Cirrhosis of the liver life expectancy: Stages, prognosis, and more

The focus on steatosis is reflected by the predominant use of monocultures of hepatocytes. Interestingly, hepatocellular ballooning has barely been explored in these studies. Although it is difficult to objectively measure the presence of ballooned hepatocytes in patients’ biopsies (Kakisaka et al., 2018), they are a pathognomonic histological feature of NASH that should be considered when studying this disease. Notwithstanding the advantages outlined above, 2D monocultures are unable to faithfully mimic in vivo NAFLD conditions due to the lack of interaction with NPC and disturbances in the extracellular environment. An improvement over this system is provided by 2D co-cultures, typically involving two cell types, such as hepatocytes and NPC, growing in a monolayer.

A Common (and Silent) Chronic Condition

Suurmond et al. (2019) co-cultured HUVEC with GelMa-encapsulated HepG2 to investigate NAFLD pathogenesis. Similarly to Gori et al., their system, distinguished by high cell viability and homogeneous cell distribution, enabled monitoring of steatosis establishment. Inclusion of KC in this in vitro model led to enhanced ROS expression and proinflammatory cytokine release. While HepG2 are a widely used cell line to investigate regulation of drug-metabolizing enzymes, PHH are the preferred choice in biotransformation studies, thanks to their in vivo-like functionality (Wilkening et al., 2003). More recently, spheroids and organoids have become the 3D in vitro models of choice for studying NAFLD (Soret et al., 2021).

How should a patient be followed/monitored after diagnosis?

Interestingly, HCC in NAFLD patients may also arise in non-cirrhotic liver (Huang et al., 2021). In a recent meta-analysis, non-cirrhotic NASH subjects were at greater risk of developing HCC than non-cirrhotic patients of other etiologies of liver disease (odds ratio 2.61) (Stine et al., 2018). Non-alcoholic fatty liver disease (NAFLD) is the term for a range of conditions caused by a build-up of fat in the liver. Liver biopsy should be considered for patients with NAFLD who are at increased risk of NASH or advanced fibrosis based on noninvasive test results.

• Chronic liver failure is caused by long-term inflammation or injury to your liver.
• Involvement of your partner or a family member can also be very helpful and supportive.
• Several foods are best avoided or consumed in moderation because they can accelerate fat buildup in the liver, exacerbate inflammation, and speed up the development of fibrosis and cirrhosis, doctors and dietitians say.
• Eat a healthy plant-based diet, exercise, and take your medications.

c. Liver biopsy as the gold standard

NAFL, non-alcoholic fatty liver; NASH, non-alcoholic steatohepatitis. The body weight increase induced by pioglitazone warrants further discussion. It may seem contradictory that losing weight can improve the condition of the liver, while a drug that increases weight can also have a positive effect on the liver. This can be explained by the balance between the calorie overload and the capacity of the fat tissue to handle this. If the calorie overload exceeds the storing capabilities of the fat, the fat tissue gets inflamed and dysfunctional. As a consequence, the fat releases substances that damage other organs and forces the fat to go elsewhere, including the liver.3 Reducing weight by lifestyle modification is one way to tackle this problem.

Can you live with chronic liver disease?

3D cultures (e.g., collagen gel sandwich, spheroids, organoids or liver-on-a-chip) have been recently introduced to elucidate NAFLD, and their development can rely on bio-printing technology. Self-aggregated spheroids present an accumulation of carbon dioxide (CO2) and waste in their core. Cell culture models are listed by increasing cost, longevity and complexity.

• (B) Barplot showing the percentage of in vitro models that have been used to study steatosis, inflammation, fibrosis, or hepatocellular ballooning.
• For example, blood tests to detect various infections (such as hepatitis B and hepatitis C) and other causes of liver damage.
• It sits mainly in the upper right portion of the stomach area, above the stomach.
• Both models can be obtained from different sources (cyan panel) -immortalized cell lines, embryonic stem cells (ESC), pluripotent stem cells (PSC), NAFLD murine models or liver from NAFLD patients.

However, liver enzymes are not sensitive nor specific for the diagnosis of NAFLD or NASH. These include genetic factors, sedentary lifestyle and hyper-caloric diets. Therefore, NAFLD can be seen in obese and in non-obese lean individuals who have features of the metabolic syndrome. Metabolic syndrome (Table 2) is defined by a combination of abnormal Body Mass Index (BMI), enlarged abdominal waist, dyslipidemia (high triglycerides and low HDL), type 2 diabetes/ insulin resistance and hypertension. In many cases, the extra fat in the liver cells does not seem to be harmful or affect how well the liver works.

• Replace sweets, processed foods and white bread products with whole fruits, vegetables and grains.
• Although it is difficult to objectively measure the presence of ballooned hepatocytes in patients’ biopsies (Kakisaka et al., 2018), they are a pathognomonic histological feature of NASH that should be considered when studying this disease.
• Thus, the liver plays an important role as the first point where nutrients are filtered and further processed.
• It is possible that the individuals who had liver biopsies may have already had more advanced NAFLD and so the aforementioned figures may overestimate the number of people who progress to advanced fibrosis and cirrhosis.
• Alternatively, models could be assessed by their ability to reproduce results obtained in ongoing clinical trials.
• However, physicians should be alert for incidental findings suggestive of NAFLD in high-risk patients and initiate prompt evaluation when such findings are noted.

NAFLD is a fatty liver disease and the acronym stands for non-alcoholic fatty liver disease.1 It is a condition in which too much fat is stored in the liver cells. As explained in Section 1.a, your liver is a key organ involved in energy regulation. What your liver is not supposed to do, however, is to store excess energy in the form of fat. The liver stores only a small amount of energy, namely some carbohydrate in the form of glycogen, but not fat.

The authors were able to validate the indirect influence of adipocytes on hepatocytes in NAFLD progression. At the cost of greater complexity, the examples above hint that body-on-a-chip devices may offer a better approximation of the in vivo NAFLD environment. Many factors determine if you will develop more severe liver disease and how quick the evolution is. Luckily, many patients will not evolve to severe liver disease and many steps in the evolution are reversible with adequate management.

Nonalcoholic fatty liver disease (now called MASLD) may be suspected if blood tests show higher than normal levels of liver enzymes. Usually, doctors will have to rule out other probable causes of higher-than-normal liver enzymes before they know for sure if someone has NAFLD. They will review a person’s medical history and will often order additional tests such as ultrasound, which can show what the liver looks like, to see if anything looks abnormal. NAFLD is becoming more common, alcoholic liver disease especially in Middle Eastern and Western nations as the number of people with obesity rises. NAFLD ranges in severity from hepatic steatosis, called fatty liver, to a more severe form of disease called nonalcoholic steatohepatitis (NASH). The availability of validated preclinical models will streamline the adoption of a quantitative approach to (a) the identification of NAFLD etiology and potential therapeutic targets, and (b) the rational design of pharmacological treatments.