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CAP is a new ultrasound-based technique for measuring fat content in the liver, but has never been tested for fatty liver caused by alcohol. Herein, we examined 562 patients in a multicentre setting. We show that CAP highly correlates with liver fat, and patients with a CAP value above 290 dB/m were highly likely to have more than 5% fat in their livers, determined by liver biopsy. CAP was also better than regular ultrasound for determining the severity of alcoholic fatty-liver disease. Finally, we show that three in four (non-obese) patients rapidly decrease in CAP after short-term alcohol withdrawal. In contrast, obese alcohol-overusing patients were more likely to have higher CAP values than lean patients, irrespective of drinking.

Infection with HEV can lead to chronic hepatitis E in about 50% of immunosuppressed patients. 1 The management of chronic hepatitis E can be challenging and is a stepwise approach. Antiviral therapy is the second step if reduction of the immunosuppressive medication does not lead to viral clearance. However, options are limited and none of the drugs are approved for chronic hepatitis E. Interferon-alpha should not be considered in patients after lung, heart or kidney transplantation because it could induce graft rejection. 2 Ribavirin given for 3-6 months is usually the only option but side effects constrain its use, e.g. in anemic patients. Ribavirin is effective in approximately 80% of patients who can tolerate its use, meaning that 20% of treated patients remain viremic (EASL CPG). 3 Reasons for treatment failure could be selection of viral variants leading to enhanced viral replication. 4,5 Thus, there is an unmet need for alternative safe and efficacious therapies. Recently, 2 studies demonstrated that the HCV polymerase inhibitor sofosbuvir inhibited HEV genotype 3 replication in vitro. 6,7 The combination of sofosbuvir and ribavirin resulted in an additive antiviral effect. However, in comparison to the strong antiviral effect of sofosbuvir on HCV in vitro, sofosbuvir had only a moderate effect on HEV. Despite this limited evidence, several patients who failed ribavirin or were ineligible for ribavirin therapy have been treated with sofosbuvir with or without ribavirin because of the imminent risk of developing liver decompensation. The results of the published case reports are conflicting. 8-13 Thus, we initiated the SofE study to investigate the antiviral efficacy and safety of sofosbuvir monotherapy in patients with chronic hepatitis E without the confounding effect of ribavirin. This study was an investigator initiated, institutionally sponsored, prospective, multicenter, phase II pilot trial, conducted in 3 clinical sites in Germany. Patients with chronic HEV infection who were older than 18 years and who either failed to achieve clearance of infection after ribavirin therapy or had contraindications for ribavirin were eligible for inclusion. All patients had to be positive for HEV RNA at least 3 months before screening and HEV RNA positive at the time of screening. After giving informed consent and screening of inclusion and exclusion criteria, patients received sofosbuvir 400 mg once daily for 24 weeks in an open labeled 1 arm trial design. The primary efficacy endpoint was defined as undetectable HEV RNA at week 24 (end of treatment). Secondary endpoints were durability of response 12 weeks after end of therapy and HEV RNA efficacy evaluations including HEV RNA changes from baseline during therapy and ALT normalization after 12 and 24 weeks of therapy and 12 weeks after end of therapy.

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