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AASLD 2016: Portal Hypertension Less Likely to Improve After HCV Treatment When Fibrosis Is Severe


Curing hepatitis C infection moderately reduces portal hypertension, but has less impact for people with more severe liver stiffness due to fibrosis, Spanish researchers reported at the 2016 AASLD Liver Meeting this month in Boston.

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Portal hypertension -- high blood pressure in the portal vein supplying the liver -- is caused by scarring of the liver due to hepatitis C, which restricts the flow of blood through the liver. If portal hypertension persists, collateral blood vessels may form to relieve the pressure, leading to the development of varices (fragile distended veins) in the esophagus and stomach and subsequent risk of gastrointestinal bleeding. Portal hypertension is a major risk factor for decompensation in people with cirrhosis.

Portal hypertension is managed through the use of beta-blockers as therapy and by use of endoscopy to tie off veins and prevent recurrence of bleeding. Many people find both medication and regular endoscopy difficult to tolerate.

Although direct-acting antivirals (DAAs) eradicate hepatitis C virus (HCV) in the vast majority of people, it is unclear if a successful response to treatment results in a reduction in portal hypertension and in the risk of decompensation in people with advanced liver disease. Previous German research found that people with Child-Pugh stage B cirrhosis or higher portal blood pressure were less likely to experience substantial reductions or normalization of portal pressure after DAA treatment.

To further investigate this question, Sabela Lens of IDIBAPS Hospital Clinic in Barcelona and colleagues carried out a prospective multicenter study of the evolution of portal pressure and hemodynamics after interferon-free DAA treatment in people who achieved sustained virological response at 12 weeks post-treatment (SVR12).

The study population comprised 198 people with HCV-related liver cirrhosis and clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] >10 mmHg).

Just over half of participants were male, with an average age of 60 and a median body mass index of 28. Most people (70%) had esophageal varices and 31% had one or more previous episode of decompensated liver disease. 80% had Child-Pugh A cirrhosis, while 20% had Child-Pugh B cirrhosis.

All were treated with all-oral direct-acting antiviral regimens. Patients had assessments of HVPG, right-heart catheterization, and liver stiffness measurements at baseline and at 24 weeks after completion of therapy.

Overall, HVPG decreased significantly after attainment of SVR. The mean baseline HVPG was 15.8 mmHg and the mean reduction was -2 mmHg. After treatment, the proportion of people with HVPG >10 mmHg fell from 100% to 83%; the proportion with HVPG >12 mmHg fell from 80% to 66%, and the proportion with HVPG >16 mmHg fell from 43% to 27%. A clinically relevant decrease in portal hypertension of at least 10% was observed in 54% of people, with 34% having a decrease of 20% or more.

After controlling for potential confounders, the only factors associated with an HVPG decrease of at least 10% were serum albumin <3.5 g/dL and baseline liver stiffness, an indicator of extent of liver fibrosis (14.5 kPa is the usual cut-off for cirrhosis in people with hepatitis C). Among those with HVPG >10 mmHg, 48% of those with baseline liver stiffness <13.6 kPA had clinically significant portal hypertension 24 weeks after treatment initiation, compared to 92% of those with baseline liver stiffness >21 kPA.

Decrease in mean HVPG did not differ according to use of beta-blockers. However, due to higher prevalence of clinically significant portal hypertension at baseline, clinically significant hypertension persisted in 95% of people taking beta-blockers compared to 77% of people not taking this type of treatment.

Paired right-heart catheterization measures were available for 82 individuals and showed a significant rise in mean arterial pressure, which the investigators attributed to increased systemic vascular resistance (+1.4 and +25%) with stable cardiac output. Moreover, other important measures, including mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance also increased after therapy (+1.5% and +21%). Pulmonary arterial hypertension (mPAP of 25 mmHG or above) developed in 9 people and worsened in 4, but only 2 individuals developed increased pulmonary vascular resistance.



S Lens, E Alvarado-Tapias, Z Mariño, et al. Impact of all-oral antiviral therapy on portal pressure and hemodynamics on HCV-infected cirrhosis patients. AASLD Liver Meeting. Boston, November 11-15, 2016.Abstract 58.