A case report on comorbidities and laboratory abnormalities of Telbivudine in Hepatitis B patients

About Authors:
DHAVAL PATEL ^*[1], Dr. PANKAJ SHAH ^[2]
1 School of Pharmaceutical Sciences,
Jaipur National University, Jaipur -302025, (Rajasthan.), India
² institute of kidney disease and research center,
Civil hospital, Ahmedabad (Gujarat), India

Abstract:
Inpresent study, comorbidities and laboratory abnormalities of telbivudine was analysed in hepatitis b patients. Clinical data were collected from hepatitis b patients that presented with laboratory abnormalities to telbivudine. We examined 100 patients of hepatitis b  who treated with telbivudine in i.k.d.r.c, civil hospital, Ahmedabad from January 2009 to February 2011, out of these twenty patients had used other nucleoside analogue in past. The main laboratory abnormalities were elevation of creatine kinase, elevation of ALT and elevation of AST. Hypertension was the major comorbidities with the hepatitis b.The laboratory abnormalities were related to telbivudine, but the biological mechanism of the reaction is not clear.

Reference ID: PHARMATUTOR-ART-1197

Introduction
Hepatitis is a general term meaning inflammation of the liver and can be caused by a variety of different viruses such as hepatitis A, B, C, D and E. Hepatitis B is a serious and common infectious disease of the liver. Hepatitis B virus (HBV) infection is a significant health problem worldwide. The hepatitis B virus is a DNA virus, meaning that its genetic material is made up of deoxyribonucleic acids. It belongs to a family of viruses known as Hepadnaviridae. The virus is primarily found in the liver but is also present in the blood and certain body fluids. ^[1]

Of the 6 billion worldwide populations, an estimated 2 billion have been infected by HBV. ^[2] It is estimated that 350-400 million people have chronic hepatitis B (CHB) infection. ^[3] There is clear epidemiologic evidence that chronic HBV infection can result in the development of hepatocellular carcinoma (HCC) and cirrhosis. ^{[4, 5]} Approximately 15%-40% of HBV carriers develop cirrhosis, liver failure, and HCC; worldwide, more than 50% of primary HCC is related to chronic HBV infection. ^[6] Each year, 500 000 deaths are expected because of complications related to hepatitis B. ^[7]

In India nearly 3%-4% of the population is infected by the virus, and chronic hepatitis B constitutes more than 50% of the chronic hepatitis cases in the country. ^[8] The prevalence ranges from 1.1% to 12.2% with maximum incidence in Madhya Pradesh, Gujarat, Arunachal Pradesh and South India and least in Kashmir and Kerala. ^[9] There is peak prevalence after the second decade of life. Most (90%) of these HBV infected subjects are HBeAg negative; the majority (80%) have normal ALT. ^[10] The prevalence of HBeAg among asymptomatic HBsAg positive persons varies from 9%-20%. ^[11]

Telbivudine is used for chronic (long term) hepatitis B infection (swelling of the liver caused by a virus) in people who may also show signs of liver damage. Telbivudine is in a class of medications called nucleoside analogue which acts as competitive inhibition of viral reverse transcriptase (DNA polymerase). It works by preventing viral cells from multiplying in the body and infecting new liver cells.  Since it came on the market in October, 2006, it has been a new option for the treating of chronic hepatitis B, because it significantly suppresses hepatitis B virus (HBV) replication. ^{[12, 13]}

Materials and Methods

Subjects: In present study we examined 100 patients who were treated with telbivudine for hepatitis B at an inpatients and outpatient department of i.k.d.r.c, civil hospital, Ahmedabad, from january, 2009 to february 2011.

Methods: A retrospective method was employed to analyze the medical records of the all patients, including: general information, medicine history, telbivudine treatment, dosage, combined medication, time of occurrence of laboratory abnormalities as well as results of laboratory tests, such as routine blood analysis, liver function, and kidney function.

Results and Discussion
In present study a  randomized observation study on 100 patients of hepatitis b was conducted who were treated with the telbivudine and examined for laboratory abnormalities of telbivudine therapy. These patients were selected with the inclusion criteria only. All the patients successfully completed the telbivudine. There were no cases of the discontinuation of the therapy.
We studied the comorbidities with the hepatitis b patients which is shown in table 1. It was observed that hypertension (45%) and diabetes mellitus (16%) was the major co-morbidities in the patients. Other comorbidities like myocardial infarction (3%), cirrhosis (1%), tuberculosis (2%), cancer (3%), urinary tract infection (8%) and congestive cardiac failure (2%) are also present in few patients.

Table 1: Comorbidities with hepatitis b infection

Out of the 100 patients, total 12 patients were found with the kidney transplantation along with the hepatitis b. Out of the 100 patients 20 patients were previously treated with the other drugs of the hepatitis b but due to reactivation or resistance of the virus to drug, they became hepatitis b positive again. So they were treated with the telbivudine to overcome resistance.

During the study we observed laboratory abnormalities of telbivudine therapy. Creatine kinase (CK) elevation was the most common side effect of telbivudine. Telbivudine produced CK elevation in 10% patients within the five to six months of telbivudine therapy.

Telbivudine also produced elevation of serum lipase (2%), serum glutamic oxaloacetic transaminase (SGOT) (3%), elevation of serum glutamic pyruvic transaminase (SGPT) (3%),  elevation of neutropenia (3%) and elevation of thrombocytopenia (2%) were also associated with telbivudine therapy.

Table 2:  laboratory abnormalities of the telbivudine treatment

Conclusion
In present study, comorbidities and laboratory abnormalities of telbivudine was studied in i.k.d.r.c, civil hospital, Ahmedabad. We observed that hypertension and diabetes mellitus was major comorbidities with the hepatitis b.
The most common laboratory abnormalities of telbivudine were CK elevation, elevation of AST, elevation of ALT, elevation of neutropenia and thrombocytopenia.

References
1. Maddrey WC Hepatitis B: an important public health issue. J Med Virol 2000, 61:362-366.
2. Lee WM. Hepatitis B virus infection. N Engl J Med 1997; 337: 1733-1745
3. Mohanty SR, Kupfer SS, Khiani V. Treatment of chronic hepatitis B. Nat Clin Pract Gastroenterol Hepatol 2006; 3: 446-458
4. Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 1988; 61: 1942-1956
5. McMahon BJ, Holck P, Bulkow L, Snowball M. Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus. Ann Intern Med 2001; 135: 759-768
6. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94: 153-156
7. Fung SK, Lok AS. Drug insight: Nucleoside and analog inhibitors for hepatitis B. Nat Clin Pract Gastroenterol Hepatol 2004; 1: 90-97
8. Chowdhury A. Epidemiology of hepatitis B virus infection in India. Hep B Annual 2004; 1: 17-24
9. Thyagrajan SP, Jayaram S, Hari R, Mohan KVK, Murugavel KG. Epidemiology of hepatitis B in India – A comprehensive analysis. In: Hepatitis B and C carrier to cancer. Sarin SK, Okuda K, editors. 1st ed. New Delhi: Harcourt India Private Ltd, 2002: 25-39
10. Tandon BN, Acharya SK, Tandon A. Epidemiology of hepatitis B virus infection in India. Gut 1996; 38 Suppl 2: S56-S59
11. Chowdhury A, Santra A, Pal S, Chakravarty R, Banerji A, Pal S, Dhali GK, Datta S, Banerji. S, Manna B, Roy Chowdhury S, Bhattacharya SK, Guha Mazumder D. Community based epidemiological study of Hepatitis B virus infection (HBV). Indian Journal Gastroenterol 2001; 20 Suppl 2:
12. Lok AS, Heathcote EJ, Hoofnagle JH Management of hepatitis B: 2000 – summary of a workshop. Gastroenterology 2001, 120:1828-1853.  
13. Moon YM, Hwang SG, Kim BS, The efficacy and safety of telbivudine in korean patients with chronic hepatitis B, Korean J Hepatol.2007; Dec;13(4):503-12.