The liver enzymes include alanine aminotransferases (ALT), aspartate aminotransferases (AST), Ý-glutamyltransferase (GGT), alkaline phosphatase (ALP),5 nucleotidase (NTP), serum cholinestarate (CHE) and glutamate dehydrogenase(GLD). The AST, ALT and ALP
43 are widely used. They have long been mistakenly called, as a group, “liver function tests.”
Despite the effective decline of the mortality and morbidity rate from HIV/AIDS as the result of highly active antiretroviral therapy (HAART), liver diseases due to chronic HBV and HCV infections become a leading cause of death. Although the direct impact of HCV upon HIV disease progression remains controversial in many reports (Sulkowski et al, 2008) the complex interactions between HIV-HBV/HCV co-infection and HAART are increasingly apparent in HIV disease progression.
2.6.1 AMINOTRANSFERASES
The aminotransferases constitute a group of enzymes that catalyze the interconversion of amino acids to 2-oxo-acids by transfer of amino groups. Aspartate aminotransferase (l-aspartate:2-oxoglutarate aminotransferase) and alalnine transferase (l-alanine: 2-oxoglutarate aminotransferase; ALT). Transaminases are widely distributed AST is found primarily in the heart, liver, muscle and kidney. ALT is found primarily in the liver and kidney. It is exclusively cytoplasmic in the mitochondria and cytoplasmic forms of AST are found (Burtis et al, 2008).
Disease is the most important cause of increased transaminases transaminase, ALT is higher than AST. Exceptionally be seen in alcohol hepatitis, hepatic cirrhosis, liver neoplasia. In viral hepatitis, AST and ALT concentrations are elevated even before physical signs and symptoms of disease (such as jaundice) is seen. Activities for both enzymes may reach values as high as 10 times the upper reference limit. The existence of increased ALT for more than 6months after an episode of acute hepatitis is used to diagnose chronic hepatitis. Most patients with chronic hepatitis have maximum ALT even seven times the upper reference limit. ALT may
44 be patiently normal in 15% to 50% of patients with chronic hepatitis C, but the likelihood of continuously normal ALTincreases with an increasing number of measurements. In patients with acute hepatitis C, ALT should be measured periodically over the following 1 to 2 years to determine if its activity returns to normal (Burtis et al, 2008).
The aminotransferase activities observed in cirrhosis vary with the status of the cirrhotic process and range from the upper reference limit to four to five times higher, with an AST/ALT greater ratio than 1. The ratio‟s elevation can reflect the grade of fibrosis in these patients. This appears to be attributable to a reduction of ALT production in a damaged liver.
Two to four fold elevations of both enzymes occur in patients with primary or metastatic carcinoma of the liver, with AST usually being higher than ALT, but activities are normal in the early stages of malignant infiltration of liver (Burtis et al, 2008). In HIV/HBV co-infections, HIV infection causes increased rates of persistent HBV infection, increased cirrhosis and liver-related mortality and increased risk of hepatocellular carcinoma at lower CD4T cell counts (Thio et al, 2009). Similarly in HIV/HCV co-infections, there is a more rapid progress to cirrhosis, end-stage liver disease and hepatocellular carcinoma (Burtis et al, 2008).
The impact of HBV and HCV could not limited in causing liver hepatotoxicity but also results in failure in immunological recovery in HIV positive patients. For example, a study in Tanzania reported slow rate of immunologic recovery after initiation of HAART treatment and higher risk of hepatotoxicity among HIV/HBV and HIV/HCV co-infected patients (Christian et al, 2010). Thus the management of HBV and HCV in HIV infection is complicated and bring high burden in particular where HIV is rampant. As the result, globally
45 HIV, HBV and HCV become the major public health concerns (Modi et al, 2007;
Leeratanapetch et al, 2008). In some countries, screening of HIV-infected individuals for HBV and HCV is highly recommended before initiation of antiviral treatment (Chung, 2006) Muhammad et al., (2016) compared the mean levels of AST, ALT and bilirubin in pateints co-infected with HBV and HCV and patients infected with only HCV and discovered that there mean levels were found to be 61 IU/L, 84 IU/L, and 1.6 mg/dL respectively in case of co-infection with HBV and HCV for AST, ALT, and bilirubin and 76 IU/L, 91 IU/L, and 1.9 mg/dL, respectively for AST, ALT and bilirubin for patients with only HCV infection.
2.6.2 ALKALINE PHOSPHATASE
Alkaline phosphatase (ALP) catalyzes the alkaline hydrolysis of a large variety of naturally occurring and synthetic substrates. Divalent ions such as Mg2+, Ca2+, and Mn2+, are activators of the enzyme in which Zn2+ is a constituentmetal ion. Phosphate, borate, oxalate, and cyanide ions are inhibitors of ALP activity. The type of buffer present in catalytic reaction may affect the rate of activity. ALP activity is presentin most organs of the body and is especially associated with membranes and cell surfaces located in the mucosa of the small intestine and proximal convoluted tubules of the kidney, in the bone, in the liver and placenta. Although the exact metabolic function of theenzyme is not understood, it appears that ALP is associated with lipid transport in the intestine and with the calcification process in bone.
Elevations of the serum ALP activity commonly originate from the liver and bone.
Consequently, serum ALP measurements are of particular interest in the investigation of hepatobiliary disease associated with increased osteoblastic activity. The response of the liver
46 to any form of biliary tree obstruction induces the synthesis of ALP by hepatocytes. In patients with advance primary liver cancer or wide spread secondary hepatic metastes, serum enzyme activity may reach 10 to 12 times the upper reference limit and usually return to normal on removal of the obstruction. Liver diseases that principally affect paranchyma cells, such as infectious hepatitis typically show only moderate (less than threefold) increase or even normal serum ALP activities (Burtis et al, 2008).