The utility of AST/ALT ratio as a non-invasive demonstration of the degree of liver fibrosis in chronic HCV patients on long-term haemodialysis

Yücel Üstündag1, Banu Bilezikçi2, Sedat Boyacioglu1, Mansur Kayatas3 and Nurhan Ödemir3

1 Departments of Gastroenterology 2 Pathology and 3 Nephrology, Baskent University School of Medicine, Ankara, Turkey

Sir,

Chronic hepatitis C virus (HCV) infection is highly prevalent among chronic renal failure patients who are on haemodialysis treatment [1]. In both uraemic and non-uraemic individuals, HCV infection leads to insidiously progressive liver disease [2,3]. There is no specific biochemical liver function test that indicates the level of liver injury in HCV infection and, absolute levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) do not correspond with the histological severity of the disease [4]. Furthermore, it is known that uraemia leads to low aminotransferase values [4]. However, some authors have suggested that progressive functional liver impairment in non-uraemic chronic C viral patients is associated with elevated AST/ALT ratio [5]. In this report, we investigated the utility of AST/ALT ratio as a non-invasive diagnostic tool in providing consistent information on the degree of liver injury in uraemic chronic C hepatitis patients.

The study included 49 chronic haemodialysis patients who were infected with HCV. Chronic HCV infection was diagnosed in patients who were positive for blood anti-HCV antibody and HCV RNA, and had elevated ALT values for the past 6 months. Anti-HCV antibody and HCV RNA measurements were done using a second generation ELISA test and nested reverse transcriptase polymerase chain reaction, respectively. Patients infected with other viral agents, and those who had a history of alcohol consumption or use of any medicine known to increase liver enzymes were excluded from the study. We also excluded individuals with biliary pathologies, diabetes mellitus, apparent atherosclerotic disease, or abnormal volume status. All patients underwent a liver biopsy, and the histology was reviewed by an experienced hepatopathologist who was blinded to the clinical status of the patients. The histological findings were graded and staged according to Knodell classification. In addition to evidence of chronic HCV, liver histopathology results consistent with amyloid deposition or haemosiderin pigment accumulation were accepted as exclusion criteria.

None of the patients in the study group were histopathologically diagnosed with cirrhosis. For each individual, we tested for statistical differences between AST/ALT ratio and necrotic inflammatory activity, and between AST/ALT ratio and degree of portal fibrosis. Twenty-six patients with minimal necroinflammatory activity (Knodell score 0–4) had an AST/ALT ratio of 0.60±0.23, 17 patients with mild necroinflammatory activity (Knodell score 5–8) had an AST/ALT ratio of 0.59±0.15, and six patients with moderate necroinflammatory activity (Knodell score 9–12) had an AST/ALT ratio of 0.63±0.18. We found that AST/ALT ratio was not significantly different among the different grades of necroinflammatory activity (P>0.05 by Mann–Whitney U test).

With regard to the various stages of fibrosis, 36 patients with no fibrosis had an AST/ALT ratio of 0.36±0.17, eight patients with mild fibrosis had an AST/ALT ratio of 0.67±0.17, and five patients with moderate fibrosis had an AST/ALT ratio of 0.86±0.07. An increasing AST/ALT ratio was noted with increasing stage of fibrosis. There were significant differences in AST/ALT ratio between the different fibrosis stages (P<0.05 by Mann–Whitney U test).

Some authors have suggested that AST/ALT ratio is strongly correlated with the level of portal fibrosis in non-uraemic HCV patients [5]. It has also been stated that the ratio is not correlated with necroinflammatory activity in the liver, and that a ratio of less than 1 excludes patients with severe fibrosis and cirrhosis [5]. In this study, we demonstrated similar results in uraemic subjects. Though the levels of liver enzymes decrease within the setting of uraemia, AST/ALT ratio provided some clues about the stage of liver fibrosis in our uraemic patients with chronic HCV infection. It is important to note that the source of serum AST and ALT in the normal person is unclear, and that the role of the kidney and the mechanisms responsible for clearance of these enzymes are uncertain. However, it has been suggested that plasma AST clearance is mainly accomplished by liver sinusoidal cells [6]. Thus, while there is no apparent effect from necroinflammatory activity, advancing fibrosis injures the sinusoidal cells and leads to a relative increase in serum AST.

Liver biopsy is recognized as the gold standard for grading and staging disease activity in chronic HCV infection. Although the AST/ALT ratio does not preclude the use of liver biopsy for the decision of antiviral therapy in uraemic patients and non-uraemic patients with chronic HCV infection, this ratio provides a non-invasive indicator of the level of liver fibrosis in such patients.

References

  1. Pereira BJ. Hepatitis C virus infection in dialysis: a continuing problem. Artif Organs1999; 23: 51–60[ISI][Medline]
  2. Lotti A, Avagnina MA, Mando O et al. Liver histology in chronic hemodialysis patients infected with hepatitis C virus. Medicina1997; 57: 541–545[ISI][Medline]
  3. Stehman-Breen CO, Emerson S, Gretch D, Johnson RJ. Risk of death among chronic dialysis patients infected with hepatitis C virus. Am J Kidney Dis1998; 32: 629–634[ISI][Medline]
  4. Caramelo C, Albalate M, Bermejillo T et al. Relationships between plasma ferritin and aminotransferase profile in haemodialysis patients with hepatitis C virus. Nephrol Dial Transplant1996; 11: 1792–1796[Abstract]
  5. Sheth SG, Flamm SL, Gordon FD, Chopra S. AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol1998; 93: 44–48[ISI][Medline]
  6. Kanimoto Y, Horiuchi S, Tanase S, Morino Y. Plasma clearance of intravenously injected aspartate aminotransferase isozymes: evidence for preferential uptake by sinusoidal liver cells. Hepatology1985; 5: 367–375[ISI][Medline]




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