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DISEASES OF THE
LIVER
Dr Shubhanshu Ranjan Singh
HEPATITIS
-Viral Hepatitis-
Outcomes
• ASYMPTOMATIC
Incidental ( B,C,D)
↑ Serum Transaminases
Antiviral antibodies
• SYMPTOMATIC PREICTERIC
Non specific
Serum sickness-like ( HBV )
↑ Serum Transaminases
• CONVALESCENCE
Recovery
• PROGRESSION
Fulminant hepatitis
Chronic hepatitis
Carrier state
Diagnosis of Acute Hepatitis
• To diagnose hepatitis
– Biochemistry
• Serum Bilirubin (Total & Conjugated)
• AST / ALT / ALP
• To determine etiology
– Serology (Initial testing)
• HBsAg, IgM Anti-HBc, Anti-HCV Ab, Anti-HAV Ab
• HBeAg, Anti-HEV Ab
– Molecular biology (Usually not required)
• HCV RNA
• HBV DNA
Diagnosis of Chronic Hepatitis
• To diagnose chronic hepatitis
– Biochemistry
• AST / ALT (persistent elevation 6 months apart)
• To determine etiology
– Serology
• HBsAg, HBeAg, Anti-HCV Ab
– Molecular biology (for quantification, guided by
serology)
• HBV DNA
• HCV RNA
Acute / Chronic Hepatitis co-
infections
• HDV occurs only along with HBV infection
• Co-infection of HBV and HCV may occur
• HBV or HCV may coexist with HIV infection
LIVER ABSCESS
Pyogenic abscess, which is most often
polymicrobial, accounts for 80% of hepatic
abscess cases in the United States.
Amebic abscess due to Entamoeba histolytica
accounts for 10% of cases.
Fungal abscess, most often due to Candida
species, accounts for less than 10% of cases
PYOGENIC ABSCESS
AMOEBIC LIVER ABSCESS
• Protozoan parasite: Entamoeba histolytica
• Exposure via fecal-oral route Humans are the
principal host
• Source of infection is the cyst-passing chronic
patient or asymptomatic carrier
• It results from spread of the organisms from
the intestinal submucosa to the liver via the
portal system
Clinical Features
 History
The most frequent symptoms of hepatic abscess include the
following:
a) Fever (either continuous or spiking)
b) Chills
c) Right upper quadrant pain
d) Anorexia
e) Malaise
- Referred pain to the right shoulder may be present.
- Fever of unknown origin (FUO) frequently can be an initial
diagnosis in indolent cases. Multiple abscesses usually result in
more acute presentations, with symptoms and signs of systemic
toxicity.
- Afebrile presentations have been documented!
 Physical Findings
Fever and tender hepatomegaly are the most common signs.
A palpable mass need not be present.
Mid epigastric tenderness, with or without a palpable mass, is
suggestive of left hepatic lobe involvement.
Decreased breath sounds in the right basilar lung zones, with
signs of atelectasis and effusion on examination or
radiologically, may be present.
A pleural or hepatic friction rub can be associated with
diaphragmatic irritation or inflammation of Glisson capsule.
Jaundice may be present in as many as 25% of cases and
usually is associated with biliary tract disease or the presence
of multiple abscesses.
Current indications for the surgical
treatment of amoebic liver abscess are-
Surgical intervention :-
– perforated amebic colitis, massive GI bleeding, or toxic
megacolon.
– Amebic liver abscess generally responds to medical
therapy alone and drainage is seldom necessary.
– When necessary, imaging-guided percutaneous
treatment (needle aspiration or catheter drainage) has
replaced surgical intervention as the procedure of
choice for reducing the size of an abscess.
Indications for drainage : -
– Presence of left-lobe abscess (>10 cm in diameter)
– Rupture and
– abscess that does not respond to medical therapy
within 3-5 days
Complications
 metastatic complications e.g., CNS infection or endophthalmitis (
usually with K pneumoniae infection.
 sepsis
 abscess rupture – presents as perotinitis or pneumoperitoneum.
 subphrenic abscess - Patients may have symptoms of diaphragmatic
irritation.
 pleuropulmonary or hepatobronchial fistula - Patients may present
with a cough, productive of purulent sputum. Metallic-tasting
sputum has been reported
 hepatic artery pseudoaneurysm
 abdominal or hepatic venous thrombosis
 liver failure - More common in people with pre-existing liver
disease, or large abscesses
 acute pancreatitis - rare complication. Presents with acute
epigastric pain and vomiting.
 fistula to adjacent organs - such as to the stomach, colon, small
bowel, or kidney
HYDATID CYST
Life cycle of E.granulosus
• The right lobe is the most frequently involved
portion of the liver.
• Once in the human liver, cysts grow to 1 cm
during the first 6 months and 2–3 cm annually
thereafter, depending on host tissue
resistance.
Surgical Management
• Indications:
1-Large liver cysts with multiple daughter cysts;
superficially located single liver cysts that may
rupture (traumatically or spontaneously).
2-liver cysts with biliary tree communication or
pressure effects on vital organs or structures.
3-infected cysts .
4-cysts in lungs, brain, kidneys, eyes, bones .
Medical therapy
• Indications: Chemotherapy is indicated in patients
with primary liver or lung cysts that are inoperable
(because of location or medical condition), patients
with cysts in 2 or more organs, and peritoneal cysts.
• Chemotherapeutic agents: Two benzimidazoles are
used, albendazole and mebendazole. Albendazole is
administered in several 1-month oral doses (10-15
mg/kg/d) separated by 14-day intervals. The optimal
period of treatment ranges from 3-6 months, with no
further increase in the incidence of adverse effects if
this period is prolonged.
• Mebendazole is also administered for 3-6 months
orally in dosages of 40-50 mg/kg/d.
PAIR
• This technique, performed using either ultrasound or
CT guidance, involves aspiration of the contents via a
special cannula, followed by injection of a scolicidal
agent for at least 15 minutes, and then reaspiration of
the cystic contents. The cyst is then filled with isotonic
sodium chloride solution. Perioperative treatment with
a benzimidazole is mandatory (4 d prior to the
procedure and 1-3 mo after).
• The cysts should be larger than 5 cm in diameter and
type I or II according to the Gharbi ultrasound
classification of liver cysts
CIRRHOSIS
Normal Histology
• Hepatocytes: Radiate from central vein to
portal tract
• Sinusoids lined by endothelial cells
• Space of Disse
• Bile canaliculus: between the hepatocytes
• Limiting plate: Cells adjacent to the portal
tract
Cirrhosis
Definition : It is an end stage of chronic liver
disease characterized by :
1.Bridging fibrous septae : Scars extending
between portal tracts; portal tract and central
vein
2.Parenchymal nodules : Proliferating
hepatocytes encircled by fibrosis
3.Disruption of the architecture of the entire
liver
Pathogenesis
Gross -Normal
Cirrhosis
Microscopy
NORMAL CIRRHOSIS
Classification
Based on the size of the nodules
• Micronodular : ( < 3 mm size) : Alcoholic liver
disease, hemochromatosis, Biliary cirrhosis.
• Macronodular : ( > 3 mm size) : Viral hepatitis,
Wilson disease, Indian childhood cirrhosis
• Micro-macro nodular (Mixed) : alcoholic, drug
induced
PORTAL HYPERTENSION
• Elevation of portal venous pressure >5mm Hg
• Clinically significant - >10mm Hg
• Risk of variceal bleeding - >12mm Hg
Pathogenesis
• Increased resistance to the portal blood flow
• Causes :
1.Prehepatic : Obstructive thrombosis, narrowing of
portal vein
2.Post hepatic: right heart failure, constructive
pericarditis, hepatic vein outflow obstruction
3.Intrahepatic : Cirrhosis, schistosomiasis, massive
fatty change, diffuse granulomatous disease
(sarcoidosis, miliary TB)
Portosystemic Venous Shunts
Sites : -
Rectum – hemorrhoids.
Cardioesophageal junction – Esophagogastric
varices- in 65% of pts with advanced cirrhosis –
life threatening hemetemesis.
Retroperitoneum
Falciparum ligament of liver –Periumbilical &
abdominal wall collaterals – caput medusae ;
important clinical hall mark of portal HT
Hepatic Failure
LIVER TUMOURS
• Benign
Adenoma
Cavernous hemangiomas
• Malignant
Hepatocellular carcinoma
Cholangiocarcinoma
Hepatoblastoma
Angiosarcoma
• Metastatic: colon, lung, and breast
• Tumour like conditions
Cavernous hemangioma
Focal nodular hyperplasia
Nodular regenerative hyperplasia.
Solitary or multiple benign hepatocellular
nodules
Focal nodular hyperplasia: localized, well-demarcated but poorly
encapsulated lesion
- hyperplastic hepatocyte nodules with a central fibrous scar
-appear in noncirrhotic livers and may reach up to many centimeters in
diameter.
-not a neoplasm but a nodular regeneration
Macroregenerative nodules appear in cirrhotic livers
- larger than surrounding cirrhotic nodules but do not display atypical
features.
Dysplastic nodules: larger than 1 mm in diameter
-appear in cirrhotic livers.
- Hepatocytes are highly proliferative and show atypical features such as
crowding and pleomorphism
Hepatocellular Carcinoma
Pathogenesis
Repeated cycles of cell death & regeneration
Genetic alterations :
- Point mutations
- Loss of heterozygosity in tumor suppressor genes
- DNA Methylation changes
- Increased expression of HGF, TGF-α
Viral protein
• Hepatocyte replication
• Hepatocyte dysplasia
• Accumulation of mutations in repeat cell cycles
• - Damage DNA repair mechanism
• Transformation of the Hepatocyte
Thank You.
Diseases of the liver
Diseases of the liver
Diseases of the liver
Diseases of the liver
Diseases of the liver
Diseases of the liver
Diseases of the liver
Diseases of the liver
Diseases of the liver
Diseases of the liver
Diseases of the liver
Diseases of the liver

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Diseases of the liver

  • 1. DISEASES OF THE LIVER Dr Shubhanshu Ranjan Singh
  • 4.
  • 5. Outcomes • ASYMPTOMATIC Incidental ( B,C,D) ↑ Serum Transaminases Antiviral antibodies • SYMPTOMATIC PREICTERIC Non specific Serum sickness-like ( HBV ) ↑ Serum Transaminases • CONVALESCENCE Recovery
  • 7.
  • 8. Diagnosis of Acute Hepatitis • To diagnose hepatitis – Biochemistry • Serum Bilirubin (Total & Conjugated) • AST / ALT / ALP • To determine etiology – Serology (Initial testing) • HBsAg, IgM Anti-HBc, Anti-HCV Ab, Anti-HAV Ab • HBeAg, Anti-HEV Ab – Molecular biology (Usually not required) • HCV RNA • HBV DNA
  • 9. Diagnosis of Chronic Hepatitis • To diagnose chronic hepatitis – Biochemistry • AST / ALT (persistent elevation 6 months apart) • To determine etiology – Serology • HBsAg, HBeAg, Anti-HCV Ab – Molecular biology (for quantification, guided by serology) • HBV DNA • HCV RNA
  • 10. Acute / Chronic Hepatitis co- infections • HDV occurs only along with HBV infection • Co-infection of HBV and HCV may occur • HBV or HCV may coexist with HIV infection
  • 12. Pyogenic abscess, which is most often polymicrobial, accounts for 80% of hepatic abscess cases in the United States. Amebic abscess due to Entamoeba histolytica accounts for 10% of cases. Fungal abscess, most often due to Candida species, accounts for less than 10% of cases
  • 14.
  • 15. AMOEBIC LIVER ABSCESS • Protozoan parasite: Entamoeba histolytica • Exposure via fecal-oral route Humans are the principal host • Source of infection is the cyst-passing chronic patient or asymptomatic carrier • It results from spread of the organisms from the intestinal submucosa to the liver via the portal system
  • 16. Clinical Features  History The most frequent symptoms of hepatic abscess include the following: a) Fever (either continuous or spiking) b) Chills c) Right upper quadrant pain d) Anorexia e) Malaise - Referred pain to the right shoulder may be present. - Fever of unknown origin (FUO) frequently can be an initial diagnosis in indolent cases. Multiple abscesses usually result in more acute presentations, with symptoms and signs of systemic toxicity. - Afebrile presentations have been documented!
  • 17.  Physical Findings Fever and tender hepatomegaly are the most common signs. A palpable mass need not be present. Mid epigastric tenderness, with or without a palpable mass, is suggestive of left hepatic lobe involvement. Decreased breath sounds in the right basilar lung zones, with signs of atelectasis and effusion on examination or radiologically, may be present. A pleural or hepatic friction rub can be associated with diaphragmatic irritation or inflammation of Glisson capsule. Jaundice may be present in as many as 25% of cases and usually is associated with biliary tract disease or the presence of multiple abscesses.
  • 18. Current indications for the surgical treatment of amoebic liver abscess are- Surgical intervention :- – perforated amebic colitis, massive GI bleeding, or toxic megacolon. – Amebic liver abscess generally responds to medical therapy alone and drainage is seldom necessary. – When necessary, imaging-guided percutaneous treatment (needle aspiration or catheter drainage) has replaced surgical intervention as the procedure of choice for reducing the size of an abscess. Indications for drainage : - – Presence of left-lobe abscess (>10 cm in diameter) – Rupture and – abscess that does not respond to medical therapy within 3-5 days
  • 19. Complications  metastatic complications e.g., CNS infection or endophthalmitis ( usually with K pneumoniae infection.  sepsis  abscess rupture – presents as perotinitis or pneumoperitoneum.  subphrenic abscess - Patients may have symptoms of diaphragmatic irritation.  pleuropulmonary or hepatobronchial fistula - Patients may present with a cough, productive of purulent sputum. Metallic-tasting sputum has been reported  hepatic artery pseudoaneurysm  abdominal or hepatic venous thrombosis  liver failure - More common in people with pre-existing liver disease, or large abscesses  acute pancreatitis - rare complication. Presents with acute epigastric pain and vomiting.  fistula to adjacent organs - such as to the stomach, colon, small bowel, or kidney
  • 21. Life cycle of E.granulosus
  • 22. • The right lobe is the most frequently involved portion of the liver. • Once in the human liver, cysts grow to 1 cm during the first 6 months and 2–3 cm annually thereafter, depending on host tissue resistance.
  • 23.
  • 24. Surgical Management • Indications: 1-Large liver cysts with multiple daughter cysts; superficially located single liver cysts that may rupture (traumatically or spontaneously). 2-liver cysts with biliary tree communication or pressure effects on vital organs or structures. 3-infected cysts . 4-cysts in lungs, brain, kidneys, eyes, bones .
  • 25. Medical therapy • Indications: Chemotherapy is indicated in patients with primary liver or lung cysts that are inoperable (because of location or medical condition), patients with cysts in 2 or more organs, and peritoneal cysts. • Chemotherapeutic agents: Two benzimidazoles are used, albendazole and mebendazole. Albendazole is administered in several 1-month oral doses (10-15 mg/kg/d) separated by 14-day intervals. The optimal period of treatment ranges from 3-6 months, with no further increase in the incidence of adverse effects if this period is prolonged. • Mebendazole is also administered for 3-6 months orally in dosages of 40-50 mg/kg/d.
  • 26. PAIR • This technique, performed using either ultrasound or CT guidance, involves aspiration of the contents via a special cannula, followed by injection of a scolicidal agent for at least 15 minutes, and then reaspiration of the cystic contents. The cyst is then filled with isotonic sodium chloride solution. Perioperative treatment with a benzimidazole is mandatory (4 d prior to the procedure and 1-3 mo after). • The cysts should be larger than 5 cm in diameter and type I or II according to the Gharbi ultrasound classification of liver cysts
  • 28. Normal Histology • Hepatocytes: Radiate from central vein to portal tract • Sinusoids lined by endothelial cells • Space of Disse • Bile canaliculus: between the hepatocytes • Limiting plate: Cells adjacent to the portal tract
  • 29.
  • 30. Cirrhosis Definition : It is an end stage of chronic liver disease characterized by : 1.Bridging fibrous septae : Scars extending between portal tracts; portal tract and central vein 2.Parenchymal nodules : Proliferating hepatocytes encircled by fibrosis 3.Disruption of the architecture of the entire liver
  • 35. Classification Based on the size of the nodules • Micronodular : ( < 3 mm size) : Alcoholic liver disease, hemochromatosis, Biliary cirrhosis. • Macronodular : ( > 3 mm size) : Viral hepatitis, Wilson disease, Indian childhood cirrhosis • Micro-macro nodular (Mixed) : alcoholic, drug induced
  • 36.
  • 38. • Elevation of portal venous pressure >5mm Hg • Clinically significant - >10mm Hg • Risk of variceal bleeding - >12mm Hg
  • 39. Pathogenesis • Increased resistance to the portal blood flow • Causes : 1.Prehepatic : Obstructive thrombosis, narrowing of portal vein 2.Post hepatic: right heart failure, constructive pericarditis, hepatic vein outflow obstruction 3.Intrahepatic : Cirrhosis, schistosomiasis, massive fatty change, diffuse granulomatous disease (sarcoidosis, miliary TB)
  • 40. Portosystemic Venous Shunts Sites : - Rectum – hemorrhoids. Cardioesophageal junction – Esophagogastric varices- in 65% of pts with advanced cirrhosis – life threatening hemetemesis. Retroperitoneum Falciparum ligament of liver –Periumbilical & abdominal wall collaterals – caput medusae ; important clinical hall mark of portal HT
  • 41.
  • 44. • Benign Adenoma Cavernous hemangiomas • Malignant Hepatocellular carcinoma Cholangiocarcinoma Hepatoblastoma Angiosarcoma • Metastatic: colon, lung, and breast • Tumour like conditions Cavernous hemangioma Focal nodular hyperplasia Nodular regenerative hyperplasia.
  • 45. Solitary or multiple benign hepatocellular nodules Focal nodular hyperplasia: localized, well-demarcated but poorly encapsulated lesion - hyperplastic hepatocyte nodules with a central fibrous scar -appear in noncirrhotic livers and may reach up to many centimeters in diameter. -not a neoplasm but a nodular regeneration Macroregenerative nodules appear in cirrhotic livers - larger than surrounding cirrhotic nodules but do not display atypical features. Dysplastic nodules: larger than 1 mm in diameter -appear in cirrhotic livers. - Hepatocytes are highly proliferative and show atypical features such as crowding and pleomorphism
  • 46. Hepatocellular Carcinoma Pathogenesis Repeated cycles of cell death & regeneration Genetic alterations : - Point mutations - Loss of heterozygosity in tumor suppressor genes - DNA Methylation changes - Increased expression of HGF, TGF-α Viral protein • Hepatocyte replication • Hepatocyte dysplasia • Accumulation of mutations in repeat cell cycles • - Damage DNA repair mechanism • Transformation of the Hepatocyte
  • 47.