Acute and chronic

liver disorders

Dr. Feisal Dahir Kahie

MMED INTERNAL MEDICINE RESIDENCY
KIU-WESRERN CAMPUS
Acute liver failure (ALF)
• Rapidly progressive and severe acute liver injury lasting ≤
26 weeks associated
with coagulopathy and encephalopathy in
individuals without previous hepatic disease.

• Subtypes are defined by the time it takes

for encephalopathy to develop after the onset of other
symptoms, e.g., jaundice.

 Hyperacute: ≤ 1 week
 Acute: 1–3 weeks
 Subacute: 3–26 weeks
Acute liver failure…..

Acute liver injury: markers of liver injury (elevated

transaminases with or without hyperbilirubinemia)
and impaired liver function (i.e., coagulopathy) in pa-
tients with no encephalopathy and no
chronic liver disease.
Etiology
• Idiopathic (20–45% of cases)
• Hepatotoxic drugs and supplements
 Acetaminophen toxicity
• Infection
 Acute viral hepatitis
 HAV infection, HBV infection, or HEV infection
 HBV-HDV coinfection or superinfection
 Other viral infections (rare): CMV, EBV, HSV, VZV, or adenovirus
 Toxoplasmosis (e.g., in transplant recipients)
• Other exogenous toxins: e.g., mushroom poisoning, aflatoxin, alcohol.
• Miscellaneous
Clinical features
• Presentation is mostly nonspecific; clinicians should maintain a high index of
suspicion in patients who acutely develop the following symptoms:
 Signs of hepatic encephalopathy (e.g., altered level of consciousness, asterixis).
 Symptoms of cerebral edema
 Nausea, vomiting
 Fatigue, lethargy, malaise
 Jaundice, pruritus
 Anorexia
 Abdominal pain: may be located in the RUQ or diffuse, secondary to ascites
 Features of the underlying etiology (e.g., Kayser-Fleischer rings in Wilson disease)
Differential diagnosis
• Decompensated cirrhosis
• Severe acute hepatitis without liver failure, e.g., acute alcohol-
associated hepatitis, acute viral hepatitis
• Chronic liver disease with superimposed illness
• Sepsis
• Other encephalitis or encephalopathy, e.g., drug- or toxin-in-
duced, uremic encephalopathy.
Diagnostics

Approach

• Obtain initial laboratory studies to support the diagnosis

and assess severity based on organ dysfunction.
• Acute Liver Failure (ALF) is confirmed if all of the
following are present:
 Encephalopathy
 Abnormal liver chemistries
 Coagulopathy (INR > 1.5)
Diagnostics….

Approach……

• Obtain imaging to rule out alternative diagnoses, e.g., head CT to rule

out other causes of encephalopathy.
• Identify the underlying cause.
 Consider causes based on patient history, e.g., alcohol-associated
fatty liver, metabolic dysfunction-associated steatotic liver dis-
ease, or drug-induced liver injury.
 Obtain additional laboratory studies based on clinical suspicion.
 Liver biopsy may be considered if the underlying cause remains
unclear.
Initial studies

Laboratory studies

• CMP
 Liver chemistries: elevated transaminases, hyperbilirubinemia
 Hypoglycemia
 Electrolytes: may show various disturbances, e.g., hyponatremia, hy-
pokalemia, hypophosphatemia
 Renal function tests: ↑ BUN and creatinine in patients with acute
kidney injury or hepatorenal syndrome
• Coagulation panel
 Prolonged prothrombin time (INR ≥ 1.5)
 Presence of other derangements (e.g., hypofibrinogenemia) is variable.
Initial studies…

Laboratory studies……….

• CBC
 Platelet count typically ≤ 150,000/mm3
 Other findings may be present depending on the underlying
cause, e.g., leukopenia in some viral infections
• Blood gas analysis
 Acid-base status can vary between acidosis , mixed acid-base
disorder, and alkalosis , depending on the underlying aetiology
 Lactate: commonly elevated; marker of severe disease
• Other
 Serum ammonia (preferably arterial): frequently elevated; values >
150 micromol/L are associated with a higher risk of increased ICP.
 LDH: typically elevated in early stages of acute liver failure
 Blood and urine cultures
Chronic Liver Disease
Alcohol
Autoimmune:
 Autoimmune hepatitis
 Primary Biliary cirrhosis (PBC)
 Primary sclerosing cholangitis (PSC)
Chronic Viral hepatitis: B & C
Non-alcoholic fatty liver disease (NAFLD)
Drugs: MTX, Amiodarone)
Cystic fibrosis, Alpha-1 antitrypsin deficiency, Wilson’s
disease
Vascular problem (portal HTN +/- Liver disease)
Cryptogenic
Others: sarcoidosis, amyloid, schistosomiasis
Manifestations

Fatigue
Malnutrition
Ascites, ankle edema, pleural effusion,
wight gain
Bleeding
Impotence
Jaundice, itch, steatorrhea
Hepatitis A

RNA virus transmitted by fecal-oral route

Jaundice begins 3 weeks after exposure, with
prolonged cholestasis up to 4 months possi-
ble
Majority of infections associated with symp-
toms but overwhelming majority recover fully
1% chance of fulminant hepatitis
Hepatitis B
Hepatitis B is a double stranded DNA hepad-
navirus
Spread through vertical, blood or body fluids
Incubation period is 6-20 weeks
Features: fever, jaundice, elevated liver en-
zymes,
Complications: chronic hepatitis, fulminant liver
failure , HCC, polyarthritis nodosa, membranous
glomerulonephritis
Hepatitis B cont….

ALT in hepatitis B rises between months 2-3

70% of patients can be asymptomatic with no jaun-
dice
Some patients can get serum sickness like picture of
with arthralgias and fever.
Fulminant hepatic failure occurs in 0.1-0.5%
Chronic hepatitis B
Occurs when virus remains > 6 months ( risk
of chronicity is 90% for infants, 5% for adults
There are 2 types of carrier states
1. Inactive carrier state
Asymptomatic with normal liver enzymes.
Need prophylaxis if they become immuno-
compromised
2. Chronic active hepatitis B Virus
Abnormal liver enzymes
Check LFT, platelet count, INR, Hep B surf Ag,
Hep B surf Ab, Hep BeAg, Hep BeAb, Hep B
DNA
Hepatitis B serology
Treatment of Chronic Hepatitis B

Treat if :
 hep BeAg+, DNA >20.000 and ALT>2x ULN
 hep BeAg-, DNA>2000 and ALT> 2x ULN
APRI score>2
cirrhosis
Rx
Tenofovir, entecavir
Pegylated interferon ( young people who may
want to shorter treatment duration, how ever in-
creased side effects)
Hepatitis B and HCC

HCC is 2% conversion per year (life time risk is

20%)
Screen every 6 months if cirrhosis is present
If non-cirrhotic, screen the following groups
 Active hep B with abnormal LFT
 Elevated VL
 Family history of HCC
Generally screen with sonogram +/- AFP
Hepatitis C

2nd only to NAFLD for number of new cases per year

¼ of HIV patients are coinfected with HCV
25% with chronic HCV get cirrhosis in 20 years
2-8% annual risk of developing HCC
Chronic HCV with cirrhosis – screen every 6 months
for HCC with sonograph and AFP
Hepatitis C associated conditions

Mixed cryoglobulinemia
• Presence of abnormal proteins in the blood
 Strongly associate with hepatitis C
 Presents as small vessel vasculitis with rash
consisting of palpable purpura
Immune complex glomerulonephritis
Porphyria cutanea tarda
 Photosensitivity leading to skin blistering
Treatment of chronic hepatitis C

Pegylated interferon/ribavirin
 Old drugs and less effective than new antiviral
drug
Antivirals plus ribavirin have excellent
viral clearance
Hepatitis D
Coexistent with HBV
Immunity to HBV implies immunity to HDV
Suspect if sudden decompensation in pa-
tients with chronic HDV

Hepatitis E
High risk for fulminant hepatitis in 3rd
trimester of pregnancy
 can lead neurological symptoms ( meningi-
tis, neuropathy)
Paracetamol toxicity

Present in many preparations

10gms (20 tablets) can cause fatal liver failure
Initial presents with nausea and vomiting with
symptoms of liver failure developing 2-3 days later
Coagulopathy and raised ALT
Paracetamol levels may be low or negative by this
stage
Treat if in doubt with N-acetylcysteine
Ischemic hepatitis

It’s a diffuse hepatic injury resulting from acute hypoperfusion

( some time known as ‘shock liver’).
Its diagnosed in the presence of inciting events ( e.g. car-
diac arrest) and marked increase in aminotransferase levels
(exceeding 1000 international units/L or 50 times the upper
limit of normal
Often it will occur in conjunction with acute kidney injury
(tubular necrosis ) or other end organ dysfunction.
Alcoholic liver disease

The recommended maximum alcohol intake per

week is 21 units for male and 14 units for female.
Alcoholic liver disease includes
– Fatty liver
– Alcoholic hepatitis
– Cirrhosis and its complications
Fatty liver (hepatic steatosis)

 Accumulation of fat with in the hepatocytes

 Mechanism:
 Increased generation of NADH reduces the activity of the TCA cycle
(krebs cycle ),the acetyl Co A is diverted to fatty acid synthesis
 Reduction in cytosolic NAD+ leads to reduced activity of glyceryl-3-
phosphate dehydrogenase resulting in increased levels of glycerol 3-
phosphate which is the backbone for synthesis of the triglycerides 
lead to fatty acid deposition in the liver leading to fatty liver syndrome
Fatty liver is asymptomatic and detected incidentally
Elevated transaminases and a background of alcoholism are
clues to diagnosis
Macro-vesicular fatty changes
 Micro-vesicular fatty changes are not
found in hepatic steatosis
An ultrasound demonstrates hyper-echogenicity and bright
liver
This is reversible with abstention from alcohol
Alcoholic hepatitis

 Right upper quadrant (RUQ) pain

 Tender hepatosplenomegaly
 Jaundice
 Fever
 Marked derangement of LFTs
 AST>ALT 2:1
 Increased alkaline phosphatase
 High IgA levels are seen in alcoholic hepatitis
 As a microscopic level: inflammation of the liver is seen
Liver cirrhosis

The hepatocytes are damaged so much that they

are replaced by scar tissue which is permanent
Alcoholic hepatitis and cirrhosis can coexist
Alcoholic hepatitis and cirrhosis may lead to en-
cephalopathy, portal hypertension and hepa-
torenal syndrome, increase risk of infection
and they are usually malnourished.
Treatment of alcoholic hepatitis
Feeding (enterally)
Thiamine and multivitamins
Corticosteroids if maddrey’s discriminant function
higher than 32
 Mortality rate is 50%
 mDF= 4.6 x (PT – control PT) + Biliru-
bin /17.1umol/L
 Prednisolone 40mg OD FOR 1 Month
Other scoring systems:
 Glasgow Alcoholic hepatitis score
 MELD score
Budd-Chiari syndrome
Definition
 Obstruction of main hepatic vein by thrombosis
 Budd-chiari syndrome or hepatic vein thrombosis is
usually seen in the context of underlying hemato-
logical disease or other procoagulant condition
Etiology
 Polycythemia rubra vera
 Thrombophilia: activated protein C resistance, an-
tithrombin 3 deficiency, protein C and S deficiencies
 Pregnancy
 Oral contraceptive pill
Features
 Abdominal pain: sudden onset, severe
 Ascites
 Tender hepatomegaly
 Signs of portal hypertension are present and pa-
tients may develop acute variceal hemorrhage as a
complication
Diagnosis
 Ultrasound doppler or contrast CT scan
 Ascitic Tap usually demonstrates a high SAAG >11g/l
Management
 Thrombolysis and subsequent anticoagulation
Prognosis
 3 years survival in patients with chronic Budd-chiari
syndrome has been reported as 50%
Hepatic Encephalopathy
It can be seen in liver disease
Etiology is not fully understood but is thought to include excess
absorption of ammonia from bacterial breakdown of proteins in the
gut
Features
 Confusion, altered GCS
 Hepatic flap/Asterixis
 Constructional apraxia: inability to draw a 5 pointed
star
 Triphasic slow waves on ECG
 Raised ammonia level (not commonly measured)
Grading of hepatic encephalopathy
Grade 1:
 Mood changes like depression or irritability and sleep ab-
normality
Grade 2:
 Confusion, inappropriate behavior
Grade 3:
 Incoherent, restless
 Grade 4
 Coma
Precipitating factors
 Infection e.g. SBP
 GI bleeding
 Constipation
 Drugs e.g. sedatives, diuretics
 Hypokalemia
 Renal failure.
Treatment of hepatic encephalopathy

 Treat precipitating cause ( e.g give Potassium)

 Lactulose
 Metabolized to lactic acid by colonic flora, converts
NH3 to NH4 which can be absorbed
 Neomycin (no longer used)
 Rifaximin ( substituted neomycin)

 Antibiotics kill colonic flora leading to decreased NH3

production
Hepatorenal syndrome (HRS)

Progressive renal failure in the setting of advanced liver disease and

portal hypertension
Rule out other caused of renal failure
Pathophysiology
 Vasoactive mediators cause  splanchnic artery va-
sodilation  reduces systemic vascular resistance 
‘under filling’ of kidneys activation of RAAS system by
juxtaglomerular apparatus  renal vasoconstriction
which is not enough to counterbalance the effect of
splanchnic vasodilation
Types of hepatorenal syndrome
Management of HRS

The ideal treatment is liver transplantation

if critically ill → vasopressor (e.g. norepinephrine or
vasopressin) plus albumin (1 g/kg, max 100 g, bolus
daily) to ↑ MAP 10 mmHg.
 If not critically ill → octreotide (100–200 mcg SC tid)
plus midodrine (max 15 mg PO tid) plus 1 g/kg (max 100
g) albumin on day of presentation followed by 20–60 g
albumin qd to ↑ MAP
 NAFLD

NAFLD= hepatic steatosis with no other etiology

Other causes of fat in liver: alcohol, amiodarone, Wilson disease
NAFLD: most common liver disorder in western countries
PMH: Obesity, DM, high cholesterol
Non alcoholic steatohepatitis (NASH)= Fat and inflammation
ALT>AST (in contrast to alcohol liver disease)
LFT can be normal
Diagnosis:
 Sonograph but some times liver biopsy is done
 Vibration-controlled transient elastography: vi-
brates liver to see how stiff, measures fibrosis
with out biopsy
 APRI score increases
Treatment is not standardized,
 weight loss is important
 Assure vaccinated for hep A and B
 HCC screening if cirrhosis
Esophageal Variceal Hemorrhage

1/3 with variceal will bleed, with 30% mortality

Only 50% of bleeding varices stop spontaneously
Varices size is important ( correlates with risk of bleeding )
Hepatic venous pressure gradient (HVPG) is difference between the
wedged HV pressure and the free hepatic venous pressure
Normal hepatic venous pressure is <6 (portal HTN >6
 >10mmHg = varices form
 >12mmHg= varices bleed
Primary therapy is endoscopic banding
Octreotide is splanchnic vasoconstrictor decreases splanchnic
blood flow and varices filling
Give all cirrhotic patient with bleeding prophylactic antibiotic which
decreases mortality ( Ceftriaxone , AASLD 2017)
Complications for Cirrhosis

Hepatic encephalopathy
Hepatorenal syndrome
Ascites
SBP
HCC
Esophageal variceal hemorrhage
 Reference

• Harrison’s Principles of Internal Medicine 20th edition

• Mercks manual, Professional version 2023
• AASLD Practice guidelines 2018
• Up to date 2023
• Medscape
Read
1.Autoimune hepatitis
2.Haemochromatosis
3.Wilson’s disease
4.Alpha 1 antitrypsin deficiency