Finn Hardt

The prognosis of patients with alcoholic liver disease. An international randomized, placebo-controlled trial on the effect of malotilate on survival

The aim of this study was to examine the effect of malotilate on survival in patients with alcoholic liver disease and to determine prognostic variables for survival. Four hundred and seven patients with alcoholic liver diseases, from seven European liver units, entered a randomized placebo-controlled, double-blind trial: 140 patients received malotilate 1500 mg/day, 133 patients received 750 mg/day, and 134 patients received placebo. The patients were included in the study over a period of 3 1/2 years, and the study was closed 1 year after the entry of the last patient. Eighty-four patients died (35, 19, 30 patients in groups 1500 mg/day, 750 mg/day, and placebo, respectively). Survival was slightly better in the 750 mg/day group than in the two other treatment groups, when tested by conventional log-rank tests (p = 0.06). However, a treatment effect was supported by a highly significant (p = 0.006) non-proportionality of the death intensity in patients receiving 750 mg/day against those receiving either 1500 mg/day or placebo. Prognostic variables for survival were evaluated using the multiple Cox regression analysis of clinical and laboratory variables and with or without liver histology variables, as determined at entry into the study. The analysis was stratified for the three treatment regimens. In the analysis including liver histology variables, independent significant prognostic variables were: years of high alcohol intake, prothrombin index, alkaline phosphatases, creatinine, immunoglobulin M, white blood cell count, and liver cell steatosis. In the analysis without liver histology variables, prognostic variables were: years of high alcohol intake, prothrombin index, alkaline phosphatases, creatinine, and immunoglobulin M.

Human Leucocyte Antigens in Patients with Alcoholic Liver Cirrhosis

No significant differences in the frequencies of HLA-B8, -B40, and other HLA-A, -B, and -C phenotypes were found among patients with histologically verified alcoholic cirrhosis compared with normal controls when the p values were multiplied by the number of comparisons. This was found both in the present study of 45 patients and in the combined data of this and three other similar studies. However, these findings do not rule out that alcoholic cirrhosis might be associated with HLA factors (for example. HLA-D/DR antigens) controlling immune responses.

Graft-versus-host reactions mediated by spleen cells from amyloidotic and nonamyloidotic mice.

SUMMARY The local graft-versus-host (GVH) reaction reported by Ford et al. (4) has been applied to a murine model. In principle, the increase in number of nucleated cells contained in the popliteal lymph node of an Fi hybrid was determined after regional injection of immunocompetent parental strain spleen cells. This assay was used to test cell-mediated immune reactivity of spleen cells from casein-treated mice at various stages of amyloid induction. Concurrently, the test was applied to casein-treated donor mice presensitized with 2 consecutive allogeneic (second parental strain) skin grafts. The number of cells in the lymph nodes showed a linear relationship to logarithmically spaced numbers of cells injected. Marked depression of the GVH reaction was observed with spleen cells from nonsensitized donors treated with 10 and 20 daily injections of casein. In contrast, 10 injections of casein in the presensitized group did not affect the GVH reactivity of donor spleen cells. After 20 casein injections the same high degree of depression was encountered with spleen cells from both grafted and nongrafted groups of donor mice. In the presensitized and nonsensitized groups the same histological changes occurred under casein treatment, i.e., 10 casein injections gave rise to perifollicular pyroninophilia and 20 injections caused perifollicular amyloid deposits. The results are suggestive of cellular immune depression attributable to amyloid formation.

The Role of Acute Hepatitis Type A, B, and Non-A Non-B in the Development of Chronic Active Liver Disease

In 19 patients followed from biopsy-verified acute viral hepatitis to chronic active liver disease and 74 patients followed to complete resolution verified by a normal liver biopsy, sera from the acute phase were studied for serologic evidence of hepatitis type A and B. Eleven of the 19 patients who developed chronic active liver disease progressed from acute hepatitis type B and 7 from acute hepatitis type non-A non-B. One patient could not be classified because the sera were exhausted. None had serological markers of actual hepatitis type A infection. Of the 74 patients with a histologically complete resolution, the acute episode could be classified as type B hepatitis in 47 and type A hepatitis in 13 patients. The remaining 14 patients were classified as having acute viral hepatitis type non-A non-B. Our findings confirm that type B and non-A non-B hepatitis may give rise to chronic liver disease, whereas type A hepatitis so far has not been demonstrated to initiate a chronic liver disease.

Humoral and Cell-mediated Immunity to Hepatitis B Virus Antigens in Acute and Chronic Liver Disease

The humoral immune response to hepatitis B virus antigens and the cell-mediated immunity to hepatitis B surface antigen (HBsAg) were investigated in 12 healthy persons and 56 patients with various liver diseases. In patients with acute viral hepatitis type B, anti-hepatitis B core antigen was present constantly in serum in all phases, and after clinical recovery simultaneously with anti-HBs. A transitory cellular immune response to HBsAg was demonstrated at the time the antigen was cleared, while a patient with persisting HBs antigenaemia and another with transient hepatitis Bc antigen showed no response during the course of the disease. Cellular immune response to HBsAg was present only infrequently in patients with chronic liver disease type B and non-B, thus suggesting that a cellular immunity to HBsAg is not a prerequisite for the development of these conditions.

Hepatitis B virus infection among household contacts of patients with acute HBsAg-positive hepatitis

Sixty-seven household contacts of 31 index cases with acute HBsAg-positive hepatitis were investigated forHepatitis B virus (HBV) markers. Follow-up findings in 50 household contacts revealed that six spouses and/or sexual partners had developed acute clinical hepatitis B. Three of these six contacts were drug addicts. A further seven contacts showed serological changes compatible with exposure to HBV, but had no signs of acute clinical hepatitis. Six of these seven contacts were spouses and/or sexual partners of their index case. Possible prophylactic or post-exposure measures only seem to be necessary in the spouses and/or sexual partners of patients with acute hepatitis B. Siebenundsechzig Personen, die in häuslichem Milieu Kontakt zu 31 Fällen mit akuter HBsAg-positiver Hepatitis hatten, wurden auf Hepatitis-B-Virus (HBV) Marker untersucht. In Verlaufskontrollen bei 50 Personen mit Kontakt zu den Hepatitis-Kranken zeigte sich, daß sechs Ehegatten und/oder Geschlechtspartner eine klinisch akute Hepatitis B entwickelt hatten. Weitere sieben Kontaktpersonen wiesen serologische Veränderungen auf, die mit einer Exposition gegenüber HBV vereinbar waren; doch hatten diese Personen keine klinisch manifeste Hepatitis. Sechs dieser sieben Kontaktpersonen waren Ehegatten und/oder Geschlechtspartner des jeweiligen Hepatitisfalles. Prophylaktische oder therapeutische Maßnahmen nach Exposition scheinen nur bei Ehegatten und/oder Geschlechtspartnern von Patienten mit akuter B-Hepatitis erforderlich zu sein.SummarySixty-seven household contacts of 31 index cases with acute HBsAg-positive hepatitis were investigated forHepatitis B virus (HBV) markers. Follow-up findings in 50 household contacts revealed that six spouses and/or sexual partners had developed acute clinical hepatitis B. Three of these six contacts were drug addicts. A further seven contacts showed serological changes compatible with exposure to HBV, but had no signs of acute clinical hepatitis. Six of these seven contacts were spouses and/or sexual partners of their index case. Possible prophylactic or post-exposure measures only seem to be necessary in the spouses and/or sexual partners of patients with acute hepatitis B.ZusammenfassungSiebenundsechzig Personen, die in häuslichem Milieu Kontakt zu 31 Fällen mit akuter HBsAg-positiver Hepatitis hatten, wurden auf Hepatitis-B-Virus (HBV) Marker untersucht. In Verlaufskontrollen bei 50 Personen mit Kontakt zu den Hepatitis-Kranken zeigte sich, daß sechs Ehegatten und/oder Geschlechtspartner eine klinisch akute Hepatitis B entwickelt hatten. Weitere sieben Kontaktpersonen wiesen serologische Veränderungen auf, die mit einer Exposition gegenüber HBV vereinbar waren; doch hatten diese Personen keine klinisch manifeste Hepatitis. Sechs dieser sieben Kontaktpersonen waren Ehegatten und/oder Geschlechtspartner des jeweiligen Hepatitisfalles. Prophylaktische oder therapeutische Maßnahmen nach Exposition scheinen nur bei Ehegatten und/oder Geschlechtspartnern von Patienten mit akuter B-Hepatitis erforderlich zu sein.

A Low-Dose Immunization Schedule for the Production of ALG in Rabbits.

ALG was produced in rabbits by intracutaneous injections of small doses (106 cells) of C3H mouse thymocytes suspended in Freunds incomplete adjuvant. The immunosuppressive potency of this ‘low‐dose’ ALG evaluated by allo‐skin graft survival proved to be comparable to that of ALG produced by intravenous injection of high doses of lymphoid cells (ad modum Levey & Medawar). In addition the ‘low‐dose’ method gave rise to negligible amounts of haemagglutinins, lymphagglutinins, and lymphocytotoxic antibodies. The ‘low‐dose’ method may represent a major advantage in overcoming the limiting factor presented by scarcity of available antigen, which is regularly the case in human ALG production.