Field of Medicine

Medicine And Surgery Program

Liver Affection in Systemic Diseases

Dr. Mohamed Basyouni Date : 5 / 11 /2023

Non-alcoholic fatty liver disease
(NAFLD)
Definition:
Excessive fat deposition in the liver of non-alcoholic patients with/without liver
inflammation.
 It is considered the hepatic manifestation of metabolic syndrome.
 It is now considered the underlying aetiology of chronic liver disease previously
called (cryptogenic cirrhosis)
 It is expected to be the most common cause of chronic liver disease worldwide in the
next decades.
 It is independent risk factor for coronary artery disease & cardiovascular mortality.

Pathogenesis:
 Steatosis: fatty infiltration (mainly TG) without inflammation.
- Microvesicular steatosis- liver cells are filled with multiple fat droplets & vacuoles
that do not displace the centrally located nucleus of hepatocytes.
- Macrovesicular steatosis:- the size of the vacuoles increases, pushing the nucleus to
the periphery of the cell giving characteristic (signet-ring appearance).
 Steatohepatitis ( Non-alcoholic steatohepatitis, NASH) : fatty acid peroxidation,
release of excessive free radicals → hepatic inflammation that may lead to fibrosis
& cirrhosis.
Etiology of liver steatosis:

 Macrovesicular Steatosis:
 Alcoholic Steatosis (alcoholic fatty liver disease): due to chronic alcohol intake.

 Non-alcoholic fatty liver disease (NAFLD):

- The exact cause is unknown
- The most accepted theory is related to insulin resistance & metabolic syndrome
( Constellation of Obesity, Type II-DM, HTN, Hypertriglyceridemia, low HDL)

 Drug-induced e.g. Amoidarone, corticosteroids, CCPs

 Idiopathic

 Microvesicular Steatosis:
 Fatty liver of pregnancy

 Rye's syndrome
Clinical picture:

 The spectrum of NAFLD includes simple liver steatosis, NASH, liver cirrhosis
that may be complicated by HCC.

 Asymptomatic in the majority of cases.

 Tender hepatomegaly: enlarged liver with rounded borders, smooth surface, soft
consistency & pain in the right hypochondrium may be present.

 Manifestations of cirrhosis & chronic liver failure in complicated NASH.

 Features of HCC in late advanced cases.

 Acute liver failure may occur with microvesicular steatosis ( Acute fatty liver of
pregnancy & Rye syndrome).
Investigations:

 Increase ALT & AST: may be the only detected abnormality

 Normal serum albumin, bilirubin & coagulation profile: except if progressed to

cirrhosis & liver failure.

 Lipid profile: Serum hypertriglyceridemia and hypercholesterolemia may be

present.

 Abdominal US: enlarged bright liver

 Abdominal MRI: is the most sensitive non-invasive method to detect fatty

infiltration.

 Liver biopsy: The gold standard for diagnosis of NASH

Treatment:
1. Lifestyle modifications: (the most important)
 Regular Exercise: at least 30 minutes daily, 3-4 times weekly.
 Dietary modifications: The best is the Mediterranean diet ( more vegetables,
fruits with fish & vegetable proteins, less fat & meat proteins)
 Stop smoking & alcohol intake
 Coffee is believed to have a protective role
 Weight loss in obese patients: avoid rapid weight loss >1.6 kg/week.

2. Pharmacological therapy :
 Insulin sensitizers: Thiazoladinediones, in diabetic patients (metformin has no
role)
 Anti-oxidants e.g. Vitamin E (800 IU/day): to decrease the oxidative stress
induced by lipid accumulation.
 Ursodeoxycholic acid (UDCA) and lipid-lowering drugs (statins): may have a
role in improving NASH histology.

3. Surgical therapy :
 Bariatric surgery : for morbid obesity
 Liver transplantation: decompensated NASH- induced cirrhosis
Systemic affection in liver diseases

1. CNS
- Liver cell failure→ encephalopathy, tremors, convulsions
- Fulminant hepatic failure→ cerebral oedema
- Wilson disease→ extrapyramidal manifestations

2. Cardiovascular
- Liver cell failure → Hyperdynamic circulation
- Obstructive Jaundice → sinus bradycardia

3. Respiratory
- Liver cell failure→ cyanosis?
- Ascites → Rt sided pleural effusion

4. Renal
- Liver cell failure → hepatorenal syndrome
- Viral hepatitis → GN
1. HBV → Membranous GN
2. HCV → Membranoproliferative GN
5. Hematology
- Liver cell failure → anemia, coagulopathy, thrombocytopenia
- Autoimmune hepatitis & Wilson disease→ hemolytic anemia
- HBV→ Aplastic anemia
6. Rheumatology
- HBV → PAN
7. Endocrine
- Liver cell failure: male feminization, salt & water retention
- Autoimmune hepatitis & 1ry biliary cirrhosis: associated with thyroiditis
- Hemochromatosis →DM
8. Skin
- Liver cell failure: palmar erythema, chylonychia, spider nevi
- Hemochromatosis → bronzed hyperpigmentation
- Biliary cirrhosis → itching
9. Ocular
- Liver cell failure →jaundice
- Wilson disease →Kayser Fleisher ring
Drug induced liver diseases:

1- Acute hepatitis: Alcohol, halothane, paracetamol

2- Chronic hepatitis: Alcohol, INH, rifampicin, methyldopa.

3- Fatty Liver: Alcohol, Amoidarone, methotrexate.

4- Liver cirrhosis: Alcohol, Methyldopa, INH, Methotrexate.

5- Cholestasis: Anabolic steroid, CCPs, Erythromycin.

6- hepatic adenoma: CCPs

7- Budd-Chiari syndrome: CCPs

LIVER & PREGNANCY
1- Cholestasis of pregnancy:
- The most common liver disorder in pregnancy
- C/P: itching & obstructive jaundice
- Treatment: UDCA & cholestyramine
- Prognosis: good but with possible recurrence in next pregnancies
2- HELP syndrome:
- Occurs with Pre-eclampsia in late pregnancy.
- Includes Hemolysis, Elevated liver enzymes & Low platelets
- Termination of pregnancy is curative
3- Acute fatty liver of pregnancy:
- Fulminant hepatic failure in the last trimester.
- Termination of pregnancy is curative if done early.
4- Hepatitis E: may lead to Fulminant hepatic failure in 20% of pregnant cases.
5- HBV: can be transmitted transplacental (vertical transmission). The newborn
baby should receive both IV-IG & HBV vaccine immediately after delivery (in the
first 12-24 hours after delivery)