Liver Disease Overview

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Questions and Answers

What condition is characterized by inflammation secondary to fatty infiltration?

Chronic Hepatitis

Cirrhosis

Alcoholic Liver Disease

Non-Alcoholic Steatohepatitis (correct)

Which of the following is NOT a requirement for diagnosing MASLD?

Fatty liver on ultrasound

Signs of liver cirrhosis (correct)

Features of metabolic syndrome

Absence of alcohol excess

What is a common CNS effect of low-level ethanol intoxication?

Nervousness

Euphoria (correct)

Seizures

Stupor

What substance is generated during the metabolism of ethanol by ADH in the liver?

Acetaldehyde Signup and view all the answers

Which of the following is considered an extra-hepatic manifestation of Alcoholic Liver Disease?

Symmetric peripheral neuropathy Signup and view all the answers

Chronic alcohol use can result in which of the following cerebellar issues?

Cerebellar atrophy Signup and view all the answers

Which treatment is primarily recommended for managing liver diseases related to fatty liver?

Lifestyle modification Signup and view all the answers

What change can abrupt alcohol withdrawal induce due to neurotransmitter channel modifications?

Seizures Signup and view all the answers

What type of virus causes Hepatitis B?

DNA virus Signup and view all the answers

Which of the following hepatitis types has a vaccine available?

Hepatitis A Signup and view all the answers

Which Hepatitis virus primarily causes chronic infections?

Hepatitis C Signup and view all the answers

What is a key risk factor for Hepatitis C transmission?

Intravenous drug use Signup and view all the answers

How long can Hepatitis C remain active on surfaces?

1 week Signup and view all the answers

Which of the following statements about Hepatitis E is true?

It usually causes acute infections Signup and view all the answers

What is the main treatment strategy for Hepatitis C?

Direct Acting Antivirals Signup and view all the answers

Which of the following groups is at higher risk for Hepatitis B infection?

Healthcare workers Signup and view all the answers

Which laboratory finding is commonly associated with alcoholic liver disease?

Elevated GGT Signup and view all the answers

What is a clinical feature of Wernicke's encephalopathy?

Ophthalmoplegia with nystagmus Signup and view all the answers

Which of the following is NOT a component of the management for alcoholic liver disease?

Regular physical activity Signup and view all the answers

Which of these is a classic symptom of Korsakoff syndrome?

Confabulation Signup and view all the answers

What role does thiamine play in the brain?

Key role in cerebral metabolism Signup and view all the answers

Which of these findings would suggest thiamine deficiency?

Neuronal cell death in the mammillary bodies Signup and view all the answers

What is the purpose of thiamine supplementation in the context of alcohol withdrawal?

To prevent Wernicke's encephalopathy Signup and view all the answers

What is a common cause for thiamine deficiency among individuals with alcohol use disorder?

Impaired intestinal absorption Signup and view all the answers

What is the primary purpose of administering lactulose in cirrhotic patients?

To reduce ammonia absorption Signup and view all the answers

What is the recommended aim for hemoglobin levels during resuscitation in variceal hemorrhage?

7-9 g/dL Signup and view all the answers

Which medication is used as long-term prophylaxis against variceal hemorrhage?

Propranolol Signup and view all the answers

What is the main treatment modality for definitive management of liver cirrhosis?

Liver transplantation Signup and view all the answers

In the event of ruptured oesophageal varices, what is a primary pharmacological option for management?

Somatostatin Signup and view all the answers

What is the role of paracentesis in managing cirrhotic patients?

To drain ascitic fluid Signup and view all the answers

Which of the following is a key preventive measure for acute liver failure in cirrhotic patients?

Obesity management Signup and view all the answers

What is the aim of using a Sengstaken-Blakemore tube during variceal hemorrhage?

To apply manual pressure to bleeding vessels Signup and view all the answers

What is the primary goal of therapy for managing viral hepatitis?

To prevent disease progression to cirrhosis or HCC Signup and view all the answers

What is hereditary haemochromatosis primarily caused by?

Homozygous mutations in the HFE gene Signup and view all the answers

Which of the following symptoms is NOT associated with excess iron deposition in haemochromatosis?

Increased appetite Signup and view all the answers

What is a common diagnostic criterion for men or post-menopausal women for hereditary haemochromatosis?

Transferrin saturation >50% Signup and view all the answers

In which organ does excess iron primarily accumulate in patients with haemochromatosis that can lead to cardiomyopathy?

Heart Signup and view all the answers

Which condition could potentially mitigate the onset of symptoms in premenopausal women with haemochromatosis?

Menstrual loss of blood Signup and view all the answers

Which of the following HFE gene mutations is associated with the majority of hereditary haemochromatosis cases?

C282Y Signup and view all the answers

What percentage of people in Ireland are believed to be carriers of the hereditary haemochromatosis gene?

1 in 5 Signup and view all the answers

What is the most appropriate treatment for a patient with hepatic encephalopathy?

Lactulose Signup and view all the answers

What is the underlying issue that causes the confusion in patients with a history of chronic liver disease?

Elevated ammonia levels Signup and view all the answers

In a patient requiring lactulose for hepatic encephalopathy, what is the target number of bowel movements to aim for each day?

3-4 bowel movements Signup and view all the answers

Which of the following medications is an antibiotic used for spontaneous bacterial peritonitis in liver disease patients?

Cefotaxime Signup and view all the answers

What role does rifaximin have in the management of hepatic encephalopathy?

It reduces intestinal ammonia production. Signup and view all the answers

During the management of hepatic encephalopathy, which medication should be avoided due to its sedative effects?

Lorazepam Signup and view all the answers

Which treatment option has no role in ammonia reduction for a patient with hepatic encephalopathy?

Senna Signup and view all the answers

What is the likely consequence if ammonia levels are not addressed in a patient with hepatic encephalopathy?

Worsening confusion and lethargy Signup and view all the answers

What is a consequence of chronic liver disease if the underlying cause is not addressed?

Fibrosis and cirrhosis Signup and view all the answers

What role do hepatic stellate cells (HSC) play in the liver's response to injury?

They transform into fibroblasts and upregulate inflammatory receptors. Signup and view all the answers

Which of the following statements about fibrosis in chronic liver disease is true?

Initial stages of fibrosis can be reversible. Signup and view all the answers

What physiological change occurs in the liver during cirrhosis that contributes to portal hypertension?

Enhanced nitric oxide production and endothelin-1 activity Signup and view all the answers

In chronic liver disease, what is the primary consequence of HSC activation?

Accumulation of extracellular matrix and fibrosis Signup and view all the answers

What is the final architectural change in the liver associated with cirrhosis?

Formation of widespread nodules Signup and view all the answers

What is the role of sinusoidal endothelial cells (SECs) in portal hypertension?

Production of excess nitric oxide and endothelin-1 Signup and view all the answers

Which statement is true regarding the transition of fibrosis to cirrhosis?

The transition from reversible to irreversible fibrosis is not fully understood. Signup and view all the answers

What is the primary risk associated with iron overload in patients with hereditary haemochromatosis?

Cirrhosis and hepatocellular carcinoma (HCC) Signup and view all the answers

Which mechanism contributes to the delay in symptom onset of haemochromatosis in premenopausal women?

Menstrual blood loss Signup and view all the answers

How is hereditary haemochromatosis primarily inherited?

Autosomal recessive Signup and view all the answers

What is the consequence of C282Y homozygosity in individuals with hereditary haemochromatosis?

Heightened iron absorption Signup and view all the answers

What percentage of hereditary haemochromatosis cases in Ireland is attributed to C282Y mutations?

85% Signup and view all the answers

Which of the following symptoms is directly associated with excess iron deposition in haemochromatosis?

Erectile dysfunction Signup and view all the answers

What laboratory findings are typical in diagnosing hereditary haemochromatosis in post-menopausal women?

Transferrin saturation >50%, ferritin >300 µg/L Signup and view all the answers

What is the primary goal in managing hepatitis B infections?

Preventing disease progression to cirrhosis or liver cancer Signup and view all the answers

What is the primary difference between Hepatitis B and Hepatitis C in terms of chronicity?

Hepatitis C primarily causes chronic infections Signup and view all the answers

Which hepatitis virus is known to have a vaccine available?

Hepatitis A and B Signup and view all the answers

Which of the following statements regarding Hepatitis C is false?

It always leads to cirrhosis Signup and view all the answers

In which scenario is Hepatitis E most commonly asymptomatic?

In immunocompetent individuals Signup and view all the answers

What characteristic of Hepatitis C contributes to its high infection rate?

It remains stable on surfaces for long durations Signup and view all the answers

Which mode of transmission is specific to Hepatitis B that is not typically associated with Hepatitis C?

Vertical transmission Signup and view all the answers

What is a key distinguishing feature of Hepatitis D in relation to Hepatitis B?

Hepatitis D can only exist in the presence of Hepatitis B Signup and view all the answers

Which treatment is specifically associated with a high cure rate for Hepatitis C?

Direct Acting Antivirals Signup and view all the answers

What is a primary cause of weight gain in patients with chronic liver disease?

Fluid retention and third spacing Signup and view all the answers

Which symptom indicates a possible cause of chronic inflammation when present in patients with ALD?

Fatigue and weakness from malnutrition Signup and view all the answers

Which cause is directly linked to the symptom of pruritis in liver disease?

Excess bilirubin deposited in skin Signup and view all the answers

What condition might cause ascites in patients with portal hypertension?

Activation of the RAA system Signup and view all the answers

Which symptom is linked to hepatic encephalopathy in liver disease?

Reduced GCS/Asterixis from ammonia accumulation Signup and view all the answers

Which sign indicates reduced production of clotting factors in chronic liver disease?

Bruising and petechiae from consumptive thrombocytopenia Signup and view all the answers

What complication can arise from an upper GI bleed in patients with portal hypertension?

Oesophageal varices leading to haematemesis Signup and view all the answers

Which mechanism contributes to nausea and vomiting in patients with chronic liver disease?

Poor gastric emptying due to ascites Signup and view all the answers

Study Notes

Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is the leading cause of chronic liver disease in Ireland and the Western world.
NAFLD is a diagnosis of exclusion:
- Ultrasound shows fatty liver.
- No history of excessive alcohol consumption.
- Features of metabolic syndrome are present.
- All other potential causes of liver disease must be ruled out.
Treatment for NAFLD: lifestyle modification, including diet, exercise, and weight management.

Alcoholic Liver Disease

Major Public Health Issue in Ireland and Worldwide.
Impact of Alcohol on the Liver
- Ethanol is metabolized by alcohol dehydrogenase (ADH) in hepatocytes.
- ADH-catalyzed ethanol oxidation uses NAD+ as a cofactor and generates reduced NADH and acetaldehyde, which is highly reactive and toxic.
Clinical features of Alcoholic Liver Disease:
- Features of chronic liver disease.
- Extrahepatic manifestations, including:
  - Nervous system:
    - Symmetric peripheral neuropathy.
    - Thiamine deficiency complications: Wernicke's encephalopathy, Korsakoff's psychosis.
  - Pancreatitis.
  - Cardiomyopathy.
Diagnosis of Alcoholic Liver Disease:
- Documentation of regular alcohol consumption.
- Clinical or biochemical features suggestive of liver injury.
- Liver function tests (LFT) pattern:
  - AST: ALT ratio >1.5
  - Elevated GGT.
- Exclusion of alternative causes of liver disease.
- Liver biopsy: histology shows steatosis, hepatocellular injury, fibrosis or cirrhosis.
Management of Alcoholic Liver Disease:
- Alcohol cessation and avoidance of risks (alcohol withdrawal seizures, Wernicke's, Korsakoff's).
- Addiction support.
- Screening for and management of cirrhosis complications (variceal bleeding, ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, hepatocellular carcinoma (HCC)).
- Nutritional support.
- Avoidance of other causes of liver injury.

Alcoholic Withdrawal

Thiamine (vitamin B1) plays a key role in cerebral metabolism.
Thiamine Deficiency can cause neuronal cell death, classically seen in the mammillary bodies.
Thiamine Deficiency is associated with alcohol use disorder, poor dietary intake, impaired intestinal absorption, and reduced hepatic stores.
Wernicke-Korsakoff Syndrome is a disease spectrum.
- Wernicke's encephalopathy is the acute, life-threatening neurological condition caused by thiamine deficiency, characterized by the triad of ophthalmoplegia with nystagmus, ataxia, and confusion.
- Korsakoff psychosis is the neuropsychiatric disorder associated with memory disturbances, confabulation, and emotional disturbances.
Management: Thiamine supplementation: intravenous pabrinex (vitamin B and C), switching to oral thiamine tablets for long-term management.

Viral Hepatitis

Hepatitis A (HAV): RNA virus.
Hepatitis B (HBV): DNA virus.
Hepatitis C (HCV): RNA virus.
Hepatitis E (HEV): RNA virus.
Incubation Period (days):
- HAV: 15-50.
- HBV: 50-180.
- HCV: 14-84.
- HEV: 15-60.
Acute vs. Chronic Liver Disease:
- HAV: Acute.
- HBV: Acute, chronic.
- HCV: Chronic.
- HEV: Acute, rarely chronic in immunocompromised individuals.
Can Cause Cirrhosis and Primary Hepatocellular Carcinoma:
- HAV: No.
- HBV: Yes.
- HCV: Yes.
- HEV: No.
Vaccine Available:
- HAV: Yes.
- HBV: Yes.
- HCV: No.
- HEV: No.

Hepatitis C

Risk factors: IV drug users, multiple sexual partners, unprotected sex, tattoos, blood transfusions, hemodialysis, vertical transmission (mother to baby), travel to endemic areas, health care workers.
Curable: Yes, with direct-acting antivirals (DAAs).
- 99% chance of cure with an 8-week course of DAA tablets.

Hepatitis B

Modes of transmission: Similar to HCV.
Highly infectious.
Environmentally stable: Can remain active on surfaces for up to a week.
Preventable: Yes, vaccination exists.
Curable: No, managed by viral suppression with nucleoside analogues (e.g., entecavir, lamivudine).
Goals of therapy:
- Prevent disease progression to cirrhosis or HCC.
- Prevent mother-to-child transmission.
- Prevent reactivation.
- Prevent HBV-associated extrahepatic manifestations.

Haemochromatosis

'Bronzed Diabetes': Named in the 1800s, referring to the skin pigmentation due to iron overload.
Excess iron absorption via the intestines leads to total body iron overload.
Iron accumulation in multiple organs, including:
- Liver (cirrhosis and HCC).
- Heart (cardiomyopathy).
- Pancreas (diabetes).
- Pituitary (pituitary hypogonadism).
- Skeletal (arthralgias/arthritis/osteoporosis).
Chronic picture: Manifests years later after significant iron deposition.
Onset in premenopausal women can be delayed by menstrual blood loss.
Symptoms:
- Cirrhosis.
- Diabetes.
- Arthralgias/arthritis/osteoporosis.
- Fatigue.
- Erectile dysfunction/loss of libido/amenorrhea.
- ECG abnormalities.
- Bronze skin hyperpigmentation (epidermal iron deposition).
Ireland has the highest prevalence of hereditary haemochromatosis in the world.
1 in 5 people in Ireland are gene carriers.
Hereditary haemochromatosis is an autosomal recessive condition caused by homozygous mutations in the HFE gene on chromosome 6:
- C282Y (Cysteine to Tyrosine at the 282nd amino acid).
- H63D (Histidine to Aspartic Acid at the 63rd amino acid).
85% of HH is due to C282Y homozygosity.
Diagnosis:
- Iron studies:
  - Premenopausal women: transferrin saturation >45%, ferritin >200 µg/L.
  - Men/postmenopausal women: transferrin saturation >50%, ferritin >300 µg/L.
- Model for End-Stage Liver Disease (MELD) score is an excellent predictor of 3-month mortality among cirrhotic patients listed for liver transplantation.
King's College Criteria: Used to diagnose acute liver failure.

Management of Liver Disease

Prevention:
- Alcohol cessation.
- Avoid hepatotoxic medications e.g., paracetamol/NSAIDs.
- Weight loss and diet management.
- Optimize diabetes management for hepatic steatosis.
- Hepatitis A and B vaccination.
Pharmacological:
- Beta blockers for varices.
- Lactulose for encephalopathy (increases bacterial uptake of ammonia).
- Rifaxamin for encephalopathy.
- Diuretics and low salt diet for ascites and edema management.
Procedures:
- Paracentesis to drain ascitic fluid.
- Oesophagogastroduodenoscopy (OGD) banding of varices.
- Transjugular intrahepatic portosystemic shunt (TIPS).
Surgical:
- Liver transplant - definitive management.
Palliative care: Can be involved early for symptom optimization and advanced care planning.

Medical Emergency: Variceal Haemorrhage

Rupture of oesophageal varices.
Mortality: Overall mortality with each episode of variceal haemorrhage remains around 15% to 25% at six weeks.
Management:
- Resuscitation: ABC; intravenous crystalloid fluids, blood transfusion aiming for Hb 7-9 g/dL.
- Pharmacological:
  - Somatostatin.
  - Terlipressin.
  - Antibiotic prophylaxis (Ceftriaxone).
- Source Control:
  - Endoscopy.
  - Band ligation.
  - Sengstaken-Blakemore tube - balloon tamponade, inserted into the oesophagus and inflated to apply manual pressure to the bleeding vessel. Indicated only in rare cases of very unstable, uncontrolled bleeding.
- Long-term prophylaxis: Non-cardioselective beta blockers (propranolol).

Chronic Liver Disease

A continuous process of inflammation, destruction, and regeneration of liver parenchyma
Can lead to fibrosis and cirrhosis if underlying cause not addressed
Fibrosis is deposition of extracellular matrix (ECM) in response to chronic liver injury
Fibrosis can be reversible in the initial stage
The transition point to irreversible fibrosis is not fully understood
Cirrhosis is the final stage of chronic liver disease resulting in disruption of liver architecture, widespread nodules, vascular reorganization, neo-angiogenesis, and ECM deposition

Pathophysiology

Injury pathway initiated by hepatic stellate cells (HSC)
HSC are usually dormant cells found in the space between sinusoids and hepatocytes
Quiescent HSC play a role in Vitamin A metabolism
In response to liver injury, HSCs are activated and transform into fibroblasts
Activated HSC upregulate the expression of inflammatory receptors
This pro-inflammatory phase makes liver cells responsive to inflammatory cytokines
Progressive activation of more HSC cells results in ECM accumulation and fibrosis

Portal Hypertension

Liver receives 25% of the cardiac output (800-1200mls/min)
Hepatic sinusoids are specialized capillaries that receive this blood volume
In cirrhosis, sinusoidal endothelial cells (SECs) produce excess nitric oxide (NO) and endothelin-1 (ET-1), leading to blood vessel constriction and high pressure within the liver vascular bed
This is termed portal hypertension

Symptoms & Causes

Fatigue and weakness: Catabolic state, malnutrition, poor diet of ALD
Nausea and vomiting: Poor gastric emptying, increased acid production, ascites causing mechanical nausea
Pruritis: Excess bilirubin deposited in skin
Jaundice: Circulating unconjugated bilirubin
Bleeding: Reduced clotting factors produced, platelets consumed due to splenomegaly
Weight gain: Fluid retention and third spacing due to a hyperdynamic state, reduced albumin production
Confusion: Encephalopathy due to reduced ammonia excretion, B12 deficiency due to alcohol (Wernicke's)
Fever/Abdominal pain: Subacute bacterial peritonitis due to ascites
Upper GI Bleed (Haematemesis, Malaena): Oesophageal varices due to portal hypertension

Signs & Causes

Reduced GCS/Asterixis: Hepatic encephalopathy due to reduced excretion of ammonia
Jaundice: Hepatocyte damage reducing conjugation of bilirubin
Bruising/Petechiae: Reduced clotting factor synthesis, consumptive thrombocytopaenia
Ascites: Due to RAA system activation, salt and fluid retention, splanchnic arterial dilation, portal hypertension, reduced oncotic pressure due to reduced albumin synthesis
Splenomegaly/Caput medusae: Portal hypertension
Peripheral oedema: Reduced albumin production
Pallor: Anaemia of chronic disease, B12 deficiency, iron deficiency

Causes of Chronic Liver Disease

Overlapping causes are common
Viral Hepatitis: HAV, HBV, HCV, HEV
- HAV: RNA virus, incubation 15-50 days, acute liver disease, no cirrhosis, vaccine available
- HBV: DNA virus, incubation 50-180 days, acute and chronic liver disease, can cause cirrhosis and HCC, vaccine available
- HCV: RNA virus, incubation 14-84 days, usually chronic liver disease, can cause cirrhosis and HCC, curable, no vaccine available
- HEV: RNA virus, incubation 15-60 days, acute liver disease, rarely chronic (immunocompromised), no cirrhosis, no vaccine available

Hepatitis C

Risk Factors: IV drug injectors, sexually transmitted (multiple partners/unprotected sex), tattoos, blood transfusion, haemodialysis, vertical transmission, travel to endemic areas (Egypt), healthcare workers
ssRNA virus
80-90% of infections become chronic
Risk of cirrhosis and HCC
Curable with direct acting antivirals (DAAs) - 99% chance of cure with an 8-week course

Hepatitis B

Modes of transmission similar to HCV
Highly infectious
Very environmentally stable (up to one week on surfaces)
Preventable with vaccination
Curable: No, managed by viral suppression with nucleoside analogues (e.g., Entecavir, Lamivudine)
Goals of therapy: prevent disease progression, prevent mother-to-child transmission, prevent reactivation, prevent HBV-associated extra-hepatic manifestations

Haemochromatosis ('Bronzed Diabetes')

Excess iron absorbed via the intestine leads to total-body iron overload
Iron accumulates in multiple organs: liver (cirrhosis, HCC), heart (cardiomyopathy), pancreas (diabetes), pituitary (pituitary hypogonadism), skeleton (arthralgias, arthritis, osteoporosis)
Chronic picture manifests years later after significant iron deposition
Onset in premenopausal women can be delayed by menstrual blood loss
Symptoms: cirrhosis, diabetes, arthralgias/arthritis/osteoporosis, fatigue, erectile dysfunction, loss of libido, amenorrhoea, ECG abnormalities, bronze skin hyperpigmentation (epidermal iron deposition)
Ireland has the highest prevalence of hereditary haemochromatosis (HH) in the world
1/5 people in Ireland are gene carriers
Hereditary Haemochromatosis is an autosomal recessive condition due to homozygous mutations in the HFE gene on chromosome 6
- C282Y (Cysteine to Tyrosine at 282nd amino acid)
- H63D (Histidine to Aspartic Acid at amino acid 63)
85% of HH due to C282Y homozygosity

Diagnosis of Haemochromatosis

Iron Studies:
- Pre-menopausal women: Transferrin saturation >45%, ferritin >200 µg/L
- Men/post-menopausal women: Transferrin saturation >50%, ferritin >300 µg/L
Physical examination: Asterixis, distended abdomen with shifting dullness, caput medusae

Case Presentation: Management of Hepatic Encephalopathy

A 65-year-old male presents with acute confusion and behavioural disturbance.
Past medical history includes chronic liver disease.
Physical examination reveals asterixis, distended abdomen with shifting dullness, caput medusae.
Appropriate treatment: Lactulose
- Lactulose lowers ammonia levels
- Indicated for treatment of hepatic encephalopathy
- Aim for 3 bowel motions per day
- Rifaxamin (not rifampicin) is also indicated in addition to lactulose
- Senna is a stimulant laxative with no role in ammonia reduction
- Lorazepam sedation will not address the underlying cause
- Cefotaxime is an antibiotic used for spontaneous bacterial peritonitis

Case Presentation: Management of Autoimmune Hepatitis

A 55-year-old female is referred for jaundice and hepatocellular derangement of liver function tests.
Non-drinker, no metabolic risk factors, normal ferritin.
AMA and SMA antibodies are positive.
Hepatology team prescribes a prolonged tapering course of prednisolone.
Most appropriate information to discuss: Bone protection should be considered with prolonged steroid use
- Prolonged steroid use can increase the risk of osteoporosis
- Gastric protection is not required with prednisolone
- Hypotension is not a primary risk of steroid therapy
- Steroids can increase the risk of diabetes

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Description

This quiz explores two crucial liver diseases: Non-Alcoholic Fatty Liver Disease (NAFLD) and Alcoholic Liver Disease. It covers the causes, diagnostic methods, and treatment options for NAFLD, alongside the impact of alcohol on liver health. Test your knowledge on these significant public health issues.