A Hepatitis C Virus-Associated Decompensated Cirrhotic Patient Who Showed the Disappearance of Hepatic Encephalopathy, Ascites, and Pleural Effusion by Antiviral Therapy with Sofosbuvir/Velpatasvir.

Oral direct-acting antivirals (DAAs) are the main therapy for hepatitis C virus (HCV)-associated liver disease in Japan. Moreover, many DAAs include an indication for compensated liver cirrhosis. However, patients with decompensated HCV-associated cirrhosis have hitherto not been indicated for therapy with DAAs. Recently, a new DAA, sofosbuvir/velpatasvir (SOF/VEL), was indicated for decompensated HCV-associated cirrhotic patients. Actually, it has been shown to eradicate HCV in many cases. However, it is not clear whether hepatic encephalopathy, ascites, and pleural effusion in patients with decompensated HCV-associated cirrhosis disappear by SOF/VEL treatment. Recently, we encountered a decompensated HCV-associated cirrhosis patient who showed the disappearance of hepatic encephalopathy, ascites, and pleural effusion with marked improvement of serum ammonia level, albumin level, prothrombin time, and platelet count after the eradication of HCV by the administration of SOF/VEL. Her consciousness was cloudy and it took many hours for the preparation of each meal just before SOF/VEL treatment, but after the disappearance of HCV-RNA by the therapy, her consciousness became clear and she could prepare meals in a short time. This case suggests the possibility of improvement from decompensated HCV-associated liver cirrhosis to compensated liver cirrhosis with disappearance of hepatic encephalopathy, ascites, and pleural effusion by SOF/VEL therapy.

Introduction

Antiviral therapy using oral direct-acting antivirals (DAAs) has recently become the main and most effective therapy for eradicating hepatitis C virus (HCV) in Japan [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. Moreover, many DAAs have been proposed to eradicate HCV in patients with compensated HCV-associated liver cirrhosis [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. However, patients with decompensated HCV-associated cirrhosis have hitherto not been indicated for therapy with DAAs. Furthermore, they were in a life-threatening state and eradication of HCV was not possible.

Now, a new DAA, sofosbuvir/velpatasvir (SOF/VEL), is indicated for eradicating HCV in patients with decompensated HCV-associated liver cirrhosis [11, 12]. We recently encountered an HCV-associated decompensated cirrhotic patient whose hepatic encephalopathy, ascites, and pleural effusion disappeared after HCV-RNA became negative due to the administration of SOF/VEL with marked improvement of the serum ammonia level, serum albumin level, prothrombin time, and platelet count.

Case Report

A 54-year-old Japanese female (height 156.0 cm; weight 73.0 kg) with HCV-associated cirrhosis (genotype Ib) visited our clinic for the treatment of cirrhosis. She was treated with the oral administration of ursodeoxycholic acid at 600 mg/day. From May 31, 2011, injection of 80 mL of Stronger Neo-Minophagen C (usually used to lower serum transaminase, 2–3 times a week) was carried out until the end of August 2019.

Abdominal computed tomography (CT) was carried out on February 10, 2011, which showed unevenness of the surface of the liver with splenomegaly, and she was diagnosed with a cirrhotic state. For eradication of HCV, PEG-IFN/ribavirin therapy was performed from August 5 to December 5, 2012, but it was not effective. Thereafter, CT performed on February 6, 2018, showed ascites and pleural effusion (Fig. 1a, b) and she was diagnosed with decompensated liver cirrhosis. Furosemide and Aldactone A were administered, but pleural effusion and ascites remained. For the low albumin level, albumin infusion was carried out from March 22, 2016, to August 30, 2019 (every 2 weeks).

Fig. 1

a Chest CT on February 6, 2018 (before the administration of SOF/VEL), showed pleural effusion in the lower part of the right lung. The white arrows show pleural effusion. b Abdominal CT on February 6, 2018 (before the administration of SOF/VEL), showed ascites in the lower part of the liver. The white arrows show ascites.

On August 3, 2019, a new DAA drug, SOF (NS5B inhibitor, 400 mg)/VEL (NS5A inhibitor, 100 mg), was administered until October 25, 2019 (about 12 weeks). HCV-RNA became negative on August 30, 2019. Abdominal CT performed on September 25 showed neither ascites nor pleural effusion (Fig. 2a, b).

Fig. 2

a Chest CT on September 25, 2019 (after the administration of SOF/VEL), showed that the pleural effusion in the lower part of the right lung had disappeared completely. b Abdominal CT on September 25, 2019 (after the administration of SOF/VEL), showed that the ascites in the lower part of the liver had disappeared completely.

Hepatic encephalopathy (grade I–II), which appeared on July 23, 2019 (the patient claimed cloudiness of sensation, serum ammonia level of 112 μg/dL), disappeared on October 7, 2019 (serum ammonia level of 85 μg/dL) (Fig. 3). She stated that her consciousness was cloudy and it took many hours for the preparation of each meal just before the SOF/VEL treatment, but after the disappearance of HCV-RNA by the therapy, her consciousness became clear and she could prepare a meal in a short time. Furthermore, she also stated that the sensation of fatigue had disappeared, and it had become easier to move by the 6th week of administration of the drugs. In addition, she also showed marked improvements in the albumin level (Fig. 4) and in prothrombin time (Fig. 5). As a result, the Child-Pugh classification [13, 14] improved from Child B to Child A.

Fig. 3

Time course of serum ammonia level after SOF/VEL administration.

Fig. 4

Time course of serum albumin level after SOF/VEL administration.

Fig. 5

Time course of prothrombin time after SOF/VEL administration.

Discussion

There are many DAA agents to eradicate HCV which include the indication for compensated cirrhosis [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. However, hitherto, there has been no DAA agent which includes decompensated liver cirrhosis as an indication.

Recently, SOF/VEL was firstly indicated for decompensated liver cirrhosis. It was confirmed that this agent improves the serum albumin level, prothrombin time, and sometimes the serum ammonia level [12] after eradication of HCV. However, it has not been confirmed whether hepatic encephalopathy, ascites, and pleural effusion disappear clinically after the eradication of HCV by SOF/VEL administration. Our case showed that hepatic encephalopathy, ascites, and pleural effusion in decompensated cirrhosis may disappear completely by the administration of SOF/VEL. In support of our findings, Younossi et al. [11] analyzed patient-reported outcomes from decompensated cirrhotic patients treated by SOF/VEL and found that SOF/VEL therapy led to a significant improvement in patient-reported outcomes by 4 weeks of administration.

In addition, our case showed marked improvements in the serum ammonia level (112→75 μg/dL), albumin level (3.3→4.1 g/dL), and prothrombin time (70.9→85.8%), respectively. With regard to these findings, Takaoka et al. [12] administered SOF/VEL for 12 weeks to 43 patients with decompensated cirrhosis, and they reported that the serum albumin level improved to 3.2 g/dL on average, and prothrombin time improved to 70% on average. Considering their results, our case demonstrated marked improvements in the serum albumin level and prothrombin time.

In summary, this case suggests the possibility of improvement from decompensated HCV-associated liver cirrhosis to compensated liver cirrhosis with disappearance of hepatic encephalopathy, ascites, and pleural effusion by SOF/VEL therapy. This drug may become an effective treatment option for decompensated HCV-associated cirrhotic patients with ascites, pleural effusion, or hepatic encephalopathy.

Statement of Ethics

The authors have no ethical conflicts to disclose. Informed consent was obtained from the patient to be included in this report. And the patient has given written informed consent to publish her case (including publication of images). This study was conducted in accordance with the Declaration of Helsinki and was approved by the Medical Ethics Committee on Human Research of Yokohama Municipal Citizen's Hospital.

Conflict of Interest Statement

The authors declare that they have no conflicts of interest.

Funding Sources

This work was supported by the Kanagawa Association of Medical and Dental Practitioners.

Author Contributions

Kazuo Tarao: follow-up of the patient's clinical course. Akito Nozaki: summary of the paper. Hirokazu Komatsu: performing clinical examinations including gastrointestinal endoscopy.