| ENTECAVIR (Baraclude)- Newest drug for hepatitis-B viral infection:
A London New drugs group publication- February-2007
Hyperactivity of the spleen, an organ that usually bears the brunt of high pressure in the portal vein, is relatively common among patients with liver cirrhosis. This hyperactivity results in drop in the red blood cell, white blood cell and the platelet counts along with enlargement of the organ. Some times the organ is so large that it can be easily felt in the abdomen and it may also cause pain in the left loin. This condition assumes greater importance in the cirrhotics since they have a tendency to bleed and some cannot undertake anti-viral treatment for hepatitis-B or C, a sthe cell count is dangerously low.
The conditions that cause hypersplenism are:
The complications are usually- pain and fever. Rarely serious infection of the dead area of the spleen has been reported. In author's personal experience there was no incidence of serious infection or abscess as adequate precautions and use of antibiotics can prevent this potentially serious complication.
Liver transplantation for Cholangiocarcinoma:
Until recent times hilar cholangiocarcinoma or cancer of the bile duct bifurcation was considered a sinister disease with very poor outcome (< 20% 3 year survival after transplant). The results following liver transplantation has generally been poor, with rapid recurrence of disease. However the clinical research published from Mayo clinic college, Rochester, MN, USA, by Rea DJ et.al, in Annals of surgery-2005-September has given a ray of hope for the patients who suffer from early cholangiocarcinoma (ie; stage-I and II). In the published data on liver transplantation in 38 of the 71 patients enrolled for the study, the one, three and five year survival of patients after neoadjuvant chemoradiation (treatment protocol in a nut shell- External beam radiation of 4500 cGy in 30 fractions with 5FU 500mg/Sq m daily bolus for first 3 days of radiation. Two to three weeks after external beam radiation, transcatheter iridium-192 brachytherapy was given with a target of 2000 - 3000 cGy. Oral Capecitabine (2000mg/ Sq m/Day) was continued until transplant. Survival after staging laparotomy and liver transplant was 92%, 82% and 82% respectively as compared to that after resection, namely 82%, 48% and 21% respectively. The post transplant disease recurrence was 13% vs recurrence after surgical resection - 27%. In essence for the first time long term results after transplantation was far superior to that of surgical resection according to the conclusions of the study. This is certainly a major advancement in treatment of this disease which caries a very poor prognosis.
TheraSphere treatment for liver cancer: Radioembolzation with Yitrium90 microsperes is the newest state of the art radiation treatment for primary and secondary liver cancer. The versatility of this modality to treat early and advanced cancers of the liver is truly amazing. Cost apart, it is the best form of treatment for very large or deep seated, inoperable liver cancers.
Y-90 Therasphere is an insoluble, biocompatible glass matrix with radioactive Yitrium-90 isotope as an integral constituent. The size of the spheres is around 0.4 microns, little bigger than a red blood cell. The Beta radiation emitted per sphere is around 2500 Bq. These spheres are provided in a liquid suspension that is ready for injection in unit doses ranging from 3 to 20 GBq. The required dose of radiation for a given is calculated by complex dosimetry involving calculations based on the target vascular bed in the liver in which the tumour lies. The microspheres are injected selectively through micro catheters under X-ray imaging into the vessels that supply the tumour in the liver. These spheres then get entrapped in the tumour microvasculature and emit radiation to the surrounding tumour until the radiation decays. Since the tumours are more vascular than the surrounding liver, they tend to trap most of the radioactive spheres in the tumour bed. The effect of radiation is limited to approximately 2 cm surrounding the bead. This natural selection is the greatest advantage of this technique. The tumour radiation is maximized without much radiation injury to the normal liver and the concentrated dose of radiation received by the tumour is several fold higher than what can normally be given by conventional external radiation techniques. 50% of the tumours treated show significant response as shown by volume reduction on CT scan and 80% show response when pre and post treatment PET scans are compared. These results are irrespective of the tumour size and numbers.
Even tumours in cirrhotic livers, vascular metastatic tumours and tumours invading the portal vein with portal vein thrombosis have been treated with varying degrees of success. The adverse reactions are tolerable and include fatigue, mild abdominal pain or discomfort, nausea and rarely stomach ulceration(related to faulty technique). It is conceivable that in the near future this treatment platform will be made suitable to treat various tumours of other solid organs (like brain tumours) as well. This technique could also become a bridge to those patients waiting for a liver transplant, who also develop cancers before or after getting on to the waiting list, by keeping the cancer in check until a cadaver liver becomes available. The only downside seems to be the cost of therapy (around 15000 USD/ treatment). The contraindications include evidence of advanced liver failure and presence of high lung shunting as shown by Tcm-MAA scans. The TheraSphere treatment is now available at selected centers in India.
MARS - THE LIVER SUPPORT SYSTEM
Liver is the storehouse of energy in the body. It is also the powerhouse for detoxification of toxins from various sources in the body and drugs, the notable among them being bile acids, bilirubin, aromatic amino acids, Indole/Phenol metabolites, toxic fatty acids, Thiols, Digoxin, Benzodiazepine agonists, Ammonia, Lactate, Diazepam, Teicoplanin, Ceftriaxone, Phenytoin, Furosemide, Ibuprofen, Glibenclamide, Naproxen, Haloperidol, Quinalapril, etc. In case of liver failure, the toxins accumulate in the body and produce widespread effects on the vital organs predominantly Kidneys and Brain. Liver has great regenerating capacity and hence as little as 30% of healthy liver may be able to support the vital functions of the body.
Patients with liver damage present in one of the following ways: -
Liver transplant is a one time solution for a failing liver. It however is a major procedure and carries a moderate risk of mortality as well as significant morbidity. The patients are on life-long follow-up and immunosuppressant drugs. There is however a huge gap between the demand and availability of cadaver livers. A large number of patients therefore die while on the waiting list for liver transplant. In such cases, MARS can be used to support the patient till the cadaver / donor for liver can be found. In cases, where the general condition of the patient is not good secondary to liver disease, the surgery carries very high risk. These patients can be improved with MARS therapy so that they are able to tolerate the surgery better.
How does MARS function?
Some of the toxins mentioned above and drugs are water-soluble and others are water insoluble. The ones soluble in water can be removed by conventional dialysis used for Kidney disease but those that are albumin bound require special treatment. MARS is based on the principle of albumin dialysis. Thus, the toxins that are water insoluble and are normally degraded in the liver can be selectively removed from the blood by MARS
The patient's blood is detoxified in a filter unit (MARS FLUX). Blood and cleaning fluid (human serum albumin) flow past each other, separated by a membrane. There is never any contact between patient blood and the adsorber columns. The cleaning fluid is freed from toxins, recirculated and reused for blood detoxification. Thus, a fixed amount of albumin (dialysate) is used for a cycle (600 ml of 20 % Hyman Albumin).
The system consists of two main components: