Biology of Non-alcoholic Fatty Liver Disease - Essay Example

? Biology of disease and The symptoms of non-alcoholic fatty liver disease Most people suffering from non-alcoholic fatty liver disease are asymptomatic, and the condition is most times, discovered accidentally, during laboratory examinations testing other conditions or diseases. These tests reveal that that there are increased liver enzyme levels (Raman & Allard, 2006). This implies that many of the patients suffering from the condition will show few or show none of the symptoms associated with the disease. The condition is the most widely known trigger of unexplainable increases in the persistent elevation of liver enzymes, after the number one trigger of the change, hepatitis (Arredondo, Amores &Guerrero, 2010) The key symptoms that lead to the discovery of non-alcoholic fatty liver disease include fatigue, malaise, and diffuse abdominal or right-upper quadrant discomfort (Tolman & Dalpiaz, 2007). Upon conducting laboratory tests, hepatomegaly is commonly attributed to the condition. In the cases that cirrhosis is detected, the stigmata that results from chronic liver conditions, including ascites, spider angiomata, hard liver body, splenomegally, asterixis or palmar arythema are likely to be identified as well (Tolman & Dalpiaz, 2007). The patients suffering from non-alcoholic fatty liver disease are likely to complain of pruritus or jaundice. In other cases, the patients suffering from these conditions are likely to suffer from a complication of portal hypertension, which may include vericeal bleeding, ascites, or encephalopathy (Arredondo, Amores &Guerrero, 2010). Many of the patients suffering from the condition have developed an association between attributes of the metabolic syndrome, including diabetes mellitus, obesity and variable cases of hypertension and hyperlipidemia (Raman & Allard, 2006). The role of the biomedical scientist in the diagnosis of non-alcoholic fatty liver disease There is no single and simple test that can be run to confirm the presence or the absence of non-alcoholic fatty liver disease. For example, the blood tests run during the diagnoses, commonly called LFTs (Liver function tests) evaluate the blood levels of some chemical enzymes that are produced by the liver cells (Arredondo, Amores &Guerrero, 2010). In the case that the tests depict an abnormal pattern of LFTs, it may indicate that the patient is suffering from non-alcoholic fatty liver disease. However, the problem associated with this testing process or phase is that many other conditions of the liver can depict abnormal LFTs. Therefore, in the case that the patient being diagnosed depicts LFTs, the medical professional will need to run other tests, to determine whether they are due to other liver conditions and not due to NAFLD (Chalasani et al., 2012). For example, other tests can be run, to detect different viruses or germs and other that will test the presence of other chemicals found at the liver. The role of the biomedical scientist during the diagnosis of non-alcoholic fatty liver disease is done on the basis of three main elements: laboratory, physical and imaging testing (Ratziu et al., 2010). However, the final/ authoritative diagnosis of the condition is done, only using liver biopsy testing, which verifies that there are fat levels beyond the normal fat levels present in a healthy liver. The liver biopsy test has remained the standard diagnoses model of checking whether a patient is suffering from the condition (Arredondo, Amores &Guerrero, 2010). Through physical examinations, the biomedical scientist may establish that the condition is not there, or may recognize the presence of extra fat levels, depending on the developmental stage of the condition. The widely common conditions discovered during the testing include splenomegaly, painless hepatomegaly, or chronic liver-disease stigmata (Arredondo, Amores &Guerrero, 2010). The tests that the doctor can be used to check the condition of the liver include “prothrombin time, complete blood count and hepatitis surface antigen B among others” (Arredondo, Amores &Guerrero, 2010). When conducting these different tests, it is possible that the medical specialist will trace transamine levels; “coagulation altered and elevated alkaline phosphatase levels” (Tolman & Dalpiaz, 2007). Sixty-five percent of the patients undergoing the testing process will show increased amounts of transferring saturation and ferritin. Many doctors agree that ultrasound imaging of the liver is the best and the most reliable diagnosis imaging model, when they are suspecting that a patient is suffering from non-alcoholic fatty liver disease (NAFLD). Further, considering that the method is relatively cheap, standardized and affordable, it is the most common diagnosis process used by healthcare personnel. When using computerized tomography testing, the doctor can detect intrahepatic fat levels of a threshold level of 30 percent (Arredondo, Amores &Guerrero, 2010). On the other hand, when using magnetic resonance testing for the diagnosis, the medical professional can detect moderate to harsh changes in liver fat levels. The role of the biomedical scientist in the management of non-alcoholic fatty liver disease In managing non-alcoholic fatty liver disease, the biomedical scientist seeks to control the risk of developing cardiovascular conditions. Medical studies have shown that patients suffering from NAFLD are more likely to die from heart attack than from liver-related problems. Therefore, the management of the condition will entail the change or the reduction of lifestyle risk factors that increase the risk of cardiovascular problems (Targher, Day & Bonora, 2010). Some of the management recommendations required from the patient include stopping smoking, checking weight gain or the need to lose weight, eating healthy balanced foods and engaging in regular physical exercise. In managing NAFLD, the doctor may also direct the patient to treatment for high cholesterol levels and high blood pressure, because treating these conditions is believed to reduce the worsening of the NAFLD. Further, for a diabetic patient, the doctor may require the patient to use medication or other control strategies that help in the reduction of blood sugar levels, which helps control the condition (Bhatia et al., 2012). Irrespective of the fact that the condition is not caused by the intake of alcohol, the intake of alcohol is not recommended, because increased intake increases the risk of worsening the condition. Alternatively, or in a complementary manner, the doctor may subject the patient to medication, which is targeted at the liver itself (Chalasani et al., 2012). For example, some of these medications are targeted at reducing or reversing NASH inflammation levels. 2. Hepatitis C virus (HCV) infection leads to the injury of the liver, after an individual is affected, and it is the leading cause for liver transplantation. The HCV virus is communicated over blood to blood exchange or contact, which is closely related to the sharing of injection devises like, needles (Lloyd et al., 2007). The primary infection by the virus is mainly asymptomatic, and in many cases, it will cause persistent infection. Chronic infection leads to progressive hepatic fibrosis which increases the risk of cirrhosis, hepatocellular carcinoma and liver failure (Lloyd et al., 2007). The clearance of the HCV virus from the body does not eliminate the possibility of infection. The host’s immunity-guided response to HCV engages adaptive and in native actions by the immunity system. The evidence collected in the area shows that difference in the characteristics of the HCV-specific response influences the outcomes of the infection. The virus and the viral factors involved in the immunopathogenesis HCV is the only member in the species hepacivirus which belongs to the family flaviviridae, which houses other viruses leading to hepatitis infection, like yellow fever and dengue viruses. The HCV virus has a positive, single sense RNA, which is about 9600 neuclotides in size. The RNA genome has an open and long reading frame, which encodes the polyprotein which is bound onto some products. The polyprotein is processed by virally and cellular encoded proteases at the endoplasmic reticulum (Lindenbach & Rice, 2005). The protein products used in this case include the “basic core, envelope proteins, short peptides (p7) and non-structural proteins” (Lloyd et al., 2007). The traits of the HCV virion, which are significant to the response of the host’s immunity, include the absence of a stable genomic intermediate, which triggers the need for the HCV to produce new proteins and new RNAs continually, if it is to maintain the persistent presence in the host. This increases the risk that the virus could be recognized by the host’s immunity response system. In order to avoid detection, it forms a stiff membrane for the protection of the dsRNA by the immunity system. The behavior of the RdRp leads to the formation of different HCV virions, which differ by 35 percent to the quasispecies creation. The quasispecies are variants of the viral model, which are availed as a cloud due to the selective operations of the immunity of the host, including antiviral drugs and cytotoxic T cell recognition (Farci et al., 2000). Viral genomes and antigens are easily detected when at other cells in the liver, including the endothelial cells and kupffer cells. For that reason, the virus targets other centers, including blood leucocytes, epithelial cells at the brain and the gut, and lymph nodes (Bierhoff et al., 1997). Therefore, CD 81 is targeted as a host cell surface, because it offers the channel for viral entry. In the case of chronic infections, the liver is infiltrated by different cells, including CD4+ and CD8+ lymphocytes, natural killer cells (NK T and NK cells) and B lymphocytes. Through the infectious activity, the limiting hepatocytes plate around the portal tracts can be eaten away, leading to cirrhosis, which results in liver failure (Bierhoff et al., 1997). Innate viral evasion and immune responses The viral infection of the host’s cells start a chain of intracellular events trigger an antiviral response or process, at the cells neighboring the cells affected, as well as inside the affected cells. The antiviral response and the state triggered depends on the initiation of IFN (type one Interferons) - and - (Lloyd et al., 2007). Pathogen recognition processes guide the operations of the immunity system, driving the initiation of interferons, and it has increased the comprehension of the response mechanisms of the host to the viral infection. The system is founded on PAMPs (pathogen-associated molecular patterns) which are noticed and classified by the given PAMP receptors of the cells of the host, after which it sends signals to start the work of antiviral effectors-genes. The main result of engaging the “PAMP receptors is the activation of interferon regulatory factor (IRF)-3(NF-xB)”, which is a transcription factor (Richmond & Nf-kappa, 2002). Also, through the “TRIF adaptor protein engagement of Kappa B (NF-xB); a transcriptional response leading to the discharge of IFN -/ “from the cell which has been affected, takes place (Richmond & Nf-kappa, 2002).The process involving the activation of NF-xB, further triggers the development of proinflammatory chemokines and cytokines, which work towards the increment of the inflammation, which facilitates leucocyte recruitment, which works together with IFN -/ when the immune system of the host responds to HCV (Lloyd et al., 2007). The IFN -/ discharged works at paracrine and autocrine pathways, through a process involving their binding with the IFN receptors to cause the Jak-STAT channel activation. The activation process results in the initiation of ISGs (IFN-stimulated genes) (Lloyd et al., 2007). The IFN-stimulated genes are the actualizers of the response of the host, towards the viral attack. So as to duplicate themselves and extend to other areas, viruses develop different strategies meant to secure them against the defenses of the host. Using the case of HCV, the PAMP channel of signaling is the main target construction for the evasion of the host’s defense mechanisms. The NS3/4A of the HCV works against the virus-affected activation of IRF-3 and the induction of IFN-/ using a blocking system of RIG-I signal communication, besides slowing down the signaling of TLR3 by attaching themselves to the TRIF protein which is downstream. The activation of the virus-affected IRF-3 activation blocks the activation of NF-B. Cellular Immune Reponses CD4+ T cells CD4+ T cells are critical to humoral immune and effective cellular activities against HCV. The failure of the production and the support of antigen-specific CD4+ cells is one of the main characteristics of viral RNA infections. The important role of CD4+ T cells is characterized by the studies done using chimpanzees, where the reduction of these cells led to continued infection. Due to the association, it is widely acknowledged that that multispecific, strong CD4+ T that takes place early during the infection is linked to disease resolution and viral clearance. On the other hand, “a narrowly channeled and delayed response is related to chronic infection” (Lloyd et al., 2007). CD8+ T cells The functions of CD8+ T cell include cytotocicity, which covers the killing of the cells that are infected. These cells also help in the killing of the “non-cytolitic discharges like TNF- and IFN-” (Lechner et al., 2000). Like in the case of CD4+ T cells responses to HCV, CD8+ T cells respond to the effects caused early after infection, leading to the clearance of viral infection (Lechner et al., 2000). T cell memory The cell responses of CD8+ and CD4+ T cells have been demonstrated to be very important for viral challenge, in the cases of rechallenge. From the cases of humans and chimpanzees that resolve “primary cases of infection depict increased protection levels from further infection upon rechannellenge, with the peak viraemia decrease and chronic infection” (Grakoui et al., 2003). The depletion of CD8+ memory T cells rechallenge showed that viraemia did not resolve, until the cells at the liver recovered (Grakoui et al., 2003). Reference List Bhatia, L. S., Curzen, N. P., Calder, P. C., & Byrne, C. D., 2012. Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor? Eur Heart J, 33, pp. 1190– 1200. Bierhoff, E., Fischer, H. P., Willsch, E., Rockstroh, J., Spengler, U., & Brackmann, H. H., et al., 1997. Liver histopathology in patients with concurrent chronic hepatitis C and HIV infection. Virchows Arch, 430, pp. 271–277. 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