Original article—liver, pancreas, and biliary tract
Portal Pressure Predicts Outcome and Safety of Antiviral Therapy in Cirrhotic Patients With Hepatitis C Virus Infection

https://doi.org/10.1016/j.cgh.2011.03.002Get rights and content

Background & Aims

There are limited data on the efficacy and safety of antiviral therapy in patients with hepatitis C virus (HCV)-related cirrhosis, particularly on the impact of portal hypertension.

Methods

We assessed hepatovenous pressure gradient (HVPG), liver stiffness (transient elastography), and interleukin (IL)-28B polymorphisms (rs12979860) in 90 cirrhotic patients with HCV infection (82% genotype 1 or 4) before antiviral therapy with pegylated interferon and ribavirin. Efficacy and safety were evaluated.

Results

Rates of sustained virologic response were significantly lower among patients with clinically significant portal hypertension (CSPH; HVPG ≥10 mm Hg; n = 50) than among patients without CSPH (HVPG <10 mm Hg; n = 40): 14% vs 51% (P = .0007). Seventy-nine percent and 83% of patients with CSPH and without CSPH, respectively, received more than 80% of planned dose (P = .647). The predictive value of HVPG (area under the curve [AUC], 0.743) was greater than that of liver stiffness (AUC, 0.647) or of baseline HCV RNA levels (AUC, 0.620). The IL-28B polymorphism was not associated significantly with a sustained virologic response. Multivariate analysis revealed that HVPG (odds ratio [OR], 14.3; P = .009), baseline HCV RNA levels (OR, 5.3; P = .019), and HCV genotype (OR, 6.5; P = .046) were independent risk factors for treatment failure. A trend toward higher incidence of anemia and neutropenia was observed for patients with CSPH. The incidence and grade of thrombocytopenia were significantly higher among patients with than without CSPH (94% vs 75%; P = .006).

Conclusions

HVPG is an independent predictor of response to antiviral therapy, with better predictive value than liver stiffness, baseline HCV RNA levels, HCV genotype, or IL-28B polymorphism. The incidence and grade of thrombocytopenia during antiviral therapy are higher among patients with CSPH. In evaluating cirrhotic HCV patients for antiviral treatment, measurement of HVPG should be considered.

Section snippets

Patients

After exclusion of Child–Pugh B/C patients, 133 consecutive patients with histologically proven (n = 121; 91%) or clinically evident (n = 12; 9%) cirrhosis as a result of chronic HCV infection were prospectively included during the study period (2006–2010). Before initiation of antiviral therapy, all patients were screened for portal hypertension. Upper gastrointestinal endoscopy was performed to screen for gastroesophageal varices,20 and portal pressure was measured by HVPG. Patients with

Patient Characteristics

During the 4-year study period, 133 patients with suspected cirrhosis as a result of chronic HCV infection were evaluated for antiviral therapy; patient characteristics are listed in Table 1. Eight patients undergoing HVPG measurement together with transjugular biopsy did not show cirrhosis in liver histology. Seventeen patients with cirrhosis in liver biopsy did not consent to undergo HVPG measurement. Eighteen patients had both liver biopsy and measurement of HVPG, but did not start antiviral

Discussion

Our data confirmed that antiviral therapy is generally less effective in cirrhotic HCV patients, but showed a clear difference in cirrhotic patients with or without portal hypertension (objectively diagnosed by HVPG). This study reveals that measurement of HVPG before starting antiviral therapy provides clinically relevant information because SVR rates were significantly worse in patients with CSPH (HVPG ≥10 mm Hg) than in patients without (14% vs 51%). Current guidelines are based on studies

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    Conflicts of interest The authors disclose no conflicts.

    Funding This study was supported by a grant from MSD (former AescaPharma) Austria and a grant from Roche Austria to MP-R.

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