Disclosing unavoidable causes of adverse events improves patients' feelings towards doctors.

The process of medical mediation involves the reconstruction of doctor-patient relationships through sharing mutual truthful information and encouraging dialogue between doctors and their patients. This study was designed to examine the effects of disclosing the avoidable as well as unavoidable causes of doctors' behavior following malpractice or perceived inconsiderate behavior on patients' feelings in medical mediation. An avoidable cause was defined as doctor's behavior that was incautious or showed insufficient empathy. An unavoidable one, however, was defined as any cause other than doctors' behavior. A questionnaire was administered to 385 Japanese hospital outpatients, in which participants were presented a range of scenarios with the above two causes for doctor's behavior or an adverse event. Participants' feelings toward the doctor in each scenario were measured on a seven-point scale following disclosure of each cause. The five scenarios provoking negative feelings toward doctors involved "(the patient) being ignored," "refusal of a request," "dominating behavior," "a minor incident," and "an adverse event." The valid response rate was 62.9% (242/385). Negative feelings were evoked in all five scenarios. After disclosure of avoidable causes, scores for negative feelings significantly increased between 3% and 33%. In contrast, after disclosure of unavoidable causes, scores for negative feelings significantly decreased between 11% and 43%. These findings imply that disclosure of causal information in medical mediation will provide the opportunity to reevaluate unexpected doctors' behavior and change patients' negative feelings. Therefore, disclosures should be made in the case of not only unavoidable causes but also avoidable ones.

A murine model of acute liver injury induced by human monoclonal autoantibody.

We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH.

A novel IgM class autoantibody to a hepatocyte-related 190 kDa molecule in patients with type 1 autoimmune hepatitis.

It has been reported that autoantibodies to hepatocytes are frequently found in patients with autoimmune hepatitis (AIH). To elucidate the nature of these hepatocyte-specific autoantibodies, we attempted to generate a hepatocyte-specific monoclonal antibody (MoAb) from Epstein-Barr virus-transformed peripheral blood mononuclear cells obtained from a patient with AIH. We established a single clone, 2E3, that continued to produce an immunoglobulin M (IgM) antibody (lambda-type). This MoAb had the following properties: it reacted mainly with hepatocyte-derived cell lines, rather than with other cell lines, and it reacted with liver tissue but not with other tissues. By immunoblot analysis, we found that this MoAb recognized a 190 kDa molecule on hepatocytes. The MoAb was able to kill hepatocyte-derived cell lines in the presence of fresh human serum. This cytotoxic effect was completely abrogated by heat inactivation of human serum prior to its addition to cell lines. In addition, an IgM autoantibody that recognized a 190 kDa molecule was also found in patients with AIH but not in those with chronic hepatitis C; its titer correlated significantly with serum alanine aminotransferase (ALT) levels in patients with AIH. In conclusion, we generated a human MoAb that recognizes a 190 kDa molecule on hepatocytes. Because of its ability to mediate complement-dependent cytotoxicity and the presence of similar IgM autoantibody in patients with AIH, we hypothesize this autoantibody may play a role in the immunopathogenesis of AIH.

In vitro binding of hepatitis C virus to CD81-positive and -negative human cell lines.

AIM: The aim of the present study is to study the mechanism of entry of hepatitis C virus (HCV) into human cells. We examined the in vitro binding of HCV to various human cell lines with or without CD81 expression. METHODS: We first used three cell lines, two hepatocyte-derived, huH-7 and HepG2, and one colon cancer cell line, Cw2. Among them, HepG2 did not express TAPA-1 (CD81) on their surface but two others did. They were incubated with HCV + serum for 1 h and HCV-RNA in extracted RNA obtained from these cells was examined by using both a quantitative test and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: We found that a significant amount of HCV-RNA was detected in huH-7 and HepG2 but not in Cw2. In addition, the titer of HCV-RNA in serum-incubated CD81-transfected HepG2 was similar to that of the non-transfected titer, and the binding between HCV and huH-7 was not inhibited by anti-CD81. Under the same condition, HCV-RNA tended to be detectable in serum-pulsed hepatocyte-derived cell lines, but not in the others. CONCLUSION: These results suggest that while CD81, as reported, specifically binds to HCV-E2 protein, the entry of HCV into human hepatocytes might be regulated by CD81-unrelated molecule(s).

Clinicopathologic features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein-L3 and seronegative for des-gamma-carboxy prothrombin in comparison with those seropositive for des-gamma-carboxy prothrombin alone.

BACKGROUND: There has been no study of the clinicopathologic features of patients with hepatocellular carcinoma (HCC) who are seropositive for lectin-reactive alpha-fetoprotein (AFP-L3) alone, or seropositive for AFP-L3 and seronegative for des-gamma-carboxy prothrombin (DCP) in comparison with those who are seropositive for DCP alone. Thus, the present comparative study was performed. METHODS: The clinicopathologic features of HCC patients with either one or two tumors who underwent a hepatectomy (n = 88) were compared among the following five groups according to the seropositivity of AFP, AFP-L3 and DCP: (i) group A, seropositive for AFP above 100 ng/mL, AFP-L3 above 15% and DCP above 100 mAU/mL; (ii) group B, seropositive for AFP-L3 and seronegative for DCP below 40 mAU/mL; (iii) group C, seronegative for AFP below 20 ng/mL, AFP-L3 below 15% and seropositive for DCP; (iv) group D, seropositive for AFP and seronegative for AFP-L3 and DCP; and (v) group E, seronegative for AFP, AFP-L3 and DCP. RESULTS: Group B patients showed a higher incidence of infiltrative-type HCC with an irregular margin (P < 0.05) and a higher frequency of poorly differentiated HCC (P < 0.01) compared with group C patients. Group A patients had larger tumors and more massive-type tumors than group B patients. Our HCC cases showed that advanced clinicopathologic features were demonstrated in the order of group B, group C and group D. Group A and B patients and group D and E patients showed similar characteristics. CONCLUSIONS: Hepatocellular carcinoma patients who were seropositive for AFP-L3 and seronegative for DCP demonstrated clinicopathologic features of more advanced HCC compared with those who were seropositive for DCP alone.