What Is Sickle Cell Disease?
It is an inherited group of disorders. Red blood cells are usually round and travel through small blood vessels carrying oxygen to various parts of the body. In this condition, the RBC becomes C-shaped or sickle-shaped. These cells usually die early, resulting in a shortage of RBC (red blood cells) in blood, affecting the oxygen-rich blood in the body. They may also clog blood vessels and cause pain and severe conditions like infections, chest issues, and even stroke. It is a debilitating disorder and ends with a damaged organ.
What Is Sickle Cell Hepatopathy?
Sickle cell hepatopathy is an uncommon complication. It is an umbrella term for various acute and chronic liver pathologies. This complication occurs in conditions of extreme hyperbilirubinemia and mild to severe liver dysfunction. It affects around ten percent of the population worldwide. Acute sickle hepatopathy occurs in intrahepatic cholestasis (a liver disorder that occurs in pregnant women), hepatic sequestration (occurs when individuals with sickle cell disease acutely sequester), and overt liver failure (a neuropsychiatric disease that occurs as a result of liver disease). Chronic sickle cell hepatopathy occurs in viral hepatitis (inflammation of the liver that occurs with viral infection), gallstone disease (stone formation in the gallbladder), transfusion overload (transfusion-associated circulatory overload in which excess fluid increases in circulation), and sickle cell cholangiopathy (a form of ischaemic cholangiopathy).
What Causes Sickle Cell Hepatopathy?
This condition results as multifactorial. HbS molecules end up bonding at the substitution site, which forms a chain along with chain polymers, causing the sickling of erythrocytes. This can cause vaso-occlusion intra-hepatically, leading to ischemic liver damage (damage to the liver caused by inadequate blood and oxygen level) and sinusoidal obstruction (severe damage and obstruction to small hepatic vessels).
When this sickling occurs in the liver, it results in dilated sinusoids (liver cells) which causes compression in the biliary tree and results in a fatal condition of acute intrahepatic cholestasis (a liver condition that occurs in pregnant women). Increased hemolysis results in hyperbilirubinemia and the formation of gallstones. Chronic transfusions lead to hepatic iron overload, which also increases the risk of hepatic infections.
Who Gets Affected by Sickle Cell Hepatopathy?
Around 50 % to 90 % of children are affected before five years of age. Ten percent of sickle cell hepatopathy is associated with abnormal liver function. They are associated with hepatomegaly in 91 % and cirrhosis in 16 % to 29 % of cases. The HbS gene is found widely in African countries, India, the Caribbean, and central and south America. In the US, one in every 600 people has an HbSS genotype.
What Are the Signs and Symptoms of Sickle Cell Hepatopathy?
This condition combines with many other hematologic entities, and the signs and symptoms are:
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Fever.
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Nausea and vomiting.
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Pruritus (itchy and uncomfortable skin).
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Clay-colored stool.
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Dark urine.
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Right upper quadrant liver pain.
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Tender hepatomegaly (enlarged liver).
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Encephalopathy (an infection that affects the functioning of the brain).
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Jaundice (yellowish discoloration of mucous membrane, skin, and whites of the eye).
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Malaise (generalized discomfort).
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Other signs results due to iron overload, like edema of the lower extremities.
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Paroxysmal nocturnal dyspnea (shortness of breath relieved in an upright position).
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Orthopnea is an indication of heart failure.
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Endocrine conditions like diabetes mellitus.
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Decreased libido (decrease in desire for sexual activity).
How Is Diagnosis Made for Sickle Cell Hepatopathy?
Diagnosis of his condition is made by routine blood investigations:
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Tests for serum alanine transaminase (ALT) are done.
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Tests for serum aspartate transaminase (AST).
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Elevated bilirubin levels in the blood.
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Alkaline phosphatase (ALP) is also elevated.
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Elevated prothrombin time (PT), due to this bleeding diathesis (tendency to bleed and bruise easily) is seen.
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Partial thromboplastin time (PTT), INR (international normalized ratio), and hypofibrinogenemia tests are done.
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Renal function tests to check elevated levels of creatinine.
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Serum ferritin levels tests are done to estimate iron levels in the blood.
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Imaging tests like CT scans are done to see any abnormalities.
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MRI (magnetic resonance imaging) annual screening is recommended in patients with ferritin levels greater than 1000 g/L.
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Other modalities like ultrasound and radionuclide scans are done in the associated condition of biliary obstruction if the etiology is unclear.
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Liver biopsy and atomic absorption spectrophotometry is recommended in the assessment of hepatic iron concentration (HIC).
What Is the Treatment and Management of Sickle Cell Hepatopathy?
Administration of antiviral therapies is done in cases involving hepatitis infections. Hepatitis B infection can be treated with nucleotide or nucleoside analogs, and vaccination is recommended for hepatitis A and B. With associated cholecystitis, broad-spectrum antibiotic therapy is given, and elective cholecystectomy is indicated.
Zinc supplementation is given in deficient patients. ERCP (endoscopic retrograde cholangiography) is indicated with choledocholithiasis. Patients with high risk are also treated endoscopically with dilation or stenting. Supportive treatment like intravenous fluids transfusion and oxygenation is effective in lowering levels of HbS. An exchange transfusion of fresh frozen plasma is done to correct coagulopathy due to hepatic dysfunction. Some cases also require dialysis due to renal failure. Liver transplantation is recommended in severe cases of sickle cell hepatopathy. Patients eligible for this procedure should have end-stage liver disease without neurologic, pulmonary, cardiovascular, or renal complications. Other treatment options include a hematopoietic stem cell transplant, which is capable of stopping the progression of liver disease. However, this process and gene editing and therapy can be of more significant benefit.
What Are the Differential Diagnosis of Sickle Cell Hepatopathy?
Conditions like:
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Acute Cholecystitis- Inflammation of the gallbladder.
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Choledocholithis- Presence of gallstones in the bile duct.
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Acute Viral Hepatitis- Inflammation of the liver due to viral infection.
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Acute Hepatic Sequestration- is caused by sickled erythrocytes, which bind and block sinusoidal blood flow.
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Autoimmune Hepatitis- Liver inflammation that results from the body's immunity towards own liver cells.
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Primary Biliary Cirrhosis- A liver disease that gets worse over time.
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Primary Sclerosing Cholangitis- Inflammation that leads to scar formation in bile ducts.
What Is the Prognosis of Sickle Cell Hepatopathy?
Sickle cell hepatopathy leads to cirrhosis and chronic liver condition in about 16 % to 29 %. Annual monitoring of liver function tests is recommended; if serum ALT is two times above the upper limit of normal, analysis for chronic underlying SCH (Sickle cell hepatopathy) is done. The risk of developing chronic liver disease is high if preventive measures are not taken against disease progression. Beneficial results are shown by interventions such as hydroxyurea with multiple vaso-occlusive crises and transfusions to keep HbS levels below 30 % and with Ursodeoxycholic acid.
Conclusion:
Sickle cell hepatopathy involves many entities. Therefore, it is essential to give the best care, treatment, and management to the affected individual. Children and adults are equally affected, but the severity is more in adults. Therefore, the exchange of transfusions is beneficial for managing this condition. It is a rapidly progressive disease that can lead to liver failure and has a high mortality rate.
