Portal hypertension less likely to fall after HCV treatment when liver stiffness is severe

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

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 in the portal vein and into the liver. If portal hypertension persists, blood vessels may form to relieve the pressure, leading to the development of varices 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 prevent the 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 in portal blood pressure or normalisation of portal pressure.

To further investigate this question, Spanish researchers carried out a prospective multicentre study of the evolution of portal pressure and haemodynamics after DAA treatment in people who achieved sustained virologic response (SVR12) on an interferon-free regimen.

The study population comprised 198 people with HCV-related liver cirrhosis and clinically significant portal hypertension (CSPH, hepatic venous pressure gradient [HVPG] > 10mmHg). All were treated with all-oral direct-acting agent regimens. Patients had assessments of HVPG, right-heart catheterisation and liver stiff measurements at baseline and at 24-weeks after completion of therapy.

Fifty-four per cent of participants were male, with an average age of 60 and a median body mass index of 28. Most people (70%) had oesophageal varices and 31% had one or more previous episode of decompensated liver disease. Eighty per cent had Child-Pugh A cirrhosis, 20% had Child-Pugh B cirrhosis.

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 > 10mmHg fell from 100% to 83%; the proportion with HVPG > 12mmHg 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 a decrease of at least 10% were serum albumin < 3.5g/dL.(p = 0.05) and baseline liver stiffness measurement (p = 0.04). Among those with HVPG >10mmHg 48% of those with baseline liver stiffness < 13.6 kPA had clinical 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 CSPH at baseline, CSPH persisted in 95% of people taking beta-blockers compared to 77% of people not taking this type of treatment (p< 0.01).

Paired right-heart catheterisation measures were available for 82 individuals and showed a significant rise in MAP, which the investigators attributed to increased systemic vascular resistance (+1.4 and +25%; p < 0.05) with stable cardiac output. Moreover, other important measures, including mPAP and pulmonary vascular resistance also increased after therapy (+1.5% and +21%; p < 0.05). Pulmonary arterial hypertension (mPAP of 25mmHG or above) developed in nine people and worsened in four, but only two individuals developed increased pulmonary vascular resistance.