II-4. Liver dysfunction (2)

肝機能障害（2）

Liver Failure — Characteristics

Most severe consequence of liver damage; develops when 80–90% of parenchyma is lost. Lethal; only cure = transplantation.
Acute: sudden loss of parenchyma. Chronic (more common): long-term harmful exposure.

Symptoms of Liver Failure

1. Portal Hypertension

Portal–hepatic vein pressure difference >10–12 mmHg (mainly chronic).
Causes: pre-hepatic (portal vein thrombosis), post-hepatic (venous obstruction), hepatic/cirrhosis (↑portal resistance — most common).
Mechanism: ↑vasoconstrictors (ANGII), ↓vasodilators (NO) + splanchnic stress/structural changes.
Symptoms: ascites (>500 ml; ↑hydrostatic + ↓oncotic pressure from ↓albumin), porto-caval shunts (deep porto-caval or superficial caput medusae → life-threatening bleeds), splenomegaly/hypersplenism.

2. Icterus (Jaundice)

Yellow skin/sclera from ↑bilirubin. Sub-icterus 1.2–2 mg/dL; icterus >2–2.5 mg/dL.
↑Unconjugated: overproduction (hemolysis, ineffective erythropoiesis), ↓uptake/conjugation.
↑Conjugated: ↓secretion into canaliculus, bile duct obstruction.
Direct hyperbilirubinemia = conjugated ≥40%; indirect = conjugated <20%.

3. Coagulopathy

↓Coagulation factor synthesis → bleeding (intracranial hemorrhage); DIC possible.

4. Hepatic Encephalopathy

Neuro symptoms (confusion → coma); hepatic coma most severe. Cause = accumulation of non-eliminated substances (NH₃).

5. Hepatorenal Syndrome

Kidney failure with chronic liver failure (no other cause); ↓urine, ↓Na⁺/H₂O excretion, ↓GFR.

6. Endocrine Dysfunction

Impaired estrogen metabolism (males) → ↑estrogen → palmar erythema, spider nevi, hypogonadism, gynecomastia.

Acute Liver Failure

Causes: drug overdose (paracetamol), mushroom (Amanita phalloides), less often HAV/HBV.
Rapid (days): nausea, vomiting, severe icterus, encephalopathy, coagulopathy. ↓Liver volume; massive necrosis. May be lethal → transplantation.

Chronic Liver Failure

Causes (developed countries): chronic HBV/HCV, NAFLD, chronic alcoholism. Often asymptomatic early; advanced → portal hypertension, HCC, varix bleeding, sepsis, MOF.
Cirrhosis: loss of structure, ECM/fibrotic bundles (porto-portal/central), pseudo-lobules, angiogenesis. Classification: Child-Pugh (compensated / partial / decompensated).

NAFLD

Fatty liver (≥5% hepatocytes with TAG) with little/no alcohol; most common chronic liver damage (20–30% in developed countries). Benign, non-progressive. Linked to obesity, metabolic syndrome, diabetes.
Mechanism: lipid/carb-rich diet + inactivity + genetics → hyperlipidemia → fat to liver + FFA → oxidative stress → cell damage (insulin resistance contributes).
NASH (20–30%): can progress to cirrhosis, liver failure, HCC; Dx ↑transaminases + biopsy.

Metabolic Liver Diseases

Hemochromatosis: uncontrolled iron absorption/accumulation → cirrhosis, diabetes, arthropathy, cardiac fibrosis, hypogonadism, skin pigmentation. Inherited (↓hepcidin, age 40–50) or acquired (transfusions, ineffective erythropoiesis/β-thalassemia). Free iron = cytotoxic → oxidative stress → stellate cell activation/fibrosis.
α1-antitrypsin deficiency: AR; ↓α1-AT (serine protease inhibitor) → dysfunctional protein accumulation → pulmonary emphysema + liver (hepatitis, fibrosis, cirrhosis, HCC). Variants PiMM (wild), PiZZ (mutant).
Wilson’s disease: AR, ATP7B mutation (copper transport) → acute/chronic hepatitis, steatosis, liver failure; neurological symptoms, Kayser-Fleischer ring.

一問一答

▶How is portal hypertension defined?

A portal–hepatic vein pressure difference >10–12 mmHg, mainly in chronic disease.

▶What is the most common cause of portal hypertension?

Hepatic/cirrhotic causes that increase portal resistance.

▶What are porto-caval shunts and why are they dangerous?

Deep porto-caval or superficial caput medusae collaterals that can cause life-threatening bleeds.

▶At what degree of parenchymal loss does liver failure develop, and what is the only cure?

When 80–90% of parenchyma is lost; the only cure is liver transplantation.

▶How does ascites form in portal hypertension?

Increased hydrostatic pressure plus decreased oncotic pressure (from low albumin) causes fluid accumulation (>500 ml).

▶Distinguish unconjugated from conjugated hyperbilirubinemia by causes.

Unconjugated rises from overproduction (hemolysis, ineffective erythropoiesis) or reduced uptake/conjugation; conjugated rises from reduced canalicular secretion or bile duct obstruction.

▶Why does coagulopathy occur in liver failure?

Decreased synthesis of coagulation factors causes bleeding (e.g., intracranial hemorrhage); DIC is possible.

▶What are the bilirubin thresholds for sub-icterus and icterus?

Sub-icterus 1.2–2 mg/dL; icterus >2–2.5 mg/dL.

▶What causes hepatic encephalopathy?

Accumulation of non-eliminated substances (notably ammonia, NH₃), producing neuro symptoms from confusion to coma.

▶What is hepatorenal syndrome?

Kidney failure occurring with chronic liver failure (no other cause), with reduced urine, Na⁺/H₂O excretion, and GFR.

▶What endocrine signs appear in male liver failure and why?

Impaired estrogen metabolism raises estrogen, causing palmar erythema, spider nevi, hypogonadism, and gynecomastia.

▶What are the main causes of acute liver failure?

Drug overdose (paracetamol), mushroom poisoning (Amanita phalloides), and less often HAV/HBV.

▶What are the developed-world causes of chronic liver failure?

Chronic HBV/HCV, NAFLD, and chronic alcoholism.

▶What are the histological hallmarks of cirrhosis, and what scoring system classifies it?

Loss of structure, ECM/fibrotic bundles, pseudo-lobules, and angiogenesis; classified by Child-Pugh (compensated/partial/decompensated).

▶What is NAFLD and how common is it?

Fatty liver (≥5% hepatocytes with TAG) with little/no alcohol; the most common chronic liver damage (20–30% in developed countries), generally benign.

▶What is NASH and why does it matter?

Non-alcoholic steatohepatitis (20–30% of NAFLD) that can progress to cirrhosis, liver failure, and HCC; diagnosed by raised transaminases plus biopsy.

▶What characterizes hemochromatosis and how does iron damage the liver?

Uncontrolled iron absorption/accumulation causing cirrhosis, diabetes, arthropathy, cardiac fibrosis, hypogonadism, and skin pigmentation; free iron is cytotoxic, causing oxidative stress and stellate cell activation/fibrosis.

▶How does α1-antitrypsin deficiency affect lungs and liver?

AR deficiency of α1-AT (a serine protease inhibitor) causes dysfunctional protein accumulation, leading to pulmonary emphysema and liver disease (hepatitis, fibrosis, cirrhosis, HCC); variants PiMM (wild) and PiZZ (mutant).

▶What is Wilson's disease?

AR ATP7B mutation (copper transport) causing acute/chronic hepatitis, steatosis, and liver failure, plus neurological symptoms and Kayser-Fleischer rings.

▶Define direct versus indirect hyperbilirubinemia by conjugated fraction.

Direct (conjugated) ≥ 40% conjugated; indirect (unconjugated) < 20% conjugated.