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Hepatitis B: A Review

Author/s: 
Wen-Juei Jeng, Terry Cheuk-Fung Yip, Anna S. Lok

Importance: Hepatitis B virus (HBV) infection affects an estimated 254 million people worldwide and causes approximately 1.1 million deaths annually. In 2022, there were approximately 1.2 million new HBV infections worldwide and 14 000 in the US.

Observations: HBV is a DNA virus transmitted through percutaneous or mucosal exposure to infected blood, semen, or body fluids. Mother-to-child transmission, which is the principal cause of chronic HBV infection globally, occurs in 70% to 90% of infants born to mothers who are hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive and in 5% to 20% of those born to HBsAg-positive/HBeAg-negative mothers. However, HBV vaccination and administration of hepatitis B immune globulin within 12 to 24 hours of birth prevent approximately 94% of perinatal infections, and adding antiviral therapy in pregnant women with high HBV DNA reduces transmission to less than 1%. Although universal birth-dose HBV vaccination is the most effective strategy for eliminating HBV infection, global birth-dose HBV vaccine coverage was only 45% in 2024. The risk of developing chronic infection (HBsAg positive for more than 6 months) is 90% if HBV infection occurs during infancy, 30% in children aged 1 to 5 years, and less than or equal to 5% in immunocompetent adolescents and adults. HBV infection is diagnosed by serologic testing: HBsAg indicates ongoing infection, antibody to HBsAg indicates immunity, and antibody to hepatitis B core antigen indicates ongoing or past infection. Serum HBV DNA levels quantify virus-replication activity. Assessment of liver inflammation and fibrosis with alanine aminotransferase (ALT) and noninvasive tests such as Fibrosis-4 index and liver elastography guide treatment decisions. Chronic HBV infection may progress to cirrhosis and hepatocellular carcinoma (HCC); the 5-year cumulative risk of cirrhosis is 8% to 15% in untreated chronic HBV infection, and annual HCC incidence is 3% to 5% among patients with cirrhosis. Antiviral therapies-pegylated interferon alfa and nucleos(t)ide analogues (entecavir or tenofovir)-suppress HBV DNA replication and reduce the risk of HCC by approximately 50%. Antiviral treatment is recommended for all patients with chronic HBV and cirrhosis and for those without cirrhosis who have high HBV DNA with elevated ALT or significant inflammation/fibrosis. Patients at high risk of HCC should undergo surveillance with ultrasonography and alpha-fetoprotein testing every 6 months.

Conclusions and relevance: HBV infection causes approximately 1.1 million deaths annually worldwide. Universal HBV vaccination, particularly birth-dose administration, is the most effective strategy to prevent HBV infection. Among patients with HBV infection, antiviral therapy decreases progression to cirrhosis and liver failure and reduces the risk of HCC.

Keywords 
hepatitis hepatitis B Hepatitis B Core Antigens Hepatitis B Surface Antigens Antiviral Agents Liver Failure vaccination

Metabolic Dysfunction–Associated Steatotic Liver Disease in Adults: A Review

Author/s: 
Herbert Tilg, Salvatore Petta, Norbert Stefan, Giovanni Targher

Importance Metabolic dysfunction–associated steatotic liver disease (MASLD) includes a range of liver conditions, progressing from isolated steatosis (characterized by fat accumulation in the liver without inflammation) to metabolic dysfunction–associated steatohepatitis (MASH), which involves fat accumulation and inflammation in the liver. The presence of MASLD is associated with increased morbidity and mortality due to liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers.

Observations The most common chronic liver disease worldwide, MASLD affects approximately 30% to 40% of the general adult population globally (with varying prevalence across continents), including approximately 60% to 70% of individuals with type 2 diabetes and approximately 70% to 80% of those with obesity. It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (<2 standard drinks/d) and for men who consume less than 210 g/wk (<3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. Other risk factors for MASLD include older age (≥50 years) and male sex (male:female ratio approximately 2). The Fibrosis-4 index (a scoring system incorporating age, serum levels of aspartate aminotransferase and alanine aminotransferase, and platelet count) and vibration-controlled transient elastography (a noninvasive imaging technique) are commonly used to stage hepatic fibrosis in patients with MASLD. Cardiovascular disease is the leading cause of death, followed by certain extrahepatic cancers (primarily gastrointestinal, breast, and gynecologic cancer) and liver-related complications, including cirrhosis, hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), and hepatocellular carcinoma. First-line treatment of MASLD involves behavioral modifications (including hypocaloric low-carbohydrate and low-fat diets, physical exercise, and avoidance of alcohol) and management of type 2 diabetes, obesity, hypertension, and hyperlipidemia. Bariatric surgery should be considered for patients with MASLD and a body mass index greater than 35. Resmetirom (a liver-directed, thyroid hormone receptor β-selective agonist) and subcutaneous semaglutide (a glucagon-like peptide-1 receptor agonist) are conditionally approved by the US Food and Drug Administration (FDA) for the treatment of adults with MASH who have moderate to advanced fibrosis.

Conclusions A highly prevalent condition among adults worldwide, MASLD is associated with liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis.

Keywords 
liver disease steatotic liver disease MASLD Steatohepatitis

Once-Weekly Semaglutide in Adolescents with Obesity

Author/s: 
Weghuber, D., Barrett, T.

BACKGROUND
A once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking.

METHODS
In this double-blind, parallel-group, randomized, placebo-controlled trial, we enrolled adolescents (12 to <18 years of age) with obesity (a body-mass index [BMI] in the 95th percentile or higher) or with overweight (a BMI in the 85th percentile or higher) and at least one weight-related coexisting condition. Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo for 68 weeks, plus lifestyle intervention. The primary end point was the percentage change in BMI from baseline to week 68; the secondary confirmatory end point was weight loss of at least 5% at week 68.

RESULTS
A total of 201 participants underwent randomization, and 180 (90%) completed treatment. All but one of the participants had obesity. The mean change in BMI from baseline to week 68 was −16.1% with semaglutide and 0.6% with placebo (estimated difference, −16.7 percentage points; 95% confidence interval [CI], −20.3 to −13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo. The incidence of gastrointestinal adverse events was greater with semaglutide than with placebo (62% vs. 42%). Five participants (4%) in the semaglutide group and no participants in the placebo group had cholelithiasis. Serious adverse events were reported in 15 of 133 participants (11%) in the semaglutide group and in 6 of 67 participants (9%) in the placebo group.

CONCLUSIONS
Among adolescents with obesity, once-weekly treatment with a 2.4-mg dose of semaglutide plus lifestyle intervention resulted in a greater reduction in BMI than lifestyle intervention alone. (Funded by Novo Nordisk; STEP TEENS ClinicalTrials.gov number, NCT04102189. opens in new tab.)

Keywords 
Cardiometabolic Risk Factors Confidence Intervals Glycated Hemoglobin A Waist Circumference Lipoproteins, HDL
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