Characteristics, Risk Factors, And Mortality of Cirrhotic

8/13/2019 Characteristics, Risk Factors, And Mortality of Cirrhotic

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Latar belakang

Hepatic encephalopathy (HE) is a common complication of cirrhosis[1,2]

Recently, acute-on-chronic liver failure (ACLF) was defined by theCanonic Study

1. acute decompensation of cirrhosis (ascites, HE, gastrointestinalhemorrhage, bacterial infections or any combination of these)

2. at least 1 organ failure3. 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 thatdevelop HE, describe the characteristics of HE in relation to the underlyingliver disease (isolated decompensated cirrhosis or ACLF), identify risk factorsfor 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, February-

September 2011; of them 1348 were included in the CanonicStudy

• The majority (n = 1047) did not exhibit ACLF,while 301 subjects were diagnosed with ACLF.

• A total of 460 patients exhibited HE at enrollment; theremaining 888 patients had no HE.

The presence of HE was diagnosed as an impairment ofcognition, consciousness, or motor function.

Severity of HE was assessed according to the West Haven scaleand grouped in 2 levels (mild: grade I or II; severe: grade III or

IV).



Patients and methods

• At enrollment we collected data from history, physicalexam, laboratory measurements, active alcoholism (> 14drinks/week in women and > 21 drinks/week in men

within 3 months), diuretic use, and the presence ofbacterial 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 riskassessment), 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).



Patients with HE (n = 460) did not differ significantly fromthose 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 historyof previous decompensations, ascites and overt HE

HE also exhibited a higher proportion of hospitalizations inthe previous 3 months, which was mainly due to higher

number of hospitalizations related to HE and bacterialinfections

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

Hasil



Patients with and without HE in the whole series



Patients without ACLF and with HE (n = 286) wereslightly older than those without HE.

HE patients had a higher prevalence of previous ascitesand HE

Among precipitating events, differences were only found forthe 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 an isolated decompensation



Patients with ACLF and HE had no statisticaldifferences in age to those without HE.

HE showed higher prevalence of previous HE andascites.

The frequency of respiratory failure at enrollment wassignificantly higher in HE but affected less patients

Hasil Role of HE as part of ACLF



Patients with HE not associated with ACLF hadsignificantly higher age, had less frequently alcoholiccirrhosis, and had more frequently priordecompensations.

There were marked differences in the prevalence ofprecipitating events between non-ACLF (higherprevalence of diuretics) and ACLF (higher prevalence ofbacterial infections, active alcoholism, and hyponatremia).

Patients with ACLF had more deteriorated bilirubin, INR,and creatinine. In addition, ACLF patients show moreabnormal inflammatory markers (leukocyte count and C-reactive protein), AST and less sodium.

Hasil HE as an isolated decompensation or as part of ACLF

R l f HE i l t d d ti t f ACLF



Role of HE as isolated decompensation; as part of ACLF

and comparison between both.



Multivariate analysis assessing independent risk factorsfor HE in the whole series of patients and in those without ACLF found prior HE and diuretic use withinthe 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



The mortality probability was significantly higher inpatients with HE compared to those without HE, itincreased 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

Hasil Risk factors for HE and survival (Cont.)



Independent predicting factors for HE at enrolment



In each subgroup (with and without ACLF) the mortalityprobability was significantly higher in patients with HE.The independent risk factors of mortality at 28 days, 90days 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.



The main causes of death in patients with and withoutHE were multiorgan failure (36.7% vs. 34.2%), septicshock (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 complicationsof cirrhosis

• Traditionally HE has been considered the effect onbrain function of a combination of factors that include

extrahepatic(infection, gastrointestinal bleeding,hyponatremia, renal failure, etc.) and intrahepaticmechanisms (worsening liver function, acute liverdamage, etc.), which lead to an increase in circulating

toxins that impact the brain



Diskusi

1. The most outstanding finding is the observation thatprevious HE is the most important risk factor for thedevelopment of HE These data indicate that even inthe most severe cases of cirrhosis, development of HE

is highly determined by the history prior to thiscomplication.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 theseverity of liver failure. We could not detect specific

abnormalities caused by diuretic treatment



DiskusiFrom 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 ofimpairment 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 disorder2. HE is not a homogeneous disorder3. 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 thissevere complication.



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Characteristics, Risk Factors, And Mortality of Cirrhotic

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