Update
Management in
Hepatic Cirrhosis RINI R. BACHTIAR
STAF ILMU PENYAKIT DALAM SUBDIVISI GASTROENTEROHEPATOLOGY
FAKULTAS KEDOKTERAN UNIVERSITAS HASANUDDIN
MAKASSAR
Hepatic Cirrhosis
Hepatic Cirrhosis
Cirrhosis may be entirely asymptomatic with no clinical signs.
Routine laboratory tests that may suggest underlying cirrhosis include: thrombocytopenia,
hyperbilirubinemia, and hypoalbuminemia.
Non - invasive tests (serum panels and transient elastography) are valuable to rule
in or rule out cirrhosis.
Decompensation of cirrhosis is often precipitated by infection, medications, and
medical procedures (especially surgery).
Child – Pugh – Turcotte Score and MELD score are used to assess prognosis in cirrhotic
patients regardless of etiology.
All patients with cirrhosis require screening for esophageal varices and ultrasound
surveillance for hepatoma.
Control of the underlying cause of liver disease may lead to fibrosis regression
with “ resolution ” of cirrhosis; however, risk of hepatocellular carcinoma (HCC)
persists.
Practice points:
optimizing medical therapy for cirrhotic patients going for surgery
Any operation in a cirrhotic patient carries an increased risk of mortality: Child ’ s C > B > A, mostly as a consequence of hypotension.
Medical optimization:
• Avoid any surgery in patients with acute severe hepatitis or Child ’ s C cirrhosis.
• Replace fluid loss with colloids (blood/albumin), minimal normal saline should be given as this will immediately lead to the formation of ascites.
Practice points:
optimizing medical therapy for cirrhotic patients going for surgery
Medical optimization:
• Avoid benzodiazepines, aminoglycosides, and NSAIDs (use acetaminophen).
Proton pump inhibitors should only be used if necessary because of the associated increased risk of infection in this population.
Practice points:
optimizing medical therapy for cirrhotic patients going for surgery
Medical optimization:
• All patients need treatment of any infection as soon as it is
suspected.
• Electrolyte abnormalities, particularly hypokalemia and
metabolic alkalosis, should be corrected to reduce the
chance of cardiac arrhythmias and hepatic encephalopathy.
Practice points:
optimizing medical therapy for cirrhotic patients going for surgery
Medical optimization:
• Reduce chance of hepatic encephalopathy by preventing
constipation and carefully monitoring the use of opioids.
• Evaluate and monitor renal function throughout hospital
stay; i.v. furosemide should be avoided.
Complication
Asites Pathogenesis
Portal Hypertension:
Transjugular Intrahepatic
Portosystemic Shunt
Portal Hypertension: Transjugular
Intrahepatic Portosystemic Shunt
Portal Hypertension:
Transjugular Intrahepatic
Portosystemic Shunt
Renal Complication of Liver Disease
Renal Complications of Liver Disease
Hepatic Encephalopathy
Hepatic Encephalopathy
Management
Management
The clinical practice guidelines on cirrhosis were
released by
the European Association for the Study of the
Liver
on April 10, 2018.
Management
the etiologic factor, should be removed,
particularly alcohol consumption and hepatitis B or C virus
infection,
as this strategy is associated with decreased risk of
decompensation and increased survival.
Management
potential benefit to decrease cirrhosis progression in patients with
decompensated cirrhosis :
Strategies based on targeting abnormalities in gut-liver axis by antibiotic
administration (ie, rifaximin),
improving the disturbed systemic circulatory function (ie, long-term
albumin administration),
decreasing the inflammatory state (ie, statins)
Reducing portal hypertension (ie, beta blockers)
Management
HMG-coA reductase inhibitors (statins), independent of cholesterol-
lowering effects,
Statin are beneficial in liver diseases by reducing endothelial
dysfunction, intrahepatic vasoconstriction, inflammation and fibrosis,
and can reduce portal vein blood pressure.
Clinically significant portal hypertension (hepatic vein wedge
pressure greater than or equal to 10mmHg) is the most important
predictor of decompensation and death in patients with cirrhosis.
Management
A diagnostic paracentesis is recommended:
all patients with new onset grade 2 or 3 ascites
Ascites those hospitalized for worsening of ascites or any complication
of cirrhosis.
Management
Neutrophil count and culture of ascitic fluid culture should be
performed to exclude bacterial peritonitis.
A neutrophil count above 250 cells/µl is required to diagnose
spontaneous bacterial peritonitis (SBP).
Management
Ascitic total protein concentration should be performed to identify
patients at higher risk of developing SBP.
Management
The serum ascites albumin gradient (SAAG) should be calculated
when the cause of ascites is not immediately evident, and/or when
conditions other than cirrhosis are suspected.
SAAG Interpretation
SAAG = serum albumin – ascites albumin
A high gradient (SAAG >1.1 g/dL) indicates
portal hypertension and suggests a
nonperitoneal cause of ascites.
A low gradient (SAAG < 1.1 g/dL)
indicates nonportal hypertension and
suggests a peritoneal cause of ascites.
Management
Cytology should be performed to differentiate malignancy-related
from non-malignant ascites.
Management
Liver transplantation (LT) should be considered as a potential
treatment option.
Since the development of grade 2 or 3 ascites in patients with cirrhosis is
associated with reduced survival,
Management
A moderate restriction of sodium intake (80–120 mmol/day,
corresponding to 4.6–6.9 g of salt) is recommended in patients with
moderate, uncomplicated ascites.
This is generally equivalent to a no-added-salt diet with avoidance of pre-prepared meals.
Adequate nutritional education of patients on how to manage
dietary sodium is also recommended.
Management
Diets with a very low sodium content (<40 mmol/day) should be
avoided, as they favor diuretic-induced complications and can
endanger a patient's nutritional status.
Management
Patients with the first episode of grade 2 (moderate) ascites should
receive an anti-mineralocorticoid drug alone, starting at 100 mg/day with stepwise increases every 72 hr (in 100 mg steps) to
a maximum of 400 mg/day if there is no response to lower doses.
Management
In patients who do not respond to anti-mineralocorticoids, as defined by a body weight reduction of less than 2 kg/wk, or in
patients who develop hyperkalemia,
furosemide should be added at an increasing stepwise dose from 40 mg/day to a maximum of 160 mg/day (in 40 mg steps).
Management
Patients with long-standing or recurrent ascites should be treated
with a combination of an anti-mineralocorticoid drug and
furosemide, the dose of which should be increased sequentially
according to the response.
Torasemide can be given in patients exhibiting a weak response to
furosemide.
During diuretic therapy, a maximum weight loss of 0.5 kg/day in
patients without edema and 1 kg/day in patients with edema is
recommended.
Once ascites has largely resolved, the dose of diuretics should be reduced to the lowest effective dose.
Management
In patients presenting with GI hemorrhage, renal impairment,
hepatic encephalopathy, hyponatremia, or alterations in serum
potassium concentration,
these abnormalities should be corrected before starting diuretic therapy. In these patients, cautious initiation of diuretic therapy and
frequent clinical and biochemical assessments should be
performed.
Diuretic therapy is generally not recommended in patients with
persistent overt hepatic encephalopathy.
Management
Diuretics should be discontinued if severe hyponatremia (serum sodium concentration <125 mmol/L), acute kidney injury (AKI),
worsening hepatic encephalopathy, or incapacitating muscle
cramps develop.
Management
Furosemide should be stopped if severe hypokalemia occurs (<3 mmol/L). Anti-mineralocorticoids should be stopped if severe
hyperkalemia occurs (>6 mmol/L).
Management
Albumin infusion or baclofen administration (10 mg/day, with a
weekly increase of 10 mg/day up to 30 mg/day) is recommended in
patients with muscle cramps.
Management
Large volume paracentesis (LVP) is the first-line therapy in patients
with large ascites (grade 3 ascites), which should be completely
removed in a single session. LVP should be followed with plasma
volume expansion to prevent post-paracentesis circulatory dysfunction (PPCD).
Management
In patients undergoing LVP greater than 5 L of ascites, plasma
volume expansion should be performed by infusing albumin (8 g/L
of ascites removed), as it is more effective than other plasma
expanders, which are not recommended for this setting.
Management
In patients undergoing LVP less than 5 L of ascites, the risk of
developing PPCD is low. However, it is generally agreed that these
patients should still be treated with albumin because of concerns
about use of alternative plasma expanders.
Management
Non-steroidal anti-inflammatory drugs should not be used in patients
with ascites because of the high risk of developing further sodium
retention, hyponatremia, and AKI.
Management
Repeated LVP plus albumin (8 g/L of ascites removed) is
recommended as first-line treatment for refractory ascites.
Management
Diuretics should be discontinued in patients with refractory ascites who do not excrete >30 mmol/day of sodium under diuretic
treatment.
Management
Antibiotic prophylaxis is recommended in cirrhotic patients with
acute GI bleeding because it reduces the incidence of infections
and improves control of bleeding and survival.
Treatment should be initiated on presentation of bleeding and continued for up to 7 days. Ceftriaxone (1 g/24 hr) is the first choice
in patients with decompensated cirrhosis, those already on
quinolone prophylaxis, and in hospital settings with high prevalence
of quinolone-resistant bacterial infections.
Oral quinolones (norfloxacin 400 mg bid) should be used in the
remaining patients.
Management
The clinical practice guidelines on cirrhosis were released by the
European Association for the Study of the Liver on April 10, 2018.
Management
The clinical practice guidelines on cirrhosis were released by the
European Association for the Study of the Liver on April 10, 2018.
Management
The clinical practice guidelines on cirrhosis were released by the
European Association for the Study of the Liver on April 10, 2018.
Management
The clinical practice guidelines on cirrhosis were released by the
European Association for the Study of the Liver on April 10, 2018.
Management
The clinical practice guidelines on cirrhosis were released by the
European Association for the Study of the Liver on April 10, 2018.
Prognosis
Prognosis
The prognosis of cirrhosis is highly variable, depending on the
etiology of liver disease, presence of complications, and comorbid
diseases.
Predictive models have been developed to help estimate the survival of patients with cirrhosis.
Child–Turcotte–Pugh score
Model for end - stage l iver d isease ( MELD )
Clinical stages of cirrhosis
Child–Turcotte–Pugh score
The minimum score is 5
• Grade A (well compensated): score of 5 – 6
• Grade B (signifi cant functional compromise): score of 7 – 9
• Grade C (decompensated disease): score of 10 – 15.
Child–Turcotte–Pugh score
The Child – Pugh grade is predictive of 1 - and 2 - year survival:
• Grade A: 100% 1 - year, 85% 2 - year survival
• Grade B: 80% 1 - year, 60% 2 - year survival
• Grade C: 45% 1 - year, 35% 2 - year survival.
The Child – Pugh score is also predictive of mortality with abdominal surgery:
Grade A 10%, Grade B 30%, and Grade C 82%.
Prognosis
The prognosis of cirrhosis is highly variable, depending on the
etiology of liver disease, presence of complications, and comorbid
diseases.
Predictive models have been developed to help estimate the survival of patients with cirrhosis.
Child–Turcotte–Pugh score
Model for end - stage liver disease ( MELD )
Clinical stages of cirrhosis
Model for end-stage liver disease
(MELD)
MELD has also been validated as a predictor of survival in the following conditions:
• alcoholic hepatitis
• hepatorenal syndrome (MELD > 20 predicts worse survival)
• acute variceal hemorrhage in cirrhotic patients
• sepsis in cirrhotic patients as long as unrelated to spontaneous bacterial
peritonitis
• abdominal, orthopedic, and cardiac surgery in known cirrhotic patients.
Model for end-stage liver disease
(MELD) Modifications have been proposed including:
• serum sodium concentration,
• serum albumin concentration, and different
• weighting of the bilirubin, INR, and creatinine.
These modifications may ultimately be adopted for organ allocation.
The MELD score is modified if HCC is present because patients may have poor
survival based on the presence of HCC despite relatively preserved liver
synthetic function, and thus low MELD scores.
Prognosis
The prognosis of cirrhosis is highly variable, depending on the
etiology of liver disease, presence of complications, and comorbid
diseases.
Predictive models have been developed to help estimate the survival of patients with cirrhosis.
Child–Turcotte–Pugh score
Model for end - stage l iver d isease ( MELD )
Clinical stages of cirrhosis
Clinical stages of cirrhosis The Baveno classification system categorizes patients with cirrhosis based on
clinical factors only, which have proven to be useful for prognostication at the
population level.
Stage 1: uncomplicated cirrhosis (no varices/ascites)
Stage 2: cirrhosis with varices (no ascites or bleeding)
Stage 3: cirrhosis with ascites with or without varices
Stage 4: cirrhosis with GI bleeding with or without ascites.
Stages 1 and 2 are compensated while Stages 3 and 4 have signs of
decompensation.