Cellular cytotoxicity against autologous hepatocytes in acute and chronic non-A, non-B hepatitis.

Abstract

SUMMARYIn a microcytotoxicity assay we tested lymphocyte cytotoxicity against autologous hepatocytes. The following cytotoxicity values were found (given mean ± SEM): acute non-A, non-B (NANB) hepatitis 45 7±4 3% (n=7), chronic NANB hepatitis 32*8±5*1% (n=11), chronic active hepatitis B (CAH-B) 27-7±6-7% (n=10), toxic lesions 18-1±4*2% (n=18), controls with normal liver histology or minimal changes 4 9±2 5% (n=8). Thus our study shows enhanced cellular cytotoxicity in acute and chronic NANB hepatitis and indicates that T cells as well as non-T cells have cytotoxic effector functions. These findings are similar to those obtained in CAH-B and suggest that cellular immune reactions play an important role in the course of NANB hepatitis. For comparison we tested cytotoxic reactions in toxic lesions. They were only moderate and well distinguishable from those observed in NANB hepatitis and CAH-B; they even may be unspecific. No correlation was seen between cytotoxicity and aminotransferase concentrations.There is convincing evidence now that the course of hepatitis B virus infections is determined by the host's immune reactions, mainly the cellular immune response1-nevertheless the target antigens and the effector cells for these reactions are still controversial. Therefore selection of an appropriate target cell system seems to be important. The use of autologous hepatocytes as targets2-7 hopefully will help to overcome some of the difficulties with allogeneic target systems such as differences in expression of alloantigens and other surface antigens.Up

Liver‐Associated Natural Killer Activity in Cirrhotic Rats

“…In patients with chronic hepatitis, it has been reported that human leukocyte antigen (HLA) non-restricted hepatic NK cells have cytotoxicity to autologous hepatocytes in the same manner as cytotoxic T lymphocytes (23,30). Thus, LGLs play an important role in the host defense mechanism (16).…”

“…In addition, a decrease in the hepatic NK activity of LGLs obtained from non-cancer liver tissues surrounding human hepatocellular carcinoma, and an increase in its activity from non-cancer liver tissues surrounding metastatic liver cancer were shown (14). Furthermore, it has been reported that hepatic NK cells play an important role in the cytotoxicity to autologous hepatocytes in the same manner as cytotoxic T lymphocytes in patients with chronic hepatitis (23,30).…”

Comparison of clinical, virologic and pathologic features in patients with acute hepatitis B and C

“…Acute HBV‐induced liver injury occurs mainly through an immune‐mediated mechanism, 4 while both direct cytopathy and immune‐mediated cytopathy have been postulated in acute HCV‐induced liver injury 5,6 . Whether the clinical, virologic and pathologic manifestations of acute HBV‐related and HCV‐related hepatitis are different is of clinical interest.…”

Alpha‐interferon therapy in chronic hepatitis due to active dual infection with hepatitis B and C viruses

“… 1 In India, nearly 14% of non‐alcoholic chronic liver disease (CLD) patients have dual infection with HBV and HCV. 2 While HCV is known to cause liver injury by both cytopathic and immune‐related mechanisms and has a milder course, 3,4 HBV causes liver injury mainly through human leucocyte antigen‐mediated immune mechanisms and has a relatively aggressive course. 5 There are equivocal reports about the interaction between the two viruses in influencing the severity and nature of liver disease.…”