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Fatty Liver Causes Symptoms Complications And Prevention

Fatty liver disease, also known as hepatic steatosis, is a condition where fat builds up in the liver. While having small amounts of fat in the liver is normal, excessive accumulation can lead to inflammation, damage, and even severe liver complications.Moreover, the awareness around fatty liver is so low that people do not realise until it's too late. So, what exactly causes fatty liver? Is it a severe condition, if yes how can it affect the infected individual? How to prevent it?

Fatty liver disease cause Fatty liver disease can be categorized into two primary types based on its cause: alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD). Both types share common mechanisms of fat buildup but differ in their triggers.

Alcoholic Fatty Liver Disease (AFLD): AFLD occurs due to excessive alcohol consumption. The liver metabolizes alcohol, but this process produces harmful substances that can damage liver cells, promote inflammation, and impair the liver's ability to break down fats. Over time, these factors lead to fat accumulation.

Non-Alcoholic Fatty Liver Disease (NAFLD): NAFLD is not associated with alcohol intake and is often linked to metabolic risk factors. Causes include:

Obesity: Excess body weight increases fat deposition in the liver.

Insulin resistance and type 2 diabetes: These conditions interfere with the body's ability to regulate fat storage and utilization.

Dyslipidemia: High levels of triglycerides and low levels of HDL ("good cholesterol") contribute to fat buildup.

Metabolic syndrome: A combination of obesity, hypertension, high blood sugar, and abnormal cholesterol levels increases the risk.

Rapid weight loss or malnutrition: These can disrupt the liver's fat metabolism.

Certain medications: Corticosteroids, tamoxifen, and methotrexate can contribute to fatty liver.

Other factors that cause fatty liverFamily history of liver disease may increase susceptibility of fatty liver. Sleep apnea can exacerbate liver inflammation. Women with PCOS are at a higher risk of fatty liver.

Fatty liver disease symptoms Fatty liver disease often progresses silently, with many individuals remaining asymptomatic in its early stages. However, symptoms may develop as the condition advances. The early symptoms of fatty liver disease include fatigue and general weakness, discomfort or dull pain in the upper right abdomen.If fatty liver disease progresses to non-alcoholic steatohepatitis (NASH) or liver fibrosis, symptoms may include abdominal swelling (ascites), enlarged spleen, yellowing of the skin and eyes (jaundice), spider-like blood vessels on the skin, red palms (palmar erythema), and confusion or difficulty concentrating (hepatic encephalopathy).

How is fatty liver diagnosed? Fatty liver disease is often detected incidentally during routine check-ups or imaging studies for unrelated conditions. Accurate diagnosis involves a combination of medical history, physical examination, and diagnostic tests.

Assessment of alcohol consumption, diet, and lifestyle habits

Evaluation of underlying conditions such as obesity, diabetes, or metabolic syndrome

Physical signs like an enlarged liver or jaundice

Liver function tests: Elevated levels of liver enzymes (ALT and AST) may indicate liver damage.

Lipid profile: Helps assess cholesterol and triglyceride levels.

Blood glucose and HbA1c: Used to evaluate insulin resistance or diabetes.

Ultrasound: A non-invasive and commonly used method to detect fat in the liver.

CT scan or MRI: Provides more detailed images of the liver and fat distribution.

FibroScan: Measures liver stiffness to assess fibrosis or scarring.

In cases where the diagnosis remains uncertain, a liver biopsy may be performed. This involves taking a small sample of liver tissue to evaluate the extent of fat accumulation, inflammation, or fibrosis.

Fatty liver disease prevention Preventing fatty liver disease requires a healthy lifestyle and addressing risk factors. The most important strategies include:Prevention of fatty liver disease is very important in reducing the risk of progression to severe liver conditions such as cirrhosis or liver cancer. A proactive approach, involving dietary and lifestyle modifications, can significantly lower the likelihood of developing this condition.One of the best ways to prevent fatty liver disease is to adopt a nutrient-rich diet. Include lots of fruits, vegetables, whole grains, lean proteins, and healthy fats like nuts, seeds, and fish. Avoid processed foods, sugary beverages, and refined carbohydrates that can promote fat accumulation in the liver. It is also good to cut back on saturated fats and trans fats, which are commonly found in fried foods and baked goods.Regular physical activity can help control weight and promote good metabolic health. A goal of at least 150 minutes a week of moderate-intensity aerobic physical activity such as brisk walking, cycling, or swimming is recommended. Incorporating strength training exercises twice a week will help build muscle and enhance fat metabolism.Obesity is a major risk factor for fatty liver disease. Gradual and sustainable weight loss should be aimed at if you are overweight or obese, as rapid weight loss can sometimes worsen the condition. Even a small percentage of body weight loss can lead to significant improvements in liver health.Alcohol consumption is the primary cause of fatty liver in AFLD but may also exacerbate NAFLD. Limit alcohol intake to moderate levels or avoid it altogether to protect the health of the liver.Controlling other medical conditions, including diabetes, high cholesterol, and hypertension, will prevent fatty liver disease. It is crucial to work closely with healthcare providers in monitoring and managing these conditions appropriately. Medications may be prescribed to help regulate blood sugar levels or lipid profiles as needed.Certain medications and environmental toxins damage the liver or enhance fat buildup. Use medication only as directed, and never take over-the-counter drugs or supplements that are harmful to the liver.Routine medical checkups can detect the early signs of fatty liver disease or its risk factors. Early treatment can prevent progression of the disease and ensure improved health outcomes.

Complications of Fatty Liver Disease Fatty liver disease can progress over time, leading to more severe liver damage and systemic complications if left untreated.Non-Alcoholic Steatohepatitis: NASH is a more advanced form of NAFLD where there is liver inflammation and damage besides fat accumulation. It progresses to fibrosis or cirrhosis.Liver Fibrosis and Cirrhosis: Fibrosis refers to the deposition of scar tissue within the liver. Advanced cirrhosis represents the end-stage of fibrosis and significantly impairs the function of the liver and may lead to portal hypertension (increased pressure in the veins supplying the liver) and variceal bleeding (bleeding from dilated veins in the esophagus or stomach) and liver failure.Liver cancer: Hepatocellular carcinoma is one of the main risks, or a liver cancer, because of chronic liver inflammation and cirrhosis.Cardiovascular disease: There is a significant relationship between NAFLD and the increased risk of heart diseases and stroke caused by shared metabolic risk factors.Kidney disease: Over time, chronic liver disease may cause impairment in the kidney.Hepatic encephalopathy: Advanced liver failure can cause toxins to accumulate in the blood, leading to confusion, memory impairment, and even a decline in cognitive function.

Understanding And Addressing Hepatocellular Carcinoma

By Dr. L. Rohit Reddy , Consultant Medical Oncologist & Hemato Oncologist, Yashoda Hospitals, Hyderabad.

When the body's cells begin to multiply and expand without regulation, cancer occurs. Liver cancer specifically originates in the liver, the body's second largest organ after the skin. It can be differentiated as primary liver cancer, which arises directly in the liver, and secondary liver cancer, where cancer from another part of the body spreads to the liver.

Hepatocellular Carcinoma

Hepatocellular Carcinoma (HCC) stands out as the predominant form of primary liver cancer, particularly prevalent among individuals with cirrhosis (an outcome of liver scarring from past injuries, such as those caused by hepatitis B or C viruses or chronic alcohol use). Notably, men are at a higher risk than women.

HCC accounts for approximately 75-85per cent of all primary liver cancers, posing a significant global health challenge. Notably, around 72per cent of these cases are found in Asia. While India's current incidence rate stands at 2.15 per 100,000, lower than global averages, the annual growth in these figures is notably higher in the country. Additionally, the male-to-female ratio for HCC in India is 4:1, highlighting the need for targeted awareness and intervention strategies.

Symptoms to Observe

A sensation of fullness beneath the ribs on the right side

A similar feeling under the ribs on the left side

Yellowing of the eyes and skin

A swollen abdomen, as if it's accumulating fluid

Unexpected weight loss

Risk factors for HCC Factors that elevate the likelihood of HCC include:

Hepatitis B infection: A viral illness transmitted through bodily fluids

Hepatitis C infection: A viral condition spread via blood

Metabolic dysfunction: A disorder that results in excess fat accumulation in the liver

Alcohol use disorder: Excessive alcohol consumption can progressively lead to cirrhosis and, ultimately, liver cancer

To support and clarify a diagnosis, doctors might consider several insightful evaluations, including:

Comprehensive blood tests

Advanced imaging scans such as ultrasound, CT and MRI

A liver biopsy for a closer look

How is HCC treated? Approach to treatment encompasses a range of innovative strategies:

Surgery: Precise surgical interventions to remove the affected liver tissue

Ablation therapy: Utilizing specialized needles to eliminate tumors

Radiation therapy

Immunotherapy: Empowering the body's immune system to combat cancer cells effectively

Targeted therapy: Advanced medications designed specifically for treating progressive HCC

Together, these options reflect cutting-edge solutions in the fight against HCC.

Prevention

To lower the chances of developing HCC, one needs to consider the following approaches:

Obtaining hepatitis B vaccination

Consulting a doctor if potential exposure to hepatitis C is suspected

Maintaining a healthy weight through nutritious eating habits

Moderating alcohol consumption

Taking steps to quit smoking

Globally, chronic hepatitis B virus infection stands out as the common risk factor for primary liver cancer, with nearly 300 million individuals affected. This significant population faces an elevated risk for developing HCC, highlighting the importance of preventing hepatitis B infection as a key strategy for liver cancer prevention. While facing a serious condition like HCC can be daunting, it's perfectly natural to experience feelings of uncertainty and apprehension. However, there are proactive steps individuals can take to support themselves as they navigate the path ahead.

(DISCLAIMER: The views expressed are solely of the author and ETHealthworld.Com does not necessarily subscribe to it. ETHealthworld.Com shall not be responsible for any damage caused to any person/organisation directly or indirectly)

Published On Jan 29, 2025 at 12:53 PM IST

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Rare Liver Cancer's Unique Characteristics Identified

Like many rare diseases, fibrolamellar hepatocellular carcinoma (FLC) mounts a ferocious attack against an unlucky few—in this case, children, adolescents, and young adults. Because its symptoms can vary from person to person, it's often missed or misdiagnosed until it has metastasized and becomes lethal. Moreover, drug therapies for common liver cancers are not just useless for FLC patients but actually harmful.

But new insights about the disease, coupled with a just-launched clinical trial of a promising drug treatment, could significantly improve health outcomes. Researchers in Rockefeller University's Laboratory of Cellular Biophysics, headed by Sanford M. Simon, has discovered that FLC has a distinct transcriptomic "signature"—a set of activated genes—that makes it unique among liver cancers.

"Identifying which molecular changes characterize FLC is an important step to understanding how it arises and evolves, which may reveal potential therapeutical targets," says first author David Requena, a senior researcher in the lab. "Ideally, our findings will refine the detection of the disease, change the course of treatment, and increase patient survival rates."

The findings, published in Nature Communications, come as Simon's lab begins a clinical trial that pairs two drugs into one treatment that preliminary results indicate is highly effective against FLC.

A decade of insights

In 2014, Simon's team—led in part by his own then-teenage daughter, Elana, who had been diagnosed with FLC a few years before—discovered that the disease was caused by the fusion of two genes, DNAJB1 and PRKACA, caused by a small deletion in chromosome 19.

The lab recently determined that what is important is not formation of the fusion, but that the formation results in an increase of the amount of PRKACA—the catalytic subunit of protein kinase A—that is made. That is the true origin of the disease. FLC tumor cells essentially have a molecular imbalance: too many catalytic PKA proteins and not enough of the inhibitory ones that normally tamp down the protein and lock it into place. Unfettered, overabundant PKA is free to wreak havoc across the cell.

For the current study, the researchers wanted to know if there is a common pathway of disease following the burst of PKA proteins. Some liver tumors are categorized as "FLC-like" but lack the fusion protein. Are they actually FLC? And since FLC is impervious to treatments that inhibit other liver cancers, what differentiates it from these other malignancies?

The signature

To find out, the researchers performed a massive analysis of multiomics sequencing data from 1,412 tumors caused by a variety of liver cancers. It was the largest such analysis to date, with 220 samples from FLC tumors—more than six times as many as have been included in any prior study.

In this way, the team determined the transcriptomic signature of each tumor, revealing which dysregulations are unique to specific tumor types and which are common to all. Single-cell analysis with spatial resolution further helped them to identify how each cell type in the tumor contributes to the overall transcriptome.

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Subscribe for FREE The result: FLC emerged as a distinct outlier. "We identified 301 genes that were expressed differently in FLC than they were in other tumors, which really underscores how unique it is among liver cancers," Requena says. "Moreover, 35 of those were highly expressed only in FLC. These genes could be tested for diagnostic applications in the clinic."

They also found that any change in DNA that increased the amount of catalytic subunit relative to its regulatory subunit produced the same changes in the transcriptome. Some patients, for example, had a fusion to PRKACA in the ductal cells of the liver, producing cholangiocarcinoma, or in the ductal cells of the pancreas, producing intraductal pancreatic oncolytic neoplasms (IOPNs). Even though these were different fusions to PRKACA and were identified in cells other than hepatocytes, where FLC is found, they produced the same changes in the transcriptome. And some patients were only missing the regulatory subunit but still had the same changes.

Recently, the Simon Lab also demonstrated that these diseases responded to therapeutics in the same way that FLC does.

"Thus, we suggest that the cancer perhaps should be defined not by its DNA change but by the change it produces in the net balance of protein activity in the cell," says Simon, the Günter Blobel Professor at Rockefeller.

They also compared the tumor transcriptomes against those of normal tissue samples taken from the margins of tumors found in FLC patients. Surprisingly, one had the FLC signature. Upon closer re-examination of the tissue, they spotted fibrous spans typical of the disease and cells that had the fusion transcript of DNAJB1::PRKACA. Removal of the tumor hadn't captured all FLC cells. Such hidden time bombs could result in new cancer growth.

This finding really demonstrates the importance of a complete examination of the margins of the tumor," says Simon.

A promising clinical trial

With these insights in hand, the researchers have just begun a clinical trial to test the pairing of two anti-cancer medications, DT2216 and irinotecan, that the lab's earlier research, published in 2022, indicated are effective against FLC when used in combination. This is being supported by the Children's Oncology Group and the Pediatric Early Phase Clinical Trials Network of the NIH.

In parallel, the Simon Lab is also developing alternative therapeutics, an effort supported by the Cancer Grand Challenge, a highly competitive initiative by Cancer Research (UK) and the National Cancer Institute (US) that offers $25 million grants over five years to consortiums of researchers working towards similar goals. Simon's lab is part of the KOODAC team, in which different labs are attempting to degrade an oncoprotein—in Simon's case, fusions with PRKACA—to prevent or kill tumors. Simon aims to present their findings at the annual meeting of the American Association for Cancer Research in late April.

"Ten years ago, it was our hope that by focusing on comprehensively characterizing a single, albeit rare, disease we could made rapid progress on developing both diagnostics and therapeutics that would not only advance FLC treatment but provide a roadmap for other diseases," he says. "The recent findings from our group validate that hope and offer the promise that these insights can be translated not just to other cancers—such as Ewing sarcoma, rhabdomyosarcoma, and neuroblastoma—but also to illnesses in which we have to eliminate a protein that is not functioning properly."

Reference: Requena D, Medico JA, Soto-Ugaldi LF, et al. Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma. Nat Commun. 2024;15(1):10887. Doi: 10.1038/s41467-024-55238-2

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