Etiologies of acute liver failure

Acute liver failure is present when any type of rapid-onset liver insult results in a common systemic pathophysiologic picture: altered mental status, vasodilation, renal and pulmonary failure, frequent infection, and poor outcome without transplantation. Identifying which of the many different causes is a first step in understanding prognosis and options for treatment. However, identifying the correct cause can be difficult and sometimes impossible. Any discussion of etiologies must take a historical perspective; there have been several evolving trends nationally and internationally over the past three decades. Etiologies also vary worldwide with considerable differences apparent between Western countries and the developing world. In Europe and North America a large proportion of cases are due to acetaminophen and to idiosyncratic drug reactions, whereas reports from emerging countries in Asia and Africa feature viral illnesses, particularly hepatitis B and E. Determining etiology is important for two reasons: specific antidotes or therapies may be indicated once the diagnosis is known, and knowing the cause provides a reasonably valid guide to predicting outcome.     

Epidemiology and outcomes of acute liver failure in Australia

BACKGROUND Acute liver failure(ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain.AIM To describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia.METHODS The database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults( 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival(OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988-2001.RESULTS Paracetamol was the most common aetiology of acute liver failure, accounting for50% of cases, with an increased incidence compared with the historical cohort(P= 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival(TFS)improved significantly compared to the historical cohort(52% vs 38%, P = 0.032).TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF(P 0.001). Fifty-nine patients were waitlisted for emergency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients(25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and72% respectively.CONCLUSION Paracetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF.     

Changing etiologies and outcomes of acute liver failure: A perspective from Japan

Acute liver failure in Japan usually consists of fulminant hepatitis (FH) due to viral infection, autoimmune hepatitis and drug-allergy-induced liver injury. The annual incidence of FH was estimated at 429 cases in 2004. FH is classified into acute or subacute type, and the prognosis of the latter is poor. Hepatitis B virus (HBV) is the most frequently identifiable agent that causes FH in Japan. Transient HBV infection is more prevalent in the acute than subacute type, whereas the frequency of HBV carriers is greater in the subacute type. FH due to HBV reactivation from resolved hepatitis B has been increasingly observed in patients with malignant lymphoma treated with rituximab and corticosteroid combination therapy. The prognosis is poor in HBV carriers with acute exacerbation, especially in patients with HBV reactivation from resolved hepatitis B. Despite careful investigation, the etiology is still unknown in 16% and 39% of the acute and subacute type of FH, respectively. Autoimmune hepatitis and drug-allergy-induced liver injury are found in 7% and 10%, respectively, and are more frequently observed in the subacute type of FH. Living donor liver transplantation is now the standard care for individuals with poor prognosis. Artificial liver support with plasmapheresis and hemodiafiltration plays a central role while waiting for a donor liver or for the native liver to regenerate. Further research is necessary to identify the causes of unknown origin. In addition, to improve the prognosis of FH, it is necessary to establish treatment modalities that are effective for liver regeneration.     

Short and long-term outcomes in patients with acute liver failure due to ischemic hepatitis

Aims  

The purpose of this study is to describe the incidence and presenting features of patients with acute liver failure (ALF) due to ischemic hepatitis and the prognostic factors associated with short (three-week) and long-term outcomes.     

Renal failure in acute liver failure.

Renal failure develops in approximately 55% of all patients referred to specialized centres with acute liver failure. The renal failure may be secondary to the liver failure itself (and is termed the hepatorenal syndrome) or the renal failure may be a secondary insult that directly affects both liver and kidney alike (for example paracetamol overdose). The pathogenesis of the hepatorenal syndrome involves the development of a hyperdynamic circulation, with a lowering of renal perfusion pressure, the activation of the sympathetic nervous system, which renders the kidneys more susceptible to modest decreases in perfusion pressure, and increased synthesis of a variety of vasoactive mediators. These mediators can cause renal vasoconstriction, but more importantly they can also decrease the glomerular capillary ultrafiltration coefficient (Kf), thus causing a decline of glomerular filtration rate over and above that caused by renal vasoconstriction alone. The treatment of the renal failure in acute liver failure involves the optimization of renal haemodynamics and haemofiltration. Renal failure will always recover when there is recovery of liver function, and in the absence of a spontaneous hepatic recovery, liver transplantation will reverse the hepatorenal syndrome.     

Thrombopoietin in acute liver failure

Thrombopoietin (TPO) is the primary regulator of platelet production. TPO is produced in the liver and levels are low in patients with cirrhosis. Because thrombocytopenia is common in patients with acute liver failure (ALF), we measured TPO concentrations (normal TPO range, 31 to 136 pg/mL) in 51 patients with ALF to determine if low levels were associated with thrombocytopenia. TPO levels from hospital day 2 were elevated in 43% of patients, normal in 47%, and decreased in 10% of patients. Levels were higher in acetaminophen-induced than in non-acetaminophen-induced ALF, 160 (12 to 549) pg/mL versus 73 (18 to 563) pg/mL, respectively, P =.031. TPO levels did not correlate with platelet count and were not related with survival or infection. We analyzed daily TPO levels for the first week of hospitalization in 12 patients with acetaminophen-induced ALF and observed a gradual increase from a median admission level of 50 (5 to 339) pg/mL to a median peak level of 406 (125 to 1,081) pg/mL occurring on day 5 (3 to 6). Platelets were reduced in 11 of the 12 patients with a nadir platelet count of 52 (19 to 156) x 10(9) cells/L occurring on day 5.5 (1 to 6). The peak TPO level did not correlate with the nadir platelet count (P =.43). In conclusion, the normal inverse relationship between platelet count and TPO levels was not observed in ALF. Despite severe hepatic dysfunction, serum TPO levels were initially normal and increased during hospitalization in acetaminophen-induced ALF, but did not prevent the development of thrombocytopenia.     

Etiologies and outcomes of rheumatology patients with acute respiratory failure requiring intensive care: a single-center medical records review study of 259 patients

Clinical Rheumatology - The etiologies of acute respiratory failure in patients with systemic rheumatic diseases (SRDs) requiring intensive care remain unknown. This study was undertaken to...     

Role of liver transplantation in acute liver failure

Orthotopic liver transplantation is employed as salvage therapy for individuals who are unable to recover from acute liver failure. Prognostic models are helpful but not entirely accurate in predicting those who will eventually require liver transplantation. There are specific criteria for United Network for Organ Sharing category 1a (urgent) listing of these patients. Unfortunately, clinical deterioration develops rapidly and many require removal from the waiting list prior to transplantation. With advances in critical care management and surgical technique, 1-year post-transplant survival rates have improved to 60 to 80%. Alternatives to conventional orthotopic liver transplantation include living donor liver transplantation, ABO-incompatible grafts, and auxiliary liver transplantation. There are many ethical and psychosocial issues inherent to transplanting these sick patients due to the urgent nature of acute liver failure. Fortunately, the long-term survival and quality of life in these transplant recipients is good.     

Flutamide-associated acute liver failure

The nonsteroidal antiandrogenic drug flutamide [4'-nitro-3'-(trifluoromethyl)isobutyranilide] is a safe and generally well-tolerated drug used for the treatment of prostate cancer. We describe the case of a 74-year-old male who developed life-threatening acute liver failure during flutamide therapy. Other causes of acute liver failure were appropriately ruled out and there was no evidence of active prostate cancer or liver metastases. The use of the Naranjo probability scale indicated a highly probable relationship between the development of acute liver failure and flutamide therapy. Severe liver dysfunction has been rarely documented in patients treated with flutamide, even though cases of fulminant liver failure have been described. A few cases have been reported also among patients with hirsutism being treated with flutamide. The mechanisms responsible for the occurrence of hepatotoxicity during treatment with flutamide are unknown. Mitochondrial dysfunction seems to be implicated. The potential of flutamide to act as a potent hepatotoxin should be borne in mind when treatment with this drug is being planned.     

儿童急性肝衰竭

儿童急性肝衰竭是一种以肝性脑病、黄疸、凝血障碍和腹水为主要表现的临床综合征,常导致多器官功能障碍,病死率较高,是重症医学面临的救治难题。由于儿童这个群体的特殊性,儿童急性肝衰竭和成人相比在定义、病因以及诊治过程中均有其独特性。近年来随着医学技术的发展,尤其是重症医学的发展使得急性肝衰竭的预后有所改善。儿童肝移植的发展也为儿童急性肝衰竭的治疗提供了更多的机会。     

Drug-induced acute liver failure

Acute liver failure is the most severe expression and represents the first cause of fatalities related to drugs. As a consequence, it is also the first cause of drug withdrawal from the pharmaceutical market. The incidence of drug-induced hepatotoxicity in the general population has been recently estimated to be around 14/100,000 inhabitants in a Western country. Drugs appear to be responsible for 10-52% of all causes of acute liver failure. In Western countries, paracetamol (acetaminophen) represents the first cause of all liver failures. The contribution of non-paracetamol drugs given at normal doses is equivalent to that of combined viral hepatitis A and B. The natural prognosis varies between drugs. The spontaneous mortality rate ranges from 32% to 50% for paracetamol intoxication and more than 75% for other drugs. The preventive occurrence of drug hepatotoxicity and the course to acute liver failure is rather limited. It is recommended to stop the administration of a suspected drug when alanine aminotransferase levels increase to more than 3-5 times the upper limit of normal. In paracetamol intoxication, the rapid administration of N-acetylcysteine is a classical antidote. At the stage of liver failure, treatment is mostly supportive. Since irreversible damage is unpredictable, early transfer to a transplantation centre should be considered.