|Year : 2014 | Volume
| Issue : 3 | Page : 186-194
Trends of chronic liver disease in a tertiary care referral hospital in Eastern India
Head of Gastroenterology Unit, Department of Medicine, B R Singh Hospital, Kolkata, West Bengal, India
|Date of Web Publication||13-Aug-2014|
Dr. Gautam Ray
Head of Gastroenterology Unit, Department of Medicine, B R Singh Hospital, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: There is scarce Indian data on time trends of hepatitis, an impediment to formulate an effective public health policy on the matter. Objective: The aim was to study secular trends and burden of hepatitis in a railway population. Materials and Methods: Outdoor, indoor, endoscopy unit and mortality records of patients attending this hospital from January 2003 to December 2011 were searched manually and relevant parameters of hepatitis patients were noted, especially etiology, clinical features, treatment, and mortality. Cochran-Armitage trend test was used to test significance of any trend in these parameters. Binary logistic regression analysis of various factors was carried out to study their effect on the liver related mortality of hepatitis B and C cases and Kaplan-Meyer survival curves were generated for significant factors. Two-sided P < 0.05 was considered to be significant. Result: Chronic liver disease (CLD) due to alcohol showed a significant rising trend with early age (mean 48.4 years) and high percentage of decompensated disease (75%) at presentation and high early mortality (63%). No trend was observed for hepatitis B and C, but significant reduction in mortality was observed when definitive therapy was given. Cryptogenic CLD showed a decreasing trend though overall it still remained the most important etiology and survival was better compared with alcohol even with conservative therapy. Only 4% patients had hepatocellular carcinoma. Conclusion: A menace of alcohol related liver disease affecting young productive work force in this part of India is foreseen, which might impact the country's economy and mandates immediate containment policy.
Keywords: Alcohol, Chronic liver disease, Hepatitis B, Hepatitis C, India
|How to cite this article:|
Ray G. Trends of chronic liver disease in a tertiary care referral hospital in Eastern India. Indian J Public Health 2014;58:186-94
|How to cite this URL:|
Ray G. Trends of chronic liver disease in a tertiary care referral hospital in Eastern India. Indian J Public Health [serial online] 2014 [cited 2020 Feb 26];58:186-94. Available from: http://www.ijph.in/text.asp?2014/58/3/186/138630
| Introduction|| |
Though medical literature is replete with Indian data on various clinical aspects of chronic liver disease (CLD) such as etiology, clinical presentation, natural history, treatment results, and outcome the public health aspects of the disease like its temporal trend or the burden of morbidity and mortality has never received attention as in Europe, USA or Australia. ,,,,,,, Studying a disease trend over a certain time period is important as it not only keeps surveillance on fluctuation of its various aspects over time, but focuses its importance in a country's public health system (including social changes that may have a bearing on it) and thus guides agencies (governmental and nongovernmental) to prioritize funds and other measures for its control. Knowing the exact burden of the disease helps in optimal, cost effective use of control measures in the country's overall disease scenario (especially in resource poor country like India). This lack of data is an important reason why government has failed to formulate effective policies for optimal use of liver transplant on a public health basis. The present study was undertaken to throw light on the above aspects.
This Tertiary Care Railway Hospital in Kolkata serves a population scattered over southern districts of the state of West Bengal and small parts of adjoining states of Jharkhand and Bihar hence the study population belonged to these areas. The medical system in Indian railways (to which the present study center belongs) caters to the need of a fixed population consisting of employees, retired employees and their dependents and thus constitutes a good platform to study time trends of diseases in a population. Each zone (like eastern zone in the present study) has a central referral hospital equipped with advanced diagnostic and therapeutic facilities (pathology, radiology, endoscopy, and surgery), specialist and super specialist doctors to which most of the difficult to treat and complicated cases are referred from a number of divisional (peripheral) hospitals within that zone (at Asansol, Malda, Kanchrapara, Howrah, Liluah), which provide primary care and maintenance care of chronic illness as guided by the central hospital. Railway rules mandate referral always to the central hospital and if any treatment is obtained in other hospital, the expenses are reimbursed through the central hospital. Thus as the beneficiaries get treatment at railway expense here, all come to the record of the central hospital and the diagnostic trend here gives a good reflection of disease scenario in this population. Moreover all beneficiaries, especially those needing prolonged or lifelong follow-up care, are provided with a treatment record book where their condition and prescribed treatment are recorded at each follow-up visit or admission whether at divisional or central hospital so old records can be easily retrieved.
| Materials and Methods|| |
This study of CLD was carried out on patients attending this hospital from January 2003 to December 2011 (except 23 cases who already had disease at entry for whom data was retrieved retrospectively). Outdoor (treatment book), indoor (bed ticket), endoscopy unit (for records of diagnosis and treatment of esophageal and gastric varices) and mortality records (death certificate including ICD number 571, 070, K70, K73) were searched for completeness of data and relevant parameters were noted, e.g., age, sex, etiology, clinical features, treatment, and mortality. In case of any missing data, divisional hospitals were consulted. The disease duration was considered from the date of diagnosis until mortality or end of study period.
Etiology and diagnosis of CLD was based on history and clinical features (gastrointestinal bleed, ascites, jaundice, encephalopathy, splenomegaly, abdominal veins) and confirmed by biochemical, ultrasonological, endoscopic, serological and histologic tests as appropriate. Only those patients were included whose complete records and follow-up were available. Being a nonliver transplant set up (so without a chance of alteration of natural history from it), treatment with curative intent with standard drug protocol could be given only to cases of hepatitis B and C, autoimmune hepatitis and Wilson's disease. Only conservative treatment could be offered to cases of alcohol related CLD (alcoholic liver disease [ALD]) and cryptogenic CLD (cryptogenic cirrhosis [CC]) including control of precipitating factor like alcohol, obesity and diabetes mellitus (DM). Fasting plasma glucose of more than 126 mg/dl on more than one occasion or a post prandial glucose more than 200 mg/dl was defined as DM. A body mass index of 25 kg/m 2 or more was labeled as obesity. In most cases of ALD, history of alcohol abuse was either self-reported or told by family members and confirmed by CAGE questionnaire. CC was diagnosed when no other etiology was found with/without DM or fatty liver.
Eligible hepatitis B (hepatitis B virus [HBV]) patients were treated with
- Injection interferon (either interferon alpha 3 MIU alternate day or pegylated interferon alpha 2b 1.5 mcg/kg subcutaneous weekly),
- Nucleoside analogs (NA) for 6 months to 1 year either singly or in combination. Primary end point of therapy was DNA negativity.
Eligible cases of hepatitis C (hepatitis C virus [HCV]) received injection interferon (either interferon alpha 3 MIU alternate day or pegylated interferon alpha 2b 1.5 mcg/kg subcutaneous weekly with capsule ribavirin 15 mg/kg/day for 6 months (in case of genotype 2, 3) or 1 year (for other genotypes). Primary end point of therapy was RNA negativity. Complications were managed appropriately. The study was approved by the hospital Ethics Committee.
Student's t-test for continuous variables and Chi-square test for discrete variables were used to test significance. Cochran-Armitage trend test was used to test significance of any trend. All these tests were done using MS Excel and its XLSTAT version. Binary logistic regression analysis of various factors (using SPSS version 13: SPSS production facility Release 13.0, ©SPSS Inc. 2001.) was carried out to study their effect on the liver related mortality (LRM) of hepatitis B and C cases. For both common factors were age, sex, viral load, treatment given, sustained virologic response (SVR) rate, disease state at presentation (compensated vs. decompensated), follow-up, presence of other diseases (including DM) and hepatocellular carcinoma (HCC), and mode of transmission. For HBV only, the e antigen status (i.e., e positive [+ve]/DNA +ve, e negative [−ve]/DNA positive, e −ve/DNA −ve) and e seroconversion were studied also. Two-sided P < 0.05 was considered as significant. Survival curves were generated using Kaplan-Meyer analysis for significant factors.
| Results|| |
Alcoholic liver disease showed a significant rising trend and CC showed the reverse though overall it still remains the most important etiology. Though hepatitis B and C showed nonsignificant trend, hepatitis B still leads hepatitis C in number though the latter is increasing in importance [Table 1]. A combination of alcohol and viruses was found in 5.2% (16/305) cases.
Clinical features and treatment
The results are shown in [Table 2] and [Table 3]. ALD and HBV presents at significantly lower age than HCV and CC, but a large percentage of ALD already has decompensated disease at presentation.
For HBV, 111/205 (54.1%) patients qualified for treatment, 81 with curative intent.
- Interferons were given to 22 cases (20 e +ve, 2 e −ve) with (four cases) or without NA for 6 months (20 cases) to 12 months (two cases). Though 21 (95.5%) had end-of-treatment response, SVR was seen in 7 (33.3%) cases (all e +ve). However, on long-term follow-up SVR was sustained in four cases only (19%)
- Only NA were given to 89 (23 e +ve, 66 e −ve). Eighty four responded at the end of 1 year, but SVR was achieved in only 8 (9.5%). Drugs used were lamivudine (50), entecavir (32), adefovir (4), telbivudine (1), tenofovir (2).
For HCV 40 qualified for treatment with curative intent, genotype (G)3-27, G1-7, G 2, 4, 6-1 each. 31 (77.5%) had SVR (G3-27, G1-3, G2-1) though end-of-treatment response was observed in 38 (95%). Relapse was seen in 8 (20%) cases, all G3.
Overall 37/919 (4%) had hepatocellular carcinoma (HCC) and mean age at presentation was 65.9 + 6.9 years. It was present at the first visit in all 13 cases of HBV and HCV associated HCC, whereas the figure for CC was 18/24 (75%).
The results are shown in [Table 4] and [Figure 1], [Figure 2] and [Figure 3]. CLD accounts for 6% (5.46-8.21%) of all cause hospital mortality over the years. Overall ALD had the highest mortality which showed significantly rising trend over the years (paralleling the increasing incidence) as also the lowest age at mortality. CC had longer survival even without definitive treatment compared with ALD. Multivariate analysis for HBV revealed decompensated liver disease at presentation to be positive predictor (odds ratio [OR]: 393.54 [confidence interval [CI]: 29.36-5274.85]) of LRM when all cases were analyzed together as well as separately for e +ve cases. Female sex (OR: 0.13 [CI: 0.02-0.93]) and e negative status (OR: 0.1 [CI: 0.01-1.06]) were weak negative predictors of LRM. Kaplan-Meyer plots in addition revealed SVR and giving treatment to reduce mortality significantly. Multivariate analysis for HCV revealed decompensated liver disease at presentation (OR: 9.37 (CI: 2.36-37.19)) and offering no treatment (OR: 8.34 [CI: 2.19-31.79]) to be positive predictors of LRM (both factors may be interrelated). Kaplan-Meyer plots in addition revealed SVR to be a negative predictor only when treated cases were considered. Thus mortality for HBV and HCV were significantly reduced by administration of definitive therapy in compensated CLD cases. Mortality was least with HBV. In 15.8% (26/165) of deaths due to CC had DM.
|Figure 2: Kaplan-Meyer curves for significant factors associated with survival of hepatitis C patients|
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|Figure 3: Kaplan-Meyer curves for significant factors associated with survival of hepatitis B patients|
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| Discussion|| |
This is the first study on the temporal trend of CLD from India and possibly also from Asia. Unlike the West (where alcohol and HCV are the principle causes of CLD), HBV still holds its sway and leads HCV as etiology in India though alcohol has fast caught up, especially after 2007 and is the leading cause of CLD related morbidity and mortality burden in 2010-2011. This is the chief point of interest in the study and is in stark contrast to our own previous observation 10 years back from the same region.  A recent publication  highlighting the "alcohol situation in India" strongly supports and possibly underlines the reason of our present observation. This article highlighted that about 21% of adult men and 2% of adult women drink alcohol, of them 20% are "problem" drinkers. The number of drinkers in young age has increased (2 to 14% in past 15 years) along with lower age of initiation (19-13 years). Two-thirds of alcohol drunk is unrecorded. The resources spent by government on addiction problem focuses on those in "acute need" (4% of alcohol population) rather on "at risk" population" (20% of alcohol population). 
Alcoholism is even more rampant in our study population (being an industrial population) resulting in the booming of ALD related morbidity and mortality in last few years. Even in a multiracial Asian population as in Malaysia, Indians have the maximum number of alcoholic cirrhosis (>50%). ALD burden in other parts of Asia mirror their local social and religious culture so that it is very high in Nepal, intermediate in Japan and South Korea (effect of westernization), low in other South East Asian countries and very low in Iran, Turkey and Pakistan [Table 5]. ,,,,,,,,,,,,,,,,,,, The high death rates from ALD in our study are also due to persistence of alcohol consumption even after onset of liver disease rather than due to alcohol etiology per se. It is noticed that even short period of abstinence after early decompensation improves liver function and quality of life. However, recidivism is very high and patients are not motivated to leave the habit on long-term even with psychiatric support. In addition lack of awareness of the disease, not caring for mild early symptoms, fear of having to stop drinking on doctors' advice, heavy continuous drinking with repeated violent behavior in inebriated state leading to social and family segregation all lead to late seeking of medical advice when the disease is advanced.
Though trend data from Asia is scarce, good amount of data is available from the developed world and even these all consistently show alcohol to be the strongest determinant of CLD morbidity and mortality trends. ,,,,,,, Worldwide data from 41 countries  revealed decreasing LRM except UK, Central and Eastern Europe, supported by other trend studies from UK. ,, CLD mortality doubled (from 1979 to 2005), two-third due to alcohol, highest in age group 45-64 and maximum percentage increase in 25-35 year age group.  Two studies from USA show strong correlation between alcohol consumption and cirrhosis mortality by both longitudinal and cross-sectional data from 1935 to 1996  and highest CLD mortality due to alcohol (39%) in 1990-1998.  One population based surveillance study on epidemiology of new CLD cases in USA  showed alcohol (30%) to be second cause after HCV where 18% presented with cirrhosis of whom 44% were due to alcohol. A very recent Australian study  showed increasing hospital admission due to ALD, especially due to cirrhosis in the 20-29 year age group.
All of the above study supports the findings of our study, namely increasing burden of ALD affecting younger work force hinting the fact that with westernization, India and Asia will follow suit. Since mortality mainly affects people in their most productive working age, its impact on national economy is disastrous. In addition, man days loss due to sickness absenteeism (very few people with alcohol dependence return to normal work) and expenditure on treatment adds to further economic loss. As is known in India that alcohol-related problems account for more than a fifth of hospital admissions including psychiatric emergencies, domestic violence, injuries, liver problems, India is in dire need of a national alcohol policy but the woeful lack of data and research on its health, social, and economic effect is an impediment.  Our present study definitely foresee an alcohol menace in the coming years and may act as an early guide for government policy in this direction.
Regarding HBV and HCV related CLD our study is consistent with other Asian countries with HBV still leading HCV and the mortality patterns reflecting access to medical facility, treatment affordability, liver disease status (and so the age) at presentation, early detection by population screening (as evident from our finding of decompensated liver disease at presentation and giving treatment being factors affecting outcome). The reason for HBV mortality being least is because the younger average age of presentation and a large percentage having e −ve/DNA −ve carrier state with excellent prognosis. This is also why HCC is much less with HBV. The increase in number of HCV cases compared to ours and other older Indian studies , may be due to the routine HCV screening which has started only recently (most of our cases were detected at screening). CC is low in most South East Asian countries (except Malaysia, Thailand near India) of whom one-third are diabetic.  India harbors a high proportion of CC [Table 5] as is evident from our study also possibly due to high prevalence of DM and nondiabetic metabolic syndrome in the region. , The decreasing trend in percentage of CC may reflect a true decrease due to better treatment of its chief precipitating factor, that is, diabetes but more likely due to increasing percentage of ALD. CC and HCV affects population of higher age than ALD and HBV. Survival for CC even with supportive treatment is good and definitive treatment is available for HCV. Though HBV affects younger population fortunately most patients are carriers who lead normal productive life for long periods and even when affected by hepatitis, available drugs better life expectancy. Thus in a resource poor country like India the costly option of liver transplantation can be judiciously chosen for end stage liver disease resulting from these etiologies, considering their reasonably good survival with treatment.
| Conclusion|| |
A significant rising trend of ALD related morbidity and mortality was observed which need urgent social and medical intervention. Therapy improves survival of hepatitis B and C patients hence their early diagnosis and treatment is important in decreasing morbidity. CC has good survival even with supportive treatment.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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