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Tag: Cirrhosis

  • Spleen stiffness measurement could revolutionize the diagnosis and management of portal hypertension

    Spleen stiffness measurement could revolutionize the diagnosis and management of portal hypertension

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    Portal hypertension (PHT) is a severe complication of chronic liver disease, like cirrhosis, where increased pressure builds up in the portal vein. This major blood vessel drains blood from the intestines, spleen, and stomach to the liver. This can lead to life-threatening complications such as internal bleeding and liver failure.

    Currently, the most accurate way to diagnose PHT is an invasive procedure that measures pressure directly in the liver. However, this procedure is uncomfortable for patients and carries a small risk of complications.

    Researchers are excited about a new, noninvasive technique called spleen stiffness measurement (SSM), which uses sound waves to assess the stiffness of the spleen. The spleen is an organ located near the stomach that filters blood and fights infection. When PHT is present, the spleen becomes enlarged and stiffer. SSM uses a painless technique similar to an ultrasound to measure these changes in stiffness.

    Several studies have shown that SSM is highly accurate in detecting PHT. SSM may be more accurate in some cases than existing methods, such as measuring liver stiffness with ultrasound. This could be because the spleen is more directly affected by changes in portal pressure than the liver.

    The benefits of a non-invasive test like SSM are numerous. First, it would eliminate the need for invasive procedures in many patients, making diagnosis safer and more comfortable. Second, SSM could be used to screen patients with chronic liver disease for PHT at an earlier stage, allowing for earlier intervention and potentially preventing complications. Third, SSM could be a valuable tool for monitoring how well treatments for PHT are working. By tracking changes in spleen stiffness over time, doctors could determine if a patient’s PHT improves or worsens in response to medication or procedures like a transjugular intrahepatic portosystemic shunt (TIPS).

    While SSM is promising, further research is needed to confirm its effectiveness in different patient populations and optimize its use in clinical practice. For example, researchers are still determining the best cut-off values for spleen stiffness to diagnose PHT definitively.

    Overall, SSM is a promising new tool that could revolutionize the diagnosis and management of portal hypertension. This non-invasive technique can potentially improve patient care, reduce healthcare costs, and ultimately save lives.

    Source:

    First Hospital of Jilin University

    Journal reference:

    Xu, X., et al. (2024). Spleen stiffness measurement as a non-invasive assessment in patients with portal hypertension. eGastroenterology. doi.org/10.1136/egastro-2023-100031.

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  • Food insecurity fuels fatty liver disease in Latinx kids

    Food insecurity fuels fatty liver disease in Latinx kids

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    For Latinx kids, unreliable access to food at age 4 raises the odds of having fatty liver disease later in childhood by nearly four times, a new UC San Francisco-led study found. 

    About 5% to 10% of children in the United States have nonalcoholic fatty liver disease, putting its prevalence on par with asthma. Pediatric cases have spiked in the last decade, with millions now affected by a disease marked by pain, fatigue and jaundice that can lead to cirrhosis, cancer and organ transplantation. Latinx children and adults have a higher prevalence of fatty liver disease than white or Black people, and the condition is the number one indicator for a liver transplant as an adult.

    In 2022, 13.2% of children in Hispanic households had unreliable access to food (food insecurity), up from 9.7% in 2021. Nearly 16% of children in Black households had unreliable access to food in 2022, up from 12% in 2021, compared to 5.5% of children in white households in 2022, up from 3.4% in 2021.

    “We’ve seen studies in adults associating food insecurity with fatty liver disease and liver fibrosis, but very few studies have looked at children,” said Sarah Maxwell, MD, a pediatrician currently completing her pediatric transplant hepatology fellowship at UCSF Benioff Children’s Hospitals and the study’s lead author. “This is especially important for Latinx children, who have both high rates of household food insecurity and fatty liver disease.”

    The study was published in Pediatric Obesity.

    Kids should be screened earlier

    The researchers recruited two groups of Latinx mothers in San Francisco during pregnancy and followed them and their children to mid-childhood, one group from 2006-07 and the other from 2011-13. They measured food insecurity at age 4 using the U.S. Household Food Security Food Module and assessed fatty liver disease – officially called metabolic dysfunction-associated steatotic liver disease (MASLD) – between ages 5 and 12. The 136 children were followed with annual visits from birth until 2021.

    Twenty-nine percent of the children had household food insecurity at age 4 and 27% had fatty liver disease in early to middle childhood. Children with fatty liver disease were more than twice as likely to live in food-insecure households (49%) at age 4 as children without fatty liver disease (21%). Food insecurity at age 4 raised the odds of having fatty liver disease by age 12 by nearly four times. 

    Children with overweight or obesity at age 2 also had higher risk of developing fatty liver disease in later childhood. 

    It’s not yet known how food insecurity leads to fatty liver disease. Past research suggests food-insecure children may have diets of poorer nutritional quality, with less produce and more sugar-sweetened beverages that directly increase fat in the liver. Household food insecurity can also cause irregular eating patterns that disrupt metabolism, leading to higher stress and greater inflammation, as well as a deterioration in the relationship between gut microbiota and the liver. 

    Given our findings and how young patients are presenting with the condition to our liver clinics, we believe screening for MASLD should begin earlier than current guidelines recommend, which is age 9-11 years for children with obesity and age 2-9 years for those with severe obesity. Food insecurity screening is also important early on, especially for Latinx children who are at higher risk and could be connected to healthier food resources in their communities.”


    Sarah Maxwell, Pediatrician, Benioff Children’s Hospitals

    Ensuring that public meal programs widely available to children, such as school lunches, offer nutritious, balanced meals is also key, she added. 

    Source:

    University of California – San Francisco

    Journal reference:

    Maxwell, S. L., et al. (2024) Food insecurity is a risk factor for metabolic dysfunction-associated steatotic liver disease in Latinx children. Pediatric Obesity. doi.org/10.1111/ijpo.13109.

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  • Nomogram could be a game-changer for predicting alcohol-related liver cancer risk

    Nomogram could be a game-changer for predicting alcohol-related liver cancer risk

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    Liver cancer, unfortunately, is the sixth most common cancer and the third most frequent cause of cancer-related death globally. However, its distribution and causes vary greatly across different regions. While areas like Eastern Asia and sub-Saharan Africa see the most cases, the reasons behind them differ significantly.

    In high-income countries, liver cancer has been on the decline thanks to widespread newborn hepatitis B vaccination and antiviral drugs. Meanwhile, low-income countries witness a worrying rise, often linked to increased hepatitis B and C infections and injectable drug use.

    While viral hepatitis remains a major concern, another factor is gaining attention: alcohol consumption. Studies show that chronic alcohol consumption can directly cause about 10% of cancer cases in men and 3%, respectively, in women. In fact, a study at the Mayo Clinic revealed that alcoholic cirrhosis was the main culprit in 29% of patients with hepatocellular carcinoma (HCC), the most common liver cancer type.

    But the study doesn’t just sound the alarm; it also offers a potential solution. Researchers identified key risk factors for HCC in people with alcohol-related liver disease, including heavy drinking, age, diabetes, male sex, and liver cirrhosis. Based on these factors, they developed a novel tool called a nomogram that can predict HCC risk with high accuracy and ease of use.

    This nomogram could be a game-changer for doctors, allowing them to personalize treatment plans and identify individuals at highest risk for HCC. Early intervention could save lives and prevent unnecessary suffering.

    This study underscores the growing public health concern of alcohol-related liver cancer. The newly developed nomogram offers a valuable tool for doctors to identify high-risk individuals and personalize treatment plans, potentially saving lives and preventing unnecessary suffering.

    While the study provides valuable insights, it acknowledges limitations like its retrospective nature and the need for further validation in larger, prospective studies. Additionally, incorporating other factors like smoking, genetics, and dietary habits could further improve the prediction model.

    The researchers also highlight the need for future research on non-alcoholic fatty liver disease and its link to liver cancer, as this area remains under-investigated.

    Overall, this study shines a light on the rising threat of alcohol-related liver cancer and offers a promising tool for early detection and intervention. Further research and public health efforts are crucial to combat this growing health challenge.

    Source:

    First Hospital of Jilin University

    Journal reference:

    Chang, B., et al. (2024). Prevalence and prediction of hepatocellular carcinoma in alcohol-associated liver disease: a retrospective study of 136 571 patients with chronic liver diseases. eGastroenterology. doi.org/10.1136/egastro-2023-100036.

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  • Blood biomarkers in TGF-β pathway identify hidden liver cancer risk

    Blood biomarkers in TGF-β pathway identify hidden liver cancer risk

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    A new research paper was published in Genes & Cancer on February 5, 2023, entitled, “Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.”

    Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers.

    In this new study, researchers Xiyan Xiang, Krishanu Bhowmick, Kirti Shetty, Kazufumi Ohshiro, Xiaochun Yang, Linda L. Wong, Herbert Yu, Patricia S. Latham, Sanjaya K. Satapathy, Christina Brennan, Richard J. Dima, Nyasha Chambwe, Gulru Sharifova, Fellanza Cacaj, Sahara John, James M. Crawford, Hai Huang, Srinivasan Dasarathy, Adrian R. Krainer, Aiwu R. He, Richard L. Amdur, and Lopa Mishra, from The Feinstein Institutes for Medical Research, Cold Spring Harbor Laboratory, University of Maryland, University of Hawaii, University of Hawaii Cancer Center, The George Washington University, North Shore University Hospital, Northwell Health, Hofstra Northwell School of Medicine, Cleveland Clinic, and Georgetown Lombardi Comprehensive Cancer Center, address this gap using the TGF-β pathway because of its biological role in liver disease and cancer, established through rigorous animal models and human studies. 

    “Alterations in the TGF-β signaling pathway could reflect a continuum of fibrosis to cirrhosis to cancer in the liver. Thus, we hypothesize that the TGF-β pathway-enriched biomarkers may serve as biomarkers in the evolution of HCC and stratify patients at risk for HCC. In addition, we hypothesized that the integrated animal model-to-human studies program would yield new TGF-β driven mechanistic biomarkers that could be valuable in yielding additional biomarkers that could stratify the risk of HCC.”

    Using machine learning methods with blood levels of 108 proteomic markers in the TGF-β family, the team found a pattern that differentiates HCC from non-HCC in a cohort of 216 patients with cirrhosis, which they refer to as TGF-β based Protein Markers for Early Detection of HCC (TPEARLE) comprising 31 markers. Notably, 20 of the patients with cirrhosis alone presented an HCC-like pattern, suggesting that they may be a group with as yet undetected HCC or at high risk for developing HCC. 

    In addition, the researchers found two other biologically relevant markers, Myostatin and Pyruvate Kinase M2 (PKM2), which were significantly associated with HCC. They tested these for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables, as well as batch and site. These markers reflect ongoing biology in the liver. 

    “They potentially indicate the presence of HCC early in its evolution and before it is manifest as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC.”

    Source:

    Journal reference:

    Xiang, X., et al. (2024). Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis. Genes & Cancer. doi.org/10.18632/genesandcancer.234.

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  • Up to 10% of dementia cases in veterans may be caused by liver disease

    Up to 10% of dementia cases in veterans may be caused by liver disease

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    As many as 10% of older U.S. veterans diagnosed with dementia may suffer instead from reversible cognitive decline caused by advanced liver disease, according to an analysis from the Virginia Commonwealth University’s School of Medicine and the Richmond VA Medical Center. 

    It can be difficult for physicians to differentiate dementia from the cognitive decline caused by cirrhosis, called hepatic encephalopathy. If undetected, patients may not receive appropriate treatment that can reverse or halt the impairment. The study, published in the journal JAMA Network Open, sought to learn more about the prevalence and risk factors of undiagnosed cirrhosis and potential encephalopathy in veterans with dementia.

    The findings suggest that physicians treating veterans with dementia, even without a cirrhosis diagnosis, should consider assessing their patients for liver disease. Identifying cirrhosis early on may unveil reversible causes of cognitive impairment, potentially improving the lives of these patients.

    This unexpected link between dementia and liver health emphasizes the importance of screening patients for potentially treatable contributors to cognitive decline.”


    Jasmohan Bajaj, M.D., lead author, gastroenterologist and world-renowned expert in hepatic encephalopathy with the VCU Stravitz-Sanyal Institute for Liver Disease and Metabolic Health and the Richmond VA Medical Center

    The researchers believe the findings would apply to non-veterans with dementia, but further research is needed. Bajaj urges clinicians, especially those who encounter patients with dementia, to incorporate liver assessments into routine care for their patients. 

    “Early detection of liver issues allows for targeted interventions and opens avenues for addressing treatable factors contributing to cognitive decline,” he said.

    Hepatic encephalopathy is a nervous system disorder brought on by cirrhosis, an advanced form of liver disease in which patients experience severe scarring of the liver. When the liver doesn’t work properly, toxins build up in the blood. These toxins can travel to the brain and affect brain function, leaving patients confused or delirious. Widely available medications can readily rid the body of toxins and reverse this condition, but without treatment, patients can lapse into coma or die. 

    Bajaj said the study was sparked by the cases of two older men who were thought to have dementia and Parkinson’s disease, but whose symptoms dramatically improved after being treated for hepatic encephalopathy. One of the men recovered to the point where he resumed driving. Bajaj and colleagues continued to pursue this link between dementia and cirrhosis, publishing findings in 2023 that about 8% of U.S. veterans with cirrhosis had dementia.

    To look at the flip side, the new study’s authors reviewed medical records of 177,422 U.S. veterans diagnosed with dementia but not cirrhosis between 2009 and 2019. The veterans studied were patients from all across the VA medical system. Roughly 30% of veterans suffer from some form of liver disease.

    Participants were overwhelmingly male, with an average age of 78, and evaluated using the Fibrosis-4, or FIB-4, score. The FIB-4 score, an initial screening index for most liver diseases that is based on multiple measurements, including age, is recommended by leading liver, gastroenterology and endocrinology associations as a first-line test to screen for liver fibrosis in the general population. The FIB-4 score was developed by VCU Health hepatologist Richard Sterling, M.D., who is the chief clinical officer of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health.

    The study revealed that 10.3% of veterans with dementia had high FIB-4 scores, meaning they were very likely to have cirrhosis. Factors that increase the risk of cirrhosis include older age, being male, congestive heart failure, viral hepatitis, alcohol use and certain health conditions. 

    Notably, the data showed that dementia disproportionately affected Black and Hispanic veterans, who also were more likely to be diagnosed later in the disease course. Non-Hispanic white veterans who did not use tobacco or had diabetes were less likely to have elevated FIB-4 scores.

    The researchers conducted a follow up study at the Richmond VA Medical Center to validate their findings and found similar results, with as many as 11.2% of the patients having high FIB-4 scores. 

    “The next step is to ensure that health care providers taking care of patients with cirrhosis and well as those with dementia are made aware of a potential overlap with hepatic encephalopathy, which is treatable,” said Bajaj, who has spent the past several years focusing on hepatic encephalopathy and the gut-brain axis. 

    “Routinely using the FIB-4 index to evaluate dementia could help a significant number of patients, families and physicians by providing an opportunity to treat and potentially reverse cognitive impairment brought on by liver disease,” he added. 

    Source:

    Virginia Commonwealth University

    Journal reference:

    Bajaj, J. S., et al. (2024). Undiagnosed Cirrhosis and Hepatic Encephalopathy in a National Cohort of Veterans With Dementia. JAMA Network Open. doi.org/10.1001/jamanetworkopen.2023.53965.

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