Metabolic Liver Disease

Def : is a general term for a group of diseases that affect the liver's
ability to function properly. Treatment / Management of Metabolic Liver Disease
Types of Metabolic Liver Disease:
Fatty liver disease Lifestyle changes: Losing weight, eating a healthy diet, and exercising
Non-alcoholic steatohepatitis (NASH) regularly can all help to improve your liver health and slow the progression
Alcoholic liver disease of metabolic liver disease.
Alpha-1 antitrypsin deficiency Medications: may help to reduce inflammation, improve liver function, or
Wilson's disease remove excess fat or iron from the liver.
Hemochromatosis Liver transplant: In some cases, a liver transplant may be the best
Glycogen storage diseases treatment option for metabolic liver disease.
Causes of Metabolic Liver Disease:
Genetics Prevention of Metabolic Liver Disease
Diet Maintain a healthy weight
Lifestyle choices Eat a healthy diet
Certain medications Exercise regularly
Symptoms of Metabolic Liver Disease Limit alcohol consumption
Fatigue Avoid smoking
Loss of appetite Get vaccinated against hepatitis
Nausea and vomiting
Abdominal pain ----------------------------------------------------------------------------------------------------
Jaundice (yellowing of the skin and whites of the eyes) Alpha-1 Antitrypsin Deficiency: Genetic disorder that can lead to liver
Dark urine damage and cirrhosis
Easy bruising or bleeding Caused by a deficiency of alpha-1 antitrypsin, a protein that protects the
Swelling in the legs and ankles lungs from damage
Symptoms may include shortness of breath, fatigue, and swelling in the legs
Diagnosis of Metabolic Liver Disease -----------------------------------------------------------------------------------------------------
Blood tests - Imaging tests - Liver biopsy Glycogen Storage Diseases:Group of genetic disorders that affect the body's
ability to store and use glycogen.( that stored in the liver and muscles)
Complications of Metabolic Liver Disease Symptoms:
Cirrhosis Hypoglycemia (low blood sugar)
Hepatocellular carcinoma(liver cancer) Lactic acidosis (a buildup of lactic acid in the blood)
Hepatic encephalopathy Fatigue
Liver failure Weakness
Portal hypertension Liver problems
 WILSON’S DISEASE HAEMOCHROMATOSIS (Bronze Diabetes)
An inborn error of copper metabolism characterized by a low serum An inborn error of iron metabolism characterized by increased
ceruloplasmin and deposition of copper in various tissues as the liver, basal absorption of iron and increased deposition in the tissues
Definition
ganglia, and the cornea, and to less extent in the kidneys, the bones and specially the liver, skin, pancreas, and the gonads.
the nails.
The normal daily dietary absorption of copper is 2 mg, which is excreted in A fibrous tissue reaction is present wherever the iron is
the bile completely. deposited.
Liver: portal zone fibrosis with deposition of iron in the
Absence of the copper-binding protein leads to deposition of the copper in periportal zone. Fibrous septa then surround groups of
the tissues. lobules and irregularly shaped nodules (holly-leaf
appearance) with maculonodular cirrhosis
Pathogenesis Pancreas: fibrosis and parenchymal degeneration with iron
deposition in islets of Langerhans.
Endocrine glands: including thyroid, adrenal cortex, anterior
lobe of pituitary, and gonads with testicular atrophy.
Skin: pigment is increased in the melanin content of the basal
layer.

A) Hepatic forms: 1. The typical picture is of a diabetic, middle-aged man with

1. Chronic active hepatitis, it occur in young age 10-30 years, pigmented skin, hepatomegaly, diminished sexual activity and
presented with jaundice,↑serum transaminases and gammaglobulins. loss of body hair.
Neurological changes occur 2-3 years later.
2. Age and sex: ten times as frequent in males as females,
2. Liver cirrhosis, because menstruating women are protected by iron loss with
presented with manifestations of liver cell failure as spiders, splenomegaly, menstruation and pregnancy.
ascites and portal hypertension.
Clinical
Liver biopsy may be necessary for diagnosis. 3. Skin pigmentation: it is maximal in the axillae, groins,
features
genitalia, old scars and exposed parts, and the skin is shiny
3. Fulminant hepatitis characterized by progressive jaundice, ascites, and and dry.
hepatic and renal failure due to massive hepatic necrosis .
In addition, acute intravascular haemolysis occurs due to destruction of red 4. Liver cirrhosis: liver is enlarged and firm with tenderness.
blood cells by the copper. The spleen is enlarged, but manifestation of hepatocellular
failure is usually absent.
4. Hepatocellular carcinoma is very rare and copper may be protective.
5. Clinical diabetes mellitus (Bronze Diabetes) is present in
 B) Neuropsychatric form: about 66% of cases. It may be difficult to control.
1. Acute progressive type, with flexion-extension tremors of the wrists,
grimacing, difficulty in writing and slurred speech with slow deterioration 6- Sexual dysfunction is shown by impotence, loss of libido,
of the personality. testicular atrophy, and loss of secondary sexual hair.
2. Chronic type, which is commoner than acute and occur in early adult life. 7. Cardiac changes (due to iron deposits in the myocardium
and conducting system), as heart failure and arrhythmia.
C) Other changes: The heart is globular in shape.
Kayser-Fleisher ring :is a greenish-brown ring at the periphery of the
cornea, usually present with the neurological abnormalities. 8- Anthropathy, affecting the metacarpophalangeal joints and
Renal changes, as glycosuria, aminoaciduria, phosphaturia, and uricosuria. also large joints.
Blue nails, gallstones, hypoparathyroidism, oesteoarthritis.

Serum ceruloplasmin and copper levels are reduced with increased Serum iron is raised to about 220ug/dl (normal 125ug/dl)
urinary excretion of copper. Serum ferritin is high, but normal values do not exclude the
Investigations Liver biopsy to measure the copper content, which exceeds 250 ug/gm dry diagnosis.
tissue (normal value is > 55 ug/gm). Liver biopsy: best method of diagnosis (pigmentary cirrhosis)
Liver imaging: CT scanning and MRI are useful if serum ferritin
is elevated.

1. D-penicillamine, TTT of choice. Repeated venesection is the best way of treatment by

It chelates copper and increase urinary excretion to 1000-3000 ug/D removing large amount of blood.
-Dose 1.2 gm daily in 4 divided doses( ORAL), may be increased to 1.5-1.8 500 ml blood is removed weekly for 2 years or until serum
gm daily iron and ferritin fall to normal.
-the response to TTT is shown by disappearance of Kayser-Fleisher ring,
and other manifestations with falling serum ceruloplasmin. Other manifestations are treated accordingly.
-Maintenance is 1.5-2 gm daily. ---------------
Treatment
OR
2. Elemental zinc, 50 mg t.d.s, between meals to inhibit absorption of TTT of Hemochromatosis:
copper from intestine. Phlebotomy: M.C treatment for hemochromatosis.
Medications: chelators can be used to bind to iron in the
3. Avoid high-copper containing foods as chocolate, peanuts, mushrooms, body and help remove it from the body.
liver and shellfish. Diet: People with hemochromatosis should avoid iron-rich
4. Liver transplantation may be indicated in the severe form and in failure foods, such as red meat and organ meats.
to improve after 2-3 months D-penicillamine.
 Veno-Occlusive Disease Budd-Chiari Syndrome
is a serious condition, IN which there is a is a rare vascular disorder of the liver characterized by obstruction of the hepatic veins, the main
Def blockage of small veins in the liver. drainage veins of the liver. → liver congestion, inflammation, and cirrhosis

Chemotherapy Blood Clots in the hepatic veins (most common cause)

Radiation therapy Compression of the hepatic veins by tumors or other masses
Causes Stem cell transplant Inflammation of the hepatic veins (primary Budd-Chiari syndrome)
Certain medications A Congenital (present at birth) abnormality of the hepatic veins

Jaundice (yellowing of the skin and eyes) Jaundice (yellowing of the skin and whites of the eyes)
Fatigue Fatigue
Abdominal pain Abdominal pain (especially in the upper right abdomen)
Symptoms Ascites Ascites

Nausea and vomiting Enlarged liver Epidemiology:

Splenomegaly (enlarged spleen) 1-2 cases per million / year.
Liver function tests Liver function tests affects all ages, MC in adults (30 and 50 year).
Blood tests Blood tests to check for clotting disorders Men are affected slightly more often than women.
Diagnosis Imaging : CT or MRI Imaging :US, CT scan, or MRI scan

Liver biopsy
Supportive care Anticoagulant therapy (blood thinners): to prevent blood clots from forming
Medications to reduce inflammation Angioplasty or stent placement: to open blocked hepatic veins
Deflazacort (Empress) Transjugular intrahepatic portosystemic shunt (TIPS): invasive procedure to create a new
TTT
connection between the portal vein and the hepatic vein.
Liver transplantation

Regular doctor visits Following a healthy diet

Liver function tests Maintaining a healthy weight
Managem
Monitoring for complications Avoiding alcohol
ent
Healthy lifestyle choices Getting regular exercise
Taking medications as prescribed by their doctor
Prognosis With prompt diagnosis and TTT : many With treatment, the 5-year survival rate for BCS is about 50%.
people can recover fully.
some people may develop complications
Complications Liver failure ,Liver cancer & Portal hypertension
 Alcoholic Liver Disease Nonalcoholic Fatty Liver Disease (NAFLD)
It is a serious consequence of excessive is a condition in which fat builds up in your liver
alcohol consumption leads to Fat NAFLD can range from simple fat storage in the liver (steatosis) to more serious inflammation
Def
accumulation, Inflammation, and Scarring (nonalcoholic steatohepatitis, NASH) that can damage your liver cells.
(Fibrosis)
Fatty Liver (Steatosis) Simple steatosis: Earliest stage - Fat accumulation - No inflammation or damage to liver
Alcoholic Hepatitis Nonalcoholic steatohepatitis (NASH): Fat accumulation + inflammation and liver cell damage →
Stages Fibrosis Progress to: Fibrosis & Cirrhosis (Most advanced stage of liver disease, permanent replacement of
Cirrhosis liver by scar tissue)
Causes of NAFLD:
The exact cause of NAFLD is unknown, may be linked
Fatigue NAFLD often causes no symptoms at all. to several factors, including:
Loss of appetite Insulin resistance: it can lead to fat buildup in the
Nausea and vomiting In some cases, people with NAFLD may experience: liver.
Abdominal pain Fatigue Obesity: more likely to develop NAFLD.
Symptoms
Jaundice (yellowing of the skin and eyes) Pain or discomfort in the upper right abdomen Genetics: genetically predisposed to NAFLD.
Confusion and difficulty concentrating Certain medical conditions: as polycystic ovary
Ascites. syndrome (PCOS) and sleep apnea can increase the
risk of NAFLD.
Medical history. Blood tests: liver enzymes that may be elevated in people with NAFLD.
Physical examination: Checking for signs Imaging tests: such as ultrasound or MRI, show signs of fat buildup.
like jaundice, abdominal swelling, or spider Liver biopsy: In some cases may be necessary to confirm a diagnosis of NAFLD.
Diagnosis
angiomas (red, spider-like veins). Complications of NAFLD:
Blood tests: Assessing liver function. Many people no complications, but in some cases may becomplicated :
Imaging tests: Ultrasound, CT scan, or MRI. Cirrhosis.
Treatment Liver cancer: NASH ↑ risk of developing liver cancer.
The primary treatment for ALD is complete Treatment Heart disease: NAFLD is a risk factor for heart disease.
abstinence from alcohol. lifestyle changes: are the cornerstone of NAFLD management. They includes:
Weight loss.
Medications: To manage inflammation, Healthy diet:that is low in sugar and saturated fat and high in fruits, vegetables, and whole grains.
reduce complications, or treat infections. Exercise: can help improve insulin sensitivity and reduce fat buildup in the liver.
Nutritional support: Ensuring adequate Prevention : the same as lifestyle changes.
intake of vitamins and nutrients. Management: the same as lifestyle changes.
Liver transplant: In severe cases of Weight loss (Aim to lose 5-10%)
cirrhosis, a liver transplant may be Aim for at least 30 minutes of moderate-intensity exercise most days of the week.
necessary.
Prevention of Alcoholic Liver Disease: Limit alcohol consumption: (For men: No more than 2 drinks/ D) (For women: No more than 1 drinks/ D).
Maintain a healthy weight, Eat a balanced diet, Get regular checkups
 Portal Vein Thrombosis
Anatomy of the Portal System : (The portal vein):
Originates behind the pancreas and travels up behind the stomach.
Receives blood from the spleen, stomach, intestines, and pancreas.
Divides into two branches that enter the liver → further into smaller vessels that deliver blood to the liver cells.

Causes of Portal Vein Thrombosis:

Cirrhosis: M.C cause of PVT, up to 70% of cases. .
Abdominal infection: appendicitis, diverticulitis, or pancreatitis, can irritate the lining of the portal vein and increase the risk of clotting.
Inflammatory bowel disease (IBD): Crohn's disease and ulcerative colitis increase the risk of PVT.
Malignancy: particularly in the pancreas, stomach, colon, or liver, can increase the risk of PVT by compressing the portal vein or causing hypercoagulability.
Hypercoagulable state: include inherited clotting disorders, pregnancy, and hormonal therapy.

Symptoms and signs of Portal Vein Thrombosis:

Abdominal pain: M.C. symptom of PVT and can be dull, aching, or sharp. It may be located in the upper right quadrant of the abdomen.
Ascites: due to increased pressure in the portal vein system.
Splenomegaly.
Fever: Unexplained fever may be a sign of an underlying infection that triggered PVT.
Gastrointestinal bleeding: PVT can increase the risk of bleeding from the esophagus or stomach.
Jaundice: can occur if PVT leads to liver damage.

Diagnosis of Portal Vein Thrombosis:

Ultrasound: This is a non-invasive imaging test that can be used to visualize the portal vein and identify any blockages.
Doppler ultrasound: to measure blood flow through the portal vien
Computed tomography (CT) scan: provide more detailed images of the portal vein and surrounding structures compared to ultrasound.
Magnetic resonance imaging (MRI): used to diagnose PVT and may be helpful in some cases, particularly when CT scans are contraindicated.
Blood tests: for hypercoagulable states, which may increase the risk of PVT

Complications of Portal Vein Thrombosis:

Portal hypertension: This can cause complications such as ascites, variceal bleeding (bleeding from enlarged veins in the esophagus or stomach), and hepatic
encephalopathy (confusion and impaired mental function due to liver dysfunction).
Liver damage: PVT can impair blood flow to the liver, which can lead to liver damage and even liver failure.
Splenic infarction.
Mesenteric ischemia: In rare cases, PVT can compromise blood flow to the intestines, leading to tissue death (ischemia) in the intestinal lining.
Treatment of Portal Vein Thrombosis
Anticoagulation therapy: This is the mainstay of TTT for PVT and involves the use of medications to prevent blood clots from forming and growing larger.
Thrombolytic therapy: In some cases, medications that dissolve blood clots (thrombolytic agents) may be used to treat PVT, particularly if the clot is recent
and causing significant symptoms.
Angioplasty and stenting: In rare cases, may be used to open a blocked portal vein. This involves inserting a small balloon into the vein to widen it and then
placing a stent to keep it open.
Treatment of underlying condition: Addressing the underlying cause of PVT, such as cirrhosis or infection, is crucial to prevent future clots.

Prognosis of Portal Vein Thrombosis:

The prognosis of PVT depends on several factors: severity of the thrombosis, the presence of underlying liver disease, and the development of complications.
Patients with PVT and no underlying liver disease generally have a good prognosis with appropriate treatment.
The presence of cirrhosis or other severe liver disease can worsen the prognosis of PVT.
Complications such as portal hypertension and liver failure can significantly decrease survival rates.

Management of Portal Hypertension in PVT

Endoscopic therapy: Procedures like endoscopic variceal ligation (EVL) can obliterate enlarged veins in the esophagus or stomach to prevent bleeding.
Transjugular intrahepatic portosystemic shunt (TIPS): In severe cases, a TIPS procedure might be used to create an alternative pathway for blood flow,
bypassing the blocked portal vein.

Long-Term Follow-Up for PVT

Regular follow-up with a healthcare professional is essential for patients with PVT.
Monitoring for complications: Regular checkups allow for early detection and management of potential complications like portal hypertension, liver damage,
or recurrent blood clots.
Addressing underlying conditions: Ongoing management of the underlying cause of PVT, such as cirrhosis or inflammatory bowel disease, is crucial to
prevent future clot formation.
Lifestyle modifications: Maintaining a healthy lifestyle with a balanced diet, regular exercise, and weight management can improve overall health and
potentially reduce the risk of future complications.