liver cirrhosis

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.

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.

Allopurinol Prevents Cirrhosis-Related Complications: A Quadruple Blind Placebo-Controlled Trial

Author/s: 
Khadija A M Glal, Sahar M El-Haggar, Sherief M Abd-Elsalam, Tarek M Mostafa

Background: Complications associated with liver cirrhosis are various and potentially fatal. The treatment options to counteract hepatic decompensation are limited. Therefore, the study aimed to explore the use of allopurinol in preventing the recurrence of liver cirrhosis-related complications.

Methods: One hundred patients with hepatic decompensation were randomized into 1:1 ratio to receive either allopurinol 300 mg or placebo tablets once daily for 6 months. The primary endpoint was the incidence of cirrhosis-related complications (overt ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, and hepatic encephalopathy).

Results: Six months following treatment, allopurinol reduced the relative risk (RR) of any first complication experienced after enrollment by 56% (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.27-0.62); P ˂ .001). Allopurinol decreased the RR of overt ascites by 67% (HR 0.33; 95% CI, 0.0098-0.94); P = .039] and reduced the RR of spontaneous bacterial peritonitis by about 75% (HR 0.25; 95% CI, 0.05-0.76; P = .01). Likewise, allopurinol was linked to an 80% reduction in the RR of developing hepatorenal syndrome (HR 0.2; 95% CI, 0.04-0.87; P = .033).

Conclusion: Allopurinol significantly decreased the recurrence of overall liver cirrhosis-related complications. Therefore, allopurinol may constitute a promising agent for patients with hepatic decompensation. These positive outcomes could be a result of its ability to reduce bacterial translocation and inflammation.

Malnutrition in hospitalized adults: A systematic review

Author/s: 
Uhl, S., Siddique, S. M., McKeever, L., Bloschichak, A., D'Anci, K., Leas, B., Mull, N. K, Tsou, A. Y.

Objectives. To review the association between malnutrition and clinical outcomes among hospitalized patients, evaluate effectiveness of measurement tools for malnutrition on clinical outcomes, and assess effectiveness of hospital-initiated interventions for patients diagnosed with malnutrition.

Data sources. We searched electronic databases (Embase®, MEDLINE®, PubMed®, and the Cochrane Library) from January 1, 2000, to June 3, 2021. We hand-searched reference lists of relevant studies and searched for unpublished studies in ClinicalTrials.gov.

Review methods. Using predefined criteria and dual review, we selected (1) existing systematic reviews (SRs) to assess the association between malnutrition and clinical outcomes, (2) randomized and non-randomized studies to evaluate the effectiveness of malnutrition tools on clinical outcomes, and (3) randomized controlled trials (RCTs) to assess effectiveness of hospital-initiated treatments for malnutrition. Clinical outcomes of interest included mortality, length of stay, 30-day readmission, quality of life, functional status, activities of daily living, hospital acquired conditions, wound healing, and discharge disposition. When appropriate, we conducted meta-analysis to quantitatively summarize study findings; otherwise, data were narratively synthesized. When available, we used pooled estimates from existing SRs to determine the association between malnutrition and clinical outcomes, and assessed the strength of evidence.

Results. Six existing SRs (including 43 unique studies) provided evidence on the association between malnutrition and clinical outcomes. Low to moderate strength of evidence (SOE) showed an association between malnutrition and increased hospital mortality and prolonged hospital length of stay. This association was observed across patients hospitalized for an acute medical event requiring intensive care unit care, heart failure, and cirrhosis. Literature searches found no studies that met inclusion criteria and assessed effectiveness of measurement tools. The primary reason studies did not meet inclusion criteria is because they lacked an appropriate control group. Moderate SOE from 11 RCTs found that hospital-initiated malnutrition interventions likely reduce mortality compared with usual care among hospitalized patients diagnosed with malnutrition. Low SOE indicated that hospital-initiated malnutrition interventions may also improve quality of life compared to usual care.

Conclusions. Evidence shows an association between malnutrition and increased mortality and prolonged length of hospital stay among hospitalized patients identified as malnourished. However, the strength of this association varied depending on patient population and tool used to identify malnutrition. Evidence indicates malnutrition-focused hospital-initiated interventions likely reduce mortality and may improve quality of life compared to usual care among patients diagnosed with malnutrition. Research is needed to assess the clinical utility of measurement tools for malnutrition.

Management of Hepatitis C in 2019.

Author/s: 
Kristen, Naggie, Susanna

In the United States, hepatitis C virus (HCV) infection affects more than 2 million adults and is the leading cause of liver-related mortality. Therapies that eradicate HCV may prevent progression to cirrhosis, liver decompensation, hepatocellular carcinoma, need for liver transplant, and death. HCV eradication also appears to reduce the risk of extrahepatic diseases, including cryoglobulinemic vasculitis and cardiovascularevents. Direct-acting antivirals (DAAs), oral drugs that target multiple mechanisms of the HCV lifecycle, have been usedincombination since 2013. Because of their efficacy and safety, the use of DAAshas substantiall yimproved HCV treatment and made HCV eradication possible for most patients, including patients with HIV infection, severe renal and hepatic impairment, and history of organ transplantation. Individuals living with HCV should be treated to reduce liver-related and all-cause morbidity and mortality and to prevent HCV transmission...

Diagnosis and Management of Nonalcoholic Liver Disease

Author/s: 
Paul, Sonali, Davis, Andrew M.

MAJOR RECOMMENDATIONS

• Patients with incidental hepatic steatosis detected on imaging who lack any liver-related symptoms or signs and have normal liver biochemistries should be assessed for metabolic risk factors (eg, obesity, diabetes mellitus, dyslipidemia) and other causes of hepatic steatosis, including alcohol consumption (>14 drinks per week for women; >21 drinks per week for men) and medications.

• Routine screening for NAFLD in high-risk groups is not advised because of uncertainties surrounding diagnostic tests and treatment options, along with lack of knowledge about long-term benefits and cost-effectiveness of screening.

• The FIB-4 (age, aspartate aminotransferase, alanine aminotransferase, platelets) and NAFLD Fibrosis Score (NFS, which adds body mass index and albumin) are clinically useful tools to predict bridging fibrosis.

• Vibration-controlled transient elastography (VCTE) or magnetic resonance elastography (MRE) can noninvasively assess for advanced fibrosis.

• Weight loss generally reduces hepatic steatosis, either by hypocaloric diet alone or in conjunction with increased physical activity.

• Pharmacologic treatments should be limited to patients with biopsy-proven nonalcoholic steatohepatitis (NASH) and advanced fibrosis.

• Statins can be used to treat dyslipidemia in patients with NAFLD, NASH, and compensated NASH cirrhosis.

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