Cho-Yu Chan

Legend of hepatitis B vaccination: The Taiwan experience

Hepatitis B, a disease entity currently affecting more than 350u2003million persons worldwide, is also a serious health problem in Taiwan. Liver cirrhosis and hepatoma, which are both closely correlated with hepatitis B, are among the 10 leading causes of death in Taiwan. A mass hepatitis B vaccination program, conducted by the government of Taiwan, was started in 1984. Prior to this vaccination program, a series of viral epidemiological surveys, transmission pattern studies, and pilot immunization trials proved the clinical, economic, and strategic benefits of mass immunization, thus providing the impetus for the implementation of this mass vaccination program. The success of this program has led to a decline in hepatitis B carrier rates among children in Taiwan from 10% to <1%. Furthermore, the mortality rate of fulminant hepatitis in infants and the annual incidence of childhood hepatoma have also decreased significantly in recent years. This is one of the most remarkable success stories in the field of public health.

Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure.

Hepatic encephalopathy is a complex neuropsychiatric syndrome seen secondary to acute liver failure, chronic parenchymal liver disease, or portal‐systemic anastomosis. Vasodilatation induced by nitric oxide (NO) may be involved in the development of hepatic coma. However, there are no comprehensive data concerning the effects of NO inhibition on the severity of hepatic encephalopathy.

Lack of detrimental effects of nitric oxide inhibition in bile duct-ligated rats with hepatic encephalopathy.

Backgroundu2002 The pathogenetic mechanisms of hepatic encephalopathy (HE) are not fully understood. Vasodilatation induced by nitric oxide (NO) may be involved in the development of HE. There is no comprehensive data concerning the effects of NO inhibition on HE in chronic liver disease.

Simvastatin for rats with thioacetamide-induced liver failure and encephalopathy.

Background and Aim:u2002 Nitric oxide (NO) inhibition aggravates hepatic damage and encephalopathy and increases mortality in rats with thioacetamide (TAA)‐induced acute liver failure. Statins enhance NO synthase expression beyond their lipid‐lowering capability, but the impact on encephalopathy remains unexplored. The aim of this study was to assess the effects of simvastatin on rats with TAA‐induced acute liver damage and hepatic encephalopathy.

Effects of endothelin‐1 on portal‐systemic collaterals of common bile duct‐ligated cirrhotic rats

Background/Aimsu2002 Endothelin‐1 (ET‐1) may induce intrahepatic vasoconstriction and consequently increase portal pressure. Endothelin‐1 has been shown to exert a direct vasoconstrictive effect on the collateral vessels in partially portal vein‐ligated rats with a high degree of portal‐systemic shunting. This study investigated the collateral vascular responses to ET‐1, the receptors in mediation and the regulation of ET‐1 action by nitric oxide and prostaglandin in cirrhotic rats with a relatively low degree of portal‐systemic shunting.

Methimazole Alleviates Hepatic Encephalopathy in Bile-duct Ligated Cirrhotic Rats

Background: Acute or chronic liver damage may lead to hepatic encephalopathy. Previous studies have indicated the hemodynamic and hormonal mimicry between portal hypertension and hyperthyroidism. Furthermore, medically or surgically induced hypothyroidism has been found to be beneficial in ameliorating hyperdynamic circulation in the portal hypertensive state and in alleviating acute or chronic liver injury in rats. However, the effect of chronic thyroid hormone inhibition on chronic hepatic encephalopathy in cirrhosis remains unknown. Methods: Liver cirrhosis was induced by bile‐duct ligation (BDL) in male Sprague‐Dawley rats. Three weeks after BDL, rats were randomized to receive either tap water (control) or 0.04% methimazole in drinking water for 3 weeks. At the end of 6 weeks after BDL, severity of encephalopathy was assessed by the Opto‐Varimex animal activity meter and hemodynamic parameters were measured. Blood samples were collected for determination of thyroid stimulating hormone, ammonia and liver biochemistry. Results: The heart rate of the methimazole‐treated group was significantly lower than that of the control group (p = 0.015), whereas there were no differences in the mean arterial pressure and portal pressure. The total amount of movements were significantly increased in the methimazole group (p = 0.029). Plasma levels of ammonia, aspartate aminotransferase and alkaline phosphatase were significantly lower (p = 0.01) and thyroid stimulating hormone significantly higher (p = 0.035) in the methimazole group. Conclusion: Chronic methimazole treatment alleviates hepatic encephalopathy and liver damage in rats with BDL‐induced hepatic cirrhosis.

Effects of long-term octreotide treatment on the response of portal-systemic collaterals to vasopressin in portal hypertensive rats

Background Chronic portal hypertension is associated with the development of portal‐systemic collaterals. Long‐term octreotide treatment has been shown to enhance the constrictive response to vasopressin in the mesenteric arteries of portal hypertensive rats. This study investigated the effects of long‐term octreotide treatment on the response of portal‐systemic collaterals to vasopressin in portal hypertensive rats.

Inhibition of prostacyclin by indomethacin ameliorates the splanchnic hyposensitivity to glypressin in haemorrhage-transfused common bile duct-ligated rats

Prostacyclin (PGI2) is an important contributor to the mediation of hyporeactivity to vasoconstrictors and the development of hyperdynamic circulation in portal hypertensive states. Inhibition of PGI2 synthesis in haemorrhage‐transfused partially portal vein‐ligated rats could ameliorate the splanchnic hyposensitivity to glypressin, a long‐acting vasopressin analogue. This study investigated whether the hyposensitivity to glypressin also exists in rats with common bile duct ligation (BDL) and whether the inhibition of PGI2 synthesis by indomethacin could potentiate the portal‐hypotensive effect of glypressin in bleeding BDL rats.

Role of Hepatic Nitric Oxide Synthases in Rats with Thioacetamide-induced Acute Liver Failure and Encephalopathy

Background: Hepatic encephalopathy is neuropsychiatric derangement secondary to hepatic decompensation or portal‐systemic shunting. Nitric oxide (NO) synthase inhibition aggravates encephalopathy and increases mortality in rats with thioacetamide (TAA)‐induced acute liver failure, suggesting a protective role of NO. This study investigated the roles of endothelium‐derived constitutive NO synthase (eNOS) and inducible NOS (iNOS) in the liver of rats with fulminant hepatic failure and encephalopathy. Methods: Male Sprague‐Dawley rats (300‐350 g) were randomized to receive TAA 350 mg/kg/day, by intraperitoneal injection or normal saline for 3 days. Severity of encephalopathy was assessed with the Opto‐Varimex animal activity meter. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin were measured. Hepatic iNOS and eNOS RNA and protein expressions were assessed by reverse transcription‐polymerase chain reaction and Western blot analyses, respectively. Results: The TAA group showed lower motor activity counts than the normal saline group. Hepatic eNOS, but not iNOS, mRNA and protein expressions were enhanced in the TAA group. In addition, hepatic eNOS mRNA expression was negatively correlated with total movement but positively correlated with ALT and AST. Protein expression of hepatic eNOS was positively correlated with ALT, AST and bilirubin. Conclusion: Upregulation of hepatic eNOS was observed in rats with TAA‐induced fulminant hepatic failure and encephalopa‐thy, which might play a regulatory role.

Cyclooxygenase expression in splanchnic hyposensitivity to glypressin of bleeding portal hypertensive rats.

Background Prostacyclin mediates, at least partly, the splanchnic vascular hyporesponsiveness to glypressin in bleeding portal hypertensive rats. This study investigated the relative contribution of cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2) in the splanchnic hyposensitivity to glypressin in rats with portal hypertension induced by partial portal vein ligation (PVL).