Diambil dari :Juan Cordoba et al. Journal of Hepatology 2014 vol.

60 j 275281

Pembimbing Dipresentasikan

: dr. Putut Bayu Purnama, Sp. PD KGEH : dr. Meldy Muzada Elfa

Latar belakang
Hepatic encephalopathy (HE) is a common complication of cirrhosis [1,2] Recently, acute-on-chronic liver failure (ACLF) was defined by the Canonic Study 1. acute decompensation of cirrhosis (ascites, HE, gastrointestinal hemorrhage, bacterial infections or any combination of these) 2. at least 1 organ failure 3. belong to a subgroup with high short-term (28 day) mortality rate (>15%). Organ failure was defined based on a modified SOFA score adapted for patients with cirrhosis (CLIF-SOFA score)
The goals of the study were to assess the characteristics of cirrhotics that develop HE, describe the characteristics of HE in relation to the underlying liver disease (isolated decompensated cirrhosis or ACLF), identify risk factors for HE, and assess short-, mid- and long-term survival in relation to the presence or absence of HE and ACLF.

Patients and methods

A total of 2145 successive patients were screened, FebruarySeptember 2011; of them 1348 were included in the Canonic Study The majority (n = 1047) did not exhibit ACLF,while 301 subjects were diagnosed with ACLF. A total of 460 patients exhibited HE at enrollment; the remaining 888 patients had no HE.

The presence of HE was diagnosed as an impairment of cognition, consciousness, or motor function. Severity of HE was assessed according to the West Haven scale and grouped in 2 levels (mild: grade I or II; severe: grade III or IV).

Patients and methods

At enrollment we collected data from history, physical exam, laboratory measurements, active alcoholism (> 14 drinks/week in women and > 21 drinks/week in men within 3 months), diuretic use, and the presence of bacterial infections, gastrointestinal hemorrhage, hyponatremia or renal failure (at the time of enrollment). Mortality at 28, 90, and 365 days following enrollment (adjusted by liver transplantation, competitive risk assessment), and causes of death were also recorded.

Distribution of patients included in the study in relation to the presence of HE (left side) or ACLF (right side).

Hasil
Patients with HE (n = 460) did not differ significantly from those without HE (n = 888) in relation to the causes: Cirrhosis alcohol Hepatitis C Hepatitis C plus alcohol Previous comorbidities: arterial hypertension, diabetes mellitus requiring treatment Gender Age

Hasil
Patients with HE, there was a more frequent clinical history

of previous decompensations, ascites and overt HE HE also exhibited a higher proportion of hospitalizations in the previous 3 months, which was mainly due to higher number of hospitalizations related to HE and bacterial infections There were no differences between patients with and without HE in the proportion of hospitalization during the previous 3 months for ascites or GI bleeding

Patients with and without HE in the whole series

Hasil
Role of HE as an isolated decompensation
Patients without ACLF and with HE (n = 286) were

slightly older than those without HE. HE patients had a higher prevalence of previous ascites and HE
Among precipitating events, differences were only found for

the use of diuretics, which was higher in patients with HE, and in the prevalence of gastrointestinal bleeding, which was lower in patients with HE.

Hasil
Role of HE as part of ACLF
Patients with ACLF and HE had no statistical

differences in age to those without HE. HE showed higher prevalence of previous HE and ascites. The frequency of respiratory failure at enrollment was significantly higher in HE but affected less patients

Hasil
HE as an isolated decompensation or as part of ACLF
Patients with HE not associated with ACLF had

significantly higher age, had less frequently alcoholic cirrhosis, and had more frequently prior decompensations. There were marked differences in the prevalence of precipitating events between non-ACLF (higher
prevalence of diuretics) and ACLF (higher prevalence of bacterial infections, active alcoholism, and hyponatremia). Patients with ACLF had more deteriorated bilirubin, INR, and creatinine. In addition, ACLF patients show more abnormal inflammatory markers (leukocyte count and Creactive protein), AST and less sodium.

Role of HE as isolated decompensation; as part of ACLF and comparison between both.

Hasil
Risk factors for HE and survival
Multivariate analysis assessing independent risk factors

for HE in the whole series of patients and in those without ACLF found prior HE and diuretic use within the prior 3 months to be associated with the development of HE. In patients with ACLF, only prior HE was significantly associated with current HE.

Hasil
Risk factors for HE and survival (Cont.)
The mortality probability was significantly higher in

patients with HE compared to those without HE, it increased significantly as the HE grade worsened. The mortality probability of patients with ACLF was much higher than that of patients without ACLF, independently of the presence or absence of HE

Independent predicting factors for HE at enrolment

Hasil
Risk factors for HE and survival (Cont.)
In each subgroup (with and without ACLF) the mortality

probability was significantly higher in patients with HE. The independent risk factors of mortality at 28 days, 90 days and 1 year in patients with HE at enrollment were age, bilirubin, INR, sodium, and creatinine

Risk factors for short, mid and long-term mortality in patients with HE.

Hasil
Risk factors for HE and survival (Cont.)
The main causes of death in patients with and without

HE were multiorgan failure (36.7% vs. 34.2%), septic shock (23.5% vs. 20.4%), and hypovolemic shock (5.1% and 5%); a variety of other causes were present. In 20.4% of patients with HE and in 21.5% of patients without HE the cause of death could not be established

Diskusi
Episodic HE is one of the most frequent complications of cirrhosis Traditionally HE has been considered the effect on brain function of a combination of factors that include extrahepatic(infection, gastrointestinal bleeding, hyponatremia, renal failure, etc.) and intrahepatic mechanisms (worsening liver function, acute liver damage, etc.), which lead to an increase in circulating toxins that impact the brain

Diskusi
1. The most outstanding finding is the observation that previous HE is the most important risk factor for the development of HE These data indicate that even in the most severe cases of cirrhosis, development of HE is highly determined by the history prior to this complication. 2. A second important finding is the poor relationship between the traditional precipitating factors and the development of HE. 3. This analysis indicates that the increase in HE with the use of diuretics was not explained by differences in the severity of liver failure. We could not detect specific abnormalities caused by diuretic treatment

Diskusi
From the results of our study we propose the existence of two presentations of HE: 1. Isolated HE: occurs in older cirrhotics, inactive drinkers (hepatitis C cirrhosis or alcoholic cirrhotics who stopped drinking). 2. HE associated with ACLF: occurs in young cirrhotics, more frequently alcoholics as a consequence of impairment in liver function and bacterial infections, active alcoholism or dilutional hyponatremia.

Kesimpulan
1. The relation of HE with prior history of HE supports the view that this is a highly recurrent disorder 2. HE is not a homogeneous disorder 3. HE as a manifestation of ACLF, characterized by severe liver failure, acute inflammatory reaction and organ failure(s) 4. A better characterization of the patient that develops HE will allow improvements in diagnosis and therapy of this severe complication.

Kriteria Banevo V

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