Isoniazid
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
The value of routine monitoring of liver function tests in detecting hepatitis has been controversial. As benign elevations of ALT are frequent in isoniazid recipients, routine liver function test monitoring is generally not recommended except in those in whom risk factors exist, such as a history of liver disease, significant alcohol intake, co-administration of other hepatotoxic drugs, elevated pretreatment ALT, or coinfection with HBV, HCV, or HIV. Some would also routinely monitor patients over the age of 35 because of their increased risk for hepatotoxicity (Saukkonen et al., 2006). All patients receiving isoniazid for IPT or as part of the regimen for treatment of tuberculosis should be questioned at regular clinical reviews about symptoms or signs of hepatitis or other toxic effects. Liver function tests should be performed if there are any symptoms. Isoniazid should be ceased if the ALT exceeds three times the upper limit of normal (or the pretreatment baseline) and symptoms of hepatitis are present or if the ALT is more than five times normal in asymptomatic patients (Romero, 1994; Saukkonen et al., 2006; Tostmann et al., 2007). Isoniazid can be re-introduced if the tests return to normal when treating active tuberculosis (O’Brien, 1989; Saukkonen et al., 2006). During IPT if the enzyme level exceeds three times the normal value, some would recommend substitution with another agent (e.g., rifampicin) rather than rechallenge (Bailey et al., 1983).
Infection and sexual health
David M. Luesley, Mark D. Kilby in Obstetrics & Gynaecology, 2016
Hepatitis B is a hepadna virus (DNA). It is endemic worldwide with high carriage rates of up to 20 percent in high-risk areas, such as South and East Asia, Central and South America, Africa and Eastern Europe. In the UK, 0.01–0.04 percent of blood donors have evidence of hepatitis B infection. In 2010, there were 5805 cases notified in England and Wales. Transmission is sexual, parenteral and vertical. The incubation is 40–160 days. It is mainly asymptomatic in children and in 10–50 percent of adults and is especially likely in coexistent HIV infection. The prodrome and icteric phases are similar to hepatitis A. Fulminant hepatitis can occur in <1 percent. Chronic infection (greater than six months) occurs in 5–10 percent and is more likely in HIV patients. Chronic active hepatitis can proceed to cirrhosis and liver cancer. Concurrent infection with HIV or hepatitis C worsens the disease. It is important to screen for other STIs, to check liver function and to advise to avoid sexual intercourse.
The Viruses
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Viral hepatitis is a common inflammatory disease of humans and a variety of animal species. A variety of viruses can cause hepatitis or infect the liver as part of their systemic spread and replication. The resulting pathologic lesions may be acute and transient as in Hepatitis A or result in chronic infections and persistent tissue damage (e.g., cirrhosis) or cancer (e.g., hepatocellular carcinoma) as in Hepatitis B infections. in animals the range of viral infections that cause infection or inflammation of the liver is broad and includes such examples as adenoviruses (infectious canine hepatitis), bunyaviruses (rift valley fever in sheep), and retroviruses (equine infectious anemia). In humans hepatitis is most commonly caused by one of five species of viruses named A, B, C, D, and E. However, as in animals the disease is caused by a variety of viruses with the common trait of hepatic tropism (Table 16.1).
TIPE2 as a potential therapeutic target in chronic viral hepatitis
Published in Expert Opinion on Therapeutic Targets, 2019
Jian Ji, Yuan-Yuan Zhang, Yu-Chen Fan
Chronic hepatitis viral infection is accompanied by variable degrees of hepatic inflammation and fibrosis with an increased risk of developing liver cirrhosis and hepatocellular carcinoma [62]. It is widely accepted that chronically hepatitis B virus (HBV) infected patients are prevalent in Asia and Africa, whereas progression to chronic hepatitis is mainly caused by the cell-mediated immune response to HBV, rather than direct injury to hepatocytes caused by the virus [63]. Meanwhile, the hepatitis C virus (HCV) infection usually accompanied by the direct injury of hepatocyte [63]. A recent study reported that TIPE2 might be responsible for viral clearance during HBV infection [64], and TIPE2 also plays an important role in CHC infection [65]. Furthermore, TIPE2 has been reported to be involved in the liver fibrosis and hepatocellular carcinoma [45,66,67].
MARCKS on Tumor-Associated Macrophages is Correlated with Immune Infiltrates and Poor Prognosis in Hepatocellular Carcinoma
Published in Cancer Investigation, 2021
Xudong Ren, Yanqin Ju, Chaoqun Wang, Ran Wei, Haoting Sun, Quanbao Zhang
Most patients with chronic hepatitis suffered liver cancer eventually. Chronic hepatitis can be caused by viral infection (HBV, HCV), alcoholism, metabolic diseases (non-fatty liver disease), and drug damage (aflatoxin, aristolochic acid). Changes in the liver microenvironment and imbalance in the proportion of immune cells play a major role in HCC promotion (32,33). As an inflammation-associated tumor, it’s well-evidenced that the immunosuppressive microenvironment of HCC can promote immune tolerance and evasion by various mechanisms (34). The role of different components (including TAMs, MDSC, Tregs, CD8+ CTLs, fibroblasts) of the tumor microenvironment (TME) in HCC has also been discussed in many studies (28,35). For instance, the antitumor effect of NK cells and CD8+ CTLs could be blocked by CD4+ CD25+ Tregs. Besides, Tregs abundantly express both co-inhibitory and co-stimulatory molecules at levels that are likely dependent on the TME. Modulating their function through stimulation of inhibitory receptors and inhibition of activating receptors could lead to the decrease of the immunosuppressive spectrum of TME, and ultimately lead to enhanced antitumor immune response. And M2 TAMs (by secreting IL-10) can induce CD4+ CD25+ Tregs, indirectly supporting tumor growth and progression (36). The exact components in TAMs supernatant were also demonstrated to support the development of HCC (37,38). TAMs act as a “bridge” between tumor and inflammation in TME and are closely associated with cancer occurrence, metastasis, and progression (39,40), making TAMs a key target in combating HCC.
Circulating liver-specific microRNAs as noninvasive diagnostic biomarkers of hepatic diseases in human
Published in Biomarkers, 2019
Ghulam Musaddaq, Naveed Shahzad, Muhammad Adnan Ashraf, Muhammad Imran Arshad
Early diagnosis of hepatitis is crucial for the prevention and treatment of hepatitis but also for the follow up of efficient treatment response. The liver typically manifests similar signs and symptoms in various inflammatory injuries induced by infectious and noninfectious origin. Likewise, typically liver functionality is not necessarily compromised in every liver injury; in fact, signs of liver injury might not appear until most of the hepatic cells are destroyed by different cell death mechanisms (Clemente and Schwarz 2011). The laboratory diagnostic tests for hepatitis are based on the detection of antigens, antibodies, liver-associated enzymes and tissue markers. Furthermore, hepatic ultrasonography, transient elastography (TE) and magnetic resonance elastography are the procedures which provide information about liver lesions such as parenchymal cysts or hemangiomas, presence of steatosis as well as level of stiffness and degree of hepatomegaly (Sandrin et al.2003, Talwalkar et al.2007). However, majority of these procedures are either invasive in nature or have modest sensitivity for mild disease and can only be useful in advanced cases (Gougelet and Colnot 2016). The late diagnosis leads to poor prognosis which emphasizes the need to broaden the range of diagnostics for liver diseases.
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