Introduction
Chronic liver failure related to using Bentazepam is classified as idiosyncratic hepatotoxicity. Hepatotoxicity refers to liver dysfunction due to the toxicity of drugs. Chronic liver failure due to Bentazepam is rare but can be fatal. Bentazepam is a drug commonly used as a muscle relaxant to treat anxiety disorders. Some patients on Bentazepam show abnormal liver function causing chronic hepatitis (inflammation and fibrosis of the liver cells). A liver biopsy aids confirmation showing histological evidence of hepatitis caused by Bentazepam. The withdrawal of Bentazepam is suggested in these cases with proper medical interventions.
What Is Chronic Liver Failure?
Chronic liver injury refers to persistent liver inflammation of more than six months. Patients may remain asymptomatic in the early stages of chronic liver injury (absence of symptoms). However, chronic liver injury can cause fibrosis and severe liver damage. Viral hepatitis (A, B, C, D, E) causes chronic liver failure.
What Is the Use of Bentazepam?
Bentazepam is also known as Thiodipine. Bentazepam is used as a muscle relaxant that relieves stress. Therefore, it is used as a sedative. It is also used as an anti-convulsant to treat seizures (a condition in which a person has attacks of sudden involuntary movements). Overdose of Bentazepam causes respiratory problems resulting in coma. Side effects of Bentazepam include nausea, constipation, hepatitis, and dyspepsia (indigestion). Studies show that Bentazepam can cause chronic hepatitis. Therefore, patients on Bentazepam should be monitored regularly.
How Does Bentazepam Cause Chronic Liver Failure?
Many drugs (Chlorpromazine, Co-amoxiclav, Rifampicin, and Isoniazid) can cause liver fibrosis and inflammation, also known as hepatotoxicity. Drug hepatotoxicity is an acute or chronic response to drugs that rarely cause liver failure. The liver is the primary site of drug metabolism, and the adverse effects of drugs cause drug-related hepatoxicity. Pre-existing liver disease may affect the liver’s capacity to metabolize drugs. When given Bentazepam in normal doses, unexpected toxicity may occur in patients with liver disease. Hence, Bentazepam should be avoided in patients with cirrhosis as it can exacerbate known complications of cirrhosis. The possibility of undiagnosed underlying liver injury should always be considered in patients exhibiting unexpected effects following drug exposure. However, hepatotoxicity due to Bentazepam is a rare occurrence. Drug-induced hepatoxicity can be caused due to Bentazepam. Drug-induced liver injury can be classified into three types based on clinical presentation:
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Hepatocellular Injury - An injury that causes damage to the liver cells.
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Cholestatic Injury - Occasionally, permanent bile duct loss (ductopenia) follows a cholestatic drug reaction due to Co-amoxiclav, resulting in chronic cholestasis with persistent systems such as itching.
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Mixed - An injury that has both the feature of hepatocellular injury and cholestatic injury.
Studies have shown evidence of cholestasis (a condition in which bile circulation is impaired) after using Diazepam, Flurazepam, and Chlordiazepoxide. The dose of Bentazepam is 25 mg/day to 50 mg/day, as the manufacturer recommends. The adverse effects of Bentazepam are discomfort in the abdomen and dry mouth syndrome. An absence of hypersensitivity symptoms (generalized itching, rashes, or fever) indicates no allergic reaction involved with the intake of Bentazepam. According to some studies, Bentazepam can cause hepatotoxicity resulting in chronic hepatitis. Patients with hepatotoxicity with Bentazepam show increased transaminase levels. If the liver function test is conducted periodically in patients on Bentazepam, then evidence of chronic liver injury can be easily seen. Therefore, the patients who are on Bentazepam should be monitored regularly.
What Are the Symptoms of Drug-Induced Hepatotoxicity?
The mechanism of hepatotoxicity is of two types: intrinsic or dose-dependent and idiosyncratic or unpredictable. The presence of jaundice is indicative of severe liver damage. The symptoms are directly proportional to dose toxicity and may subside once the drug is withdrawn. Symptoms of hepatotoxicity are as follows:
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Severe itching.
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Jaundice.
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Weakness.
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Abdominal pain.
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Hepatomegaly (enlarged liver).
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Dark stools.
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Dark urine.
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Nausea.
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Pruritus (itching of the skin).
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Fever.
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Rashes.
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Eosinophilia.
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Increase in weight.
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Swelling in feet and hands.
How Is Chronic Liver Injury Related to the Use of Bentazepam Diagnosed?
A detailed medication history of the patient, pre-existing liver disease, and tabulation of other drugs help to diagnose chronic liver injury due to Bentazepam. Drug toxicity should always be considered a differential diagnosis in patients with acute liver failure, jaundice, or abnormal liver biochemistry. The most common presentation of Bentazepam toxicity is mixed cholestatic hepatitis. The presence of jaundice indicates severe damage. However, chronic liver damage due to Bentazepam is rare.
The following are the ways to diagnose drug-induced hepatotoxicity;
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Liver Function Test (LFT) - Long-term use of Bentazepam shows increased transaminases.
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Blood Test - Complete blood count will show infection and allergy if present. Jaundice is the most common feature of hepatotoxicity, and bilirubin levels can confirm it.
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Alanine Aminotransferase Test - Large increase in aminotransferase activity favors hepatocellular damage.
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Biopsy - A liver biopsy finds histological changes occurring in liver cells, if any, indicative of chronic hepatitis.
How to Treat Chronic Liver Injury Related to the Use of Bentazepam?
Where chronic hepatitis is suspected due to long-term use of Bentazepam, then Bentazepam should be discontinued unless it is impossible to do so safely. The discontinuation of the drug should be only under a doctor’s consultation. Glucocorticoids can be given for the symptomatic treatment of hepatitis. Antipyretics drugs (Ibuprofen, Paracetamol) can cure high fever. Severe toxicity can result in hospitalization of the patient.
Conclusion
Although all drugs can unknowingly cause unexpected hepatotoxicity, Bentazepam can affect the liver adversely, causing epilepsy, anxiety disorders, etc. But, the potential of Bentazepam to cause chronic liver injury is low. Hepatotoxicity due to Bentazepam derivatives shows marked features of cholestasis. An abnormal liver function test (increase in transaminase level) confirms hepatotoxicity. Studies have shown that liver abnormalities resolve within a few weeks after the withdrawal of Bentazepam. Physicians should educate the patients about the consequences of long-term use of Bentazepam and monitor the patient frequently.
