Does portal hypertension always improve after hepatitis C cure?

10 May 2018 Keith Alcorn
Originally published on www.infohep.org

Although portal hypertension improves in the majority of people with hepatitis C and cirrhosis after hepatitis C is cured, not all people experience improvement, and oesophageal varices may continue to progress despite successful hepatitis C treatment, researchers from Austria and Italy reported last month at the 2018 International Liver Congress in Paris.

Portal hypertension – high blood pressure in the portal veins – develops as a consequence of cirrhosis. Scarred liver tissue obstructs blood flow in the liver, raising blood pressure in veins in the abdomen, intestines, stomach, spleen and pancreas that feed into the liver. Eventually, these veins become swollen and may bleed. These swollen veins are called varices.

Varices that develop at the junction of the stomach and the oesophagus are most likely to bleed and the bleeding can be life-threatening. Mild or moderate varices may already be present in around a third of people with compensated (Child-Pugh A) cirrhosis.

Portal hypertension can be treated with beta blockers and nitrates but without an improvement in the underlying cirrhosis, portal hypertension will tend to worsen over time.

In people with hepatitis C treated with direct-acting antivirals, the progression of cirrhosis can be halted or reversed by curing hepatitis C. Eliminating the infection allows the liver to begin a slow process of renewal but this may not happen in people with more advanced cirrhosis.

What is less clear is how frequently portal hypertension and varices improve after hepatitis C is cured. Two studies presented at The International Liver Congress reported on the evolution of these conditions and attempted to identify predictors of regression or progression.

A Spanish study published in 2017 found that clinically significant hypertension persisted in 68% of people with cirrhosis cured of hepatitis C, despite a significant improvement in liver stiffness. Persistence of portal hypertension was associated with a higher hepatic venous pressure gradient and a smaller reduction in liver stiffness.

In a poster presentation at this year's Congress, Austrian researchers reviewed the outcomes of 77 people with portal hypertension after treatment with direct-acting antivirals. The majority of people had less advanced cirrhosis (81% had Child-Pugh A cirrhosis) and the average MELD score was 8, further indicating early-stage cirrhosis.

The median hepatic venous pressure gradient (HVPG) was 13mmHg in this patient cohort. Twenty-two people had an HVPG of 6-9 mmHg prior to treatment. None of those with HVPG > 10 mmHg progressed to clinically significant portal hypertension (> 10 mmHg) after treatment. Fifty-five had clinically significant portal hypertension prior to treatment and in 65% HVPG declined by at least 10% following completion of treatment. However, only 24% experienced resolution of clinically significant portal hypertension during a median follow-up period of two years after the completion of treatment.

Liver decompensation occurred in ten people with clinically significant portal hypertension after treatment (five cases of hepatic encephalopathy, four of ascites and one of variceal bleeding) and two of these people required a liver transplant. The presence of clinically significant portal hypertension after treatment was a significant predictor of further hepatic decompensation during the follow-up period (p = 0.002), and events were most likely to occur in the first six months after treatment.

Those who had liver stiffness measurements below 18kPa during the follow-up period did not experience further decompensation and a liver stiffness below 11.8kPA was associated with a lack of clinically significant portal hypertension.

Italian researchers from Palermo and Messina reported on the development or progression of oesophagogastric varices in 280 people with Child-Pugh A cirrhosis who were cured of hepatitis C infection after direct-acting antiviral treatment. Individuals underwent oesophagogastroscopy to detect varices at baseline and after sustained virologic response, and again during a median follow-up period of two years. Liver stiffness, HVPG and the spleen diameter/platelet ratio were also measured to analyse risk factors for the progression of varices. The spleen diameter/platelet ratio measures spleen enlargement and platelet levels and it can be used as a non-invasive test to predict the presence or development of varices.

One hundred people (32%) had no evidence of varices at baseline or during the follow-up period but 24% with no evidence at baseline subsequently developed varices during the follow-up period. In all but one case the varices were classified as mild.

One hundred and eighty people had mild varices at baseline. Varices disappeared in 11%, remained stable in 71% and progressed in 16% of people.

A higher spleen diameter: platelet ratio of 3 or above was associated with a higher risk of the development or progression of varices despite cure of hepatitis C.