Liver Fibrosis Develops Early, Progresses Quickly After Hepatitis C Virus Seroconversion

By Will Boggs MD

December 14, 2014

NEW YORK (Reuters Health) - Liver fibrosis develops early after hepatitis C virus (HCV) seroconversion and progresses quickly to cirrhosis in many patients, according to new findings.

"Within 10 years of HCV infection, about 18% have developed cirrhosis, and this is 3 times higher than controls," Dr. Adeel A. Butt from University of Pittsburgh School of Medicine in Pennsylvania told Reuters Health by email. "Most of this occurs within the first 5 years after infection."

Dr. Butt and colleagues used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) to identify 1,840 patients who seroconverted to HCV antibody and then to determine their rate of liver fibrosis progression, compared with 1,840 matched controls who remained HCV antibody-negative.

They plotted the FIB-4 score, which provides an estimation of the degree of liver fibrosis based on routinely obtained blood tests, over time. A FIB-4 score greater than 3.5 indicates cirrhosis.

FIB-4 score progression started early after seroconversion, was most pronounced within the first five years, and continued over a period of 11 years. Progression was consistently higher among HCV-positive patients than among HCV-negative patients, the researchers report in JAMA Internal Medicine, online December 8.

In the HCV-positive group, 18.4% of patients went on to develop cirrhosis, compared with only 6.1% in the HCV-negative group, and the HCV-positive patients had a significantly shorter time to development of liver cirrhosis.

By five years, more than 15% of HCV-positive patients had a diagnosis of cirrhosis, compared with less than 5% of HCV-negative controls.

Only 3.1% of patients in the HCV-positive group developed hepatic decompensation (compared with 1.4% of HCV-negative patients), but their time to first hepatic decompensation was significantly shorter than it was for HCV-negative patients. More than half of the hepatic decompensation events occurred within the first two years of diagnosis of cirrhosis.

Factors associated with a higher risk of cirrhosis among HCV-positive patients included increasing age, white race, hypertension, history of alcohol abuse or dependence, and anemia. Diabetes, hypertension, and anemia were associated with a higher risk of developing hepatic decompensation.

"Future studies should look at a risk prediction model to determine which characteristics most accurately predict future cirrhosis in a given individual," Dr. Butt said. "Contrary to popular thought, a significant proportion of hepatic decompensation occurs without prior diagnosis of cirrhosis. Hence careful follow-up and evaluation for hepatic decompensation should be carried out in all HCV-infected persons regardless of duration of infection and prior diagnosis of cirrhosis."

"If newer treatments demonstrate slowing or reversal of fibrosis progression and delaying development of cirrhosis, our data would suggest treating early in the course of infection," the authors conclude. "On the other hand, if the cirrhosis has already set in, treatment may be helpful in preventing hepatic decompensation in only a small number of those with cirrhosis, since the number who go on to develop this complication is small."

Dr. Marc G. Ghany from the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, addressed the ongoing debate of whom to treat for chronic HCV in a related editorial.

"All patients with chronic HCV infection should be considered candidates for therapy, and mild liver disease is not a reason to deny a patient therapy who otherwise qualifies for treatment," he told Reuters Health by email.

But treatment is expensive, with costs ranging from $66,000 for 12 weeks of treatment with simeprevir to $84,000 for 12 weeks of treatment with sofosbuvir.

"The hope is that with the approval of other regimens, competition will drive down costs," Dr. Ghany said. "It remains to be seen how much cheaper the drugs will become, but it is unlikely in the near future that costs will decrease to the point where we will be able to treat everyone who is infected with hepatitis C virus."

"We still have to identify the large number of people who are unaware of their diagnosis and get them into care, including counseling on measures to prevent transmission, disease progression, and treatment," he concluded.

"This kind of study should remind physicians about the importance of non-viral, modifiable factors of accelerated liver fibrosis progression," Dr. Francesco Negro from Geneva University Hospital in Switzerland, who has published extensively on HCV infection, told Reuters Health. "One may think that treating HCV with antivirals may be the end of the story, thus forgetting about the formidable impact of alcohol drinking, cannabis smoking, and the metabolic syndrome. The VA population is particularly vulnerable in this respect."

"That their progression seemed to slow down once the diagnosis of cirrhosis was made suggests (although other explanations may be possible) that these persons became aware of the severity of their liver disease and tried to adopt a healthier lifestyle," said Dr. Negro, who was not involved in the research. "If this is true, our job should be to avoid reaching the cirrhotic stage, a stage when the risk of developing liver cancer may be hard to eliminate completely."

"We still have a lot of things to learn regarding the pathophysiology of hepatitis C," he said.


JAMA Intern Med 2014.


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