Laboratory diagnostics of chronic liver diseases

Abstract

Chronic liver diseases are conditions that are clinically manifested by duration longer than six months. According to etiological factors, they are classified as follows: infectious (chronic viral hepatitis), toxic (alcoholic hepatitis, drug- and toxin-associated), hereditary metabolic diseases, autoimmune and neoplastic diseases. Pathological changes include: hepatitis, cirrhosis and cholestasis. Diagnosis of these diseases is based on clinical picture, results of medical-biochemical and serological analyses, liver biopsy and other diagnostic methods, such as: ultrasonography, computerized tomography, esophagoduodenoscopy and endoscopic retrograde cholangiopancreatography. Chronic hepatitis is a clinical syndrome of heterogenous etiology, i.e., a group of diseases with necroinflammatory process in the liver, often followed by fibrosis and duration of more than six months. The impairment may progress to cirrhosis and hepatocellular cancer. Etiologically, chronic hepatitis is classified into several groups, such as: viral (hepatitis B and hepatitis C), autoimmune hepatitis (types 1, 2 and 3), autoimmune cholestatic diseases (primary biliary cirrhosis-PBC, and primary sclerosing cholangitis-PSC), drug-associated hepatitis, Wilson's disease, α 1 -antitripsine deficit, primary idiopathic hemochromatosis, cryptogenic hepatitis and non-alcoholic steatohepatitis. For differential diagnosis of these diseases, it is essential that initial evaluation includes the complete history of drug usage, alcohol consumption and ALT, AST, HBsAG and anti-HCV measurements. In persons with increased catalytic ALT activity and negative HBsAg and anti-HCV, it is necessary to determine the auto antibodies, Fe, TIBC and UIBC, ceruloplasmin, and α 1 -antitripsine phenotype. The diagnosis of chronic viral hepatitis requires determination of catalytic activity of ALT and specific serological tests: HBsAG, anti-HBs, HBeAg, anti-HBe, HBV-DNA, anti-HCV and HCV-RNA. Alcoholic liver disease is developed in several phases: from normal liver, through steatosis, alcoholic hepatitis to cirrhosis. In patients with verified history of alcohol consumption, it is necessary to determine the catalytic activity of γ-GT, AST, ALT, MCV and CDT. Determination of CDT and γ-GT is needed for monitoring of therapeutical effects, while liver biopsy is required for definite diagnosis. Cirrhosis is the end-stage of chronic liver diseases, and the most frequent causes are: acute and viral hepatitis, long-term and excessive alcohol consumption, metabolic and biliary diseases, autoimmune hepatitis, effects of drugs, chemical agents, etc. Chronic hepatitis developing to cirrhosis is characterized by two basic processes: necroinflammatory impairment and fibrosis. Necrotic inflammation is characterized by higher De Ritis coefficient with considerably higher activity of γ-GT and LDH. Reduced synthetic function is indicated by: lower ChE activity, decreased albumin concentration with predominant serum gamma-globulin and high IgG and IgA concentrations, lower concentrations of haptoglobin and transferrin as well as longer prothrombin time. Although liver biopsy is considered the method of choice for diagnosis of hepatic cirrhosis, determination of PGA index or Fibro test-Acti test (α 2 - macroglobulin, haptoglobin, γ-GT, total bilirubin, Apo-A I and ALT) is recommended as the alternative to biopsy, which exhibits the highest sensitivity, specificity as well as best predictive value for diagnosis of cirrhosis. HCC is the most common form of malignant liver tumors and may be the result of hepatic cirrhosis due to effects of hepatitis B and C, some toxins, α 1 AT deficit or hemochromatosis. Diagnosis is based on clinical picture, US, CT and MR imaging, liver biopsy and values of tumor markers, primarily: α-fetoprotein, carcinoembryonic antibody, and des-γ-carboxy prothrombin. The changes of biochemical parameters are not specific for tumor, but may serve to substantiate the diagnosis. In patients who are not alcohol consumers, chronic disease similar to alcoholic hepatitis, followed by steatosis, parenchymal inflammation and different forms of fibrosis is defined as non-alcoholic steatohepatitis (NASH). Liver biopsy is crucial for verification of NASH diagnosis. Metabolic liver diseases include: familial hyperbilirubinemia, primary hereditary hemochromatosis, Wilson's diseases, alpha-1-antitripsin deficiency, Reye's syndrome, etc. Diagnostic guidelines for differential diagnosis of familial hyperbilirubinemia are based on measurement of total and direct bilirubin concentrations. Primary hereditary hemochromatosis is an autosomal, recessive disorder where the iron is absorbed in larger quantities and deposited in parenchymal organs. The initial evaluation of hemochromatosis is grounded on verified higher saturation of transferrin (>45%) and unsaturated capacity of iron binding (<28 μmol/L). Genetic analysis is needed for definite diagnosis. Wilson's disease is hereditary disorder of copper metabolism characterized by deposition of toxic copper concentrations in tissues and organs. The most common diagnostic finding is low level of blood ceruloplasmin (< 0.17 g/L), higher concentration of free serum copper (>7 μmol/L), lower concentration of total copper, increased copper excretion via urine (up to 20 μmol/24h) and higher concentration of copper in liver tissue. α 1 AT deficit is an autosomal, recessive disorder with significantly lower α 1 -antitripsin values, giving rise to pulmonary emphysema, chronic liver diseases, cirrhosis and hepatocellular cancer. For making a diagnosis, it is necessary to measure serum α 1 AT concentration, phenotyping and genotyping. Reye's syndrome is a disease defined as acute, non-inflammatory encephalopathy associated with fat degeneration of the liver, with unknown etiology, and followed by general mitochondrial dysfunction. Differential diagnosis is necessary to rule out congenital metabolic defects, and determination of aminotransferases, glucose, PT, ammonia and free fat acids along with liver biopsy are crucial for verification of diagnosis. Autoimmune hepatic diseases include: autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Differential diagnosis involves the following measurements: anti-nuclear At, smooth muscle At, At to hepatic-renal-microsomal Ag, At to soluble-hepatic Ag, anti-mitochondrial At and perinuclear anti-neutrophil-cytoplasmic At, as well as utilization of endoscopic retrograde cholangiopancreatography.