The Prognosis in Long-Term Infection
Their study, published in the September issue of the journal Clinical Gastroenterology and Hepatology, suggests that people infected with hepatitis for at least 60 years will likely develop advanced liver disease eventually. It's the highest rate of hepatitis C-related cirrhosis predicted in the medical literature thus far, they say.

"As far as I know, this was the largest study that has evaluated a cohort infected for this long," explained chief investigator Graham Foster, PhD, a professor of Hepatology at Queen Mary's School of Medicine and Dentistry in London, in an interview.

The investigators stated that, prior to this study, it wasn't really known how many patients infected with the virus for longer than 30 years might develop cirrhosis. They cited other studies that suggested up to one-fifth of HCV patients may develop cirrhosis after being infected with HCV for 20 years.

"Hence, chronic HCV infection appears to be a slowly progressive disease that is unlikely to cause cirrhosis in the majority of patients," wrote the study team at Queen Mary's School of Medicine and Dentistry and the Royal Free University College Medical School, both in London. However, there may be a different story for patients chronically infected with the virus for more than 30 years, they wrote.

A Topic of Debate
But there's been a debate about the prognoses of long-term hepatitis C patients. For instance, if fibrosis 
development eases over time, does that mean cirrhosis will likely not result? And if HCV infection continues with age, does this mean that the likelihood of someone developing cirrhosis increases over time?

The aim of this study was to answer some of those questions.

Cirrhosis is a type of liver disease characterized by scar tissue that invades the liver's tissue, replacing normal, healthy cells. This also blocks the flow of blood through the liver, and prevents it from functioning normally. According to estimates, cirrhosis is the 12th leading cause of death by disease in the United States, killing about 26,000 people each year. In addition to infection with the hepatitis virus, other causes of cirrhosis include alcoholic liver disease, autoimmune hepatitis, certain inherited diseases, nonalcoholic steatohepatitis (NASH), blocked bile ducts, and certain drugs, toxins, and infections.²

Scouring Patient Records for Answers
To answer their questions about long-term hepatitis prognosis, the research team gathered information from a hospital database on a group of 143 elderly Asian immigrants who were infected with hepatitis C in childhood. Their histories were compared with those of a group of 239 Caucasian patients, also with HCV infection. All patients had previously undergone a liver biopsy as confirmation of their infection.

The median age of the Caucasian patients was 47, although the Asian patients were significantly older, on average, with a median age of 56. The oldest patients in this latter group were 80 years old.

Cirrhosis Development in the Two Groups
The prevalence of cirrhosis in the Caucasian patients was extremely rare early in the course of infection, was uncommon in middle-age, but increased in later years. It averaged about 25% in those over age 61, the research team reported.

In the group of Asian patients, in those who lived beyond age 60, nearly 80 percent eventually developed cirrhosis, the study found. This finding, the investigators pointed out, can be applied to the general population, as well, because of the similarity in which the disease progresses in all ethnic groups.

Rates Varied, but Likely Due to Time, Not Ethnicity
While cirrhosis was more common in the Asian patients in this study, the study group theorized that it might have been due to the fact that these patients had been infected with the virus for a longer period, or to an increase in fibrosis development, or both. While it was possible that the ethnic differences between the two groups may account for the different rates of cirrhosis development, fibrosis (a precursor to cirrhosis) developed at nearly the same pace in both groups of patients, implying that the pace of cirrhosis development is similar between different ethnic groups, the researchers pointed out.

In examining fibrosis development, the researchers found it had advanced further in the Asian patients, but the rate of its progression was similar in each 10-year increase in age in both groups, they noted. As a result, the rate of fibrosis development was similar in both groups, but more advanced in the Asian patients because they had been infected for a longer period of time, the researchers theorized.

Confirming Their Findings Through Biopsy
In a separate analysis, the team analyzed liver biopsy results from smaller, separate groups of untreated Asian and Caucasian HCV patients. In comparing the extent of their liver disease from their initial biopsies to a second biopsy taken several years later, they found the illness had advanced at about the same rate in both groups.

"This study suggests that prolonged infection with hepatitis C leads to cirrhosis in the majority of those who are infected," said study leader Foster.  "While previous studies have found differences in disease progression in various ethnic groups, our findings confirm that fibrosis progression is the same across these groups, and leads to the development of cirrhosis and liver disease at the same rate in everyone."

The reasons behind the progression of cirrhosis over time in people with HCV wasn't explored in this study, but Foster has some theories. "I think that at this stage, any thoughts are pure speculation, but my view is that liver cells become less able to withstand infection as they age, and the immune response declines over time. We are looking at studies to assess these possibilities," he said.

'Treatment Should be Universal' for HCV Patients
In an editorial accompanying the study,³ Leonard Seeff, MD,  and James Everhart, MD, MPH, of the National Institutes of Health, wrote that if the study's findings are "indeed a true reflection of the long-term impact of chronic HCV infection", this would suggest that many more people infected with this virus are likely to reach end-stage liver disease than had been thought previously.

"It also implies that treatment should indeed be universal for all HCV-infected persons, regardless of their histological [health of their liver] status, in the hope of blunting this progression," the two physicians wrote. "In addition, it raises the issue of the need for even more transplantation services, to accommodate the anticipated 'epidemic' of cirrhosis-related end-stage liver disease and cancer that awaits these patients."

But they added that until more research is conducted in other patient populations, these conclusions are "preliminary".

1. Prevalence of hepatitis C-related cirrhosis in elderly Asian patients infected in childhood. Clin Gastroenterol Hepatol 2005 Sep;3(9):910-17.
2. National Institute of Diabetes and Digestive and Kidney Diseases. (NIDDK). National Institutes of Health (NIH). Cirrhosis of the Liver. Available at:  http://digestive.niddk.nih.gov/ddiseases/pubs/cirrhosis/index.htm. Accessed September 9, 2005.
3. Seeff LB, Everhart JE. Is cirrhosis an inevitable consequence of chronic hepatitis C virus infection? Clin Gastroenterol Hepatol 2005 Sep;3(9):840-2.

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