Hepatology
RCT: Tirzepatide Significantly Improves MASH Resolution Without Worsening Fibrosis Over 52 Weeks – N Engl J Med
10 Aug, 2024 | 19:53h | UTCStudy Design and Population: This phase 2, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of tirzepatide in 190 participants with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and moderate to severe liver fibrosis (stage F2 or F3). Participants were assigned to receive subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo weekly for 52 weeks.
Main Findings: Tirzepatide significantly improved MASH resolution without worsening fibrosis compared to placebo. Resolution rates were 44% for 5 mg, 56% for 10 mg, and 62% for 15 mg, versus 10% for placebo. Improvement in fibrosis stage without worsening MASH was also higher in tirzepatide groups (51-55%) than in the placebo group (30%). The most common adverse events were mild to moderate gastrointestinal symptoms.
Implications for Practice: Tirzepatide shows promise as a treatment for MASH with moderate to severe fibrosis, significantly improving disease resolution without worsening fibrosis. However, further research with larger and longer trials is needed to confirm these findings and evaluate long-term safety.
Phase 2 Trial: Survodutide Improves MASH Without Worsening Fibrosis, But Increases GI Side Effects – N Engl J Med
10 Aug, 2024 | 19:47h | UTCStudy Design and Population: This 48-week, phase 2 randomized trial evaluated the efficacy and safety of survodutide, a dual agonist of the glucagon and GLP-1 receptors, in 293 adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis (F1-F3 stages). Participants were randomized to receive weekly injections of survodutide (2.4, 4.8, or 6.0 mg) or placebo.
Main Findings: Survodutide significantly improved MASH without worsening fibrosis compared to placebo, with 47% to 62% of participants in the survodutide groups achieving histologic improvement versus 14% in the placebo group. A reduction in liver fat content by at least 30% was observed in 57% to 67% of participants receiving survodutide, compared to 14% in the placebo group. However, adverse events such as nausea, diarrhea, and vomiting were more common with survodutide.
Implications for Practice: The findings suggest that survodutide could be a promising treatment for MASH, with potential benefits for liver histology and fat content. However, the increased gastrointestinal side effects warrant careful consideration in future phase 3 trials to better evaluate the drug’s safety profile and long-term efficacy.
Phase 2 RCT: Low-dose aspirin significantly reduces hepatic fat in MASLD patients without cirrhosis
20 Mar, 2024 | 17:48h | UTCStudy Design and Population: This phase 2, randomized, double-blind, placebo-controlled clinical trial was carried out over six months at a single hospital in Boston, Massachusetts. The study included 80 participants aged 18 to 70 years diagnosed with metabolic dysfunction–associated steatotic liver disease (MASLD) but without cirrhosis. Participants were randomly assigned to receive either 81 mg of daily aspirin (n=40) or placebo (n=40).
Main Findings: The trial revealed that aspirin significantly reduced the mean absolute change in hepatic fat content by -10.2% compared with placebo, as measured by proton magnetic resonance spectroscopy (MRS), with a statistically significant difference (P=0.009). Furthermore, aspirin treatment notably decreased relative hepatic fat content, increased the proportion of patients achieving a 30% or greater reduction in hepatic fat, and reduced both absolute and relative hepatic fat content as assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Adverse events were mostly minor, with upper respiratory infections and arthralgias being the most common.
Implications for Practice: These findings suggest that low-dose aspirin may be an effective intervention for reducing liver fat in adults with MASLD without cirrhosis, potentially offering a simple, accessible treatment option. However, the results are preliminary and call for further confirmation in larger, more diverse populations. The study underscores the importance of considering low-dose aspirin as part of management strategies for MASLD, pending further research.
Reference
Simon TG et al. (2024). Randomized Clinical Trial: Low-Dose Aspirin Significantly Reduces Hepatic Fat in MASLD Patients Without Cirrhosis. JAMA, 331(11), 920-929. DOI: 10.1001/jama.2024.1215. Access the study here: [Link]
Perspective | Clinicians debate the usefulness of NAFLD name change
11 Aug, 2023 | 15:39h | UTCClinicians debate the usefulness of NAFLD name change – MDedge
Original article: From NAFLD to MASLD | New consensus changes fatty liver disease terminology to avoid stigmatization
M-A | Percutaneous catheter drainage superior to needle aspiration for liver abscess treatment success
9 Aug, 2023 | 15:12h | UTC
Clinical Trial Update | Long-term Givosiran treatment shows sustained acute hepatic porphyria symptom improvement
8 Aug, 2023 | 13:05h | UTCOriginal Study: Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria – New England Journal of Medicine
Review | Diagnosis and management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome
4 Aug, 2023 | 11:50h | UTC
Review | Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options
1 Aug, 2023 | 14:19h | UTCRelated:
From NAFLD to MASLD | New consensus changes fatty liver disease terminology to avoid stigmatization
Nonalcoholic fatty liver disease from a primary care perspective – Diabetes, Obesity and Metabolism
Management of NAFLD in primary care settings – Liver International
Non-alcoholic fatty liver disease: A patient guideline – JHEP Reports
RCT | Bictegravir regimen noninferior to dolutegravir regimen in HIV-1, HBV co-infection treatment
31 Jul, 2023 | 14:00h | UTC
Systematic Review | Dual therapy of Rifaximin and lactulose potentially reduces risk in hepatic encephalopathy
24 Jul, 2023 | 12:57h | UTC
M-A | Hepatic, extra-hepatic outcomes and causes of mortality in NAFLD
20 Jul, 2023 | 10:59h | UTC
RCT | Midodrine show promise as an alternative to albumin for the prevention of circulatory disturbance in paracentesis between 3 and 5 L
18 Jul, 2023 | 13:47h | UTC
AHA Statement | Indications, evaluation, and outcomes for dual heart-kidney and heart-liver transplantation
14 Jul, 2023 | 12:51h | UTC
EASL Guidelines on the management of liver diseases in pregnancy
13 Jul, 2023 | 13:05h | UTC
AASLD Guidance | Use of TIPS, variceal embolization, and retrograde transvenous obliteration in variceal hemorrhage
11 Jul, 2023 | 13:59h | UTC
Guideline | Acute liver failure
10 Jul, 2023 | 13:59h | UTCAcute Liver Failure Guidelines – The American Journal of Gastroenterology
Related:
EASL Clinical Practice Guidelines on acute-on-chronic liver failure – Journal of Hepatology
Guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU
Acute-on-chronic liver failure: far to go—a review – Critical Care
Review | Acute-on-chronic liver failure
7 Jul, 2023 | 16:09h | UTCAcute-on-chronic liver failure: far to go—a review – Critical Care
Related:
EASL Clinical Practice Guidelines on acute-on-chronic liver failure – Journal of Hepatology
Guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU
From NAFLD to MASLD | New consensus changes fatty liver disease terminology to avoid stigmatization
30 Jun, 2023 | 15:01h | UTCA multi-society Delphi consensus statement on new fatty liver disease nomenclature – Hepatology
Commentary on Twitter
Big news in the field of Hepatology
In 1980, Jurgen Ludwig and his colleagues at Mayo Clinic, identified a severe type of fatty liver disease in people who did not drink signficant amounts of alcohol. The disease was more common in women, most patients were obese and suffered… pic.twitter.com/aAq2vneIov
— TheLiverDoc (@theliverdr) June 25, 2023
Phase 2 RCT | FGF21 analogue Pegozafermin treatment leads to improvement in NASH fibrosis
30 Jun, 2023 | 14:58h | UTCSummary: In a phase 2b, multicenter, double-blind, randomized, placebo-controlled trial, the fibroblast growth factor 21 (FGF21) analogue pegozafermin was examined for its efficacy and safety in treating patients with biopsy-confirmed noncirrhotic nonalcoholic steatohepatitis (NASH). A total of 222 patients with moderate or severe fibrosis (stage F2 or F3) were assigned to receive either subcutaneous pegozafermin at varying doses or a placebo. The primary endpoints were an improvement in fibrosis and resolution of NASH without worsening of fibrosis at 24 weeks.
The results showed that a larger percentage of patients receiving pegozafermin met the criteria for fibrosis improvement and NASH resolution compared to those receiving placebo. The most significant improvements were observed in the 44-mg pegozafermin group, with 27% showing fibrosis improvement and 26% meeting NASH resolution criteria, compared to 7% and 2% in the placebo group, respectively. Adverse events were mainly gastrointestinal and included nausea and diarrhea. These findings support the progression of pegozafermin into phase 3 development.
Article: Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
Late breaking at #EASLCongress: In this phase 2b, placebo-controlled trial involving patients with nonalcoholic steatohepatitis, pegozafermin, a long-acting glycopegylated FGF21 analogue, reduced fibrosis at 24 weeks. Full results by @drloomba et al.: https://t.co/mfRRrV2yX2
— NEJM (@NEJM) June 24, 2023
Liver Transplantation 2023 | Status report, current and future challenges
29 Jun, 2023 | 13:50h | UTC
RCT | Bulevirtide reduces HDV RNA and ALT levels in chronic hepatitis D patients
28 Jun, 2023 | 13:20h | UTCSummary: This randomized phase 3 trial evaluated the efficacy of bulevirtide, an inhibitor of HDV entry into hepatocytes, in patients with chronic hepatitis D. Patients were randomized to receive either 2 mg or 10 mg of bulevirtide daily for 144 weeks, or no treatment for 48 weeks followed by 10 mg bulevirtide daily for 96 weeks. The study involved 150 patients, 49 in the 2-mg group, 50 in the 10-mg group, and 51 in the control group.
After 48 weeks of treatment, 45% and 48% of patients in the 2-mg and 10-mg groups respectively achieved the primary end point of undetectable HDV RNA level or a decrease of at least 2 log10 IU per milliliter from baseline, and normalization of ALT level. Only 2% in the control group reached the primary endpoint. ALT levels normalized in 51% and 56% of patients in the 2-mg and 10-mg groups respectively, a significant difference from the 12% normalization in the control group. Notably, loss of HBsAg did not occur by week 48 in the bulevirtide groups. No serious adverse events related to the treatment were reported, though side effects including headache, pruritus, and fatigue were more common in the bulevirtide groups.
These results demonstrate the effectiveness of bulevirtide in reducing HDV RNA and ALT levels in patients with chronic hepatitis D. However, the absence of HBsAg loss in bulevirtide groups raises questions about its long-term implications.
Article: A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
Presented today at #EASLCongress: In a randomized trial, 48 weeks of treatment with bulevirtide, which inhibits hepatitis D virus entry into hepatocytes, reduced HDV RNA and alanine aminotransferase levels in patients with chronic hepatitis D. https://t.co/Q8RNZFbQlQ
— NEJM (@NEJM) June 22, 2023
EASL Clinical Practice Guidelines on acute-on-chronic liver failure
27 Jun, 2023 | 14:00h | UTCEASL Clinical Practice Guidelines on acute-on-chronic liver failure – Journal of Hepatology
Commentary on Twitter
?NEW@EASLnews Clinical Practice Guidelines on acute-on-chronic liver failure
Available here: https://t.co/GCNg1AIX9X pic.twitter.com/aKd0DUJBkL
— Journal of Hepatology (@JHepatology) June 24, 2023
Review | Update in the treatment of the complications of cirrhosis
21 Jun, 2023 | 13:20h | UTCUpdate in the Treatment of the Complications of Cirrhosis – Clinical Gastroenterology and Hepatology
Podcast | Inpatient cirrhosis management
20 Jun, 2023 | 12:30h | UTC# 398:Live! From SHM: Inpatient Cirrhosis Management – The Curbsiders
Cohort Study | Alcohol consumption and risks of more than 200 diseases in Chinese men
16 Jun, 2023 | 13:55h | UTCAlcohol consumption and risks of more than 200 diseases in Chinese men – Nature Medicine
News Release: Alcohol consumption increases the risks of over 60 diseases – University of Oxford