Successful hepatitis C treatment reduces portal hypertension and its complications

Direct-acting antiviral therapy for hepatitis C that produces a sustained virological response can lead to reduction in portal vein pressure, which causes some of the most serious complications of cirrhosis, according to a report in the May 26 online edition of the Journal of Hepatology. However, the researchers cautioned, reversal of portal hypertension is less likely if liver damage is too advanced, providing an argument for earlier treatment.

Over years or decades chronic hepatitis C virus (HCV) infection can result in serious liver complications including cirrhosis and liver cancer. In advanced cirrhosis scar tissue replaces functional liver cells and can impede the flow of blood through the liver, causing high blood pressure in the portal veins coming from the digestive system. This in turn can lead to ascites (abdominal fluid accumulation) and bleeding varices, or varicose veins in the oesophagus and stomach.

The advent of direct-acting antivirals (DAA) used in interferon-free regimens has revolutionised hepatitis C treatment, making it shorter, better tolerated and much more effective, with cure rates exceeding 90%. But the new drugs are expensive, leading many public payers and private insurers to limit treatment to people who have already progressed to advanced liver disease.

Mattias Mandorfer and Markus Peck-Radosavljevic of the Medical University of Vienna and colleagues conducted a study to investigate the impact of sustained virological response (SVR) to interferon-free DAA therapy on portal hypertension in people with paired hepatic venous pressure gradient (HVPG) measurements taken before and after successful treatment.

This retrospective analysis included 104 people living with hepatitis C who had portal hypertension (HVPG > 6mmHg) who underwent HVPG and liver stiffness measurements before DAA therapy. Among the 100 participants who achieved SVR, 60 received additional HVPG and transient elastography (FibroScan) tests after completing therapy and post-treatment follow-up to determine if they were cured.

The researchers found that achieving SVR significantly decreased portal pressure across all baseline HVPG strata:

• 6-9mmHg at baseline: from 7.37 to 5.11mmHg (-2.26)
• 10-15mmHg at baseline: from 12.2 to 8.91mmHg (-3.29)
• > 16mmHg at baseline: 19.4 vs 17.1mmHg (-2.3).

In the subgroup of people with 6-9mmHg at baseline, 63% (12 of 19) saw their HVPG fall within the normal range (< 6mmHg) and none had increased to 10mmHg or higher.

In the subgroup of people with >10mmHg at baseline, 635 (26 of 41) experienced a clinically relevant HVPG decrease of at least 10% and 24% (10 of 41) saw their follow-up HVPG fall below 10mmHg.

However, people classified as Child-Pugh stage B – indicating more impaired liver function – were less likely to have a HVPG decrease than people with less advanced Child-Pugh stage A (hazard ratio 0.103).

In the subgroup of people with clinically significant portal hypertension at baseline, a larger relative decline in liver stiffness according to FibroScan predicted a HVPG decrease of at least 10%.

"SVR to interferon-free therapies might ameliorate portal hypertension across all baseline HVPG strata," the study authors concluded. "However, changes in HVPG seemed to be more heterogeneous among patients with baseline HVPG of >16mmHg and a HVPG decrease was less likely in patients with more advanced liver dysfunction."

Transient elastography, which is commonly used for non-invasive staging of liver disease, might identify people without clinically significant portal hypertension after successful treatment, they suggested.

Reduced portal hypertension is a relief for people because they can stop taking medications with unpleasant side effects to manage cirrhosis complications and they do not need to undergo endoscopic monitoring as frequently, according to a press release issued by the Medical University of Vienna.

"As a general rule, the probability of portal vein hypertension diminishing is greater, the earlier treatment was started," Mandorfer said. "However, despite the promising results, we still strongly recommend that patients attend for check-ups, because portal vein hypertension does not diminish in all patients and, irrespective of whether it does or does not, there is a risk of developing liver cancer as a result of cirrhosis."