8th International Symposium On Alcoholic Liver And Pancreatic Diseases And Cirrhosis
ILBS hosted the “The 8th International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis (ISALPD/C)” in New Delhi from Nov 15-17, 2013. This Symposium held in conjunction with National Institute for Alcohol Abuse and Alcoholism and National Institute of Health (NIAAA/NIH), USA had a panel of over a dozen world class specialists talking on this subject over two days. About 400 national and 200 international delegates are expected to attend the same.
Exciting Discoveries shown in the treatment of difficult to treat Hepatitis C virus infection
On 15th Nov there was a preconference symposium on various aspects of Hepatitis C Virus (HCV). Hepatitis C Virus infects about 1 percent of the population of India. Moreover, HCV can coexist with other viruses like HIV and hepatitis B. Coexistence of these viruses with HCV leads to accelerated course of HCV infection and present unique challenges for treatment of such patients. The experts discussed various aspects of natural history and management of such co-infected patients.
About 170 million people around the world are infected with hepatitis C. The standard treatment until recently was interferon injection along with oral drug Ribavirin. This regimen is effective in only 40-50% of genotype 1 patients and about 70% of HCV infected patients with genotype 3. Rest of the patients do not respond to conventional therapy. Interferon injections have many side effects including decreasing blood counts, fever, fatigue, depression etc. About ten percent of the patients are not able to tolerate this therapy and so the treatment has to be discontinued. Experts in this area discussed various treatment options for such patients.
HCV also poses unique challenges in kidney and liver transplant recipients. Various management issues were discussed in such difficult to treat patients were discussed by Dr. Hari Conjeevaram from University of Michigan, USA.
New drugs acting against hepatitis C Virus have become available in recent times in India. Dr. Shyam Kottilil presented the data about newer breakthrough drugs Sofusbuvir and simepravir, which are likely to get the FDA approval in the next few weeks and act against the virus at critical steps in its replication. Prof Shiv Kumar Sarin, Director of Institute of Liver and Biliary Sciences (ILBS), New Delhi, discussed the role of Boceprevir in combination with Pegylated Interferon and Ribavirin. Recent trials have demonstrated excellent cure rates to the tune of 80-90% among patients of Hepatitis C including those patients who have failed previous therapy. These interferon free drug regimes are a major breakthrough in the treatment of Hepatitis C and likely to be available soon in India (See Figure). These new drugs also give hope to thousands of kidney transplanted patients with hepatitis C or those on dialysis waiting for transplantation.
Hepatitis C universally reinfects the new liver after transplantation. Prof. Didier Samuel, honorary professor of Hepatology and Gastroenterology from University of Paris, Villejuif, France, showed new data on the benefit of using bocepravir and other directly acting antiviral agents (DAAs) in patients who had received liver transplant in the past.
Alcohol liver and pancreatic disease – Newer frontiers in mechanisms and management
Drink alcohol to reduce your immunity and increase chances of cancers – any hopes !
At this international event, various national and international experts of the field discussed the various mechanisms of liver and pancreatic damage secondary to alcohol intake and also brought into light a plethora of newer drugs and interventions available for such patients.
Globally, alcohol consumption and its medical harmful effects are on the increase. Liver and Pancreas are two major end organs effected. In India, alcohol comprises more than half of all causes of cirrhosis in adults. Patients with alcoholic liver disease (ALD) often present late with limited treatment options and high morbidity and mortality in the form end stage liver disease and liver cancer. Viral and bacterial infections add-up to the poor outcome in these patients.
Chronic use of alcohol leads to decrease in the body host defenses, thus increasing susceptibility to infections including pneumonia. Alcohol also interferes with several host anti-tumor mechanisms, thereby facilitating tumor development. Ongoing research is enhancing our insights into alcohol-induced liver cancer (HCC) formation and offers hope in developing better therapeutics.
Factors accentutating liver injury are dose, duration and patterns of alcohol use, age, gender, race/ethnicity, obesity and diabetes. Obese persons who drink alcohol have further high risk of liver cancer – thus both the culprits act in a synergistic way. Role of obesity was discussed by Prof Hari Conjeevaram from University of Michigan, USA.
Chronic alcoholics suffer from malnutrition. This is again responsible for their poor immunity to fight against infections. Nutritional therapy forms an important component in their management.
Alcoholic hepatitis is a unique scenario which develops when a chronic alcoholic patient goes on a binge leading to exacerbation of liver injury. There is deep jaundice with rapid worsening of liver functions. This condition, when severe, has a 40-50% mortality within a month of presentation. Corticosteroids and pentoxifylline, only available current treatment options, provide only about 50% survival benefit. Emerging data on the benefit of liver transplantation for select patients with first episode of severe alcoholic hepatitis with non-response to steroids are encouraging.
Recently, therapeutic targets that inhibit inflammation, ameliorate hepatocyte death, and promote liver repair in ALD, have ben identified and many new drugs have become available to treat alcohol related liver injury. Some of these options were discussed by Prof Bin Gao, Chief, Laboratory of Liver Diseases, National Institute of Alcohol abuse and Alcoholism (NIAAA).
Liver Cancer or Hepatocellular carcinoma (HCC)
Liver cancer also known as Hepatocellular carcinoma (HCC) is one of the common cancers in India. Nearly 350 new cases of liver cancer are seen at the Institute of Liver and Biliary Sciences (ILBS), New Delhi. It has been observed that besides the hepatitis B and C viruses, the commonest causes of liver cancer are fatty liver disease, diabetes and alcohol. In fact, Dr Keigo Machida showed experimental data that hepatitis C infection in animals on high fat diet and drinking alcohol have 65 times more chances of development of liver cancer – thus ‘One and one evil make eleven’.
Unfortunately, majority of patients with liver cancer come very late to the doctors. Dr Takahiro Yamashika from Japan showed a new therapy ; by depleting iron from the body by giving common drugs like desferroxamine. These workers had shown in a seminal paper in the New England Journal of medicine that by chelating iron, many patients with unresectable liver cancer can have a prolonged life. Prof. Yaron Ilan from Israel showed new data on oral immune therapy by giving hepatitis B orally and suppressing liver injury and growth of HCC. Immune therapy for HCC is a new exciting area that revives hope for treating liver cancer.
Irreversible Electroporation (IRE) is a new ablation technique where cell death is achieved by short electrical pulses with a high voltage but low ampere. This causes cell death without causing heat, no damage to tissue. This exciting strategy has been used in advanced pancreatic cancer or liver tumours, with good success. Dr Anders Nilsson from Germany showed the beneficial role of IRE on various cancers including liver and pancreatic cancers.
Organ dysfunction in Liver disease
Kidney involvement in Liver disease – Role of liver dialysis
On 17th November, dedicated national and international hepatologists discussed the prevalence and mechanisms of infections in liver disease patients and also how come simple infections cause multi-organ dysfunction and pose a threat to life in a cirrhotic individual.
Alcohol, hepatitis B, hepatitis C and Non –alcohol fatty liver disease are important causes of end-stage liver disease or cirrhosis in the country. Acute insult over such a diseased liver culminates into rapid deterioration of liver functions and a state of liver failure which is a more serious condition known as Acute on Chronic liver failure (ACLF). Alcohol constitutes the majority (~ two-thirds) of causes of ACLF and mostly affects the young patients. Majority of patients with ACLF i.e.in 60-70% require liver transplantation on an emergency basis, but that itself is a difficult option in scenarios with living-donor liver transplantation and the huge cost involved. Toxin mediated injury is primarily responsible for vital organ dysfunction like kidneys, brain, circulatory and immune systems in patients with ACLF which makes these patients different from patients with cirrhosis.
Liver dialysis is a special form of treatment which is almost similar to kidney dialysis, only difference being it, in addition, also removes liver related toxins which are albumin bound. Usage of liver dialysis in cases with ACLF has shown definite improvement in liver and renal functions by removal of the circulating toxins.
Kidney damage is very serious complication in patients with cirrhosis and is amongst one of the important parameters to decide the need of liver transplantation in the commonly used MELD score across the world. Kidney involvement is very rapid and more common (~51%) in ACLF patients as compared to patients with cirrhosis (~32%) and is associated with higher risk of mortality in these patients as seen from the data of our own experience of patients of cirrhosis (~3000) and of ACLF (~700) in ILBS over the last 4 years. Also the drugs which improve kidney failure in only 50% patients with cirrhosis are even less effective in patients with ACLF because the mechanism of damage to kidney is different from patients with cirrhosis i.e it is mostly toxin-mediated. The mortality of patients with ACLF without kidney failure is only 30 % as against 70% in patients who also get kidney failure and in these patients even liver transplantation cannot be done. In such patients liver dialysis could be an effective therapy as it can improve kidney functions and hence can be used also as a bridging therapy to transplantation.
ISALPD/C 2013 symposium thus provided a special research platform and an outstanding forum for exchanging the newest and cutting-edge research on both clinical problems and basic molecular mechanisms underlying alcoholic liver and pancreatic diseases and Hepatitis C. World renowned national and international experts contributed on the best way forward.