Tshering Penjor^{1,5 *}, Kuenzang Chhezom², Sithar Dorjee³, Guru Prasad Dhakal^4,5

¹Faculty of Postgraduate Medicine, Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, Bhutan.
²Faculty of Postgraduate Medicine, Basic and Clinical Biochemistry, Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, Bhutan.
³Faculty of Postgraduate Medicine, Epidemiology, Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, Bhutan.
⁴Faculty of Postgraduate Medicine, Gastroenterology, Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, Bhutan.
⁵Department of Medicine, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan.

*Corresponding Author: Tshering Penjor, Faculty of Postgraduate Medicine, Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, Bhutan.

Abstract
Background and Aim: Chronic liver disease (CLD) is a major cause of morbidity and mortality worldwide. Etiologically there are many factors including hepatitis B virus (HBV) and C virus (HCV) infections, alcohol, non-alcoholic fatty liver disease, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson’s disease, hemochromatosis, etc. Though there is evidence in the literature regarding the etiologies of CLD, no study was done in Bhutan in this area. Therefore, this study was conducted to assess the etiology of CLD in patients admitted in the National Referral Hospital, Thimphu.

Methods: A descriptive study was conducted with 71 patients admitted to the National Referral Hospital. The study was done after seeking ethical clearance from the Research Ethics Board of Health (REBH) (Annexure 3) and was conducted from 1st January to 31st December 2020. The data were collected in pro forma and entered in Epi Data version 3.1 and analyzed using Epi Data Analysis version 2.2.2.183 and STATA version 15.1.

Results: Out of 71 patients who had CLD, majority 80.3 % were due to alcohol and the least 2 (2.8 %) was due to the combination of alcohol and HBV infection.

Conclusion: The study found that the commonest cause of CLD in patients admitted at the National Referral The hospital was alcohol. The findings from this study could help in strengthening the implementation of alcohol policy in the country.

According to a study done, in Bhutan, CLD is a major cause of morbidity and mortality [6]. The prevalence of CLD in Bhutan is largely unknown but is assumed to be high. Alcohol is assumed to be the major cause of CLD in Bhutan. However, no proper study was done to find out the other causes of CLD. Alcohol liver disease was reported as the number one cause of death [6]. In Bhutan, although alcohol is the main cause of the chronic liver disease (CLD), causes of liver disease other than ALD are often not described. The layperson is often led to believe that alcohol abuse is the only etiological factor in CLD.

Although some of the causes of chronic liver diseases have no treatments, such as α1- anti-trypsin deficiency, cryptogenic hepatitis, and primary sclerosing cholangitis, other causes, such as primary biliary cirrhosis, have treatments that delay progression even though not curable [7]. This study was thus conducted to estimate the proportion of CLD attributable to different etiologies as there is no study in the country on this subject.

Results
A total of 71 patients were enrolled in this study. Of these patients, 46.5 % were male and 53.5 % were female with an average age of 50.46 years (SD=11.75, Range=28-76 years). A total of 65 (91.5 %) of patients were married, 45.1 % of the participants had no education followed by 18.3 % with non-formal education and the least with a college education of 1.4 %. Of the total patients, 32.4 % were doing private business followed by homemakers at 29.6 % and farmers at 21.1 %. 45 % of the total patients belonged to the eastern region as shown in table 1 below.

Table 1: Demographic characteristics of patients with CLD* admitted in Medical Ward, Jigme Dorji Wangchuck National Referral Hospital from 1st January - 31st December 2020.

The descriptive statistics on alcohol consumption of CLD patients enrolled in this study are presented in Table 2. As shown in the table 73.2 % of the patients in this study consumed alcohol and 66.2 % of them consumed alcohol on a daily basis. Commercially brewed liquor (CBL) was the commonest type of alcohol consumed. The mean duration of alcohol consumption was 13.65 years with SD 11.3 and a range of 0-45 years.

Table 2: Alcohol consumption by patients with CLD* admitted in Medical Ward, Jigme Dorji Wangchuck National Referral Hospital from 1st January - 31st December 2020.

*Chronic liver disease, **commercially brewed liquor, ***non-alcoholic

None of the participants had Anti-HCV detected but ten of them had HBsAg (14.1 %). And two of them had a metabolic syndrome (2.8 %) as shown in table 3.

Table 3: Laboratory parameters of patients with CLD* admitted in Medical Ward, Jigme Dorji Wangchuck National Referral Hospital from 1^st January - 31^st December 2020.

**Chronic liver disease, **Hepatitis C Virus antibodies, ***Hepatitis B surface antigen

Child-Pugh score
As shown in Table 4, of the 71 patients, 41 (57.7 %) of them had a CLD with the Child Score C and 28 (39.4 %) of them had Child Score 

B. Only two of the patients had a good prognosis with the Child Score A.

Table 4: Child-Pugh score* of the patients with CLD** admitted in Medical Ward, Jigme Dorji Wangchuck National Referral Hospital from 1^st January - 31^st December 2020.

*CHILD score A 5-6 points, B 7-9 points, C 10-15 points, **Chronic liver disease

Etiology
Table 5 shows the etiology CLD. In this study, it was found that alcohol (80.3 %) was the commonest cause of CLD, followed by hepatitis B infection (11.3 %), while 2.8 % had both hepatitis B and alcohol, 2.8 % had NASH and 2.8 % had others.

Table 5: Etiology of CLD* in patients admitted in Medical Ward, Jigme Dorji Wangchuck National Referral Hospital from 1^st January - 31^st December 2020.

*Chronic liver disease, **Non-Alcoholic Fatty Liver Disease,***Could not confirm the diagnosis

Discussion
The commonest cause of CLD among the study participants was alcohol consumption followed by Hepatitis B (80.3 %). The findings were contrary to that from a study done by Mukherjee P.S et al in India which reported HBV to be the commonest cause of CLD (33.3 %) among their study participants. These differences could be largely explained based on differences in the prevalence of HBV and HCV, and alcohol policy and cultural differences in alcohol consumption acceptability. In many states of India, the sale of alcohol is banned and culturally not accepted. One of the reasons for less HBV causing CLD in our country could be because of the initiation of immunization program and also early screening and preventive measures put in place by Ministry of Health. Similarly, we need to emphasize the existing programs for alcohol as it is one of the preventable causes of CLD. Other causes of CLD found in this study were NAFLD (2.8 %) and 2.8 % with unknown causes. As we do not have previous data on causes of CLD in our country it's difficult to comment whether there has been a change in the trend.

Important observations of this study include the finding of more than half of the CLD patients present at a remarkably advanced stage and with poor prognosis. It is also observed that most of the CLD patients were with no education (45.1 %) and with non-formal education (18.3 %). Care for liver disease is maximally effective if instituted early [1]. In view of this, creating awareness on liver diseases is recommended as it is considered as one of the important strategic interventions in liver disease a policy that needs to be prioritized in the Bhutanese context. The spectrum of ALD includes steatosis (fatty liver), alcoholic steatohepatitis, progressive fibrosis, cirrhosis, and the development of hepatocellular carcinoma. Although many individuals consuming more than 60 g of alcohol per day develop fatty liver, only a minority 29 of the patients with fatty liver progress to alcoholic steatohepatitis and 10-20 % develop cirrhosis [9]. This study also found that the majority of the patients consumed alcohol on daily basis and in excess amount (100 g per day).

There is an established relationship between the dose, amount, and the likelihood of developing ALD due to alcohol consumption. Fatty liver can be found in the 60 % of those who drink more than 60 g of alcohol per day and the risk of developing cirrhosis is highest in those who drink more than 120 g per day [9]. The alcohol consumption of more than 40 g per day increases the risk of progression to cirrhosis to 30% in patients with uncomplicated fatty liver and to 37 % in those with fibrosis [9].

Similarly in this present study, it was observed that those patients who had CLD with Child-Pugh score C had more amount and longer time of consumption of alcohol. As alcohol was the major cause of CLD we need to strengthen the existing programs for alcohol consumption reduction and develop comprehensive, evidence-based control on alcohol as it has major implications on public health, particularly considering exponential growth in non-communicable diseases in a country. In a study done by Khokar N and Niazi SA, in Pakistan, it was found that CLD was the commonest cause of mortality and it was mainly because of HCV infection [8]. However, in this study none of the participants had HCV infection and the commonest cause of mortality was alcohol.

In the study done by Setiawan et al, NAFLD was the common cause of CLD [5]. Even in this present study, it was observed that two of the participants had CLD due to NAFLD.

The most common presenting complaints in my study was abdominal distention followed by edema (69 % and 66.2 % respectively). However, in the study done by Khokar N and Niazi SA, the most common presenting complaint was upper gastrointestinal bleeding. Although it was not found to be common in this study, it was the third most common presenting complaint.

Acknowledgment: I am very grateful to Ms. Tshering Cheki, QASD, Jigme Dorji Wangchuck National Referral Hospital, Thimphu for helping me with the writing and proofreading of the article.

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