patients with AIH increased significantly between 2000 and 2009 compared to the rate between 1990 and 1999 (P = 0.002). In recovered patients with AIH without transplantation after 2000, coma grade was lower, alanine aminotransferase level, prothrombin time activity and alfa-fetoprotein level were higher than in the others with statistical significance. AIH is not a rare cause of FH and LOHF, and the number of patients with unknown causes would surely decrease in concert with the precise diagnosis of AIH.

Alpers syndrome presenting with anatomopathological features of fulminant autoimmune hepatitis

A 6-month-old girl with normal psychomotor development presented with fulminant hepatitis. Interestingly, liver biopsy demonstrated features of autoimmune hepatitis, whereas autoantibodies and raised immunoglobulin G (IgG) were absent. There was extensive centrolobular necrosis with bridging (Fig. 1a) and ductular reaction (Fig. 1b). There were numerous lymphocytes and plasmocytes (polyclonal on kappa and lambda stain) (Fig. 1c). Biochemical investigations excluded alternative causes of fulminant hepatitis. Steroid treatment was started, but the patient soon evolved to liver failure and received a liver transplantation. Three months posttransplant, the patient developed myoclonic and generalized tonic-clonic fits. Computed tomography (CT) scan, normal at presentation, revealed evolution toward severe brain atrophy. Mitochondrial assays on postmortem muscle biopsy revealed normal activity of respiratory chain complex II and decreased I, III, and IV activity. This is indicative of mitochondrial DNA (mtDNA) depletion in this clinical setting (Hargreaves et al. 2002). DNA analysis revealed two known POLG mutations (p.Ala467Thr and p. Gly848Ser), diagnostic for Alpers syndrome. We show here for the first time that a mtDNA-depletion syndrome can present with the anatomopathological features of autoimmune hepatitis. Alpers syndrome therefore should not be excluded from the differential diagnostic list based on these features. Whether this is also the case in older children, or even adults, presenting with cryptogenic acute liver failure and pathological features of autoimmune hepatitis remains to be determined.

Hépatite fulminante et sub-fulminante : étiologie et traitement

Fulminant hepatitis is an emergency because within a few hours, the physician must find the cause of the hepatitis (not identified in 15 to 20% of cases), rule out any contraindication to liver transplantation, verify that it is indicated, and prevent and/or treat the complications associated with liver failure. Viruses (especially hepatitis viruses A and B), drugs, and toxic agents are the most common causes of fulminant hepatitis, with the proportions varying between countries. Hepatitis viruses, the leading cause through 1995-1996, have fallen behind drugs and in particular paracetamol, which is now the leading cause of this disease in Europe and in the United States. There are also other rarer causes: other viruses (e.g., herpes virus HSV1 or 2, hepatitis virus E, parvovirus B19, and chickenpox-herpes zoster), Wilson Disease, acute Budd-Chiari and Reyes syndromes, autoimmune hepatitis, neoplastic infiltration of the liver, hypoxic hepatitis, heatstroke, acute pregnancy-related steatosis, and the HELLP syndrome. Prognosis is essentially determined by neurological status, but is also affected very rapidly by damage to other organs. Liver transplantation has revolutionized the prognosis of fulminant hepatitis, causing survival to increase from 10-20% (all causes combined) to 75-80% at 1 year and 70% at 5 years. These patients can be treated only in specialized centers with access to liver transplantation and to different modern means of liver resuscitation (hypothermia, artificial liver support, albumin dialysis, monitoring intracranial pressure and cerebral perfusion, etc.) -all from the onset of the disease.

Current status of liver diseases in Korea: Toxic and alcoholic liver diseases

The study of the epidemiology of toxic liver injury has been limited in Korea. The number of hospitalizations for toxic liver injury has been estimated to be 2,400 persons per year. About 30~40% of fulminant hepatitis was attributed to toxic hepatitis. The frequent causative agents of toxic hepatitis in Korea are herbal medicines (34-40%), folk remedies (23-34%), and prescribed medicines (24-55%). However, the most common agents causing severe liver injury including fulminant hepatitis are herbal medicine and folk remedies. Antituberculosis drugs and acetaminophen are two common causes of fulminant hepatitis among prescribed drugs. Alcohol is one of the leading causes of chronic liver disease in Korea. No nationwide study on the epidemiology of alcoholic liver disease (ALD) has been carried out, but 7-31% of cirrhosis has been reported to be alcoholic in a few single-center studies. Alcohol could be a risk factor for the development of hepatocellular carcinoma (HCC) in chronic viral hepatitis. Several studies have shown that alcohol increased the risk of HCC in liver cirrhosis with HBsAg or anti-HCV. Furthermore, alcoholic cirrhosis with occult hepatitis B virus infection increased the risk of HCC.

Clinical epidemiology of fulminant hepatitis in Japan

The annual incidence of fulminant hepatitis (FH) in Japan has decreased from 3700 patients in 1972 to 1000 patients in 1989, 1050 patients in 1995 and 426 in 2004. The most frequent cause of FH in Japan is hepatitis B virus (HBV)-related hepatitis, which accounts for around 40%, with hepatitis A accounting for around 10%; drug reaction accounts for around 10%; other hepatitis, including an unknown cause, accounts for around 40%. The acute type FH, which has a disease duration as 10 days or shorter before the development of encephalopathy (onset-coma days [OCD]), mainly consists of hepatitis A and B and has relatively better prognosis, with an approximately 40% survival rate without transplantation. The subacute type FH, which has 11 to 56 days OCD, mainly consists of unknown hepatitis including acute-onset autoimmune hepatitis and has poorer prognosis of about 20% survival. Approximately 25% of FH patients underwent liver transplantation and about 80% of them survived. High volume plasma exchange (PE) and hemodialysis filtration (HDF) have been the most common and principal therapies and they are administered to about 90% and 70% of patients, respectively. The progress of artificial liver support such as combination treatment of PE with HDF is considered to play a role in the slight improvement of the survival proportion of patients with acute type FH in recent years.

Etiology and prognosis of fulminant hepatitis in adults

1. Establishing the cause of fulminant hepatitis is an important step in the management of acute liver failure, so that specific therapy can be initiated and any contraindications to liver transplantation can be eliminated. 2. The etiology of fulminant hepatitis varies in different countries and at different times. A viral etiology (in particular hepatitis B virus) is now less frequent, and paracetamol-induced fulminant hepatic failure is more common. 3. Many patients have miscellaneous causes of fulminant hepatitis. It is important to establish the main clinical and biological characteristics for specific management. 4. Assessment of the prognosis of fulminant hepatitis is important for distinguishing patients requiring liver transplantation from those whose will improve spontaneously. Prognosis depends on several factors, including the gold standard, the King's College Hospital criteria and Clichy's criteria.

Postoperative issues and outcome for acute liver failure

1. Establishing the cause of fulminant hepatitis is an important determinant in outcomes after liver transplantation. 2. Liver transplantation is an integral part of the management of ALF. 3. In addition to generic posttransplant care, neurologic, septic, and hematologic issues need to be addressed. 4. Outcomes after liver transplantation are poorer than those for elective transplantation but superior to those found for comparably ill patients being transplanted for chronic liver disease. 5. Multiple factors have an influence on outcome, and risk stratification is beginning to emerge.

Hépatite fulminante à virus Epstein-Barr : évolution favorable après transplantation hépatique

Viral hepatitis are the leading cause of fulminant hepatitis. Epstein Barr virus is the viral agent involved in infectious mononucleosis, associated with a frequent and usually benign hepatitis, except in case of immunodeficiency, congenital or acquired. We report the case of an immunocompetent young woman who presented an EBV induced fulminant hepatic failure, requiring liver transplantation that was successful. This observation emphasizes that EBV must be known as a possible cause of fulminant hepatitis and that liver transplantation is probably the unique therapeutic option to avoid a usually fatal course.

Fulminant Epstein-Barr virus (EBV) hepatitis in a young immunocompetent subject

We report a case of fulminant hepatitis related to a primary Epstein-Barr virus (EBV) infection in an immunocompetent 15-year-old male patient. The main causes of fulminant hepatitis are viral infections, drugs, and autoimmune diseases. Primary Epstein-Barr virus infection is usually a benign, self-limited disease in pediatrics but can exceptionally be fatal.