Ischemic Hepatitis: Unforeseen Challenge Following Postpartum Hemorrhage

Introduction

Gibson and Dudley first published an article on ischemic hepatitis in 1824. ¹ Ischemic hepatitis is a consequence of liver hypoperfusion caused by acute heart failure, shock of different etiologies, and/or passive organ congestion. ² Acute systemic hypotension lasting >24 hours with systolic pressure <80 mm Hg initiates hepatocellular damage. ³ The basic morphologic change is a massive centrilobular necrosis caused by hepatic hypoxia, free oxygen radical damage, and preservation of the periportal zone.

The clinical features of ischemic hepatitis resemble acute viral or toxic hepatitis with serum transaminases rising up to 100 times normal, and similar increase in lactic dehydrogenase (LDH) is striking as well, but alkaline phosphatase remains normal. This condition is reversible if liver hypoperfusion is restored within 72 hours, but longer duration leads to more severe liver damage and worse prognosis.

Case

A 22-year-old primipara presented to the labor room after a normal delivery, with excessive bleeding. She had delivered an average-sized newborn at the first referral unit, followed by excessive bleeding. On examination, her pulse was 160 beats/minute and her systolic blood pressure was 70 mm Hg. On abdominal examination, her abdomen was soft and her uterus was flabby. She was bleeding profusely. Oxytoxic agents were given along with bimanual compression of uterus and abdominal aortic compression. but the patient continued bleeding. Informed consent for laparotomy was given. Modified B-lynch sutures were applied in addition to uterine artery and ovarian artery ligation. The patient was shifted to the intensive care unit for stabilization. On the 2nd postoperative day, she started complaining of pain in her abdomen localized to the epigastrium and right hypochondrium. Detailed evaluation revealed abnormal liver function tests (aspartate transaminase [AST] and lactate dehydrogenase [LDH]>25 upper limit of normal [ULN], alanine transaminase [ALT]>10 ULN with ALT/LDH ratio of 0.05). However, serum bilirubin and alkaline phosphatase were normal. Sonography of the abdomen, viral and autoimmune markers, hemolytic profile, serum copper, and ceruloplasmin levels were within normal limits. There was no past history of pre-eclampsia or hepatitis. Provisional diagnosis of acute ishemic hepatitis was made. On the 5th postoperative day, all the liver enzymes showed a downward trend and normalized within 2 weeks. Alkaline phosphatase levels, as expected in acute ischemic hepatitis, remained normal throughout the course of the illness. The patient was discharged in a stable condition 2 weeks after admission.

Discussion

Ischemic hepatitis (hypoxic hepatitis, acute hepatic infarction, post-traumatic hepatic insufficiency, shock liver) is not a common disease. It is a particularly frequent in coronary units where it affects 22% of those with low cardiac output. ² This disorder is documented in the intensive care units in 0.16%–0.50% patients in total. ⁴ Ischemic hepatitis is associated with a decrease in cardiac output caused by heart failure, hypovolemic (traumatic, hemorrhagic) shock, severe dehydration, pericardial tamponade, cardiorespiratory arrest, open heart surgery, asphyxia, prolonged seizures, heart stroke, and interruption of hepatic blood flow during tumor resection. Hematologic diseases (sickle cell anemia) can lead to occlusion of the hepatic artery, thus leading to hepatic hypoperfusion also. ³ The most frequent cause of ischemic hepatitis is left- sided heart failure because of coronary artery disease and/or cardiomyopathy when hypotension or reduced cardiac output develops. ⁵ Mechanisms of liver damage are related to severity and duration of fall of blood pressure. Marked hepatic arterial and portal vein vasoconstriction may further reduce liver perfusion >70%, thus representing an important contributory factor to hypoxia/anoxic hepatocellular injury.

In ischemic hepatitis, laboratory abnormalities are very important.^3,5 After the initial insult, marked and rapid elevation of serum transaminases, especially AST, occurs within 24–48 hours. Their return to normal depends upon the duration of liver ischemia. Serum concentrations decrease to normal in 3–11 days if perfusion and oxygenation are restored and urine output is normal. A similar rise and fall of serum LDH concentration occurs because of liver hypoperfusion and metabolic acidosis. This helps in differentiating ischemic from viral hepatitis, in which LDH is mildly increased only.^4,6 Alkaline phosphatase generally remains normal. Serum bilirubin may occasionally rise but is rarely greater than four times ULN. This pattern of biochemical changes was seen in the patient discussed here, with a striking increase in serum aminotransferase and LDH while alkaline phosphatase was normal. Definite diagnosis of ischemic hepatitis is based on liver biopsy if the general condition and hemostasis status allow. In this case, biopsy was not taken because of the unstable condition of the patient, and diagnosis was made only provisionally.

Conclusions

The outcome of ischemic hepatitis is poor if the cause of hypotension and liver anoxia is not corrected. In ischemic hepatitis, prognosis depends upon the cause of hypotension and the patient's cardiovascular status. The disease is often mild, and sometimes is not even diagnosed. Long-lasting liver hypoperfusion or circulatory failure superimposed on an already damaged liver and associated diseases of the organs may, in turn, cause fulminant hepatitis and have a bad prognosis. ⁴