Defining acute-on-chronic liver failure: will East and West ever meet?
The definition of ACLF by the Asia-Pacific Association for the Study of Liver ( APASL) is: “Acute hepatic insult manifesting as jaundice and coagulopathy. Mar 18, Currently, acute-on-chronic liver failure (ACLF) has been defined Defining acute-on-chronic liver failure: will East and West ever meet?. Dec 21, The designation and concept of acute-on-chronic liver failure . Bajaj JS: Defining acute-on-chronic liver failure: Will east and west ever meet?.
Previous studies from the West have concluded that hepatic decompensation in the past was an independent predictor of mortality in patients with ACLF[ 18 ]. As expected, the former group also showed a significantly higher mortality at 28 d Also, for any given value of leucocyte count, the probability of mortality was significantly higher in those without prior decompensation compared to in those with[ 3 ].
This could imply that those without previous decompensation have an inappropriately exaggerated inflammatory response and immune dysfunction leading to worse outcome than those with previous decompensation. In a retrospective study, patients who met the APASL criteria for ACLF but also had prior decompensation in addition were older, more often had non-hepatic insults as a cause for acute worsening and generally had less severe hepatic damage compared to ACLF patients without any decompensation in the past[ 19 ].
The d survival was however similarly high A study from India with a smaller number of patients showed similar results[ 11 ].
Defining acute-on-chronic liver failure: will East and West ever meet? - Semantic Scholar
Further research is needed to explore this issue. Liver biopsy continues to be an important tool to differentiate between the underlying cirrhotic and non-cirrhotic liver disease and to establish the etiology of CLD in certain situations. Coagulopathy being a necessary part of the definition, the trans-jugular approach, needing expertise and adding to the cost of care, would be necessary for obtaining the liver biopsy in almost all who need the same.
In the absence of liver biopsy, there is a possibility that conditions such as acute Budd-Chiari syndrome or abdominal tuberculosis with hepatic and peritoneal involvement might be mistaken for ACLF, though these conditions are rather uncommon.
The differences in the two definitions would not matter if they identified mostly the same patients. Data from the literature however suggests they do not. Two studies from Asia in patients with acute worsening of CLD looked at how the two definitions fared in these patients. Zhang et al[ 20 ] found that The relative proportion of patients with ACLF by one or the other definition may vary from study to study depending on the background liver disease population from which they are drawn. But the proportions differing in the same study when the two definitions are applied clearly shows that they identify different patients with some overlap.
This would mean that the former would have a higher inflammatory response from the acute event compared to the latter, other factors being equal.
Clinical Classification of Liver Failure: Consensus, Contradictions and New Recommendations
Shi et al[ 21 ] have shown recently that ACLF precipitated by acute hepatic injury and by extra-hepatic insults are distinct but overlapping conditions which have similarly high transplant-free, d mortality The former group had compensated cirrhosis, liver and coagulation failure being frequent in them, while the latter had advanced underlying cirrhosis and a high frequency of extra-hepatic organ failure.
As would be expected from these, infections are less frequent in Asian patients with ACLF compared to their Western counterparts[ 8 ]. It thus becomes clear that the patients defined by the two definitions actually differ considerably.
Further studies using the World Gastroenterology Organization WGO consensus definition see below would help confirm this. The first study was retrospective, and the second one included a small number of patients. The reasons for this are multifactorial and include dysfunction of the reticuloendothelial and cellular immune system and defects in the barriers to bacterial translocation.
Because infection has such an intimate relationship with ACLF, infection may in fact be the central feature of this entity, although this is yet to be proven. The powerful association between infection and deleterious outcomes in cirrhosis mandates aggressive surveillance and early treatment of suspected infection.
In the East, reactivation of hepatitis B or superimposed viral hepatitis is common, whereas alcohol and drugs predominate in the West.
Injury is indicated by both hepatic and nonhepatic precipitating events by Western experts. However, this may not always be easy to discern. Bacterial translocation may play a pivotal role in the progression from compensated to decompensated liver cirrhosis as marked by the development of ascites, variceal bleeding, encephalopathy via the systemic inflammatory response syndrome SIRS.
However, a considerable proportion of patients with ACLF have no precipitating events. This finding places an impetus into the discovery of novel biomarkers that could predict ACLF development that occurs without 'classic' precipitating factors. Inflammation and neutrophil dysfunction are of major importance in the pathogenesis of ACLF. The clinical pictures of ACLF and septic shock are strikingly similar, characterized by progressive vasodilatory shock and multiple organ failure.
The transition from a stable cirrhotic condition to acute decompensation leading to liver failure is based on acute SIRS, mainly mediated by cytokines. However, change in CRP levels over time was able to discriminate survivors from nonsurvivors. Poorer outcome in the patients whose CRP levels failed to improve leads to the hypothesis that inability to resolve inflammation may be pathophysiologically important in this syndrome.
Recent data clearly show that the patients who recover from organ failure and are discharged from the hospital have almost universal mortality over the next three years, suggesting that the natural history of cirrhosis is altered by the occurrence of organ failure.
These results demonstrate the need for careful definition of the population under study. Coagulation tests are usually abnormal in cirrhotic patients due to impaired synthesis and increased consumption of coagulation factors.
Prolongation of the prothrombin time is common but spontaneous bleeding is rare. A relative decrease in anticoagulant factors serves to offset the decrease in procoagulant factors. Kidney dysfunction The most common organ to fail besides liver is the kidney.
Acute-on-chronic liver failure
Renal failure may be categorized into four types: For ACLF grade 2, liver failure was the most prevalent organ failure, followed by kidney, cerebral, and coagulation failures. For ACLF grade 3, the prevalence of all organ failures was high or moderately high. As this syndrome occurs in the background of existing cirrhosis and chronic portocaval shunting, brain atrophy may be protective against brain swelling, resulting in a moderate increase in intracranial pressure.
Unlike in decompensated cirrhosis, where cardiac output remains elevated, in ACLF, cardiac output can be reduced where both systolic and diastolic function are affected.Wicked Dub Division meets North East Ska Jazz Orchestra - Mama [Official Video 2017]
This cardiovascular abnormality is associated with an increased risk of death, particularly in those patients who present with renal dysfunction. Patients with cirrhosis are at increased risk of pneumonia. The risk of aspiration pneumonia is also high because of altered consciousness, gastric stasis, increased intra-abdominal pressure due to ascites, and ileus resulting from infection and electrolyte abnormalities. It has been shown that liver function is not the main determinant of clinical outcome for patients with decompensated cirrhosis; thus liver-specific scoring systems, such as the CTP or the MELD score, have limitations in accurately predicting the outcome of patients with ACLF.
The perfect system for early identification of patients with cirrhosis who are likely to suffer from ACLF has not been defined. In the Asia-Pacific region, the majority of ACLF is precipitated by hepatitis B flares and acute hepatitis A or E superimposed on chronic liver disease which is not necessarily cirrhosis. In sharp contrast, in Western societies, these viral etiologies are largely supplanted by nonviral insults, especially bacterial infections, in patients who are either known or are discovered to have cirrhosis upon admission Table 3.
Different combinations of each insult may result in the same level of decompensation. Some definitions of LF as ACLF might be conducive to evaluation of short-term prognosis and be harmful to early intervention of disease, versus other definitions.
This classification of LF proposed by the author might be more suitable for determining therapy and estimating prognosis. Hence, our classifications are new and more rational classification scheme.
This classification, if adopted worldwide, could help achieve uniformity in the classification and therapeutic guidelines for liver failure. However, the validity of this classification should be further tested in clinical practice. References Wang YM New concept in nomenclature, classification and diagnosis of liver failure. Chin J of Hepatol The management of acute liver failure. Diagnostic and treatment guidelines for liver failure.
Diagnostic and treatment guidelines for liver failure version. Chin J of Clin Infect Dis 5: Acute liver failure in the global village. J of Gastro and Hepatol Graziadei IW The clinical challenges of acute on chronic liver failure.
People's Medical Publishing House. Chin J Infect Dis American College of Gastroenterology Hepatic encephalopathy.