Viral Eradication Reduces Both Liver Stiffness and Steatosis in Patients With Chronic Hepatitis C Virus Infection Who Received Direct-acting Anti-viral Therapy

T. Tada; T. Kumada; H. Toyoda; Y. Sone; K. Takeshima; S. Ogawa; T. Goto; A. Wakahata; M. Nakashima; M. Nakamuta; J. Tanaka

Disclosures

Aliment Pharmacol Ther. 2018;47(7):1012-1022. 

In This Article

Abstract and Introduction

Abstract

Background Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear.

Aims To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR).

Methods A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24).

Results Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70–4.18) kPa and 2.80 (2.40–3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7–3.4)% and 1.9 (1.3–2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24.

Conclusion Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020).

Introduction

Chronic infection with hepatitis C virus (HCV) infection affects approximately 180 million individuals worldwide. It is a common cause of chronic liver disease and hepatocellular carcinoma in Japan, the United States and many European countries.[1,2] Chronic infection with HCV is a major cause of progressive liver damage and long-term sequelae such as cirrhosis and hepatocellular carcinoma. Although most HCV-associated liver damage is immunomediated,[3] some histopathological features, such as liver steatosis, suggest a viral cytopathic effect.[4]

Liver steatosis can develop secondary to obesity, diabetes mellitus, alcohol abuse, protein malnutrition, total parenteral nutrition, acute starvation, drug therapy, carbohydrate overload[5–8] and chronic HCV infection. In patients with chronic HCV infection, the prevalence of steatosis ranges from 40% to 86%.[9] Steatosis occurs more frequently in patients with chronic HCV infection (55%) than in the general adult population (20%–30%) in the Western world.[6] The majority of patients with steatosis (78%) have mild steatosis, with less than 30% of hepatocytes affected.

Interferon-based therapy has been used to treat patients with chronic HCV infection. Many investigators have reported that interferon-based treatment is effective in reducing serum alanine aminotransferase (ALT) levels, eradicating HCV RNA and reducing liver fibrosis in patients with chronic HCV infection.[10–14] However, interferon-based therapy is associated with several severe treatment-related side effects. Direct-acting anti-virals have recently been developed to treat chronic HCV infection. They have resulted in higher sustained virological response (SVR) rates, shorter and simpler regimens, and minimal treatment-related side effects.

The assessment of the severity of liver fibrosis and steatosis is important when staging chronic HCV. Magnetic resonance elastography is a magnetic resonance imaging (MRI)-based method for quantitatively imaging tissue stiffness. Several manufacturers of MRI scanners provide magnetic resonance elastography capabilities as an option through special hardware and software. Magnetic resonance elastography has been reported to be a useful method for diagnosing liver fibrosis in patients with chronic liver disease, even in the early stages.[15–18] In addition, proton density fat fraction (PDFF) measurement is an MRI-based method for quantitatively assessing liver steatosis. It is an optional addition to MRI scanners from several manufacturers. MRI-determined PDFF correlates with histologically determined steatosis grade in patients with chronic liver disease.[18–20]

Kumar et al[21] reported that viral eradication using interferon-based therapy reduced the steatosis in patients with chronic HCV genotype 3 infection. However, steatosis in chronic HCV patients with genotype 1 or 2 infection who achieve SVR using direct-acting anti-virals has not been sufficiently studied.

In this study, we investigated changes in liver stiffness and steatosis as determined by MRI in patients with chronic HCV genotype 1 or 2 infection who received direct-acting anti-viral therapy and achieved SVR.

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