Ischemic hepatitis, hepatic infarction, and ischemic ...



Ischemic hepatitis

INTRODUCTION

• The liver's complex vascular supply and high metabolic activity make it particularly vulnerable to circulatory disturbances.

• The severity and characteristics of hepatic injury depend upon the blood vessels that are involved and the degree to which injury is related to passive congestion or diminished perfusion.

• There are several well-recognized forms of vascular injury to the liver including:

o Budd-Chiari syndrome.

o Hepatic veno-occlusive disease.

o Passive congestion due to heart failure.

o Hepatic infarction.

o Ischemic hepatitis.

ISCHEMIC HEPATITIS (SHOCK LIVER, HYPOXIC HEPATITIS)

• Definition: refers to diffuse hepatic injury resulting from acute hypoperfusion.

• The syndrome is characterized by three criteria:

o Clinical setting of circulatory failure.

o Sharp but transient increase in either ALT or AST to levels greater than 20x upper limit of normal.

o Exclusion of all other causes of acute hepatitis especially drug and viral induced causes.

Etiology

• Ischaemic hepatitis is a consequence of reduced blood flow into the liver due to acute hypotension caused by low cardiac output or shock of various aetiology.

|Congestive, backward heart failure |

|Forward heart failure (myocardial infarction, arrhythmia) |

|Shock of diverse etiology |

|Chronic respiratory insufficiency |

|Thromboembolism |

|Hematological diseases (Sickle cell syndrome) |

|Dissecting aortic aneurysm |

|Postoperative conditions in thoracic and abdominal surgery |

|Occlusion of hepatic artery |

PATHOGENESIS:

• Hepatic ischemia develops when there is an imbalance between hepatic oxygen supply and demand.

Regulation of blood flow

• Hepatic oxygen delivery is related to:

o Oxygen content of blood perfusing the liver.

o Total hepatic blood flow.

• Once oxygen delivery is decreased( compensatory mechanisms ( increased oxygen extraction by hepatocytes.

• Autoregulation of blood flow

• Blood flow is regulated primarily by the activity of smooth muscle cells that surround hepatic arterioles ( constant total hepatic blood flow.

• When portal flow declines( smooth muscle cells around hepatic arterioles relax ( increased arteriolar flow.

Blood flow under systemic stress

• Under situations of systemic stress ( redistribution of blood flow to more vital organs( compensatory decrease in peripheral and splanchnic blood flow.

• The resulting decrease in hepatic blood flow ( exceeds capacity of the liver to increase oxygen extraction ( hepatocellular hypoxia.

Reperfusion injury

• Mediated by generation of reactive oxygen species once ischemic hepatocytes are reexposed to oxygen ( cell injury via lipid peroxidation.

• Kupffer cells react to ischemia by producing cytokines, including TNF-alpha ( triggers the recruitment and activation of PNLs.

Cellular mechanisms of ischemic injury

• Disruption of mitochondrial respiration (

o Depletion of adenosine triphosphate.

o Rise in cytosolic calcium (and possibly sodium) levels.

o Activation of cellular proteases.

Clinical settings that increase the risk of ischemic injury

• Patients who have preexisting liver disease and portal hypertension

o Total hepatic blood flow may already be reduced due to blood shunting through collateral circulation.

• Patients who have preexisting passive congestion of the liver

o Elevated central venous pressure ( leads to atrophy of hepatocytes ( fibrosis( impairs diffusion of nutrients to hepatocytes.

• Sickle cell anemia

o Focal interruption of the hepatic blood supply in occlusive crisis.

• Preexisting portal vein thrombosis

Clinical manifestations:

Type of patient

• Shocked or hemodynamically unstable admitted to the ICU with:

o Myocardial infarction.

o Heart failure.

o Accident.

o Acute respiratory failure.

o Sepsis.

o Severe bleeding.

o Postoperative complication.

History

• The patient may have history of coronary heart disease, valvular disease, sickle cell anemia, liver cirrhosis or portal hypertension, chronic obstructive pulmonary disease.

Presentation

• The patient is shocked with hypotension, pallor, tachycardia and arrhythmia.

• The patient may have cyanosis, tachypnea, acidosis.

• Fever, sweating, bleeding from body orifices or wound sepsis.

• Right upper quadrant tenderness.

• Physical examination may provide clues toward underlying liver disease.

• Rare patients have symptoms suggesting acute hepatitis, including nausea, vomiting, anorexia, malaise, and right upper quadrant pain.

• Occasional patients develop changes in mental status, which generally reflect impaired cerebral perfusion rather than hepatic encephalopathy.

• Hepatopulmonary syndrome develops in nearly one-half of patients but appears to be reversible following normalization of hepatic function.

Investigations:

• Picture of the cause

|Elevated cardiac enzymes |Leukocytosis |Disturbed blood gases |

|Anemia |Elevated serum urea & creatinine |DIC |

|Elevated ESR |Hypoglycemia |Electrolyte disturbances |

• Ischemic hepatitis is usually first detected because of elevations in liver biochemical tests following a hypotensive episode.

• The typical pattern of liver biochemical tests consists of:

o A rapid rise in serum aminotransferase levels.

o Peak 25 to 250x upper limit of normal reached within 1- 3 days.

o Decline steadily returning to normal within 7 to 10 days with stabilization.

o Early massive rise in LDH levels.

o Serum bilirubin level 4x upper limit of normal, usually beginning its rise after aminotransferase levels have begun to decline.

o Serum ALP levels are rarely higher than twice the upper limit of normal.

o Hepatic synthetic function usually remains normal or is only mildly impaired.

• Reasonable evaluation might include:

o Serologic testing for acute viral hepatitis.

o Blood acetaminophen level.

o Right upper quadrant ultrasound with Doppler studies of the portal and hepatic veins and hepatic artery.

o Evaluation for suspected underlying causes of ischemic injury such as cardiac or respiratory failure.

Differential diagnosis

• Ischemia should always be considered in the differential diagnosis of

|Acute viral hepatitis |Spontaneous reactivation of |Superimposition of HDV in a |Drugs & toxins (acetaminophen or herbal |

| |chronic HBV. |chronic carrier of HBV |medications) |

|Acute fatty liver of pregnancy |Metabolic disorders |Hepatic veno-occlusive disease |HELLP syndrome |

|Acute Budd-Chiari syndrome (especially those with concomitant |Acute exacerbation of autoimmune |Hepatic infarction |

|portal vein thrombosis). |hepatitis | |

• Features that suggest an ischemic rather than other causes:

o Early rapid rise in the serum LDH level is unusual in viral hepatitis.

o Ratio of serum ALT to LDH of less than 1.5 early in the course of acute hepatitis may be more likely to suggest ischemic hepatitis.

o Rapid fall in serum aminotransferase levels after the initial rise is characteristic of ischemic liver injury and atypical for other causes of hepatitis.

o End-organ hypoperfusion, especially acute tubular necrosis of the kidney.

o Concomitant, early rise in the serum creatinine.

Pathology:

• The histologic hallmark ( necrosis of hepatocytes in zone 3 of the hepatic acinus with few inflammatory cells.

• In patients with chronic or recurrent heart failure ( sinusoidal engorgement and collagen accumulates in zone 3.

• Hepatic architecture may return to normal after recovery from the ischemic event.

Management: (3As)

• There is no specific therapy for ischemic hepatitis.

• Aim: Restoring cardiac output and reversing the underlying cause of hemodynamic instability.

• Avoid aggressive diuresis since it may worsen hepatic perfusion.

• Augmentation of cardiac output enhances hepatic perfusion by Dopamine, at either "renal" or "cardiac" doses.

• Supportive ventilation may be needed.

• Correction of anemia, electrolyte and acid-base abnormalities.

• IV broad spectrum antibiotics to correct infection.

• Patients should be monitored closely for evidence of end-organ hypoperfusion, particularly decreased renal function and altered mental status.

Prognosis

• The severity of the liver injury correlates with the duration and extent of the hemodynamic compromise.

• A continually rising bilirubin and progressive prolongation of the prothrombin time are poor prognostic signs.

• Rare patients develop fulminant hepatic failure.

• Mortality rates may reach 60 to 100 %.

HEPATIC INFARCTION

• Definition: focal ischemic injury of the liver.

• It is rare because the liver has a dual blood supply.

• Causes of hepatic infarction:

|Liver transplantation |Tumor embolism |Thrombosis of the h. a. due to atherosclerosis |

|Hypercoagulable state |Infective endocarditis |therapeutic embolization or chemoembolization |

|Iatrogenic ligation of the hepatic artery after laparoscopic cholecystectomy |

|Toxemia of pregnancy |Sickle cell anemia |Following radiofrequency ablation of HCC |

|Polyarteritis nodosa |cocaine intoxication |Hepatic artery aneurysms |

Clinical manifestations:

• Precipitating cause is evident before hepatic infarction develops.

• Asymptomatic hepatic infarction detected only on an imaging study.

• Fever, epigastric or right upper quadrant pain, back or right shoulder pain, jaundice, nausea, and vomiting.

• The aminotransferases rise transiently, sometimes to massive levels.

Diagnosis:

• Suggested radiographically in patients with a compatible clinical history.

• Abdominal CT scan with IV contrast( focal, wedge-shaped lesion of low attenuation, which may extend to the capsular surface of the liver.

o Gas in the lesion is highly suggestive of infection.

o Splenic and renal infarcts suggest an embolic source of the liver findings.

o No displacement hepatic blood vessels.

• Ultrasound or CT-guided needle aspiration establishes a definitive diagnosis.

• Magnetic resonance angiography or celiac arteriography in HA occlusion.

• Doppler ultrasound should be performed to assess the patency of the hepatic artery.

Pathology:

• Complete coagulative necrosis involving all three zones of the hepatic acinus.

Management:

• No specific therapy.

• Identify and treat the cause (e.g. emboli, infective endocarditis).

• In the absence of such a source, hypercoagulable states, including proteins C and S or antithrombin III deficiency, factor V Leiden mutation, lupus anticoagulant, paroxysmal nocturnal hemoglobinuria, polycythemia Vera, and possibly oral contraceptive use should be considered.

• Serial CT scans may show resolution of the infarct over weeks, residual scarring, or atrophy of the involved lobe of liver.

• In some patients, anticoagulation is indicated to prevent further systemic emboli or thrombosis.

• Patients who develop hepatic infarction after liver transplantation often require urgent retransplantation.

ISCHEMIC CHOLANGIOPATHY

• Involves principally the large intra- and extrahepatic bile ducts.

|Following liver transplantation |Vascular injury during biliary tract surgery |

|Hypercoagulable states |Arterial infusion of the chemotherapeutic agent |

|Chemoembolization and radiation therapy |

Clinical manifestations:

• Biliary obstruction, such as pruritus, dark urine, clay-colored stools, and jaundice.

• Elevations of serum bilirubin and alkaline phosphatase and variable elevations in serum aminotransferase levels.

• Ascending cholangitis or cholangitic liver abscesses, with associated fever.

Diagnosis

• ERCP or PTC or MRCP although it does not permit therapeutic intervention or biopsies.

• Cholangiographic findings consist of multiple intra- and extrahepatic strictures with diffuse irregularity or beading of the ducts, (usually affecting the large perihilar bile ducts).

• In liver transplantation ( Doppler ultrasound +/- arteriography to rule out HA thrombosis

Pathology: Liver biopsy is rarely useful and misleading ( biliary obstruction.

Management:

• ERCP with dilation and stenting is effective for treatment of biliary strictures.

• Ischemic cholangiopathy occurring within the first month after liver transplantation frequently requires urgent retransplantation.

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