• HLH
• HSV 1 and 2
• epidemiology
• mortality

• Humans
• Acetaminophen/adverse effects
• Acute Kidney Injury/therapy
• Acute Kidney Injury/chemically induced
• Acute Kidney Injury/etiology
• Acute Kidney Injury/diagnosis
• Analgesics, Non-Narcotic/adverse effects
• Antidotes
• Brain Edema/etiology
• Brain Edema/therapy
• Drug Overdose/therapy
• Liver Failure, Acute/therapy
• Liver Failure, Acute/chemically induced
• Liver Failure, Acute/diagnosis
• Liver Transplantation

• Adult
• Dysfunction
• Failure
• HLH
• Hemophagocytosis
• Hepatic
• Hepatitis
• Liver
• Lymphohistiocytosis
• Transplant

• Adult
• Humans
• Early Diagnosis
• Liver Diseases/complications
• Liver Transplantation
• Lymphohistiocytosis, Hemophagocytic/complications
• Lymphohistiocytosis, Hemophagocytic/diagnosis
• Rare Diseases/complications

• Acute liver injury
• Hemophagocytic lymphohistiocytosis
• Hepatitis

• COVID-19 vaccine
• acute liver failure
• hemophagocytic lymphohistiocytosis
• multisystem inflammatory syndrome

• aih
• autoimmune hepatitis
• hemophagocytic lymphohistiocytosis
• hlh
• liver injury

Hemophagocytic lymphohistiocytosis (HLH) is an aggressive hematologic disorder involving hyperstimulation of immune responses and severe inflammation. HLH has been well documented in lymphoid cancers and leukemias, but more rarely in solid tumors. The non-specific clinical characteristics of HLH can cause a diagnostic dilemma and delay in proper treatment, resulting in poor outcomes. We present a case of a patient with metastatic renal cell carcinoma who developed unexplained acute liver failure and was later found to have HLH. This case highlights the importance of including this syndrome on the differential diagnosis for acute liver failure of indeterminate cause and cytopenia in the setting of malignancy to facilitate proper timely treatment to improve outcomes and increase odds of survival.

• COVID-19/complications
• Cytokine Release Syndrome/complications
• Cytokine Release Syndrome/virology
• Cytokines
• Humans
• Liver Diseases/virology

The multi-organ failure syndrome associated with acute and acute-on-chronic liver failure (ACLF) is thought to be mediated by overwhelming systemic inflammation triggered by both microbial and non-microbial factors. Therapeutic plasma exchange (TPE) has been proven to be an efficacious therapy in autoimmune conditions and altered immunity, with more recent data supporting its use in the management of liver failure. Few therapies have been shown to improve survival in critically ill patients with liver failure who are not expected to survive until liver transplantation (LT), who are ineligible for LT or who have no access to LT. TPE has been shown to reduce the levels of inflammatory cytokines, modulate adaptive immunity with the potential to lessen the susceptibility to infections, and reduce the levels of albumin-bound and water-bound toxins in liver failure. In patients with acute liver failure, high volume TPE has been shown to reduce the vasopressor requirement and improve survival, particularly in patients not eligible for LT. Standard volume TPE has also been shown to reduce mortality in certain sub-populations of patients with ACLF. TPE may be most favorably employed as a bridge to LT in patients with ACLF. In this review, we discuss the efficacy and technical considerations of TPE in both acute and acute-on-chronic liver failure.

• Therapeutic plasma exchange
• High volume plasma exchange
• Acute liver failure
• Acute-on-chronic liver failure
• Cirrhosis
• Liver transplantation
• Cytokines

• Clinical
• gastroenterology
• haematology (incl blood transfusion)
• infection (gastroenterology)
• liver disease

• ACLF, acute on chronic liver failure
• AFLP, acute fatty liver of pregnancy
• AKI, Acute kidney injury
• ALF, Acute liver failure
• ALFED, Acute Liver Failure Early Dynamic
• ALT, alanine transaminase
• ANA, antinuclear antibody
• AP, Alkaline phosphatase
• APTT, activated partial thromboplastin time
• ASM, alternative system of medicine
• ASMA, antismooth muscle antibody
• AST, aspartate transaminase
• ATN, Acute tubular necrosis
• ATP, adenosine triphosphate
• ATT, anti-TB therapy
• AUROC, Area under the receiver operating characteristics curve
• BCS, Budd-Chiari syndrome
• BMI, body mass index
• CBF, cerebral blood flow
• CBFV, cerebral blood flow volume
• CE, cerebral edema
• CHBV, chronic HBV
• CLD, chronic liver disease
• CNS, central nervous system
• CPI, clinical prognostic indicator
• CSF, cerebrospinal fluid
• DAMPs, Damage-associated molecular patterns
• DILI, drug-induced liver injury
• EBV, Epstein-Barr virus
• ETCO2, End tidal CO2
• GRADE, Grading of Recommendations Assessment Development and Evaluation
• HAV, hepatitis A virus
• HBV, Hepatitis B virus
• HELLP, hemolysis
• HEV, hepatitis E virus
• HLH, Hemophagocytic lymphohistiocytosis
• HSV, herpes simplex virus
• HV, hepatic vein
• HVOTO, hepatic venous outflow tract obstruction
• IAHG, International Autoimmune Hepatitis Group
• ICH, intracerebral hypertension
• ICP, intracerebral pressure
• ICU, intensive care unit
• IFN, interferon
• IL, interleukin
• IND-ALF, ALF of indeterminate etiology
• INDILI, Indian Network for DILI
• KCC, King's College Criteria
• LC, liver cirrhosis
• LDLT, living donor liver transplantation
• LT, liver transplantation
• MAP, mean arterial pressure
• MHN, massive hepatic necrosis
• MPT, mitochondrial permeability transition
• MUAC, mid-upper arm circumference
• NAPQI, n-acetyl-p-benzo-quinone-imine
• NPV, negative predictive value
• NWI, New Wilson's Index
• ONSD, optic nerve sheath diameter
• PAMPs, pathogen-associated molecular patterns
• PCR, polymerase chain reaction
• PELD, Pediatric End-Stage Liver Disease
• PPV, positive predictive value
• PT, prothrombin time
• RAAS, renin–angiotensin–aldosterone system
• SHF, subacute hepatic failure
• SIRS, systemic inflammatory response syndrome
• SNS, sympathetic nervous system
• TB, tuberculosis
• TCD, transcranial Doppler
• TGF, tumor growth factor
• TJLB, transjugular liver biopsy
• TLR, toll-like receptor
• TNF, tumor necrosis factor
• TSFT, triceps skin fold thickness
• US, ultrasound
• USALF, US Acute Liver Failure
• VZV, varicella-zoster virus
• WD, Wilson disease
• Wilson disease (WD)
• YP, yellow phosphorus
• acute liver failure
• autoimmune hepatitis (AIH)
• drug-induced liver injury
• elevated liver enzymes, low platelets
• sALI, severe acute liver injury
• viral hepatitis

Acute liver failure (ALF) and acute-on-chronic liver (ACLF) carry high short-term mortality rate, and may result from a wide variety of causes. Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant. Other cohort studies demonstrated potential improvement in survival in patients with ACLF.

To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.

Databases MEDLINE via PubMed, and EMBASE were searched and relevant publications up to 30 March, 2019 were assessed. Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange, with or without another alternative non-bioartificial liver assist device.

Three hundred twenty four records were reviewed, of which 62 studies were found to be duplicates. Of the 262 records screened, 211 studies were excluded. Fifty-one articles were assessed for eligibility, for which 7 were excluded. Twenty-nine studies were included for ALF only, and 9 studies for ACLF only. Six studies included both ALF and ACLF patients. A total of 44 publications were included. Of the included publications, 2 were randomized controlled trials, 14 cohort studies, 12 case series, 16 case reports. All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment (SMT) for ACLF, a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60 (95%CI 0.46-0.77, P < 0.01).

The level of evidence for use of high volume plasma exchange in selected ALF cases is high. Plasma exchange in ACLF improves survival at 30-and 90-d in non-transplanted patients. Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.

• Acute-on-chronic liver failure
• Acute liver failure
• Plasmapheresis
• Plasma exchange
• Liver failure

• Acute-On-Chronic Liver Failure/mortality
• Acute-On-Chronic Liver Failure/therapy
• Hospital Mortality
• Humans
• Liver Failure, Acute/mortality
• Liver Failure, Acute/therapy
• Plasma Exchange/methods
• Randomized Controlled Trials as Topic
• Survival Rate
• Time Factors
• Treatment Outcome

Haemophagocytic syndrome (HPS) is a rare and potentially life-threatening condition that requires early diagnosis and prompt combined treatment. This case report describes a male patient with HPS, presenting as acute liver failure, that underwent a thorough evaluation for the cause of his symptoms. A final diagnosis of acute lymphoblastic leukaemia was established more than 2 months after the first presenting symptom appeared. Furthermore, the patient had an unusual chromosomal abnormality with a t(9; 22)(p24; q11.2) translocation, but the reciprocal janus kinase 2-breakpoint cluster region (JAK2-BCR) and BCR-JAK2 fusion transcripts were not be amplified.

• Haemophagocytic syndrome
• acute liver failure
• acute lymphoblastic leukaemia
• q11.2)
• t(9;22)(p24

We report the case of an immunocompetent young woman who developed multisystem organ failure following herpes simplex virus type 2 and hemophagocytic lymphohistiocytosis. Despite intravenous acyclovir and supportive measures, she rapidly progressed to acute liver failure and died before she could receive orthotopic liver transplant.

• liver diseases
• hepatitis

• Adolescent
• Adult
• Aged
• Bilirubin/analysis
• Female
• Fever/complications
• Follow-Up Studies
• Hepatitis/blood
• Hepatitis/complications
• Humans
• International Normalized Ratio
• Jaundice/complications
• Liver Failure/complications
• Liver Failure/diagnosis
• Lymphohistiocytosis, Hemophagocytic/complications
• Lymphohistiocytosis, Hemophagocytic/diagnosis
• Male
• Methylprednisolone/therapeutic use
• Middle Aged
• Pancytopenia/complications
• Retrospective Studies
• Splenomegaly/complications
• Young Adult

Herein we report a case of acute liver failure (ALF) and hemophagocytic lymphohistiocytosis (HLH) induced by varicella infection, successfully rescued by a combination therapy of acyclovir, supportive care, and immunosuppression with dexamethasone and etoposide. A previously healthy 16-year-old boy presented with generalized rash, fever, severe abdominal pain, and abnormal liver function within 4 d. Chickenpox was suspected, and acyclovir and intravenous immunoglobulin were started on admission. However, the patient’s condition deteriorated overnight with soaring transaminases, severe coagulopathy and encephalopathy. On the fourth day of admission, pancytopenia emerged, accompanied by hypofibrinogenemia and hyperferritinemia. The patient was diagnosed with ALF. He also met the diagnostic criteria of HLH according to the HLH-2004 guideline. Polymerase chain reaction (PCR) amplifications of varicella-zoster virus (VZV) were positive, confirming that VZV was a causative trigger for ALF and HLH. In view of the devastating immune activation in HLH, immunosuppression therapy with dexamethasone and etoposide was administered, in addition to high dose acyclovir. The patient’s symptoms improved dramatically and he finally made a full recovery. To our knowledge, this is only the second report of a successful rescue of ALF associated with HLH, without resorting to liver transplantation. The first case was reported in a neonate infected by herpes simplex virus-1. However, survival data in older children and adults are lacking, most of whom died or underwent liver transplantation. Our report emphasizes the clinical vigilance for the possible presence of HLH, and the necessity of extensive investigation for underlying etiologies in patients presenting with indeterminate ALF. Early initiation of specific therapy targeting the underlying etiology, and watchful immunosuppression such as dexamethasone and etoposide, together with supportive therapy, are of crucial importance in this life-threatening disorder.

• Acute liver failure
• Immune dysregulation
• Hyperferritinemia
• Hemophagocytic lymphohistiocytosis
• Varicella infection
• Skin rash

• Autoimmunity
• Hepatitis
• Liver
• Primary immunodeficiency
• Transplantation

• Acquired immune hyperactivation
• Acute liver failure
• Hemophagocytic lymphohistiocytosis
• Liver injury
• Liver transplantation
• Pancytopenia

• cyclosporine
• hemophagocytic lymphohistiocytosis
• interleukin-1-directed therapy
• kidney transplant recipient
• plasma exchange

• Adrenal Cortex Hormones/therapeutic use
• Antirheumatic Agents/therapeutic use
• Combined Modality Therapy
• Cyclosporine/therapeutic use
• Diagnosis, Differential
• Diagnostic Imaging
• Humans
• Immunosuppressive Agents/therapeutic use
• Interleukin 1 Receptor Antagonist Protein/therapeutic use
• Kidney Transplantation
• Lymphohistiocytosis, Hemophagocytic/etiology
• Lymphohistiocytosis, Hemophagocytic/therapy
• Male
• Middle Aged
• Plasmapheresis

Hemophagocytic lymphohistiocytosis (HLH) and newly diagnosed malignant infiltration of liver are rare presentations of acute liver failure associated with poor prognosis. We report a case of a patient with acute liver failure caused by malignant infiltration by diffuse large B-cell lymphoma and secondary HLH.