HEPATIC MANIFESTATIONS IN

TROPICAL INFECTIOUS DISEASES

DR.S.PAVITHRAN,
Asst prof.,
Dept. Of Internal Medicine.,
GTMCH, TVR.,

Consultant Physician,
Navajeevan hospital, TVR &
SK hospital, SannaNallur.
 LFT

LIVER ‘FUNCTION’ TEST

 FUNCTIONS OF LIVER

 Synthesis of most essential serum proteins - Albumin,

carrier proteins, coagulation factors. many hormones &
growth factors
 Production of bile & its carriers (bile acids , cholesterol,
lecithin, phospholipids)
 Metabolism & conjugation of lipophilic compounds
(bilirubin, anions, cations & drugs)
 Detoxification of toxic compounds and metabolites /
Defense from microbes
WHY LIVER GETS AFFECTED IN INFECTIONS
 Liver contains approximately one-third of
reticuloendothelial system

 Because of its role as a filter, the liver is

exposed to many systemic infectious
pathogens.
 LIVER FUNCTION TEST

Function tests Biochemical markers of

liver injury
 S. Billirubin  SGOT
 Albumin  SGPT
 PT/ INR  ALP
 GGT
 5’Nucleotidase
TROPICAL DISEASES

Bacterial Parasitic Viral

Fungal Toxins
BACTERIAL - leptospIrosis , scrub
typhus , tuberculosis, MELIODOSIS, ENTERIC
FEVER

viral - dengue fever, covid , flu

parasite - malaria
 LEPTOSPIROSIS
 Common during late summer
and early fall.
Hemorrhage
 RRR SPHS

TRIAD OF
WEILS
 Leptospiremic phase & SYNDROME
Immune phase
Acute kidney
injury Jaundice

 Two phases: Anicteric and

icteric.
 Icteric phase of this disease is
called WEILS DISEASE.
 Commonly presented as sudden onset
high grade fever, conjunctival
suffusion, headache , nausea ,
vomiting , abdominal pain.

 Intense severe muscle pain over back,

calf and abdomen

 Complications are SPHS , Renal

failure,ARDS, DIC, MODS,
Meningitis, pancreatitis,
rhabdomyolysis , arrythmia and
hypotension
 WHAT HAPPENS TO LIVER ?
 Immune complex mediated capillary injury
leads to thrombocytopenia in the absence of
overt DIC

 Conjugated bilirubin may rise upto 80mg/dl

and Jaundice may persists for weeks.

 Transaminases are mild to moderately

elevated(usually 5 times the normal level)

 Clinically tender hepatomegaly is seen

 HISTOPATHOLOGY OF LIVER

 Focal necrosis( widespread necrosis not seen) foci of

inflammation and bile canalicular plugging.

 Experimental study: Leptospira in disse’s space and

migration through hepatocytes with detachment of
intercellular junction and disruption of bile canaliculi
leading to bile leakage.
 ENTERIC FEVER
 Salmonella typhi

 Transmission : Contaminated food and water

 Common symptoms are prolonged high grade fever, headache,

malaise, myalgia, arthralgia, cough and abnromal sweating.

 GI symptoms like anorexia, abdominal pain, nausea, vomiting,

diarrhea>>constipation

 Clinical signs includes rose spots, salmon colored blanchable

maculopapular rashes over trunk, hepatosplenomegaly and
relative bradycardia.
 MECHANISM OF LIVER DAMAGE IN TYPHOID
Hemolysis in patients
with thalassemia or G-
6-PD deficiency

Causes of JAUNDICE in
Hepatomegaly
observed in enteric Ascending cholangitis

typhoid fever
fever is caused by the
hypertrophy and
hyperplasia of Salmonella liver abscess
Kupffer’s cells

Suppurative
pyelophlebitis

Choleocystitis
 A severe form disease with jaundice can occur in 0.4-26%
of cases.

 The increase in transaminases are usually 3 to 5 times of

normal level with AST higher than ALT.

 Around 20% of patients have elevated bilirubin.

 TUBERCULOSIS

 Caused by Mycobacterium
tuberculosis.
 Transmission : Airborne droplets.

 Tuberculous bacilli can reach the

liver via hematogenous
dissemination, generally from the
lungs, or by local spread from the
gastrointestinal tract
 HEPATIC TB

TB in Liver

Localized Miliary
Granulomatous
TB

With bile Without bile

involvement involvement

Localised
Biliary TB
hepatic TB
 LFT alterations

 Modest increase in serum transaminases (35% - 70%) which are not

more than 200 U/L and hepatic calcifications on plain abdominal
films have been observed in diagnostic tests.

 Marked elevation of alkaline phosphatase (200-750 U/L) , GGT

(100-400 U/L) and a slight elevation in bilirubin have been
observed.

 Rarely ,tuberculosis can also involve biliary system leading to

obstructive jaundice.
 Miliary Hepatic TB Local Hepatic TB
Prevalence 79% 21%
Infection origin Lungs Gastrointestinal system
Dissemination Hepatic artery Portal vein
Tubercle size 0.6-2.0 mm in diameter >2.0 mm in diameter
Location of tubercles Lobules of liver Near portal triad

Cough, sputum Weight loss,

Clinical signs/symptoms
production, hepatomegaly hepatomegaly, jaundice

CT scan; liver biopsy is

Diagnosis Liver biopsy more helpful
less helpful
Large, low-density
Multiple, dispersed, low- nodules with calcification
CT findings
density micronodules and peripheral
enhancement
4-drug regimen; consider
Treatment 4-drug regimen drainage of abscess or
surgery
 SCRUB TYPHUS

 Scrub typhus is a disease caused by a bacteria Orientia

tsutsugamushi.

 Transmission to people is through bites of infected

chiggers.

 The infection of Orientia tsutsugamushi is

characterized pathologically by focal or disseminated
vasculitis and perivasculitis in involved organs.

 Common symptoms are High grade fever, myalgia,

headache,cough and GI symptoms

 Signs includes classical eschar with regional

lymphadenopathy and maculopapular rash
TSUTSUGAMUSHI
ESCHAR
 Complications are intertitial pneumonia , ARDS,
renal failure , liver failure, encephalitis ,
myocarditis & DIC

 Scrub typhus is speculated to cause mild focal

inflammation of liver due to intrahepatic
sinusoidal endothelial vasculitis and increases
the levels of aminotranferases due to direct
cytopathic liver damage
 .
The proportion of
Aminotransferases abnormalities
Elevated AST, ALT, ALP, total (ALT and AST >40 IU/L)was
bilirubin, and Prothrombin time greater than the proportion of
Decreased albumin patients with abnormal ALP
(>130U/L)and total bilirubin
(>1.2mg/dl)

The scrub typhus patients with Hyperbilirubinemia and

underlying liver cirrhosis showed
significant hypoalbuminemia, thrombocytopenia may be
hyperbilirubinemia and related to poor outcome in
thrombocytopenia patients with scrub typhus
VIRAL
 DENGUE

 Dengue fever commonly known s

break bone fever is a flu like
illness caused by the dengue
virus.[DENV 1 TO DENV 4]
Dengue
Dengue haemorrhagic
 Mode of transmission : Aedes shock fever
mosquito syndrome

 Symptoms Mild dengue

fever
 Three phases
 Dengue with or without warning
signs
 Severe dengue/DSS/DHF
 Expanded dengue syndrome
 DENV INFECTION AND LIVER

Liver is the commonest organ to be involved in dengue.

Hepatic manifestations are either as a result of direct viral toxicity or

dysregulated immunologic injury in response to the virus.

Hepatocytes and Kupffer cells are the prime targets for DENV infection.

Heparan sulfate plays a vital role for the intrusion of the DENVs into
liver cells.

Multiple mechanisms are responsible for liver injury in dengue such as

direct viral cytopathic effects, immune mediated injury and hypo
perfusion
Hepatomegaly is more commonly found in dengue
hemorrhagic fever

Elevation of AST is more than ALT, more during the 1st

week of infection ,which decreases to normal within 3
weeks

Hypoproteinemia or hypoalbuminemia have been observed in

12.9% patients.

Coagulation abnormalities have been observed .INR >1.5

have been observed in 11% of cases ,abnormal PTT and PT
noted in 34 5 to 42.5% cases

Liver damage have been found to more commonly occur in

females than males
 HISTOPATHOLOGY
 Histological changes include

Fatty changes

Destruction of
Kupffer cells

Hepatocyte
necrosis

Hyperplasia

Councilman
bodies
 Hepatocyte injury including necrotic changes commonly
involves the midzonal area followed by the centrilobular
area.

 Sinusoidal congestion have been observed.

 Dengue Viral Hepatitis vs Other Acute Viral Hepatitis

(A,B,E)
 Dengue hepatitis Acute Viral hepatitis
 Transamintis / LFT alteration  After defervescence , LFT
during febrile phase derangements will appear

 Acute fulminant hepatic failure is  Rare, but comparatively higher

very rare. incidence than dengue

 Hypoalbuminemia is present  Not present during first two weeks

 AST >>>ALT  ALT>>AST

 COVID & FLU
 Liver damage is seen in patients affected by COVID-19, and factors
including viral direct damage, immune damage, systemic inflammatory
response, drug-induced, ischemia-reperfusion injury, mechanical
ventilation, and underlying diseases contribute to liver injury.
 The association between liver damage and adverse clinical outcomes in
patients affected by COVID-19 and the mechanism of SARS-CoV-2 in
creating this injury is also unclear.
 patients with COVID-19 have maintained their normal liver function
during the disease, but patients with more severe disease probably had
an abnormal liver function.
 Most patients with COVID-19 have a mild increase in aspartate
aminotransferase, alanine aminotransferase, or total bilirubin. The
highest rate of liver damage is in adult patients and AST levels had the
highest relevance with mortality compared to other indices reflecting
liver injury
MALARIA
- Malaria is a protozoan disease transmitted by
the bite of infected female Anopheles
mosquito.

- Species of Plasmodium: P.Vivax, ovale,

malariae, falciparum and knowlesi

- High grade intermittent fever with chills and

rigor, headache , myalgia, abdominal
discomfort and fatigue

- Severe malaria includes high parasitemia on

PS, cerebral malaria, severe acidosis, severe
acute anemia, renal failure, ARDS,
Hypotension/shock, hypoglycemia, Bleeding
and DIC, Liver failure.
MECHANISM OF LIVER DAMAGE IN MALARIA

Human infection occurs by inoculation of sporozoites

by female anopheles mosquito during blood meal,from where
they are carried to the liver via the bloodstream.

Further amplification of sporozoites take place in liver. They

invade the liver parenchymal cells and begin the asexual
reproduction .A single sporozoite produces >30000 daughter
merozoites.

The swollen infected liver cells burst and release merozoites into the
bloodstream.These merozoites invade the RBCs to become tropozoites.
Since asexual phase occurs in liver ,liver cells are predominantly
affected and manifests with a abnormal liver function tests
 MALARIAL HEPATOPATHY
MULTIFACTORIAL
CAUSES OF JAUNDICE

Hemolysis Cytoadherence and

after RBC sequestration of
lysis due to parasites within small
severe blood vessels leads to
infestation by microvascular
Rupture of P.falciparum obstruction with
hepatocytes result can rise resultant ischemia
in cellular damage. bilirubin leading to liver
dysfunction
 Occlusion of portal
venous branches by
parasitized red blood
cells
Intrahepatic cholestasis due to
reticuloendothelial damage
&hepatic microvillous
dysfunction
Apoptosis and oxidative
stress
Endotoxemia due
to severe systemic
infection

MULTIFACTORIAL
CAUSES OF JAUNDICE
Malarial hepatopathy is characterized by increased serum bilirubin along
with rise in serum glutamate pyruvate transaminase levels to >3 times
the upper limit of normal

Co infection with hepatitis E or A can accentuate jaundice.

Disseminated intravascular coagulation can lead to hepatocellular

dysfunction in severe malarial infection.
 Elevated Serum bilirubin with conjugated fraction more
than 50% have been observed.

 Liver enzymes are elevated 3 to 5 times the normal but may

be elevated much beyond this.

 INR is usually normal , it is elevated only in cases of DIC.

 USG shows significant HEPATOMEGALY.

 UDCA- URSO DEOXYCHOLIC ACID

 Protection of injured cholangiocytes against toxic effects

of bile acids

 Stimulation of impaired biliary secretion

 Stimulation of detoxification of hydrophobic bile acids

 Inhibition of apoptosis of hepatocytes.

Role of UDCA
THANK YOU
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