In General

Liver cirrhosis and liver cancer are the major health problems in Asia. This is because various causes of chronic liver diseases are common in many parts of Asia. Chronic hepatitis B is common in countries like China, Hong Kong, Thailand, and Taiwan, with approximately 10-20% of the general population being hepatitis B carriers. Chronic hepatitis C is also common in certain countries such as Mongolia, Pakistan, Myanmar, and parts of Indonesia. In addition, fatty liver disease, a disease that is associated with prosperity such as overweight, obesity, hypertension, and diabetes mellitus is also becoming more prevalent in Asia, as many Asian countries are enjoying good economic growth and prosperity over last few decades.

There is little official data on prevalence of liver diseases in Cambodia. But my own person anecdotal experience suggest both hepatitis B and C are prevalent in Cambodia.

 Hepatitis B

Many potent antiviral agents are now available to treat chronic hepatitis B but with lesser side effects. About 2 decades ago, the only available treatment for hepatitis B was standard interferon, requiring three injections every week, and was associated with significant adverse effects. But newer and better-tolerated oral agents against hepatitis B have been available for the last 10 yrears.

The first generation of oral antiviral agents was lamivudine (Zeffix?). It has similar potency as standard interferon but was not associated with so much adverse effects. However, hepatologists soon realized that longterm usage of lamivudine was associated with development of hepatitis B virus mutation, at a rate of 15% yearly. In other words, lamivudine loses its efficacy after a few years. 

The second generation of oral agents was adefovir (Hepsera?). It is associated with lesser risk of hepatitis B mutation, but unfortunately, it was associated with small percentage of renal toxicity.

The latest generation of medicines was entecavir (Baraclude?). It is the most potent antiviral agent against hepatitis B, but was not associated with adverse effects such as hepatitis B resistance, or kidney toxicity. Recently, another new drug, telbuvidine (Sebiro?), became available but the use of telbuvidine was also associated with 10% of hepatitis B resistance so its use is not widespread.

Recent studies from Taiwan and China have also showed that level of hepatitis B virus is directly related to risk of development of cirrhosis and liver cancer. Hence, it is not standard practice for many hepatologists to use medication such as entecavir to suppress hepatitis B viral load so as to reduce risk of development of complication

It is, however, important to realize that current antiviral agents are expensive and not completely risk-free so patients with hepatitis B must consult a hepatologist or gastroenterologist before commencing on any antiviral agents.

Hepatitis C

The standard treatment for hepatitis C is pegylated interferon pluse ribavirin. The old, standard interferon, which requires thrice weekly injection is now outdated. Pegylated interferon only requires a weekly injection so administration is much more convenient. 

Pegylated interferon plus ribavirin is used for 6-12 months, depending on the genotype of the hepatitis C virus which the patient is harbouring. Approximately 50-90% of hepatitis C patients can now be cured of the virus.

Though pegylated interferon and ribavirin are associated with significant adverse effects, effect medicines are now available to counteract the adverse effects to enhance compliance.

Newer anti-hepatitis C treatment such as protease inhibitors are currently under investigations  and should be available to the public in 3-5 years? time

Fatty liver disease

With better nutrition, prosperity, and western lifestyle, more and more Asians are now having problems like obesity, hypertension, and diabetes mellitus. These factors are now also known to cause a newly recognized liver disease called fatty liver disease. To date, studies on medication  to cure fatty liver disease have not been successful. The only proven treatment for fatty liver disease remains weight loss, doing regular exercise, and eating a healthy diet.

Liver cirrhosis

Liver cirrhosis is an endstage liver disease characterized by significant scarring of the liver. It is the end result of chronic liver injuries such as chronic hepatitis B, C, and fatty liver disease. As the liver performs many functions for the human body like maintaining water balance, nutrition, fighting infection, removing toxins, etc, patients with liver cirrhosis also suffer from complications like accumulation of fluid in the abdomen, weight loss, infection, and mental confusion. (Figure 1)

Management of cirrhosis is divided into palliative and curative. Palliative treatment aims at relieving symptoms of complications of cirrhosis, such as endoscopic variceal ligation for variceal bleeding, diuretics for ascites, laxatives for hepatic encephalopathy. But palliative measures do not prolong lifespan of patients with advanced cirrhosis, which in general, is less than 2 years. Definitive treatment is liver transplantation, where the whole sick liver is removed and a new piece put in for replacement.  

Liver cancer

Liver cancer is the 3rd commonest cancer in Singaporean males, and is among the top cancers in most Asian countries. Similar to many other cancers, patients with early liver cancer do not have any symptoms. By the time patients present with symptoms like abdominal pain, weight loss, or jaundice, their cancer is already in the advanced stage. (Figure 2)

It is recommended that patients with any form of chronic liver diseases such as hepatitis B or C to be reviewed by a doctor every 6-12 months to screen for any caner. Liver cancer that is diagnosed on screening is usually still in the curable stage.

Management of hepatocellular carcinoma is also divided into palliative and curative. Palliative measures include chemoembolisation, radiofrequency ablation, and systemic chemotherapy. Unfortunately, survival of patients with any of these palliative measures is poor, and most patients die within 18 months. Even with the latest oral chemotherapy agent, Sorafenib, only prolongs median survival of patients with unresectable HCC from 8 to 11 months. Longterm cure is unattainable.

Curative treatment for liver cancer consists of either surgical resection or liver transplant. If the tumor is limited within anatomical margin, with good remaining liver reserve, then liver resection is the best treatment. But for patients with liver cancer spaning both left and right lobes of the liver, or if the liver reserve is poor due to presence of cirrhosis, then liver transplant would be the best treatment, as it removes the cancer, and replaces the cirrhotic liver

Live donor liver transplant

The human liver has an extraordinary reserve and potential to regenerate. A healthy person can lose 70% of his/her liver, and the remnant liver would be sufficient to maintain normal liver function. And within 2 months, the liver would regain almost 100% of its original function. And by 12 months, the liver would have regrow to its original size. It is this regenerative potential that allows us to perform liver donor liver transplant.

At the time of transplant, the whole liver of a cirrhotic patient is removed. Concurrently, 50-60% of a healthy liver is removed from the healthy donor, which is then repositioned, or transplanted, into the cirrhotic patient. By 8 weeks, both the patient and the donor would have regain their liver function. And both can live well afterwards.

Criteria for being a liver donor are (1) healthy; (2) of compatible blood group; (3) volunteering without cohersion or financial gain; (4) emotionally or genetically related. At our center, 25-30 liver donor liver transplants are performed yearly. 70% of the donors are relatives of the patients like their children, parents, or nephews. The other 30% of donors are friends, employees, or colleagues of the patients.

Nowadays, at experienced centers such as our unit in Singapore, longterm survival rate after live donor liver transplant is approximately 85%, giving a new lease of life to many patients with liver cirrhosis and liver cancer.

Conclusion

Many new treatments are now available for individual liver diseases such as hepatitis B, C, and fatty liver disease. However, once the patient develops cirrhosis or liver cancer, they must be quickly evaluated at a tertiary liver center, and to consider various palliative and curative options including live donor liver transplant. 

By Dr Desmond  Wai, Consultant Gastroenterologist and Hepatologist
Asian Center for Liver Diseases and Transplantation, Gleneagles Hospital

Healthline.com recently launched a free interactive “Human Body Maps” tool. To make use of this tool, you may visit here: http://www.healthline.com/human-body-maps/liver

 Stay Healthy!

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