the liver meeting

In this episode, Nancy Reau, MD, discusses new data on hepatitis B virus presented at AASLD 2023, including:

• Current therapies
  • Studies 108 and 110: Factors Linked With Lack of Virologic Suppression After 8 Yr of TAF or TDF
  • Kaiser Permanente Northern California: HCC or Death With TDF vs ETV for Chronic Hepatitis B
  • Early vs Late Postpartum Cessation of TDF Initiated for Prevention of Vertical HBV Transmission
• Investigational functional cure strategies
  • B-Together: Sequential Bepirovirsen and PegIFN Added to NA Therapy for Chronic HBV Infection
  • MARCH Part B: VIR-3434 ± VIR-2218 ± PegIFN Added to NA Therapy for Chronic HBV Infection
  • REEF-IT: JNJ-3989 + NA ± JNJ-6379 With PegIFN Add-on Consolidation in Patients With HBeAg-Positive CHB
  • HBV003: VTP-300 + Nivolumab Added to NA Therapy for Chronic HBV Infection
  • CVP-NASVAC: Nasally Administered Therapeutic Vaccine for Chronic HBV Infection

Presenter:
Nancy Reau, MD
Professor of Medicine
Richard B. Capps Chair of Hepatology
Chief, Section of Hepatology
Associate Director, Solid Organ Transplantation
Rush University Medical Center 
Chicago, Illinois

Link to full program: 
https://bit.ly/47XJlU4

During the 2023 American Association of the Study of Liver Diseases (AASLD) conference, exciting and important results from many primary biliary cholangitis (PBC) clinical trials were reported, including 3 late-breaking studies on the PPAR-delta agonist seladelpar, the dual PPAR agonist elafibranor, and the combination of the FXR agonist obeticholic acid and a fibrate.

In this episode, Stuart C. Gordon, MD, FAASLD, discusses topline results from one of these late-breaking studies and more, including: 

• A phase III study of an investigational PPAR-delta agonist (seladelpar) in people with PBC who had failed to respond to ursodeoxycholic acid
• A study that explored racial differences as they relate to the presentation and diagnosis of PBC

Presenter: 
Stuart C. Gordon, MD, FAASLD
Director of Hepatology
Henry Ford Health System
Professor of Medicine
Wayne State University School of Medicine
Detroit, Michigan

Link to commentary:
https://bit.ly/3GzRMt2

Link to reviews of other PBC studies from AASLD 2023:
https://bit.ly/3RvXXEI

Last week's posting consisted of 1:1 interviews with four KOL from different spheres, each talking with Roger Green about what they are looking forward to seeing at this week's The Liver Meeting 2023. This week, two of those KOLs, co-host Jörn Schattenberg and hepatology KOL Naim Alkhouri, join Roger and co-host Louise Campbell, FRCP, in a free-wheeling review of key abstracts that will be presented at TLM2023.
The discussion begins with Jörn spotlighting the first item in the abstract book, a presentation titled MASH Resolution Without Fibrosis Worsening After Bariatric Surgery Improves Long-Term Survival. Jörn spotlights this study for demonstrating survival benefits, a significant benchmark for drug approval processes. This study of bariatric patients with concomitant MASH and fibrosis reveals that MASH resolution often comes before fibrosis regression. This suggests that MASH resolution itself might predict improved long-term outcomes, contrasting with earlier beliefs that only linked fibrosis regression to positive prognoses. Louise comments that reducing inflammation should logically lead to fibrosis regression, comparing it to the treatment of hepatitis C. Naim agrees, emphasizing the liver's remarkable ability to heal if the initial injury stops, such as with alcohol cessation or hepatitis treatment. However, he points out challenges in clinical definitions and trial inclusions based on the current focus on MASH histology.
The conversation shifts as Naim shares his excitement that both the ENLIVEN trial with FGF-21 agent pegozafermin and the ALPINE-4 trial with FGF-19 agent aldafermin demonstrate the potential for these agents to reduce fibrosis one level (and occasionally even two!) in patients with cirrhosis. The group agrees that treating cirrhosis is the most urgent challenge facing MASLD hepatology today because patients are close to decompensation and antifibrotic pharmacotherapy does not exist. This leads Roger to ask whether the presence of these agents will drive more aggressive screening for cirrhosis patients and for the group to list the benefits early screening will offer.
Louise shares two papers she intends to follow, both of which focus on gender disparities in liver health. She reminds the group of Roberta Forlano's research (shared in S4 E44) and comments during that discussion that women in liver failure experience higher rates of death that man -- they do not fare as well  on liver transplant lists and exhibit higher rates associated with hepatic renal syndrome. The group concurs that this disparity needs more attention and fits into a broader issue of inequality in medical treatment based on gender and other demographic factors.
Roger shares two posters on lanifibranor with an eye toward how payers are likely to assess agents when they come to market. As the group discussed in earlier episodes, there are significant challenges identifying which patients are likely to succeed prospectively on a MASH drug and another on determining in a reasonable timeframe whether the medication is working. Of the two lanifibranor posters, one suggests that changes in adiponectin levels can predict level of therapeutic success, while the other shows that presence of a mutated PNPLA3 gene has minimal or no impact on the likelihood of therapeutic success.
The group discusses a few other papers and concepts. One paper of note came from the NAIT-NIT consortium and suggests that biopsy can lead to an overestimation of liver fat levels compared to MRI-PDFF. Naim and Jörn comment on behavioral or attitudinal constructs from hepatologists that might lead to this result.
Finally, the group comments on the importance of late-breakers as a vital conduit or cutting edge research and each member notes one other paper or session at the meeting they find intriguing.

STAY SAFE AND SURF ON!

In this episode, Stefan Zeuzem, MD, discusses new viral hepatitis data from AASLD 2022, including:

• Hepatitis B
• Prevention of HBV vertical transmission when HBIg is unavailable
• Therapeutic vaccination for HBV cure
• Antiviral therapy to prevent HCC in patients with CHB in the indeterminate phase
• Hepatitis delta
• HDV prevalence in ethnically diverse, urban, safety-net populations
• Bulevirtide ± pegIFN-α2a for chronic HDV in the French cATU study
• Bulevirtide monotherapy for patients with HDV and compensated cirrhosis in the HEP4Di study
• HDV functional cure with lonafarnib-based therapy
• Hepatitis C
• Integrated community HCV service for PWUD: the ITTREAT study
• Helios-3 study of treatment of people with HCV by specialists or nonspecialists
• Risk of HCC after SVR in patients with HCV

Presenter:

Stefan Zeuzem, MD
Professor of Medicine
Chief, Department of Medicine I 
JW Goethe University Hospital 
Frankfurt, Germany

Follow along with the downloadable slideset at: 
https://bit.ly/3FxIOwZ

Link to full program: 
https://bit.ly/3Y1tD6f