- Email: [email protected]
The Liver Meeting 2017
News
The Liver Meeting 2017 Myrcludex B in hepatitis D
There is currently a lack of specific treatment regimens for hepatitis D virus (HDV) infection. Heiner Wedemeyer and colleagues (Hannover, Germany) presented the results of a multicentre, open-label, phase 2b randomised trial of a first-in-class entry inhibitor of HDV. 120 HBsAg-negative patients were randomly allocated (1:1:1:1) to receive 2 mg, 5 mg, or 10 mg myrcludex B in combination with tenofovir disoproxil fumarate (TDF) or TDF alone. At week 12, HDV RNA levels declined in all patients receiving any dose of myrcludex B, with no HDV RNA reduction in the TDF alone group. Myrcludex B appeared to be safe and well tolerated.
The L-PLUS-2 trial
Nezam Afdhal (Boston, MA, USA) and colleagues presented the results of a phase 3 controlled trial of lusutrombopag for thrombocytopenia in patients with chronic liver disease undergoing non-emergency invasive procedures. 215 patients with a baseline platelet count of less than 50 x 109 cells per L, Child-Pugh class A or B cirrhosis, and a planned nonemergency invasive procedure were randomly assigned (1:1) to receive oral lusutrombopag 3 mg once daily or placebo for up to 7 days, with planned invasive procedure s performed on days 9–14. The most common invasive procedures were endoscopic variceal ligation (28%), endoscopy (27%), dental extraction (11%), and TACE (9%). 64·8% of patients on lusutrombopag met the primary endpoint of no requirement for platelet transfusion before the invasive procedure, compared with 29·0% on placebo (p<0·0001). Treatment-emergent adverse events were reported for 47·7% of patients on lusutrombopag versus 4·6% of patients on placebo, with three patients on lusutrombopag and six on placebo experiencing bleeding-related treatment-emergent adverse events.
The AESOP trial
Kris Kowdley (Seattle, WA, USA) and colleagues presented data from a randomised, double-blind, placebocontrolled study of obeticholic acid in patients with primary sclerosing cholangitis. 76 patients were randomly assigned (1:1:1) to receive placebo (n=25), 1·5–3 mg obeticholic acid (n=25), or 5–10 mg obeticholic acid (n=26) once-daily for 12 weeks, stratified by ursodeoxycholic acid use and total bilirubin level. At week 24, mean reduction in alkaline phosphatase was –27 (SE 37) in the placebo group, –105 (38) in the 1·5–3 mg group, and –110 (34) in the 5–10 mg group (p<0·05). Adverse events were similar between groups, with the exception of pruritis, which increased with obeticholic acid use in a dosedependent manner (46% of patients on placebo, 60% of patients on 1·5–3 mg, and 70% of patients on 5–10 mg). A 2-year open-label extension study is ongoing.
The REDUCE study
Gloria Sanchez-Antolin (Valladoid, Spain) and colleagues presented 52-week data from the REDUCE study, assessing the safety and effect on kidney function of an immunosuppressive regimen based on tacrolimus and everolimus compared with tacrolimus and mycophenolate mofetil (control) in patients receiving a first liver transplant. eGFR improved significantly on everolimus compared with control at week 52. The percentage of patients achieving clinical benefit was similar between groups (82% on everolimus group vs 85% on control). Tacrolimus exposure was reduced by 41% in the everolimus group compared with the control group. There was no significant difference in incidence of clinically suspected acute rejection (17·1% on everolimus vs 15·1% on control) or survival (94% in the everolimus group vs 97% in the control group) between groups. Numbers of
patients discontinuing due to adverse events were similar between groups (18·9% in the everolimus group vs 15·6% in the control group).
GS-0976 for NASH
Rohit Loomba (San Diego, CA, USA) and colleagues presented the results of a phase 2, randomised controlled trial of GS-0976, an acetyl-coA carboxylase inhibitor, in patients with NASH. 126 patients with NASH with no cirrhosis were randomly assigned (2:2:1) to receive 20 mg GS-0976, 5 mg GS-0976, or placebo daily for 12 weeks. At week 12, a 30% or greater decline in MRI proton density fat fraction was seen in 48% of patients on 20 mg GS-0976, 23% of patients on 5 mg GS-0976, and 15% of patients on placebo. Changes in liver stiffness by magnetic resonance elastography did not differ between groups. Asymptomatic grade 3 or 4 triglyceride elevations (>500 mg/dL) were noted in seven patients on 20 mg GS-0976 and nine on 5 mg GS-0976.
Lancet Gastroenterol Hepatol 2017 Published Online October 27, 2017 http://dx.doi.org/10.1016/ S2468-1253(17)30330-8 The Liver Meeting 2017 was held on Oct 20–24 in Washington DC, USA
The ITCH trial
Benjamin Shneider (Houston, TX, USA) and colleagues presented the results of a multicentre, double-blind, randomised controlled trial assessing the safety and efficacy of maralixibat, an ileal, apical, sodium-dependent bile acid transporter inhibitor for pruritis in Alagille syndrome. 37 children with Alagille syndrome, an autosomal dominant genetic disorder, were randomly assigned to receive placebo or 70 µg/kg, 140 µg/kg, or 280 µg/kg maralixibat once-daily for 13 weeks. The primary outcome of mean change in Itch Reported Outcome (reported by a parental observer) was –0·58 in the placebo group, –1·47 in the 70 µg/kg group, –1·49 in the 140 µg/kg group, and –0·62 in the 280 µg/kg group. Adverse events were similar between groups.
Jennifer Thorley
www.thelancet.com/gastrohep Published online October 27, 2017 http://dx.doi.org/10.1016/S2468-1253(17)30330-8
1
The Liver Meeting 2017 Myrcludex B in hepatitis D
There is currently a lack of specific treatment regimens for hepatitis D virus (HDV) infection. Heiner Wedemeyer and colleagues (Hannover, Germany) presented the results of a multicentre, open-label, phase 2b randomised trial of a first-in-class entry inhibitor of HDV. 120 HBsAg-negative patients were randomly allocated (1:1:1:1) to receive 2 mg, 5 mg, or 10 mg myrcludex B in combination with tenofovir disoproxil fumarate (TDF) or TDF alone. At week 12, HDV RNA levels declined in all patients receiving any dose of myrcludex B, with no HDV RNA reduction in the TDF alone group. Myrcludex B appeared to be safe and well tolerated.
The L-PLUS-2 trial
Nezam Afdhal (Boston, MA, USA) and colleagues presented the results of a phase 3 controlled trial of lusutrombopag for thrombocytopenia in patients with chronic liver disease undergoing non-emergency invasive procedures. 215 patients with a baseline platelet count of less than 50 x 109 cells per L, Child-Pugh class A or B cirrhosis, and a planned nonemergency invasive procedure were randomly assigned (1:1) to receive oral lusutrombopag 3 mg once daily or placebo for up to 7 days, with planned invasive procedure s performed on days 9–14. The most common invasive procedures were endoscopic variceal ligation (28%), endoscopy (27%), dental extraction (11%), and TACE (9%). 64·8% of patients on lusutrombopag met the primary endpoint of no requirement for platelet transfusion before the invasive procedure, compared with 29·0% on placebo (p<0·0001). Treatment-emergent adverse events were reported for 47·7% of patients on lusutrombopag versus 4·6% of patients on placebo, with three patients on lusutrombopag and six on placebo experiencing bleeding-related treatment-emergent adverse events.
The AESOP trial
Kris Kowdley (Seattle, WA, USA) and colleagues presented data from a randomised, double-blind, placebocontrolled study of obeticholic acid in patients with primary sclerosing cholangitis. 76 patients were randomly assigned (1:1:1) to receive placebo (n=25), 1·5–3 mg obeticholic acid (n=25), or 5–10 mg obeticholic acid (n=26) once-daily for 12 weeks, stratified by ursodeoxycholic acid use and total bilirubin level. At week 24, mean reduction in alkaline phosphatase was –27 (SE 37) in the placebo group, –105 (38) in the 1·5–3 mg group, and –110 (34) in the 5–10 mg group (p<0·05). Adverse events were similar between groups, with the exception of pruritis, which increased with obeticholic acid use in a dosedependent manner (46% of patients on placebo, 60% of patients on 1·5–3 mg, and 70% of patients on 5–10 mg). A 2-year open-label extension study is ongoing.
The REDUCE study
Gloria Sanchez-Antolin (Valladoid, Spain) and colleagues presented 52-week data from the REDUCE study, assessing the safety and effect on kidney function of an immunosuppressive regimen based on tacrolimus and everolimus compared with tacrolimus and mycophenolate mofetil (control) in patients receiving a first liver transplant. eGFR improved significantly on everolimus compared with control at week 52. The percentage of patients achieving clinical benefit was similar between groups (82% on everolimus group vs 85% on control). Tacrolimus exposure was reduced by 41% in the everolimus group compared with the control group. There was no significant difference in incidence of clinically suspected acute rejection (17·1% on everolimus vs 15·1% on control) or survival (94% in the everolimus group vs 97% in the control group) between groups. Numbers of
patients discontinuing due to adverse events were similar between groups (18·9% in the everolimus group vs 15·6% in the control group).
GS-0976 for NASH
Rohit Loomba (San Diego, CA, USA) and colleagues presented the results of a phase 2, randomised controlled trial of GS-0976, an acetyl-coA carboxylase inhibitor, in patients with NASH. 126 patients with NASH with no cirrhosis were randomly assigned (2:2:1) to receive 20 mg GS-0976, 5 mg GS-0976, or placebo daily for 12 weeks. At week 12, a 30% or greater decline in MRI proton density fat fraction was seen in 48% of patients on 20 mg GS-0976, 23% of patients on 5 mg GS-0976, and 15% of patients on placebo. Changes in liver stiffness by magnetic resonance elastography did not differ between groups. Asymptomatic grade 3 or 4 triglyceride elevations (>500 mg/dL) were noted in seven patients on 20 mg GS-0976 and nine on 5 mg GS-0976.
Lancet Gastroenterol Hepatol 2017 Published Online October 27, 2017 http://dx.doi.org/10.1016/ S2468-1253(17)30330-8 The Liver Meeting 2017 was held on Oct 20–24 in Washington DC, USA
The ITCH trial
Benjamin Shneider (Houston, TX, USA) and colleagues presented the results of a multicentre, double-blind, randomised controlled trial assessing the safety and efficacy of maralixibat, an ileal, apical, sodium-dependent bile acid transporter inhibitor for pruritis in Alagille syndrome. 37 children with Alagille syndrome, an autosomal dominant genetic disorder, were randomly assigned to receive placebo or 70 µg/kg, 140 µg/kg, or 280 µg/kg maralixibat once-daily for 13 weeks. The primary outcome of mean change in Itch Reported Outcome (reported by a parental observer) was –0·58 in the placebo group, –1·47 in the 70 µg/kg group, –1·49 in the 140 µg/kg group, and –0·62 in the 280 µg/kg group. Adverse events were similar between groups.
Jennifer Thorley
www.thelancet.com/gastrohep Published online October 27, 2017 http://dx.doi.org/10.1016/S2468-1253(17)30330-8
1