Category Archives: Hepatology

Hepatitis B Therapy for Patients with Mildly Elevated Liver Enzymes Associated with Lower Risk of Cancer and Cirrhosis

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J Wang et al. Clinical Gastroenterology and Hepatology, 2026; 24, 2742-2751. Open Access! Antiviral Therapy Reduces Hepatocellular Carcinoma and Cirrhosis Risk in Chinese Chronic Hepatitis B Patients With Mildly Elevated Alanine Aminotransferase

Background: “Generally, patients with normal or mildly elevated ALT levels have a low risk of disease progression and HCC, and regular follow-up instead of immediate antiviral therapy is recommended in most international CHB guidelines.3–6 However, emerging evidence suggests that a considerable proportion of patients with CHB and normal or mildly elevated ALT levels have significant histological changes and relatively high risk of HCC and cirrhosis, especially in individuals with high HBV DNA levels.7–13 The interim results from a recent randomized controlled trial (ATTENTION) add important evidence that early antiviral treatment with tenofovir alafenamide (TAF) reduces the risk of liver-related adverse events in patients with non-cirrhotic livers and normal or mildly elevated ALT levels compared with untreated patients.14“

Methods: This retrospective multicenter study included 3734 non-cirrhotic patients (mean age 36.5 yrs) with chronic hepatitis B (CHB) with ALT <2 × the upper limit of normal (ULN); ALT values used a more stringent definition of normal or mildly elevated ALT, as recommended by the 2025 AASLD guideline. To balance baseline characteristics between treated and untreated patients, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were applied. Of all patients, 37.8% received nucleos(t)ide analogues (NA) treatment.

Key findings:

  • After IPTW, treated patients had a significantly lower 5-year cumulative incidence of HCC (0.9% vs 4.4%; P < .001) and cirrhosis (4.0% vs 8.9%; P < .001) than untreated patients
Comparison of cumulative incidence of HCC between treated group and untreated group with IPTW
Comparison of cumulative incidence of cirrhosis between treated group and untreated group with IPTW

Discussion:

“Our real-world evidence supports the ongoing shift toward a more proactive treatment approach for expanding eligibility to include patients with lower threshold ALT levels (>ULN) and HBV DNA (>2000 IU/mL), as recently recommended by the 2025 European Association for the Study of the Liver (EASL) guidelines and the 2024 World Health Organization (WHO) guidelines.4,6“

My take (borrowed in part from the authors): “NA therapy reduced the risk of HCC and cirrhosis in non-cirrhotic CHB patients with mildly elevated ALT levels (1–2 × ULN). These findings support the expansion of antiviral treatment criteria for the early treatment of these patients.” The benefits of NA therapy, though, may vary significantly in younger patients, especially those in the pediatric age group.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

A Natural Experiment: Sugar Rationing and Metabolic Dysfunction-Associated Steatotic Liver Disease

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J Zheng et al. Clinical Gastroenterology Hepatology 2026; 24: 2168-2180. Open Access! Sugar Rationing in the First 1000 Days After Conception and Long-Term Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease and Major Adverse Liver Outcomes: A Natural Experiment Study

A previous blog post (The Hidden Dangers of Early Sugar Exposure) reviewed the beneficial effects of sugar rationing in Britain around WWII. There were lower rates of type 2 diabetes and hypertension.

Today’s article, reviews the effects of sugar rationing on liver outcomes.

Methods:

Key findings:

  • Among 63,698 participants, early-life sugar rationing was associated with a 30% reduced risk of MASLD (hazard ratio, 0.70), 17% lower risk of metabolic dysfunction-associated steatotic liver disease with alcohol consumption, 35% for major adverse liver outcomes, and 32% for cirrhosis. 
  • The protective effect increased with longer exposure.

My take: Reducing sugar, including in the prenatal period, reduces the risk of adverse liver outcomes in addition to type 2 diabetes and hypertension.

Related blog posts:

From AGA Today in Medicine on 8/19/26 – Ongoing Cyclospora Outbreak:

Bepirovirsen: Breakthrough for Chronic Hepatitis B Infection

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  • J Hou et al. NEJM 2026. DOI: 10.1056/NEJMoa251513. Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection
  • A Lok. NEJM 2026. DOI: 10.1056/NEJMe2605575. A Major Step toward a Cure for Hepatitis B Infection (editorial)

Methods:

The B-Well trials enrolled patients with noncirrhotic chronic hepatitis B with suppressed HBV DNA during receipt of NA therapy and a low HBsAg level (≤3000 IU per milliliter). A total of 1838 patients were randomly assigned in a 2:1 ratio to receive bepirovirsen or placebo administered as a weekly subcutaneous injection for 24 weeks. The patients who had undetectable HBsAg and unquantifiable HBV DNA from week 24 to week 46 were eligible to discontinue NA therapy at week 48. The primary outcome of a functional cure was assessed at week 72.

Key findings:

  • In two phase 3 trials, 19% of patients with chronic hepatitis B infection had a functional cure with the antisense oligonucleotide bepirovirsen, 24 weeks after stopping all HBV treatment; functional cure was not seen with placebo.

Adverse events of grade 3 or higher were more common in the bepirovirsen groups than in the placebo groups (16% vs. 3%), with an increase in alanine aminotransferase (ALT) being the most common (6%) with bepirovirsen. In addition, adverse events requiring a dose interruption or delay were reported in 16% of the patients in the bepirovirsen groups as compared with 2% in the placebo groups.

My take:

  1. Currently, it is estimated that 240 million persons worldwide are living with chronic HBV. These trials represent a big step forward showing that many patients can achieve a functional cure (no detectable HBV) off all medications. Prevention of HBV, though, via immunization holds much more promise in reducing the number of individuals with poor outcomes due to HBV.
  2. Several of the adverse events — an increase in the levels of ALT and creatinine and a decrease in the platelet count — can be potentially serious if stringent monitoring (every 1 to 2 weeks) and strict trial-adopted guidelines regarding the pausing of therapy are not followed.

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What to Make of Popular “Liver Detox” Therapies

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An excerpt:

A cross-sectional study of the 20 highest-ranked purported “liver-cleansing” products sold on Amazon found that they generated almost $40 million in annual revenue, yet their detoxification claims and ingredients were unsupported by data and, in some cases, these products caused adverse events…evidence assessment showed that even the most common ingredients have limited scientific support.

The most common ingredient in the analyzed products was milk thistle, which appeared in 19 of 20 products. This was followed by dandelion root (13) and turmeric root (13). Other, less common ingredients included zinc (12), beetroot (11), artichoke extract (10), choline (10), ginger (9), chicory (8), and berberine (7)…

The investigators recommended “several policy improvements, including mandatory pre-market safety testing, standardized manufacturing practices, enhanced post-market surveillance, and requirements for scientific substantiation of marketing claims.”

My take: Herbal and dietary supplements can cause drug-induced liver injury, sometimes life-threatening. It would be best for those who claim these products are effective to provide proof of this.

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Major Update of AASLD IDSA Practice Guideline on Treatment of Chronic Hepatitis B (Part 2)

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MG Ghany et al. Hepatology 83(4):p 974-997, April 2026. Open Access! AASLD IDSA Practice Guideline on treatment of chronic hepatitis B

Yesterdays’ blog post summarized the 6 key questions that are reviewed in the updated guidelines. Today’s post provides more details on treatment and a direct link to the practice guideline.

Background: “CHB affects ~258 million individuals (2022) globally8 and leads to an estimated 1.1 million deaths annually due to complications of cirrhosis and HCC…This guideline focuses on six specific issues related to management of CHB. Other recommendations for management of CHB addressed in the 2018 guidelines will continue to be applicable and the reader is referred to this document.1“

Treatment Recommendations for Patients without Cirrhosis Based on HBeAg Results, HBV DNA and ALT Values

AASLD guidelines favor continuing nucleos(t)ide analogs (NAs) therapy until loss of HBsAg. However, there are additional criteria in new the guidelines for shared decision-making on stopping therapy in those with very low HBsAg levels (<100 IU/mL).

Criteria for stopping NA therapy if ALL are met:

Criteria for resuming therapy immediately (need only 1)

Other Criteria for resuming therapy

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Major Update on AASLD IDSA Practice Guideline on Treatment of Chronic Hepatitis B (Part 1)

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Hepatology 83(4):p 970-973, April 2026. Open Access! Visual Brief Summary: Updated AASLD Guidelines for Chronic Hepatitis B Treatment

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Trends in Liver Transplantation: Alcoholic Liver Disease and MASH/NASH Now Top Indications

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Z Younossi et al. Liver Transplantation 2026; 32(4):p 549-557. Steatotic liver disease is the dominant indication for liver transplantation in both Europe and the United States: Trends and outcomes in the past 2 decades

Methods: Adult data from 2 large LT registries: the US Scientific Registry of Transplant Recipients (SRTR) and the European Liver Transplant Registry (ELTR), years 2000–2022, were compared. There were 109,048 recipients of transplant from ELTR (30 countries), and 128,765 from SRTR.

Key findings:

  • #1 cause in 2022: Alcohol-associated liver disease (ALD) increased: SRTR 15%to 45%, and ELTR 25% to 41%
  • #2 cause in 2022: NASH/MASH also increased: SRTR 9% to 28%, and ELTR 5% to 12%
  • Chronic hepatitis C decreased: SRTR 40% to 7%, and ELTR 25% to 7%

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Health Insurance Improves Survival and Outcomes in Patients with Liver Disease

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In a previous blog post in 2019, it was noted how the IRS proved that having health insurance saved lives (How The IRS Proved That Health Insurance Saves Lives); just receiving a letter recommending getting coverage reduce deaths by ~1 in 1600. Another study in 2014 (in Massachusetts) showed that for “every 830 additional people who got insurance under Massachusetts’ health reforms prevented roughly one death.” If this were extrapolated to broaden health care coverage to everyone in the U.S this could amount to preventing 20,000-45,000 deaths per year (A Leading Cause of Mortality in U.S…. and 45,000 Unnecessary Deaths Per Year).

A new study shows how important ACA expansion has been to improved liver outcomes:

TL Walker et al. Clinical Gastroenterology and Hepatology 2026; 24: 312 – 327. The Affordable Care Act Improves Access, Survival, and Racial Disparities of Patients With Liver Disease: A Systematic Review

This review identified twenty-seven studies that met inclusion criteria across 4 clinical categories: hepatitis C virus (n = 4), liver transplantation (n = 10), hepatocellular carcinoma (n = 9), and cirrhosis or CLD (n = 5).

Key findings:

  • Twenty-three out of 27 studies showed patients benefited from the ACA, which notably included improved liver-related mortality in Medicaid-expansion (ME) states.
  • “Difference-in-difference analyses showed liver transplantation listing increased by 1.8% to 6.0% in ME vs NME states; early-stage hepatocellular carcinoma (HCC) diagnosis increased by 5.4%, and cirrhosis-related mortality rose more slowly in ME states (0.5–1.0 per 100,000 vs 1.4–10.4 per 100,000).”

From Related summary: ACA expansion linked to better liver disease outcomes (GI & Hepatology News):

  • HCV studies showed improved access to direct-acting antiviral therapy in ME states. Expansion states consistently reported higher direct-acting antiviral prescription rates and Medicaid reimbursement levels compared with NME states.
  • HCC survival outcomes improved more consistently in ME than in NME states after ACA implementation (median overall survival, 7.3 months versus 4.5 months, respectively).
  • Of the five studies that examined chronic liver disease and cirrhosis, ME was associated with lower emergency department readmissions, shorter hospital stays, and reduced hospitalization costs.

My take: The study findings, while not surprising, quantifies some of the improvements in survival and outcomes for patients who gained access to health insurance.

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    Does Liver Histology Still Help with Risk Stratification in Advanced Liver Disease Due to MASLD?

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    The editorial provide a succinct critique and summary of this retrospective study. An excerpt:

    For many decades, liver biopsy specimens and HVPG measurements have served as the cornerstone for risk stratification of patients with cirrhosis. Fibrosis staging, particularly the distinction between F3 and F4, as well as HVPG measurements, have informed prognoses and patient enrollment in therapeutic trials…

    Noninvasive tests, particularly liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), are increasingly used for risk stratification in MASLD patients with cirrhosis and may inform treatment decisions.3 The ANTICIPATE–nonalcoholic steatohepatitis (NASH) models, which combine LSM, platelet count, and body mass index, have been proposed to predict the risk of CSPH [clinically significant portal hypertension] progression and liver-related events (LRE) in patients with MASLD.4–6 …

    First, the authors examined a multicenter cohort of 699 biopsy specimen–proven MASLD patients with LRE (hepatic decompensation, hepatocellular carcinoma, transplantation, or liver-related death) as the end point. Second, they examined a validation cohort of 1396 F3 or F4 patients from 4 clinical trials…

    The results can be summarized as follows: In the first cohort, 56 LREs (8%) occurred during a 3-year follow-up, mostly in F4 patients. The second cohort had 33 composite end points (2.3%) during a median follow-up of 16 months. The ANTICIPATE-NASH model showed excellent discrimination for LRE (C statistic, 0.93), which was higher than that for histology (C statistic, 0.67). However, adding histology to the model did not improve prediction… These findings highlight the limitations of biopsy specimens and underscore the ability of noninvasive models to capture the dynamic and continuous nature of disease progression…

    The clinical and research implications are substantial. In daily clinical practice, the widespread adoption of the ANTICIPATE-NASH model could allow hepatologists to identify high-risk patients who require closer monitoring or early therapeutic intervention while sparing low-risk patients from invasive biopsies and unnecessary procedures. For clinical trials, model-based enrichment could increase event rates, reduce required sample sizes, and shorten follow-up duration.

    My take: This study, while limited by its retrospective design, indicates that histology is no longer the “gold” standard for prognostication in adults with MASLD and advanced fibrosis.

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    More Pediatric Data Supporting GLP-1 RA Efficacy for MASLD

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    AM Tou et al. J Pediatr Gastroenterol Nutr. 2026;82:146–155. Glucagon‐like peptide‐1 receptor agonists in pediatric metabolic dysfunction‐associated steatotic liver disease

    Methods: Retrospective study in patients ≤18 years old with a diagnosis of MASLD, who were prescribed a GLP-1RA from January 2, 2018 and January 10, 2024 at the Children’s Hospital of Philadelphia. 42 patients met inclusion criteria (out of a cohort of 111 that had received GLP-1RA with diagnosis of MASLD). Of the GLP-1RA medications, liraglutide was most frequently prescribed (44%), followed by semaglutide (27%), dulaglutide (25%), and exenatide (4%).

    Key findings:

    • ALT improved by a mean of 56 U/L at 6 months (p = 0.04), and by 37 U/L at end of treatment (p = 0.004)
    •  71% of patients had a therapeutic indication for T2DM and 29% for obesity
    • “Improvements were also observed in aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), glycated hemoglobin (HbA1C), and triglycerides. Body mass index (BMI) percentile and z-score showed no significant changes, but BMI stabilization was observed”

    My take: While Semaglutide has an FDA indication for MASLD treatment, there is limited pediatric data. This study indicates that GLP1-RAs are likely to have similar efficacy in adolescents. The lack of weight loss in this study is likely related partly to use in T2DM which has a lower response and the use of GLP-1RAs known to have lower response with regard to weight loss.

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