	Caffeine reduces risk of elevated alanine aminotransferase
	Cardiac alterations in cirrhosis: reversible after liver transplant
	Researchers Target Risk Factors for Liver Cancer

Caffeine reduces risk of elevated alanine aminotransferase

In a large study including persons at high risk for liver injury, consumption of coffee and especially caffeine has been found, in the most recent issue of Gastroenterology, to be associated with lower risk of elevated alanine aminotransferase activity.

Dr Ruhl and colleagues from Maryland in America designed a study to investigate whether coffee and caffeine consumption reduced the risk of elevated alanine aminotransferase (ALT) activity in persons at high risk for liver injury.

In this national, population-based study the researchers recruited a total of 5944 adult participants from the Third US National Health and Nutrition Examination Survey, 1988–1994.

The participants exhibited excessive alcohol consumption, viral hepatitis, iron overload, overweight, or impaired glucose metabolism.

Liver injury was indicated by abnormal serum ALT activity (>43 U/L).

The researchers found elevated ALT activity in 8.7% of this high-risk population.

In unadjusted analysis, the research team noted that lower ALT activity was associated with increasing consumption of coffee and caffeine.

Relationships were relatively unchanged when analyses included the entire population

Gastroenterology

The researchers performed multivariate logistic regression analyses in order to show that risk of elevated ALT activity declined with increasing intake of coffee and caffeine.

The research team found that on comparing persons who drank more than 2 cups per day with noncoffee drinkers, the odds ratio was .56.

Comparing persons in the highest caffeine quintile with the lowest, the odds ratio was .31.

The researchers found that these relationships were consistent across subgroups at risk for liver injury.

Relationships were relatively unchanged when analyses included the entire population or when limited to persons without impaired liver function or right upper quadrant pain.

Fasting insulin concentrations did not mediate the effects.

Dr Ruhl concluded, "In this large, national, population-based study, among persons at high risk for liver injury, consumption of coffee and especially caffeine was associated with lower risk of elevated ALT activity."

Gastroenterology; 2005: 128 (1)
07 January 2005

Cardiac alterations in cirrhosis: reversible after liver transplant

Researchers report in January's Journal of Hepatology that cardiac alterations in cirrhosis presenting with mild increases in ventricular wall thickness, and diastolic dysfunction that worsens with ascites and physical stress, can be reversed by liver transplantation.

Liver cirrhosis induces cardiac alterations.

Dr Genescaa and colleagues from Barcelona, Spain undertook a study in order to define these alterations and assess their reversibility after transplantation.

The researchers oversaw echocardiography and stress ventriculography for 40 cirrhotic patients and 15 controls.

The research team reevaluated 15 cirrhotics 6–12 months after transplantation.

The researchers found that cirrhotics had higher left ventricular wall thickness and ejection fraction than controls.

Basal diastolic function was similar.

During stress, cirrhotics presented lower increases of heart rate, left ventricular ejection fraction, stroke volume and cardiac index, and diastolic dysfunction with lower ventricular peak filling rate.

Ascitic patients exhibited more diastolic dysfunction at rest and during stress compared to non-ascitic patients

Journal of Hepatology

The researchers noted that exercise capacity was reduced and ascitic patients exhibited more diastolic dysfunction at rest and during stress compared to non-ascitic patients.

Liver transplantation caused regression of ventricular wall thickness and improvement of diastolic function.

The researchers also noted normalization of systolic response and exercise capacity during stress (significant increases in heart rate, ventricular ejection fraction, stroke volume and cardiac index).

Dr Genescaa concluded, "Cardiac alterations in cirrhosis present with mild increases in ventricular wall thickness, diastolic dysfunction that worsens with ascites and physical stress, and abnormal systolic response to stress limiting exercise capacity."

"Liver transplantation reverses these alterations."

Journal of Hepatology; 2005: 42 (1): 68-74
07 January 2005

Researchers Target Risk Factors for Liver Cancer
by John C. Martin	Article Date: 01-12-05

It's well known that people diagnosed with hepatitis C (HCV) face a higher risk of developing liver cancer.¹But now, a team of Japanese researchers has identified specific risk factors for the disease, known medically as hepatocellular carcinoma.²

What's the Risk in Hidden Hepatitis C?
Doctors in Osaka, Japan focused on the risk of liver cancer in people with asymptomatic hepatitis C. "The risk for hepatocellular carcinoma (HCC) among asymptomatic hepatitis C virus carriers is not well understood," they wrote.

To answer that lingering question, the investigators focused on nearly 2,000 people aged 40 years or older who had been diagnosed with hepatitis C and who had donated blood between 1991 and 1993. They were compared to a group of 150,000 people without the virus. All of the study participants were then followed for more than 8 years.

Some 2,500 individuals who were positive for hepatitis B surface antigen (HBsAg) (an indicator of HBV infection) and 25 people who had tested positive for both antibodies to HCV and HBsAg were included to determine the risk of cancer in those with the two indicators of hepatitis infection.

Risk Factors Uncovered
"The incidence of HCC among the HCV-positive individuals increased with age in both genders," wrote Hideo Tanaka, MD, who led the study, and his fellow researchers. Tanaka is a researcher in the department of Cancer Control and Statistics at Osaka Medical Center for Cancer and Cardiovascular Diseases.

"In the HCV-positive individuals, the cumulative risk of developing HCC between the ages of 40 and 74 years was 21.6% among males and 8.7% among females," the investigators wrote.

Tanaka's group also learned that hepatocellular carcinoma risk rose in a stepwise fashion as liver enzymes increased. These enzymes, such as alanine aminotransferase (ALT), are released into the bloodstream by the liver when it is damaged. Doctors use these higher enzyme levels as indicators of liver disease.³ By contrast, the risk of liver cancer increased as cholesterol levels incrementally dropped in these patients, the researchers reported.

"The 9-year cumulative incidence of HCC among individuals positive for HCV alone, those positive for HBsAg alone, and those positive for both was 3.0%, 1.0%, and 12.0%, respectively," they wrote.

Thus, the risk of liver cancer is increased in certain people with hepatitis C, Tanaka and his colleagues wrote, adding that "coinfection with HBV and HCV carried a superadditive risk" of liver cancer.

The Fifth Most Common Cancer
Hepatocellular carcinoma is the most common primary tumor of the liver in adults. It accounts for nearly 6% of all cancers, and is the fifth most common cancer in the world. In the United States and other Western countries, hepatitis C infection is a leading cause of liver cancer. Experts have found it usually develops in older people who have liver cirrhosis.⁴

It's estimated that 17,500 new cases of primary liver cancer and bile duct cancer will be diagnosed in the United States this year.⁵

1. Pons-Renedo F, Llovet JM. Hepatocellular carcinoma: a clinical update. Med Gen Med 2003 Jul 22;5(3):11.
2. Tanaka H, Tsukuma H, Yamano H, Ohima A, Shibata H. Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus-positive blood donors focusing on demographic factors, alanine aminotransferase level at donation and interaction with hepatitis B virus. Int J Canc 2004 Dec 20;112(6):1075-80. Epub 2004 Aug 18.
3. Summaries for patients. New definitions for healthy ranges of alanine aminotransferase, a blood test of liver function. Ann Inern Med 2002 Jul 2;137(1):I37.
4. Pons-Renedo F, Llovet JM. Hepatocellular carcinoma: a clinical update. Med Gen Med 2003 Jul 22;5(3):11.
5. American Cancer Society. Overview: Liver Cancer: How Many People Get Liver Cancer? Available at: http://www.cancer.org/docroot/CRI/content
/CRI_2_2_1X_How_many_people_get_liver_cancer_25.asp?rnav=cri. Accessed January 5, 2005.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.

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