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Liver function improves in most people with cirrhosis after hepatitis C cure

Keith Alcorn
18 May 2021
Image: Jelena Stanojkovic/

Most people with hepatitis C and liver cirrhosis experience improvement in liver function after direct-acting antiviral treatment, but a small minority – mainly those with a history of liver decompensation – may suffer further deterioration in liver function after being cured of hepatitis C, a large Italian cohort study has reported.

Direct-acting antiviral treatment cures hepatitis C and leads to improvement of liver function in people with less advanced liver disease. What has been less clear is whether people with advanced liver disease experience improvements in liver function, or if severe liver damage in the form of decompensated cirrhosis is irreversible despite hepatitis C cure.

The Italian Platform for the study of viral hepatitis therapy (PITER) is a multicentre cohort that follows previously untreated people with hepatitis C. The cohort includes people co-infected with hepatitis C and HIV.



An accumulation of fluid in the abdomen; may be caused by liver damage, especially cirrhosis. 

decompensated cirrhosis

The later stage of cirrhosis, during which the liver cannot perform some vital functions and complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.


A disease or infection affecting the brain.

To assess outcomes of people with cirrhosis, PITER researchers identified all cohort members recruited between 2015 and 2019 who had cirrhosis prior to treatment and who were cured of hepatitis C after direct-acting antiviral treatment (defined as sustained virological response 12 weeks after completion of treatment).

Cirrhosis was diagnosed by liver stiffness measurement or the presence of portal hypertension and classified according to Child-Pugh stage. Child-Pugh stage B indicates substantial loss of liver function. Child-Pugh C indicates that the liver has decompensated, meaning that the liver is no longer able to function. Symptoms of decompensation include ascites (build-up of fluid in the abdomen), jaundice, mental confusion (hepatic encephalopathy) and gastrointestinal bleeding. A liver transplant is often necessary after decompensation.

The researchers identified 1242 people with hepatitis C alone and 108 people with hepatitis C and HIV who were eligible for inclusion in the analysis. People with HIV and hepatitis C were significantly younger (52 years vs 64 years median age), more often male (81% vs 58%) and more likely to be current alcohol users (27% vs 9%) and to have Child-Pugh B stage cirrhosis (27% vs 8%) (all p<0.001). Hepatocellular carcinoma was more common in monoinfected people (6% vs 0.9%).

HIV infection was the only factor associated with more severe cirrhosis. People with HIV were almost four times more likely to have Child-Pugh B or C stage cirrhosis (adjusted odds ratio 3.73, 95% CI 2-6.98). The study investigators say that this finding reflects the fact that more than a quarter of co-infected people had reached Child-Pugh class B or C before receiving direct-acting antiviral treatment.

People with HIV and hepatitis C were followed for a median of 27 months after sustained virologic response and people with hepatitis C alone were followed for a median of 24 months. Eighty-five per cent of co-infected people and 64% of monoinfected people experienced an improvement in cirrhosis, defined as a change in Child-Pugh class (from C to B or from B to A) during the follow-up period.

In most cases, cohort members experienced improvement from Child-Pugh stage B to stage A (16 out of 20 co-infected people and all monoinfected people who experienced improvement).

Approximately 10% of each group of patients experienced a decompensating event after completing direct-acting antiviral treatment, most commonly ascites, hepatic encephalopathy or gastrointestinal bleeding. Just under half of those who experienced decompensation (46%) had a previous history of liver decompensation, showing that people with decompensated cirrhosis remain at higher risk of liver disease progression after being cured of hepatitis C.

Worsening of cirrhosis (measured by change in Child-Pugh status), was associated with male sex, platelet count below 100,000ul or increased International Normalised ratio (INR measures blood clotting; people with a higher INR are at increased risk of haemorrhage).

The study investigators say, “Our findings confirm the existence of a point of no return after which antiviral treatment may be too late to influence the natural history of HCV-related liver disease.”


Quaranta MG et al. Liver function following hepatitis C virus eradication by direct acting antivirals in patients with liver cirrhosis: data from the PITER cohort. BMC Infectious Diseases 21: 413, 2021.