Liver: A vital organ in the human body.
The liver (Jigger) is the largest organ in the human body that works like an engine and performs more than 500 vital functions which amongst others include the formation of bile and several proteins, storing glycogen as a ready source of blood glucose, metabolism of nutrients, detoxification of drugs and other toxic products including NH3 and regulation of blood clotting.
There are more than a hundred different liver diseases of diverse nature that are being identified as the leading causes of disability, disease, and death globally.
Liver diseases are broadly caused by hepatitis viruses (A to E), alcohol, non-alcoholic fatty liver disease (NAFLD), drugs, autoimmune and genetic diseases, cryptogenic and liver tumors-benign and malignant.
Liver deaths occur predominantly because of liver cirrhosis, acute liver failure, and liver cancer and account for over 2 million deaths globally per year.
Liver diseases in India: an ongoing epidemic.
Liver disease is fast spreading like an epidemic in India with one out of every five adults getting affected. Liver-related deaths in India have reached a staggering figure of 268,580 (3.17% of all deaths) per year contributing to 18.3% of global 2 million liver-related deaths.
Worrying are the data that liver disease deaths in India have shown a study increase from 1980 onwards as against China where it remained stationary and even showed a downward trend (Fig). Liver disease has made a significant impact on the economy and healthcare resources in India.
Apart from the causes of liver diseases seen in the West, India has the distinction that several tropical diseases affect the liver and are significant players in the story of disease, disability, and death. It is satisfying to know that our group has identified several of these diseases and made significant advances in their epidemiology, natural course, management, and control. These include hepatitis E, hepatobiliary and pancreatic ascariasis, hydatid disease with an innovative PAIR technique to treat it, portal biliopathy (a biliary disease in those with portal cavernoma), and hepatolithiasis (gallstones in hepatic ducts and liver parenchyma as an aftermath of dead worms). Other tropical diseases which affect the liver include portal cavernoma, amebic liver abscesses, malaria, leptospirosis, scrub typhus, drug hepatitis caused by anti-tubercular drugs, herbal medications, and yellow phosphorus poisoning. In addition, challenges faced in managing liver diseases in India include limitations of resources and healthcare facilities, cultural beliefs, dependence on untested and unproven traditional practices and herbal medication, lack of education on the transmission of infections causing liver diseases, and poor socio-economic conditions which support the spread of disease.
Hepatitis B & hepatitis C
Both hepatitis B and hepatitis C spread through infected blood and blood products and sharing needles, syringes, or other drug-injection equipment. In addition, hepatitis B shows mother-to-child transmission and sexual transmission, especially in men who have sex with men. Both cause acute hepatitis, chronic hepatitis, liver cirrhosis, and liver cancer. Global numbers of hepatitis B and hepatitis C are staggering. In India, the prevalence of hepatitis B surface antigen (HBsAg) is 3-4.2% with over 40 million HBV carriers and anti-HCV is around 0.5% with 4.7 to 10 million HCV carriers.
Over the years, several breakthrough measures have been adopted to fight hepatitis B and hepatitis C and India has been a beneficiary of all these measures. Screening of blood and blood products by sensitive tests has markedly reduced the risk of post-transfusion hepatitis B, hepatitis C, and HIV, though zero-risk, the ultimate goal is yet to be achieved. Unsafe injections account for 5%, 32%, and 40% of new HIV, HBV, and HCV infections in developing countries including India. WHO has organized a safe injection campaign and this has reduced new HIV, HCV & HBV infections by 87%, 83% & 91% respectively, and may lead to the ultimate goal namely the elimination of such infections. Hepatitis B vaccine has been a breakthrough in the fight against global hepatitis B. In India, hepatitis B vaccination was integrated into the Universal Immunization Program in 2011-2012, and children born after the introduction of vaccination have a lower prevalence of hepatitis B. It is a matter of pride that Govt; of India has taken aggressive steps to make costly antiviral drugs available and brought down the costs which can be afforded by the common man. Drug treatment with nucleoside analogues suppresses HBV replication resulting in biochemical remission, histological improvement, and reversal of clinical decompensation. However, HBsAg seroconversion (cure) is rare and liver cancer can continue to develop especially in those with underlying cirrhosis. Lastly, the availability of all oral direct-acting antiviral (DAA) drugs has revolutionized the treatment of hepatitis C, with a cure rate of over 90%, improved clinical outcomes, decrease mortality, and decreased the occurrence of liver cancer. Several countries including Georgia are looking for hepatitis C elimination (90% reduction in prevalence) through test and treat policies for society and have made substantial gains in this area.
Hepatitis E virus (HEV) has turned out to be the most enigmatic human agent since we discovered the agent in 1980. One-third of the World’s population is infected with hepatitis E; with an estimated 14 million symptomatic cases, 300 000 death, and 5200 stillbirths annually. In India alone, over 2.2 million cases of hepatitis E are thought to occur annually. HEV causes large-scale waterborne epidemics in developing countries involving hundreds and thousands of adult populations. Around half to two-thirds of endemic hepatitis in such countries is caused by HEV. HEV has increased incidence and severity in pregnant women and is the commonest cause of acute liver failure in our society. In recent years, hepatitis E is recognized as a clinical problem in industrialized countries. HEV agent has entered into a foodborne chain and is spread by consuming raw or undercooked pig livers available in supermarkets in such countries. Because of the impact of this infection globally, measures must be taken to control this python. Clean drinking water and safe sewage disposal are the cornerstones of control. Two HEV candidate vaccines have successfully completed phase 3 trials and are ready for prime time. The Chinese vaccine HEV-239 is safe and highly efficacious against hepatitis E and is commercially available in China and marketed as Hecolin in 30ug doses for 3 dose regimen (o, 1 and 6 mon).
Alcoholic Liver Disease
Chronic alcohol abuse is an important player in the causation of chronic liver disease and liver-related deaths. In India, around 16 crores in the age group of 10-75 are consumers of alcohol with Chhattisgarh, Tripura, Punjab, Arunachal Pradesh, and Goa having the highest prevalence of liquor use. Alcohol kills 2.6 lakh Indians every year either by causing liver cirrhosis, or cancer or leading to road accidents caused by drunk driving. The burden of alcohol-attributable liver cirrhosis and liver cancer is high and entirely preventable. Solutions for this growing epidemic must be multi-faceted and focused on both population and patient-level interventions.
Non-alcoholic Liver Disease
Non-alcoholic fatty liver disease (NAFLD) has taken us by storm globally. NAFLD is the most prevalent liver disease in human history, with prevalence estimates indicating it affects almost two billion people globally. NAFLD has become the leading cause of chronic liver disease and the number one indication for liver transplantation worldwide. Alongside progressive liver damage, NAFLD is becoming an established risk factor for other leading causes of death and disability in the twenty-first century, namely cancer, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Despite the already staggering number, the NAFLD burden is expected to grow in the coming decades, compromising individual health, burdening health- care systems, and causing substantial economic and well-being losses. Remarkable progress in the understanding of the pathogenesis of NAFLD has identified several pathways of fat accumulation and injury. However as of today, apart from a combination of a hypocaloric diet, moderate-intensity exercise, and weight loss and few pharmacological options of doubtful significance, little can be offered to patients with progressive NAFLD to arrest liver inflammation and fibrosis. Thus, prevention through changing life patterns should be the focus to control NAFLD as of today.
In this despair and hope for challenges posed by liver disease, where does liver transplantation stand in India? Liver transplant story started in India in 1998 and at present around 1800 liver transplants are performed annually in 90-100 active liver transplant centers. Unlike in the Western world, where Deceased Donor Liver transplants (DDLT) are predominant, Live Donor Liver Transplants (LDLT) constitute around 85% of transplants in India. The liver transplant program in India is facing several obstacles. There is a large discrepancy between the number of patients requiring a liver transplant and the number of transplants being done in our country. Liver transplant costs at present are exceptional, and not affordable for most families. Donor availability is another major issue. All these issues need to be addressed through ingenious means appropriate for a 1.3 billion population of diverse cultures and varying economic structures.
To conclude, for the medical fraternity in India, there have never been more challenges thrown by liver disease, and yet there shall never be more tools/hope available to us to overcome these. Thus, liver disease is passing through both despair and hope; an excellent opportunity for young minds to exploit for the better.
(Khuroo is MD, DM, FRCP (Edin), FACP, Master American College of Physicians (MACP, Emeritus).
Former Director, Professor and Head Gastroenterology, Chairman Dept. Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India.
Director, Digestive Diseases Centre, Dr.Khuroo’s Medical Clinic, Srinagar, Kashmir, India. E-mail: firstname.lastname@example.org, email@example.com, Website: www.drkhuroo.com.)
DISCLAIMER: The views and opinions expressed in this article are the personal opinions of the author.
The facts, analysis, assumptions and perspective appearing in the article do not reflect the views of GK.