Prospective Study of Drugs Used to Treat Hepatic Impairment Patients with or without Comorbidities at a Tertiary Care Teaching Hospital in Davangere

Introduction

The principal location for drug metabolism is the liver, the biggest organ in the body.¹ This process primarily functions as a detoxification mechanism, turning pharmacologically active lipid-soluble medicines into inactive hydrophilic metabolites that may be eliminated by kidneys. In some cases, the conversion of pro-drugs into their active components also requires metabolic enzymes. Hydrophilic medications are more significant for renal excretion than lipid-soluble pharmaceuticals, which are more vital for liver metabolism. Therefore, although there are few exceptions, medications that mostly undergo renal excretion are less likely to require dosage adjustment in individuals with liver impairment than medications that primarily undergo hepatic metabolism.²

The primary diseases that cause morbidity and mortality around the world are cirrhosis, hepatocellular carcinoma (HCC), hepatitis B, hepatitis C, non-alcoholic fatty liver disease, and alcoholic liver disease (ALD).

ALD is a serious medical issue and is linked to higher levels of alcohol usage. Hepatic steatosis (a fatty liver) without heavy alcohol usage is what distinguishes non- alcoholic fatty liver disease (NAFLD) from alcohol-associated liver disease.

One of the most prevalent chronic conditions that might change a drug's disposition and action is liver cirrhosis. It is challenging to implement a straightforward rule to individually tailored drug treatment for cirrhotic patients due to the complexity of effects of liver disease on various routes of drug metabolism, the variability in these pathways' rates, and the lack of a routinely measurable test for the liver's metabolic function.³

Hepatitis

Hepatitis causes the liver to enlarge and become inflamed. The phrase is frequently used to describe a viral liver illness. Hepatitis is an outcome of body's immune system attacking the liver, which results in autoimmune hepatitis, viral infections (such as hepatitis A, B, C, D, and E). Hepatic Encephalopathy (HE) is the final stage of chronic liver disease (CLD) and is characterised by brain dysfunction. It has terrible effects on the quality of life for both patients and the people who care for them.⁴ HE is a typical neurologic cirrhosis consequence that affects 30 to 70% of cirrhosis patients, according to estimates. The spectrum of HE comprises symptomatic (overt) HE, which may cause coma in the most severely affected patients, and covert HE, which is defined by neurologic impairment that is not clinically evident.

Need for the Study

The liver, essential for metabolizing and detoxifying internal and external substances, plays a critical role in the body. Any harm to this vital organ can have a substantial impact, leading to bacterial and parasitic infections, alcohol-induced liver damage, poisoning from mushrooms or toxins, and complications from medications, including the potential fatality associated with an acetaminophen overdose. Elevated drug exposure can have a variety of negative consequences and toxicity due to portal vein shunting, decreased plasma protein synthesis, reduction or impairment in drug metabolizing enzymes, and decreased or impaired plasma protein synthesis. Therefore, the main goal of this prospective study was to reduce the negative effects of medication by encouraging its safe and effective delivery with the aid of drug use evaluation studies.

Since hepatotoxic medicines including anti-epileptics, anti-tubercular, and antiretroviral, as well as obesity and alcohol consumption are the main causes of liver diseases, patient counseling and dosage adjustments are necessary while treatment is at its most effective. Therefore, the goal of the study was to determine the prescription behavior in patients with or without comorbidities having impaired liver function.

Objectives

Primary Objective

• To evaluate the prescribing pattern of drugs in hepatic impairment patients with or without comorbidities admitted in the inpatient general medicine wards of a tertiary care teaching hospital.

Secondary Objectives

• To categorize the patients based on Child-Pugh score.
• To categorize the patients based on Maddrey’s score.
• To evaluate the prescription pattern of non hepatospecific drugs.
• To analyze the distribution of patients according to social habits.

Materials and Methods

This prospective observational study was conducted for six months in Chigateri Government Hospital, Davangere, after conducting a pilot study. The sample size was taken as about 10 percent of the patient admission in the hospital and 150 was proposed.

Source of data and materials used

• Patient case sheet
• Laboratory analysis report
• Past history of any hospitalization with similar complaints with its corresponding documents
• Information collected from patient and from patient's representatives
• Past medical and medication history 
• Laboratory investigation charts
• V1D PLUS CALC (for calculating Child Pugh Score and Discriminant Score)
• MS Word (software)

Study criteria

The study was carried out by considering the following inclusion and exclusion criteria.

Inclusion criteria

• Male or female patients aged above eighteen years 
• Patients admitted for a minimum of two days in general medicine ward
• Only inpatients of general medicine ward
• Patients with or without co-morbidities
• Patients willing to give informed consent to participate in the study

Exclusion criteria

• Patients admitted to the emergency ward
• Patients treated in outpatient department, not requiring hospital stay
• Patients not willing to give informed consent for participating in the study
• Patients having missing and insufficient data

Study Phases

Phase - 1

• Review of literature.
• A data collection form was prepared including demographic details of the patient, present complaints, current medication, co-morbidities, length of hospitalization, past medical and medication history along with discharge medication and the data was collected from the patients who were admitted for more than two days, satisfying the above mentioned inclusion criteria. 
• Obtained IEC clearance.
• Obtained permission from the general medicine department of the hospital.

Phase - 2

The collected data from the patient profile was then categorized, assessed, analyzed for the following parameters: 

• The most common drugs and drug classes prescribed for hepatic impairment patients were identified.
• The drug related problems were evaluated.
• Child Pugh Score and Discriminant Scale were calculated using the laboratory investigation reports, the severity of the disease was assessed and the life expectancy of the patient was calculated.
• The treatment given was evaluated to determine any dosage adjustment or if any hepatotoxic drugs have been given.

Phase - 3

• Data were collected, tabulated and analyzed.

Method of data collection

• A prospective observational study was conducted involving the inpatients of general medicine ward with hepatic impairment in Chigateri District Hospital, Davangere. The data required for the study was collected from the patient case sheets, previous records of hospitalization and from laboratory investigation reports.
• Inpatients in general medicine ward with or without co-morbidities, meeting the inclusion criteria were enrolled in the study.
• The demographic details, dose, route and frequency both during admission and discharge, along with history of any allergy, information regarding the patient's habits were recorded in a properly designed data collection form. 
• Patients Child Pugh Score was calculated in order to assess the disease severity and to predict the mortality rate of the patient.
• All the prescriptions meeting the inclusion criteria were assessed for Drug Utilization Evaluation and the results were tabulated in Microsoft Excel.

Statistical method

All the data were recorded and analyzed using software Microsoft Word 10, Microsoft excel 10, SAS and represented graphically.

Ethical clearance from the institution for the study

The protocol was submitted to the Institutional Ethical Committee of S.C.S College of Pharmacy, Harapanahalli for obtaining ethical committee clearance before starting the study.

Results

Distribution of hepatic impairment patients based on gender

A total of 150 hepatic impairment patients were evaluated during a period of six months. Out of the 150 patients included, 128 (85.33%) were males and 22 (14.66%) were females.

Distribution of patients according to social habits involved in hepatic impairment

Out of 150 patients, 139 (92.67%) patients were found to have various social habits. Out of these 139 patients, 57 (38%) patients had a habit of alcohol consumption, 85 (56.67%) patients had the habits of alcoholism and smoking, while 8 (5.34%) patients reported no social habits.

Distribution of hepatic impairment patients based on age

Majority of the patients in the present study belonged to 41-50 years age group (n=54), followed closely by patients in 31-40 years age group (n=39), and 10 patients were in the age group of 18-30 years. Around 23 patients were in the age group of 51-60 years and 24 patients were above 61 years of age.

Distribution of patients according to Child-Pugh score

According to the severity of disease, 92 patients were in Class-B (Moderate), followed by 40 patients in Class-C (Severe) and 18 patients were in Class-A (Mild).

Distribution of hepatic impairment patients according to Maddrey’s score

Based on the score, out of 150 patients, 43 showed good prognosis and 107 showed poor prognosis.

Distribution of hepatic disease with or without comorbidities (Table 1)

Prescription pattern of Hepatospecific drugs

A total of 1511 drugs were prescribed among the study population, out of which 789 (100%) were hepatospecific drugs and those included, liver protectants 42 (5.32%), Gall stone dissolution agents 126 (15.96%), laxatives 14 (1.77%), Enzymes 09 (1.14%), Sugars 92 (11.66%), Diuretics 130 (16.47%), β-Blocker 87 (11.02%), Antibiotics 111 (14.06%), Antihemorrhagic agents 116 (14.70%), Corticosteroids 08 (1.01%) and Transfusion 54 (6.84%).

In this study, a total number of 1511 drugs were prescribed among which 722 were non-hepatospecific drugs. It was observed that the maximum number of drugs were Nutritional supplements 197 (27.28%), followed by Antibiotics 163 (22.57%), Antiulcer agents 105 (14.54%), Corticosteroids 52 (7.20%), Antiemetic’s 41 (5.67%), Antidiarrheal agents 33 (4.57%), Antidiabetics 32 (4.43%), Anticoagulants 23 (3.18%), Anticonvulsants 19 (2.63%), Miscellaneous agents 18 (2.49%), Analgesics 12 (1.66%), Antihistamines 09 (1.24), Alkalizers 09 (1.24%), Antihypertensives 03 (0.41%), Bronchodilators 03 (0.41%), Antiviral drugs 01 (0.13%), Antipsychotics 01 (0.13%) and Antimuscarinics 01 (0.13%).

Discussion

CLD and ALD are both considered the leading causes of morbidity and mortality in developing countries. The present study included 150 cases of ALD and CLD. Out of the 150 patients included, males were Hepatospecific Drugs Prescription pattern of Hepatospecific Drugs predominant (85.33%) compared to females indicating greater susceptibility among males compared to female subjects. It was also found that most of the patients (36%) were in the age group of 41-50 years. Huma S et al., however reported the predominant age group as 31-40 years.⁵ The most common co-morbid conditions were found to be hypertension, hepatic encephalopathy, ascites, and pancreatitis with CLD. Natish B et al. in their study reported anemia, hepatic encephalopathy and portal hypertension as the frequently observed comorbid conditions.⁶ Most patients with chronic liver disease had at least one co-morbidity. The majority of patients had personal history of alcoholism and smoking (56.67%) which is similar to the findings of Sathish Kumar V et al.⁷ A total number of 1511 drugs were prescribed among the study population, of which the most commonly prescribed drugs were Nutritional Supplements (197), Antibiotics (163), Diuretics (130), Gall stone dissolution agents (126), Antiulcer agents (105), Liver Protectant (42) and these findings were confirming with the findings of Sathish Kumar V et al.⁷ Proton pump inhibitors (PPI) and Lactitol have been the most frequently used drugs among gastro intestinal agents. Although PPI are considered as safest among the gastro protective drugs, the dose of the drugs must be reduced in the patients with liver damage. Antibiotics were the most common drugs that were prescribed to the study population. Among these, Ceftriaxone was the most frequently used antibiotic. Among the 150 patients included in the study, 61.33% (92) patients had a ChildPugh score of Class-B which is in concurrence with the findings reported by Manjula Devi AS et al. As per the Model for end-stage liver disease (MELD) score, 43 patients were found to be with good prognosis (<32) and 107 patients with poor prognosis (≥32) which is similar to a study conducted by Fatih Tekin et al.⁸

Conclusion

In our study, males were found more prone to hepatic impairment compared to females. Most patients were primarily classified into class B of the Child-Pugh Score, in contrast to classes A and C. Additionally, the Discriminant score indicated a better prognosis for patients with a good diagnosis compared to those with a poor diagnosis, as per Maddrey's score. Patient counseling can have a good impact on patients for abstinence from alcohol, thereby preventing further harm to the liver.

Conflict of interest

None