HCV New Drugs

Fred Poordad, M.D.

An estimated eight million Americans suffer from chronic liver disease, with more than half a million living with cirrhosis. Several factors contribute to the rising rates of liver disease.

Recent news coverage pointed the spotlight on hepatitis C and the baby boomer population, but the elderly population also is particularly susceptible to liver disease, and its care often falls into the hands of skilled nurses in long-term care facilities across the country.

The Leading Causes of Liver Disease
The most common underlying causes of cirrhosis in the Unites States are hepatitis C and non-alcoholic fatty liver disease (NAFLD).

Hepatitis C is the most common indication for liver transplantation and the major driver of primary liver cancer. A recent recommendation by the Centers for Disease Control and Prevention (CDC) to test Americans born between 1945 and 1965 will lead to a higher diagnosis rate in this baby boomer cohort. Increasingly viable treatments for hepatitis will allow more patients to be treated over the coming five to 10 years if they can be diagnosed.

NAFLD may afflict 20% of the population. Five percent have an aggressive variant of the condition called steatohepatitis. Largely driven by obesity and insulin resistance, steatohepatitis will be an emerging health concern in the elderly population as well.

The diagnosis of advanced liver disease is important to make in the elderly population since many of the condition's features are treatable and can lead to improved quality of life and, most importantly, decrease the likelihood of acute care hospitalization, which carries a high risk of nosocomial infections and therapeutic mishaps in the aged population. Patients with risk factors for hepatitis should be screened for liver disease, along with those that have a family history of liver disease, or a history of long term or heavy alcohol consumption.

Advanced Liver Disease Can Affect the Body and the Mind
Advanced liver disease is defined by the presence of fibrosis or scar tissue in the liver. This clinical finding may include the presence of esophageal varices, ascites, and jaundice.
Resistance to flow of blood through the liver is a condition called portal hypertension. The presence of collagen or fibrous tissue in and around the liver cells or hepatocytes leads to a change in architecture and hampers blood flow and hepatic function.

This increased resistance to blood flow leads to dilation of blood vessels flowing into the liver, namely the portal vein and the veins comprising it, such as the superior mesenteric vein and splenic vein, esophageal vein, and gastric veins, which are susceptible to rupture and bleeding when dilated and under high pressure. This manifests as intestinal bleeding, which can present as emesis of blood or passage of blood per rectum, often leading to urgent hospitalization in an acute care setting.
The high pressures associated with portal hypertension also lead to leakage of serum into the abdominal cavity, and the formation ascites. This fluid leads to distention of the abdomen, and can lead to compromised breathing, infection and even renal insufficiency. The treatment for this condition is sodium restriction and the use of diuretics.

Hepatic encephalopathy (HE) also can occur as a result of portal hypertension. Resistance to blood flow leads to shunting of blood around the liver, allowing blood from the gut containing ammonia and other byproducts of bacterial metabolism to bypass the liver and reach the systemic circulation. Exposing the brain to these chemicals can result in interference with normal synaptic transmission of electrical and chemical signaling in the brain. As a result, cognition and memory are affected, leading to memory loss, impaired thinking, and an inability to perform fine motor tasks.

Diagnosing and Treating Hepatic Encephalopathy in the Elderly
In an elderly population, there are pitfalls to making the diagnosis of hepatic encephalopathy since other conditions can mimic the findings. The most important first step is to accurately diagnose liver disease. Organic brain syndrome can be confused with hepatic encephalopathy since it is prevalent in the elderly and the cognitive and memory impairment can be similar.
Another condition that can be confused with encephalopathy is delirium due to medication adverse events or “polypharmacy” and drug interactions. Additionally, elevated ammonia occurs with uremia due to renal failure, which can present like hepatic encephalopathy. Rarely, a defect in the urea cycle leads to elevated ammonia and this can sometimes present with cognitive changes.
HE is treated by lowering ammonia levels. This can be done through administration of lactulose by mouth or rectally, or via administration of a non-absorbed broad spectrum antibiotic called rifaximin (Xifaxan), both of which are FDA approved therapies with proven safety records. Many prefer rifaximin due to the lack of diarrhea associated with lactulose, which can often lead to dehydration in the frail elderly population.

Preparing for the Rise in Liver Disease
A significant increase in the numbers of Americans with advanced liver disease is expected over the next decade, in large part due to the aging baby boomer population that has a hepatitis C prevalence of 3.3%. It is thought that roughly one third of hepatitis C infected patients currently has advanced fibrosis, and will likely progressive to more advanced disease before they can be diagnosed and treated. This will create a tremendous burden to the health care system, including skilled nursing and long-term care facilities.

Fred Poordad, M.D., is the chief medical officer at Alamo Medical Research.

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