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Successful Hepatitis C Treatment Reduces Portal Hypertension

Direct-acting antiviral therapy 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 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 hypertension 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 esophagus and stomach.

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

Mattias Mandorfer and Markus Peck-Radosavljevic from 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 patients with paired hepatic venous pressure gradient (HVPG) measurements taken before and after successful treatment.

This retrospective analysis included 104 hepatitis C patients with portal hypertension (HVPG >6 mmHg) who underwent HVPG and liver stiffness measurement 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.

Results

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

o   6-9 mmHg at baseline: from 7.37 to 5.11 mmHg (-2.26);

o   10-15 mmHg at baseline: from 12.2 to 8.91 (-3.29);

o   >16 mmHg at baseline: 19.4 vs 17.1 mmHg (-2.3).

• In the subgroup of patients with 6-9 mmHg at baseline, 63% (12 of 19) saw their HVPG fall within the normal range (<6 mmHg), and none had an increase to 10 mmHg or higher. 
• In the subgroup of patients with >10 mmHg at baseline, 63% (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 10 mmHg.
• However, people classified as Child-Pugh stage B -- more impaired liver function -- were less likely to have a HVPG decrease than less advanced Child-Pugh stage A patients (hazard ratio 0.103).
• In the subgroup of patients with clinically significant portal hypertension at baseline, a larger relative decline in liver stiffness according to FibroScan was a predictor of 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 >16 mmHg 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 patients without clinically significant portal hypertension after successful treatment, they suggested.

Reduced portal hypertension is a relief for patients 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."

6/23/16

Reference

M Mandorfer, K Kozbial, P Schwabl, Markus Peck-Radosavljevic, et al. Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension. Journal of Hepatology. May 26, 2016 (online ahead of print).

Other Source

Medical University of Vienna. Hepatitis C: once the viral infection has healed, high-risk portal vein hypertension also diminishes. Press release. June 15, 2016.