A 45-yod woman with a history of cholecystectomy, and chronic

abdominal pain was admitted to hospital for worsening

abdominal pain. She had previously been prescribed
acetaminophen for chronic abdominal pain. Preoperative
laboratory investigations revealed elevated ALT and AST
levels, an international normalized ratio (INR) of 2.5, and a
platelet count of 93,000 cells/μL. She underwent emergent
exploratory laparotomy for continued progressive abdominal
pain. On postoperative day 2, the neurologic status worsened,
necessitating intubation and mechanical ventilation for airway
protection. The patient’s hospital course was complicated by
cerebral edema requiring intracranial pressure monitoring, acute
renal failure, fever, and pleural effusion. Treatment was initiated
with lactulose, continuous venovenous hemodialysis, and
broad-spectrum antibiotics. Over the next several days, her
neurologic status improved, renal failure resolved
 Supriono
Divisi Gastroentrohepatologi Bagian Ilmu Penyakit Dalam
RSU Dr. Saiful Anwar –Fak. Kedokteran
Universitas Brawijaya Malang
Introduction
 Acute liver failure (ALF) is a relatively uncommon
disorder affecting only about 2500 patients in the
United States each year
 Its presentation is rapid, dramatic and frequently
leads to death over the course of a few days in
the absence of emergency liver transplantation.
 The mortality rates near 85% before
transplantation;
 However, in the post-transplant era, 1-year
survival rates are estimated at 60% to 80%.
DEFINITION OF ALF
1. absence of chronic liver disease
2. acute hepatitis (elevation in
AST/ALT) accompanied by elevation
in INR >1.5
3. any degree of mental alteration
(encephalopathy)
4. illness less than 26 weeks duration
The common causes of ALF
Selected Drugs Known to Cause
Acute Liver Failure
PATHOPHYSIOLOGY
 The principal mechanism involved in ALF is alterations
in hepatic morphology, resulting in cell death either by
cellular NECROSIS or APOPTOSIS
 Necrosis occurs as a result of depletion of ATP due to
oxidative stress, which leads to a disruption in cellular
homeostasis and a loss of membrane integrity.
 These intricate intracellular changes promote
remodeling of the plasma membrane and formation of
balloon-like structures on the surface of the cell.
 These structures can burst, triggering the release of
cellular contents and culminating in an inflammatory
response.
PATHOPHYSIOLOGY (cont_)
 Apoptosis involves receptor-mediated signaling
pathways and the sequential activation of proteolytic
caspases
 The 2 main pathways in ALF-associated apoptosis.
1. THE EXTRINSIC PATHWAY involves a class of death
receptors on the cell surface that induce cell death via a
receptor ligand complex, prompting activation of the caspase
cascade.
2. THE INTRINSIC PATHWAY is characterized by the release of
cytochrome c from the mitochondria, which occurs in response
to oxidative stress. In the presence of ATP, cytochrome c
activates the caspase cascade with the help of other
proapoptotic factors
Necroapoptosis
 Mitochondrial permeability transition has been well
described and is thought to be an important regulator in
cell death.
 In response to physiologic stress, the mitochondrial
membrane undergoes a series of events that leads to
the opening of permeability transition pores.
 As a result, mitochondrial contents (eg, cytochrome c)
are extruded into the intracellular medium and the
pathway of necrosis or apoptosis ensues depending on
the availability of ATP.
The mechanism of hepatocyte death in ALF
APPROACH TO EVALUATION
 The clinical presentation of ALF varies, and
symptoms can range from mild
gastrointestinal upset to generalized malaise
to confusion.
 A detailed patient history is essential for
identifying the cause of ALF.
 Physical examination is useful in evaluating
for evidence of encephalopathy and chronic
liver disease and may offer clues to the
underlying cause of hepatic injury
Clinical Clues to Acute Liver Failure in
History and Physical Examination
 Initial Diagnostic Tests for ALF
 Complete blood count  Prothrombin time, partial
 Basic metabolic panel thromboplastin time, international
 ALT/AST  normalized ratio
 Alkaline phosphatase  Anti–liver/kidney microsomal
 Bilirubin antibody
 Acute hepatitis panel  Ammonia
(hepatitis A and B  HIV antibody
viruses)  Serum acetaminophen
 Antinuclear antibody  Serum and urine copper
 Smooth muscle  Urine toxicology
antibody  Lactate dehydrogenase
 Amylase and lipase  β-hCG (females)
General management of ALF
 Time is of the essence in the management of patients with
ALF because rapid deterioration is a particular feature
 Neurologic or circulatory disturbance progressing to
needing inotropic support for hypotension and ventilation
 Close clinical monitoring is important during the
observation period and particularly when moving a
patient
 either between hospitals or between different wards
 Most of the patients with ALF will require liberal volume
expansion. The choice of fluid is not crucial and usually a
mixture of crystalloids and colloids is used
 General management of ALF (cont_ )
 Close attention to acid–base balance and correction of
hyperlactatemia is important because they can impact upon
circulatory function and also aggravate cerebral hyperemia
 Hyperthermia should be prevented as it worsens
intracranial Hypertension
 Glucose levels need to be maintained to prevent cerebral
and systemic effects of hypoglycemia. Hyperglycemia
worsens cerebral edema in patients with ALF
 Hyponatremia is a bad prognostic sign and values less than
125 mmol/l result in worsen brain edema
 Hypercapnia should be avoided as it induces cerebral
hyperemia and increases ICP.
Management of Complications of ALF
Selected Therapies for Causes of
Acute Liver Failure
The Molecular Absorbent and
Recirculating System (MARS)
NAFLD
NON-ALCOHOLIC FATTY LIVER DISEASES
Introduction
 NAFLD encompasses a spectrum of disease ranging
from simple steatosis, to inflammatory steatohepatitis
(NASH) with increasing levels of fibrosis and ultimately
cirrhosis.
 NAFLD is closely associated with obesity and insulin
resistance, and is now recognised to represent the
hepatic manifestation of the metabolic syndrome.
 The prevalence
 NAFLD is estimated to be between 20% and 30% in Western
adults, rising to 90% in the morbidly obese.
 NASH is estimated prevalence of 2–3% in the general population
and 37% in the morbidly obese.
Causes of nonalcoholic fatty liver
disease
 Primary
 Features of the metabolic syndrome
 Secondary
 Nutritional : Total Parental Nutrition
 Drugs: estrogen, tamoxifen, amiodaron
 Toxins : toxic mushroom
 Metabolics : lipodystropy, acute fatty liver in
pregnancy
 Others : IBD, HIV diverticulosis
NAFLD as a manifestation of
syndrome-X.
Pathogenesa
 the pathogenesis of steatosis and
progression to steatohepatitis and
fibrosis ⁄ cirrhosis is not yet fully
understood.
Pathogenesa
Progression of NAFLD to cirrhosis
 Steatosis relatively benign prognosis
 factors known to be involved in progression to
more advanced disease include:
 inflammatory cytokines ⁄ adipokines,
 mitochondrial dysfunction and oxidative stress.
 Insulin resistance causes impaired suppression of
adipose tissue lipolysis, leading to increased efflux of
free fatty acids (FFA) from adipose tissue to the liver.
 FFA promote insulin resistance, inflammation and
oxidative stress, and thus rather than being harmful,
Clinical manifestation of NAFLD
 Most patients with NAFLD are
asymptomatic
 Incidentally during routine laboratory
examination or workup of conditions.
 When symptoms occur, they are usually
nonspecific: Fatigue, right upper
quadrant discomfort,
 Jaundice occurs late in the course of
NASH and indicates advanced liver
disease.
Physical Examination
 There are no pathognomonic
 Obesity (30%–100%)
 Hepatomegaly (50%)
 A smaller percentage of patients have
stigmata of chronic liver disease.
Clinical presentations of patients
with NAFLD
1. Features of the metabolic syndrome*
2. Abnormal liver biochemistry
3. Abnormal hepatic imaging suggestive of fatty
infiltration
4. Non-specific symptoms (fatigue, abdominal
discomfort)
5. Upper gastrointestinal bleeding (portal
hypertension), liver failure or liver cancer
When to consider a liver biopsy
 Persons suspected to have NAFLD
 a biopsy can confirm the histological
diagnosis of fatty liver gold standar
disease and exclude other disorders.
 liver biopsy is currently the only
available method to distinguish between
simple steatosis and steatohepatitis
Non-invasive assessments of
NAFLD severity
 Assessment of fibrosis
 The AST-to-platelet ratio index (APRI)
 AST⁄ALT ratio
 Fibroscan. Transient elastography
 Radiological assessment (USG)
 Assessment of NASH inflammation and
steatosis.
 The inflammatory marker C-reactive protein
(CRP)
 vascular endothelial growth factor (VEGF)
Histologic features of fibrosis in NAFLD
Potential rational targets for biomarkers
development in NAFLD
Management of NAFLD
 No consensus guidelines
 In broad terms, therapy should target:
1. Components of the metabolic syndrome
2. Steatohepatitis
3. Advanced liver disease (screening for
treatable complications of portal
hypertension, e.g. large esophageal
varices, gastric arterio-venous ectosia).
Potential pharmacotherapeutic agents for
use in NAFLD.
LIVER ABSCESS
Pyogenic And amoebic Liver Abscess
Aetiology
 Bacterial, parasitic, or fungal in origin.
 85% to 90% bacterial or pyogenic.
Bacteria access the liver via the biliary tree
or portal vein.
Other causes include
 biliary obstruction,
 diverticulitis,
 trauma,
 inflammatory bowel disease,

36
INCIDENCE
 Liver gets infected by Entamoeba histolytica commonly
 The most common location of a pyogenic abscess is the
right lobe.
 Chronic alcoholics - prone to get this infection
 Entamoeba histolytica is endemic in many parts of the
world
PATHOPHYSIOLOGY
 The amoebic cyst is ingested
 Cyst develops into the trophozoite form in the colon
 Reaches the liver through portal circulation
 Pyogenic abscess may also occur due to the infection
by streptococcus milleri and Escherichia coli.
 Many a time the pyogenic infection follows amoebic
infection

37
 CLINICAL FEATURES
Often the diagnosis of a bacterial abscess is
suggested clinically.
Fever
Pain right hypochondrium
Chills
Rigors
Toxicity
Right upper quadrant discomfort
Diarrhea
weight loss
Intercostal tendreness
Swelling in the right hypo chondrium or epigastrium
tender, enlarged liver.
38
39
COMPLICATIONS:
Pneumonitis
Pleural effusion
Rupture of the liver abscess into the pleural cavity - causing
empyema
Rupture into the peritoneal cavity

TREATMENT
percutaneous or surgical drainage (Ultrasound guided repeated
aspiration)
antibiotics.
Metronidazole
Antibiotics like cephalosporins, aminoglycosides, tetracyclines
In rare cases it may need insertion of a drain.
mortality rate is almost 100% if the abscess remains untreated
41