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Japanese study shows benefits of treating hepatitis C early

Keith Alcorn
24 August 2021

Curing hepatitis C in people with mild fibrosis by the age of 50 reduces their risk of death to the same level as the rest of the population, Japanese researchers report in the Journal of Viral Hepatitis.

The findings underscore the importance of early detection and treatment of hepatitis C to maximise the health gains of curing hepatitis C with direct-acting antiviral treatment.

Although studies have shown that curing hepatitis C results in reduced liver-related mortality and fewer cases of hepatocellular carcinoma (HCC; liver cancer) in people with advanced fibrosis, evidence has been lacking in people with mild fibrosis.



A protein made in the liver, needed to maintain a balance of the fluids in the body. In a blood test, lower than normal levels of albumin and total protein may indicate liver damage or disease. If there is not enough albumin, fluid may accumulate in the abdomen (ascites).

Dr Takashi Kumada of Gifu Kyoritsu University, Japan, and colleagues investigated the long-term outcomes of 1243 people with hepatitis C diagnosed between 1995 and 2017 who had at least three years of follow-up, no history of liver cancer and a FIB-4 score of 1.45 or less, indicating mild fibrosis. All participants were screened for liver cancer and laboratory tests to assess liver disease progression every three to six months.

In the study population, 657 people were cured of hepatitis C: 337 on an interferon-based regimen and 320 on a direct-acting antiviral regimen (the clearance group). The remaining 586 had not started treatment by December 2017 (the no clearance group).

The clearance group were significantly younger than the no clearance group (45 vs 52 years, p<0.001) and more likely to abuse alcohol. The clearance group had a higher proportion of patients with dyslipidaemia and higher HCV RNA, albumin, bilirubin, ALT and AST values. The no clearance group had a higher proportion of patients with diabetes and higher values for fasting glucose and platelet count.

Deaths were more common in the no clearance group (25.3% vs 5.2% died during the follow-up period, P<0.001). Twenty-four of 148 deaths in the no clearance group were liver-related (17 due to HCC) compared to five of the 34 deaths in the clearance group (three due to HCC).

Clearance of hepatitis C (presence of HCV RNA) reduced the risk of HCC by 73% (adjusted hazard ratio 0.2653, 95% CI 0.1147-0.6136, p=0.0019), of all-cause mortality by 65% (aHR 0.2157-0.5409, p<0.0001) and of liver-related mortality by 75% (aHR 0.2474, 95% CI 0.0802-0.8917, p=0.0318).

Increased risk of development of HCC during follow-up was associated with a higher ALBI grade, type 2 diabetes, higher levels of gamma GTP and male gender. The risk of all-cause mortality was raised by higher AFP levels, higher ALBI grade, type 2 diabetes, age over 65 years and male gender. The risk of liver-related mortality was raised by type 2 diabetes.

When the mortality rate in the clearance group was compared to the general population, matched by age, sex and follow-up duration, the clearance group as a whole had a higher all-cause mortality rate (3.6% vs 0.2% at 20 years, 351 in each group).

However, when the mortality rate was compared by age group, people who achieved hepatitis C clearance before the age of 50 did not have a significantly higher all-cause mortality rate compared to the general population (1.7% vs 0% at 20 years, 91 in each group, p=0.1570). Nor did people who achieved clearance after the age of 70 (3.1% vs 1%, 83 in each group, p=0.3343).

“Antiviral therapy should be started as early as possible to achieve the largest benefit,” the researchers conclude.


Kumada T et al. Long-term outcomes of viral eradication in patients with hepatitis C virus infection and mild hepatic fibrosis. Journal of Viral Hepatitis, 28: 1293-1303, 2021.