Chapter 1: Introduction1.1 Background of the Study

Complementary and alternative medicine (CAM) is becoming popular among patients with liver disease (Levy et al., 2004). According to National Centre for Complementary and Alternative Medicine (NCCAM, 2014), complementary generally refers to using a non-mainstream approachtogether withconventional medicine while alternative refers to using a non-mainstream approachin place ofconventionalmedicine. Meanwhile, according to World Health Organization, they refer complementary and alternative medicine to a broad set of health care practices that are not part of that country's own tradition and are not integrated into the dominant health care system (WHO, 2014).

There are two subgroups under CAM (NCCAM, 2014). One of it is natural products. Herbs, vitamins and minerals, and probiotics are categorized in this group and also known as herbal supplements. Another group is mind and body practices. Acupuncture, massage therapy, meditation, movement therapies, relaxation techniques, spinal manipulation, tai chi, qi gong, healing touch, hypnotherapy and yoga are fall under this group. However, some methods such as the practices of traditional healers, Ayurvedic medicine, traditional Chinese medicine, homeopathy, andnaturopathy may not neatly fit into either of these groups (NCCAM, 2014).

However, in Malaysia the meaning of CAM slightly differ since there is no universally agreed one definition.Traditional medicine has made a significant contribution to the health care of the Malaysian community and knowing the importance of it the Traditional and Complementary Medicine Unit was born in 1996 and later upgraded to the Traditional and Complementary Medicine Division (T&CMD) in the Ministry of Health in 2004.Traditional and Complementary Medicine is a form ofhealth-related practice designed to prevent, treat, and/or manageillnesses and/or preserve the mental and physical well-being ofindividuals and includes practices such as traditional Malaymedicine, Islamic medical practice, traditional Chinese medicine,traditional Indian medicine, homeopathy, and complementarytherapies, and excludes medical or dental practices utilised byregistered medical or dental practitioners.National Policy of Traditional & Complementary MedicineMinistry of Health Malaysia (2007).

There are 6 major classes in Malaysia. The 6 classes are Traditional Malay Medicine, Traditional Chinese Medicine, Traditional Indian Medicine, Homeopathy, Complementary Medicine and Islamic Medical Practice. Nowadays, the general public is using CAM very commonly (Ernst, 2000).

The liver plays an important role in many bodily functions from protein production and blood clotting to cholesterol, glucose and iron metabolism. Liver disease is any disturbance of liver function that causes illness.Patients with liver disorder here also mean patients with liver diseases. According to medicine net, liver disease is a broad term that covers all the potential problems that cause the liver to fail to perform its designated functions. Usually, more than 75% or three quarters of liver tissue needs to be affected before decrease in function occurs. There are various types of liver diseases existing in this world currently. It can be caused by genetic disorder, autoimmune disorder, due to drugs and toxins and also cancer (Canadian liver foundation, 2014). Alagille Syndrome, Alpha 1 Anti-Trypsin Deficiency, Autoimmune Hepatitis, Biliary Atresia, Cirrhosis, Cystic Disease of the Liver, Fatty Liver Disease, Galactosemia, Gallstones Gilberts Syndrome, Hemochromatosis, Liver Cancer, Liver disease in pregnancy, Neonatal Hepatitis, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis, Porphyria, Reyes Syndrome, Sarcoidosis, Toxic Hepatitis, Type 1 Glycogen Storage Disease, Tyrosinemia, Viral Hepatitis A, B, C, and Wilson Disease are some of the important liver diseases that can see in daily life (Canadian Liver Foundation, 2014). Patients will be undergoing treatment and follow up doctors regularly to know the condition of liver and to consider liver transplantation.The use of complementary and alternative medicine becomes popular among these patients. In US, the use of CAM in chronic liver disease patients has been reported to range from 27.3% to 39% (Ferruci et al., 2010) and (Strader et al., 2002).

1.2 Statement of Problem

Thus so far, there is a paucity of information on the use of CAM in liver disorder patients in Malaysia. In Malaysia, the prevalence of herbal use, which is a form of CAM, was estimated to be around 34% by Aziz & Tey, 2009. There are studies of use of CAM in cancer patients such as Al-Naggar et al., 2013 and in postnatal care such as Rahman et al., 2008 have been in Malaysia. However, there are no studies on CAM use in liver diseases patients. According to certain studies, it is known that there must be a special need for physicians to be aware of CAM use among patients with existing liver damage and possible interaction with conventional chronic liver disease treatments (Levy et al., 2004). Herbal medicines, dietary supplements, and vitamins pose the greatest potential danger because of some of the substances are metabolized by the liver (Ferrucci et al., 2010). However, the concern now is to know the prevalence of CAM use in liver disease patients in Malaysia and not to identify the effects of it as it is hard to detect and given time is insufficient for such studies.

1.3 The Significance of the Study

To date, there has been a lack of studies conducted locally to investigate and for documentation of CAM use in liver disease patients. Our studys aim was to provide baseline data regarding the use of CAM in liver disease patients. The findings of this study will help to determine the incidence and types of CAM commonly used by liver disease patients in Malaysia. This will enable healthcare providers and authorities concerned to develop and implement strategies to minimize or resolve any CAM related problems in liver disease patients in Malaysia. There are guidelines in Malaysia for on Herbal Therapy as an Adjunct Treatment for Cancer and for Malay Postnatal Care. This helps in reducing the mortality and morbidity associated with CAM use in liver disease patients and consequently will reduce healthcare expenditure on such problems. In addition, healthcare providers can focus more on the common CAM use by counseling geriatric patients on means of preventing or resolving any adverse effects of it in future with evidence based studies. In conclusion, the study will serve as a preliminary study regarding the prevalence of CAM use in liver disorder patients in Malaysia and will definitely help for further researches.

Chapter 2: Literature Review2.1 Global liver diseaseAccording to Office for National Statistics, 2008 liver disease is the only major cause of death still increasing year-on-year. It kills more people than diabetes and road deaths combined. In England & Wales, liver disease is the fifth big killer after heart, cancer, stroke and respiratory disease (British Liver Trust analysis, 2008). A 4.5% increase since 2007 was detected after 16,087 people in the UK died from liver disease in 2008 (National statistics, 2008). However, Trust believes that these statistics are not comprehensive. This is due to two major reasons for under recording which are the stigma associated with liver disease and attempts to avoid distress to the bereaved,and attribution of liver deaths to other codes as liver disease frequently causes multiple organdysfunctions. It is important to remember that as people can survive with 70% liver damage,there is a substantial burden of morbidity from liver disease, a high cost to the National Health Service and a hugeeconomic and human cost from liver-related ill health. Web Med says more than 15 million people in the U.S. abuse or overuse alcohol and almost all of them (90% till 100%) develop fatty livers. Nonalcoholic fatty liver disease is now the most common cause of chronic liver disease in the U.S. due to excess fat in the liver. In 2011 July 28th Centers for Disease Control and Prevention release the following statistics due to World Hepatitis Day. Approximately 1 in 12 persons worldwide, or some 500 million people, are living with chronic viral hepatitis. Viral hepatitis is among the top 10 infectious disease killers and the leading can cause of liver cancer and cirrhosis. In an article by Medscape Medical News, 2013 entitled Global Burden of Liver Disease Substantial, Dr. Cowie pointed out certain information. In USA had an estimated 19,500 liver cancer and 49,500 cirrhosis deaths in 2010. HepatitisC was a primary cause, accounting for 41% of liver cancer and 40% of cirrhosis deaths. Alcohol and hepatitisB were less common causes. In China, by contrast, hepatitisB caused 54% of liver cancer and 46% of cirrhosis deaths in 2010. There were 370,000 liver cancer and 110,000 cirrhosis deaths in 2010. HepatitisBassociated cirrhosis was also more common in sub-Saharan Africa, where it accounted for 47% of liver cancer and 39% of cirrhosis deaths. The region also had a disproportionate burden of other cirrhosis deaths. In Australia, hepatitisB is associated with 41% of liver cancer deaths and alcohol is responsible for 38% of cirrhosis deaths. The following are the latest statistics available from the American Liver Foundation, 2014. The statistics on the prevalence of liver disease in the United States are startling. More than 30 million people in the U.S. have liver disease or it can be said that 1 in 10 Americans has liver disease. Liver diseases such ashepatitisC, non-alcoholic fatty liver disease, andliver cancerare on the rise. Up to 25% of Americans may have non-alcoholic fatty liver disease. Four million Americans are infected withhepatitis Cand more than 1 million Americans are infected with hepatitis B. Approximately 15,000 children are hospitalized every year with pediatric liver disease or disorders.

2.2 Overall liver disease incidence and burden in Malaysia Death rate per 100000 due to liver disease is low in rate in Malaysia which is 2.4% and ranked 187th country in worldwide (WHO, 2011). 470 people which means 0.46 % of the Malaysia total deaths by cause is due to liver disease. It has 33rd place in top 50 causes of death (WHO, 2011). Liver disease is in 32nd place in age-standardized death rate per 100000 populations of Malaysia with the rate of 2.43. It has a good ranking in world wide. The most common one is hepatitis B as this can lead to very serious implications later in life. Among them is the development of hepatoma or hepatocellular carcinoma (cancer of the liver). The hepatitis B virus, which causes infection and inflammation of the liver, can go on to cause scarring and cirrhosis of the liver, and later to cancer of the liver. In 5-10 % of people infected with hepatitis B virus, their bodies are unable to produce the antibodies, and they land up as carriers, or with chronic hepatitis B infection in their bodies. About 5.24 % of all Malaysians have chronic hepatitis B infection, with great risk of long-term liver damage that may lead to death. A survey by the Ministry of Health, Malaysia showed that the presence of hepatitis B surface antigen (HBsAg) or hepatitis B virus (HBV) exposure was highest for ethnic Chinese followed by Indians, compared to Malays and was increased among dentists and assistant nurses. In a study by Seng Qua et al., 2011, the main etiology of liver cirrhosis in Chinese and Malays, hepatitis B and for Indians are alcohol. Although liver disease in Malaysia not in danger zone, proper care and treatment is essential to reduce its occurrence.

2.3 Conventional therapy methods for liver diseasesIf it is detected early enough such as acute liver failure caused by an overdose of acetaminophen can sometimes be treated and its effects reversed. Likewise, if a virus causes liver failure, supportive care can be given at a hospital to treat the symptoms until the virus runs its course. In these cases, the liver will sometimes recover on its own. Some liver problems can be treated with lifestyle modifications, such as stopping alcohol use or losing weight, typically as part of a medical program that includes careful monitoring of liver function. Other liver problems may be treated with medications or may require surgery. For liver failure that is the result of long-term deterioration, the initial treatment goal may be to save whatever part of the liver is still functioning. If this is not possible, then a liver transplant is required. Fortunately,liver transplantis a common procedure that is often successful.

2.4 Prevalence of CAM use in liver disease patientsThe use of Complementary and Alternative Medicines (CAM) is widespread for general health maintenance and management of disease symptoms. Use of alternative therapy in the general population United States increased from 34% in 1990 to 42% in 1997 (Einsberg et al., 1998). In Strader et.al 2002, 39% of liver patients were using some form of CAM therapy within the month of being seen. Seeff et al., 2001 found that 41% of outpatients with diagnosis of liver disease had used some form of CAM. In the study of White et al., 2007, a total of hepatitis C virus patients were using CAM therapies. In the study by Ferrucci et al., 2013, 27.3% reported current use of atleast one type of CAM. I n the same study it was found that 8.3% used more than one CAM. It was stated that Asians were more likely than non-Asians to use CAM. 2.5 Types of CAM The major forms of CAM used of liver disease patients in U.S. were herbals followed by self-prayer, relaxation, megavitamins, massage, chiropractic therapy and spiritual healing (Strader et al., 2002). In the same study, it was stated that the most common herbals used were milk thistle, garlic, ginseng, gingko, echinacea and St.Johns wort. However, only milk thistle and licorice root were used by patients to treat liver disease and the rest are for their health supplement. According to Seeff at al., 2001, besides Silymarin (Milk thistle) and Glycrrhin (Licorice Root Extract), blended herbal formulations an extracts such as Chinese Traditional Medicine, Japanese Traditional Medicine, Ayurvedic medicine and other traditions also included. In addition to the list vitamins, antioxidants and immune modulators such as vitamin E, gluthathione prodrugs also used by patients to improve their chronic liver diseases in which immune deregulation appears to plays role. In Ferrucci et al., 2013 study, vitamins or other dietary supplements were highest in use followed by herbal medicine and homeopathy. Among the herbal medicines were milk thistle, Echinacea, St. Johns wort, valerian and gingko biloba. However this study is going to focus on Malaysians. Although the above herbal medicines available in Malaysia. There are many other forms of CAM. As mentioned in introduction, they are divided in 6 groups such as Traditional Malay Medicine, Traditional Chinese Medicine, Traditional Indian Medicine, Homeopathy, Complementary Medicine and Islamic Medical Practice by Traditional and Complementary Medicine Division. Therapeutic concept refers to healing, such as a form of medicine or therapy that has the capability to help in treating a disease or disability. On the other hand, wellness concept refers to modalities that assist in balancing positive health in an individual by increasing quality of life and a sense of well-beingThe examples in each category as below:1. Traditional Malay Medicine : Therapeutic - Herbal Medicine, Urut Melayu (Malay Massage), Indigenous Massage, Bekam (Cupping)2. Traditional Chinese Medicine: Therapeutic - Herbal Medicine Acupuncture and Moxibustion, Tuinalogy, Cupping Wellness - Qi Gong

3. Traditional Indian Medicine: Therapeutic Ayurveda, Siddha, Unani Wellness - Yoga

4. Homeopathy: Therapeutic - Homeopathy5. Complementary Medicine: Therapeutic Chiropractor, Naturopathy, Osteopathy, Nutritional therapy, Hypnotherapy, Psychotherapy, Therapeutic Massage Wellness - Spa Therapy, Reflexology, Aromatherapy, Thai massage, Swedish massage, Balinese/Javanese massage, Shiatsu massage, Colour Vibration Therapy, Crystal Healing, Reiki, Aura metaphysic, Raoha, Ozone Therapy, Chelation Therapy 6. Islamic Medical Practice: Therapeutic Islamic Medical Practice (Ruqyah)

2.6 Sociodemographic factors related to CAM In the study of Strader et al., 2002, the 5 variables were found to be predictive of alternative therapy use were female sex, young age, level of education, annual income and geographic location. Taylan Kav also confirmed gender and educational level were predictive variables of CAM usage. The uses of CAM in educated, young women were high. The use of CAM could be predicted by social. Cultural and geographic factors such as sex, age, higher education level or marriage status of patients associated with a different use of herbal products (Bruguera et al., 2004) and (Yang et al., 2002). A Spanish study identified women with higher education and being divorced or widowed as major predictors for use of CAM. However in Ferrucci et al., 2013, male sex, younger age, higher education, higher family income and current employment were the sociodemographics factors associated with CAM.

2.7 Sources of information regarding CAM Many patients get the information about CAM from their family or friends, from information obtained from magazine articles, from Internet browsing or from an alternative medicine practitioner without the encouragement or knowledge of their physicians (Strader et al., 2002).

2.8 Reasons of using CAM From the study of Taylan Kav, it was clearly seen that most of the respondents using herbal therapies believe that natural equates with safe and almost 30% of patients that such preparations cannot cause any harm. Most of them do not realize herbal medicines. The relative failure or limitations of conventional therapies for conditions such as HCV, hepatitis B (HBV), non-alcoholic fatty liver disease and hepatocellular cancer (HCC) and relative cost factor are the reasons of using CAM in liver disease patients (Verma et al., 2007). In addition, in the study by Astin, 1998, it was stated that chronic disease people use CAM since it promotes greater personal control over health decision, empowers people to manage their chronic condition and helps to avoid dissatisfaction associated with conventional therapy.

2.9 Disclosure of CAM from healthcare practitioner In Strader et al., 2002 study, it was stated 74% of patients stated that they informed their physicians or medical care provider about their use of alternative therapies. However, in the study done by Einsberg et al., 1993 was stated 31% - 40% of respondents do not disclose the use of CAM to their physicians. Robinson et al., 2004 stated in his study that patients often do not disclose use of CAM to their medical practitioners because of concerns about a possible negative response by the practitioners, the belief that the practitioner did not need to know about their CAM use and the fact that their practitioner did not ask.

Chapter 3: Aim and Objectives of the Study

2.1 AimTo study the prevalence and the pattern of use of complementary and alternative medicine (CAM) among liver disorder Malaysian patients at University Malaya Medical Centre (UMMC)

2.2 Objectives2.2.1 To determine the socio-demographic factors that may relate to the use of complementary and alternative medicine (CAM) and liver disorders2.2.2 To explore the type of complementary and alternative medicine used by Malaysian liver disorder patients2.2.3 To determine the source of supply of complementary and alternative medicine (CAM) and reasons of use2.2.4 To determine the disclosure regarding complementary and alternative medicine (CAM) use by the subjects to the healthcare practitioners

Chapter 4: Methodology

4.1 Study Design and Setting

This study will adapt a non-interventional cross-sectional survey using structured questionnaires regarding complementary and alternative medicine use in liver disorder patients after receiving approval from Medical Ethics Committee of UMMC. The survey will be conducted in a hepatology clinic at University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia which is operating on Tuesday mornings and Thursday evenings. UMMC is a major teaching hospital which is government-funded and located in Pantai Dalam, southwest corner of Kuala Lumpur.

4.2 Study PopulationAll the patients who are going to seek treatment at the hepatalogy clinic in UMMC from January to April 2015 will be included in this study. 4.2.1 Inclusion Criteria1. Patients who are Malaysians and attending clinic from Jan to April 2015.2. Adult patients who are aged 18 years old and above.3. Patients who are willing to sign consent form and agree for the short interview.4.2.2 Exclusion Criteria1. Patients who are not Malaysians.2. Any patient who did not turn up for their appointment in hepatology clinic on their appointment date. 3. Any patient who was admitted to the ward on their appointment date.4. Patients who are refuse to sign consent form.4.3 Sample Size

The method of sampling that will be carried out in this study is census. As mentioned above, the setting will be hepatology clinic which is operating only on Tuesday mornings and Thursday afternoons. This study will be carried for 4 months only. Thus, all the liver disease patients who are seeking for treatment in the clinic will be included according to inclusion and exclusion criteria. After considering all the factors above and limitations, the expected number of patients is 200. Therefore around 200 patients will be interviewed face to face.

4.4 Development of questionnaire The questionnaire was developed based on literature reviews and other similar studies. It is in English only as the survey is going to be face to face interview and patients do not have to read and answer by themselves. The questionnaire will have questions pertaining demographic data, medical history data as well as information regarding the CAM in use. For demographic data, gender, age, ethnic background, marital status, education background and occupation are included to know the relationship between demographic characteristic and use of CAM. Besides, the type of liver disease and what kind of therapy that has been going through by the patients are elements need to be investigated for the sake of medical history data. Such examples, pattern of questions will be asked would relate to source of information about CAM, are they used CAM and what kind of CAM that they using, reasons behind the use of CAM either as treatment of illness or as maintenance of health. Moreover, the cost that they spend for CAM in a month will be asked too. The names of herbal medicines will be asked as open - ended question as there are many in current market now in Malaysia. One of most important question is the disclosure about the CAM in use to their health care practitioner will fall under regarding the CAM use category.Overall questionnaire consisted of 15 questions which were designed to assess the usage of CAM among cancer patients. 4.5 Outcome measures

1) Demographic characteristic of patients involved2) Type of CAM use by patients3) Sources of information of CAM4) Reasons of using CAM 5) Disclosure regarding the CAM use bt patients to their health care practitioners

4.6 Data Collection Procedure 4.6.1 Pilot StudyA pilot study will be conducted on 10 liver disorder patients whom meet the inclusion criteria. This is to test the feasibility and practicability of the study method and validity of questions. Furthermore, the comprehensibility of subjects to the content and terms used in the questionnaire can be determined. . Some changes will be made to the questionnaire form to improve the clarity of some questions and to ensure that all data required for the study could be collected. 4.6.2 Main study1. The researcher has to attend the hepatology clinic every Tuesday mornings and Thursday afternoons.2. The researcher will identify those patients who meet the inclusion criteria while the patients waiting for the general practitioner to call for their turn. 3. A face to face interview which will take about 10 min will be conducted with the aid of questionnaire.4. All important data will be collected. If there is language barrier questions will be asked to the family member or friends who accompany the patient.5. All the data was recorded and analyzed.6. To ensure confidentiality of the collected information, a few measures will be taken. First, the patients' records will never be left unattended and will never be revealed to anyone. Secondly, each record will be assigned in a special coding number so that the patients' identity will not be revealed. Thirdly, the patients' name will not be included in the electronic data collection form during and after completion of data collection and analysis and finally, the researcher will not attempt to contact the patients to seek further information regarding their records.

4.7 Data Analysis of findingsThe data obtained from the survey will be analysed using Statistical Package for the Social Sciences (SPSS) version 20.0 (IBM Inc. Armonk NY, USA). Continuous data will be reported as mean and standard deviation (SD), while categorical data will be represented as frequency (n) and percentage (%). Means and percentages will be calculated for demographic factors such as age and patients will be categorized as CAM users and CAM non-users, males and females besides categorize them following ethnicity. Chi-square test and t test will be used to determine which of the socio demographic and medical variables were related to use CAM therapy, whilst means were compared among groups using ANOVA. Binary logistic regression analysis will be performed in order to identify predictors of CAM usage amongst respondents. A p-value of less than 0.05 is set to be statistically significant.

4.8 Work schedule20142015

ActivitiesSeptOctNovDecJanFebMacAprilMayJuneJuly

Literature Review

Proposal Submission and Presentation

Ethics Online Submission

1st Preliminary Report Submission

Pilot Study and Analysis

Main Study Data Collection

Data Analysis

Dissertation writing

Submission of Dissertation

Presentation of Dissertation

4.9 Work Flow

Approval from MEC

Pilot study

Identify potential patients using inclusion criteria

Face to face interview using questionnaire

Collect data

Analyze data using SPSS