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
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
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.”