Malignancies following long-term azathioprine treatment in chronic liver disease. A report from the Copenhagen Study Group for Liver Diseases.

One hundred and fifty-four patients with histologically verified non-alcoholic chronic liver disease were randomized to azathioprine or prednisone treatment. After a median of 91 months observation time, the cause of death was assessed retrospectively. Autopsy was performed in 82% of 71 deaths. In the azathioprine group 33% (13/39) died from malignant neoplasia, and in the prednisone group (13%) (4/32) (p = 0.08). Considering a possible fatal outcome as a consequence of treatment, this finding urges caution in the long-term application of azathioprine at the usual dose level.

Mortality of alcohol abusing men prospectively assessed in relation to history of abuse and degree of liver injury.

A prospective evaluation of mortality in relation to a broad range of alcoholic abuse and biopsy-assessed stage of alcoholic liver injury was carried out by following 315 men admitted to hospital for various medical disorders. During 10-13 years, 184 patients (58%) died, which, according to national mortality statistics, corresponds to a mortality ratio of 3.07. 43% of the excess mortality could be attributed to liver disease. Our results indicate that the alcohol abuse, irrespective of its magnitude and duration, is associated with a rather constant excess mortality and that the occurrence and severity of hepatic injury ranging from normal liver to active cirrhosis is directly associated with a subsequent liver-disease-related excess mortality.

Prospective evaluation of alcohol abuse and alcoholic liver injury in men as predictors of development of cirrhosis.

258 alcohol-abusing men, free from cirrhosis on primary liver biopsy, were followed for 10-13 years during which cirrhosis developed in 38, corresponding to a rate of 2% per year. The likelihood of cirrhosis developing proved to be independent of duration of abuse and of daily consumption before the primary biopsy. This indicates that the effect of alcohol abuse is not cumulative over time, but rather establishes conditions for the development of cirrhosis. The rate of cirrhosis increased stepwise with degree of steatosis in the primary biopsy, and in those with alcoholic hepatitis was nine times higher than in those with no steatosis. This finding, together with the results on alcohol abuse, indicates that steatosis and alcoholic hepatitis, despite their reversibility, are causally associated with cirrhosis rather than epiphenomena of alcohol abuse. In the alcohol-abusing man, a liver biopsy provides more information than alcoholic history about the likelihood of future cirrhosis.

Biliary calculi in chronic Salmonella carriers and healthy controls: a controlled study.

A controlled study was performed to evaluate the incidence of gall bladder and biliary duct disease in chronic typhoid and paratyphoid carriers. Eight chronic carriers were compared with a comparable group of control persons who had previously had acute typhoid or paratyphoid fever without developing a chronic carrier state. By combined surgical and radiological evaluation biliary calculi were detected in 88% of the carrier group and in 11% in the control group. This difference is statistically significant (p less than 0.02). No difference in biliary function was found between the two groups.

An epidemic of acute viral hepatitis in male homosexuals. Etiology and clinical characteristics.

Among 130 male patients admitted during a 30-month period with acute hepatitis in the Copenhagen Clinic for Infectious Diseases, 31 were homosexuals. Hepatitis B virus occurred in an endemic fashion in the homosexual subpopulation while hepatitis A infection caused a small epidemic among homosexuals during the winter 1977-78. The course of these infections showed no serological or clinical differences from the findings in 38 heterosexual male patients seen during the same period.

Viral hepatitis in a venereal clinic population. Relation to certain risk factors.

In the present survey 3 groups of patients were studied: 95 homosexual males, 117 heterosexual males and 68 females attending clinics for venereal diseases in Copenhagen. 10 cases of hepatitis B infection were found, all in homosexual males. Chronic carriership of hepatitis B surface antigen (HBsAg) and presence of hepatitis B e-antigen (HBeAg) was demonstrated in 8 and 5 cases, respectively and liver biopsy showed chronic liver disease in 5 out of the 8 former. The prevalence rate of hepatitis B antibody was significantly higher in all patient groups than in the general population in the area. Two patients had non-B hepatitis, 1 homosexual male and 1 female, but the prevalence rate of hepatitis A antibody (anti-HAV) was not increased in the venereal clinic population. The serological tests identified certain high risk groups regarding hepatitis B infection: (1) homosexual males > 25 years with anti-HAV and a high promiscuity; and (2) heterosexual males and females > 25 years with a past history of venereal disease and clinical hepatitis. The data are compatible with the hypothesis that sexual transmission plays an important role in the spread of hepatitis B infection. It is recommended that routine serological tests for hepatitis be taken in the high risk groups of venereal clinic populations.

Chronic hepatitis B infection in male homosexuals.

Ten cases of hepatitis B virus infection were identified among asymptomatic male homosexuals. These patients shared a number of characteristics: A subclinical origin and course of infection; Persistence of HGsAg for periods exceeding six to 25 months; Persistent GPT elevation of two to five times upper normal limit; Morphological changes in the liver with portal and parenchymal inflammation (chronic persistent hepatitis, six cases; non-specific reactive hepatitis, 2 cases; cirrhosis and acute hepatitis with signs of chronicity, one case each). HBeAg was found in six cases, anti-HBe in none. These results indicate that screening for hepatitis B should be performed whenever these individuals come under medical attention in order to detect asymptomatic chronic liver diseases and to detect these silent vectors of an infection that presently shows an increased frequency among homosexuals.