End-stage liver disease in a young woman.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
F Schaffner
Publications and source records attributed to F Schaffner.
Autoantibodies against integral membrane proteins of the nuclear envelope in patients with primary biliary cirrhosis.
BACKGROUND/AIMS: Autoantibodies against nuclear membrane proteins have been identified in patients with primary biliary cirrhosis (PBC). The aim of the present study was to determine the incidence of these autoantibodies in patients with PBC and examine their significance. METHODS: An assay using recombinant polypeptides was designed to unequivocally detect autoantibodies against gp210 and the lamin B receptor, integral proteins of the nuclear membranes. RESULTS: Autoantibodies against gp210 were detected in 15 of 159 patients with PBC and 0 of 46 controls. Autoantibodies against lamin B receptor were detected in 2 patients with PBC and 0 controls. The presence of these autoantibodies had a sensitivity of 11% and specificity of 100% for the diagnosis of PBC. Autoantibodies against gp210 were present in 4 of 19 (21%) patients with PBC who did not have detectable antimitochondrial antibodies. Patients with PBC and gp210 autoantibodies had a higher incidence of associated arthritis. CONCLUSIONS: Autoantibodies against gp210 and the lamin B receptor are present in approximately 10% of patients with PBC. These autoantibodies are highly specific for the diagnosis of PBC and may be useful in diagnosing individuals without antimitochondrial antibodies and in identifying a subgroup of patients with an increased incidence of associated arthritis.
Autoantibodies↗
Familial primary biliary cirrhosis.
To estimate the prevalence of primary biliary cirrhosis in family members with this disease and determine if a family history of primary biliary cirrhosis predisposes to the development of this disease, we performed a retrospective review of charts and a prospective mail survey of patients with primary biliary cirrhosis. Prevalence of primary biliary cirrhosis in family members of 405 patients with disease was compared to known prevalence of disease in the general population. Twenty-six patients with primary biliary cirrhosis had at least one family member with primary biliary cirrhosis. The estimated prevalence per 100,000 was 6420 or 6.4%. Exclusion of family members with primary biliary cirrhosis who were patients in our practice, in order to avoid duplication, changed the prevalence to 4282 per 100,000 or 4.3%. Affected family members included mothers, daughters, sisters, brothers, aunts and cousins. Estimates of prevalence of primary biliary cirrhosis are between 0.7 and 7.5 cases per 100,000. Therefore, compared to estimates in the general population, the prevalence of primary biliary cirrhosis in family members of patients with this disease is markedly increased. A family history of primary biliary cirrhosis is therefore a predisposing factor for the development of this disease.
Causality↗
Consultation in hepatology.
Explore the source record for details and available documents.
Gastroenterology↗
HLA-DR expression in bile duct damage in hepatitis C.
Several investigations have demonstrated aberrant expression of HLA-DR on damaged bile duct epithelium of patients with primary biliary cirrhosis, liver allograft rejection, graft versus host disease, and AIDS. Since bile duct damage is a prominent feature of chronic hepatitis C, it may also be associated with HLA-DR induction. Therefore, we examined the expression of HLA-DR antigen in formalin-fixed, paraffin-embedded liver biopsy sections of 30 patients with chronic hepatitis C by the avidin-biotin peroxidase complex method using a monoclonal antibody to HLA-DR. HLA-DR was not detected on bile duct epithelium in any of the cases, although bile duct damage of varying degree was observed in 90% of the cases. HLA-DR was expressed by Kupffer cells; inflammatory infiltrates in portal tracts, and in areas of piecemeal necrosis and lobular necrosis; dendritic cells in portal and periportal areas; and occasionally hepatocytes. These observations suggest that the mechanism of bile duct injury in chronic hepatitis C may be different from that of other conditions such as primary biliary cirrhosis, liver allograft rejection, and graft versus host disease.
Antibodies, Monoclonal↗
The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis.
Before the availability of serological markers for hepatitis C, the morphological features of this diagnosis, which represents most non-A, non-B hepatitis, could not be confirmed. We examined biopsy specimens from 50 patients with chronic hepatitis C and 21 patients with autoimmune chronic hepatitis. Each biopsy specimen was graded on 19 different histological features. The results indicated that at the time of biopsy, the average age of patients with chronic hepatitis C was 46 yr vs. 36 yr for autoimmune chronic hepatitis. Cirrhosis was seen more frequently in autoimmune chronic hepatitis (90%) than in hepatitis C (58%). Features more commonly observed in chronic hepatitis C were bile duct damage (91% vs. 40%), bile duct loss (91% vs. 20%), steatosis (72% vs. 19%) and lymphoid cell aggregation (follicles) within portal tracts (49% vs. 10%). Severe lobular necrosis and inflammation (76% vs. 38%), piecemeal necrosis (81% vs. 10%), multinucleated hepatocytes (29% vs. 6%) and broad areas of parenchymal collapse (76% vs. 6%) were seen more often in autoimmune chronic hepatitis. Exclusion of five patients with autoimmune chronic hepatitis who received immunosuppression before biopsy accentuated these differences. In conclusion, morphological criteria, in addition to serological data, may be useful for differentiating chronic hepatitis C from autoimmune chronic hepatitis, which histologically is a more aggressive disease.
Adult↗
Prediction of survival of patients with primary biliary cirrhosis. Examination of the Mayo Clinic model on a group of patients with known endpoint.
Increasing use of liver transplantation and new treatment regimens necessitate an accurate estimate of prognosis in primary biliary cirrhosis. To test the usefulness of the Mayo model for this purpose, the R value of the model was calculated for a group of 28 patients after each patient encounter and plotted against time. The data were best described by two linear regressions. For the period 10-2 years before death, the average increase in R value was 0.23 annually [R = 7.1-0.23 x time (in years)]. In the last 2 years of life, the average increase in R value was 1.4. This period could be fit by the expression R = 8.2-1.4 x time (in years). The increase in R value represents the natural progression of primary biliary cirrhosis and can be used for evaluating treatment of patients.
Forecasting↗
Hepatic histopathology in the acquired immunodeficiency syndrome.
Involvement of the liver with the same opportunistic organisms and neoplasms affecting other organs has been recognized since the beginning of the AIDS epidemic. In this overview of hepatic histopathologic features in AIDS, we review the range of opportunistic infections and neoplasms accompanying HIV infection. Hepatic disease may result from viral, bacterial, protozoal, or fungal infection, or secondary to drugs and neoplasms. Liver involvement in AIDS usually reflects disseminated rather than primary disease. CMV and mycobacteria are the most common organisms in liver identified in biopsy and autopsy studies. A variety of nonspecific features, including steatosis, granulomas, and sinusoidal abnormalities may also be seen. HIV-1 itself was recently identified in the liver. Speculation regarding the significance of this finding has been discussed in this review. Hepatitis B, C, and D may also complicate the course of disease in patients with AIDS. Hepatitis B behaves differently in the population with AIDS than in immunocompetent patients. We concluded our review with a discussion of the present recommendations regarding the use of liver biopsies in these patients. This topic continues to be widely debated in the literature.
Acquired Immunodeficiency Syndrome↗
Structural and functional aspects of regeneration of human liver.
Regeneration of human liver was long suspected to occur. It was proven in animals 100 years ago but could not be demonstrated in man until liver biopsy and modern hepatic tests became available. Structural changes in the regenerating liver mainly concern the arrangement of liver cell plates and the size and appearance of hepatocytic nuclei. A return to normalcy in test results depends on the factors responsible for regeneration since various test results change at different rates. Mass, estimated by imaging procedures, is restored parallel with the return of function. Shape is not restored but the pressure of neighboring organs and structures molds the growing remnant so that it almost resembles the original. Factors regulating regeneration in man are beginning to be recognized as they have been in animals. The hope is that regeneration can be accelerated or that cells can be transplanted to replace those lost.
Hepatectomy↗
Excessive weight gain after liver transplantation.
Twenty-eight patients (19 females, 9 males) were evaluated pre- and posttransplant to determine the frequency and find predictors of excessive weight gain after orthotopic liver transplant. Posttransplant, 21 patients gained and 7 patients lost weight as compared with their pretransplant dry weight. The majority of weight gain occurred between 2 and 16 months; 64.3% of patients (18/28 pts.) became overweight. All patients overweight prior to transplant (11 pts.) were more overweight posttransplant (P less than 0.005). Overweight and nonoverweight patients were similar in age, female predominance, etiology of liver disease, hypercholesterolemia, and hypertriglyceridemia pretransplant, as well as diabetes mellitus and medications including prednisone posttransplant. Overweight patients more commonly had a family history of diabetes mellitus, arteriosclerotic heart disease, and hypertension. They also had more hypertension, hypercholesterolemia, hypertriglyceridemia, abnormal physical findings related to the liver, and abnormal results of hepatic tests posttransplant. Mean rate of weight gain for overweight patients compared with nonoverweight ones during the first 16 months after transplant was 1.5 kg/month +/- 0.9 vs 0.4 kg/month +/- 0.4 for those not overweight. After 16 months mean rate of increase was slower for overweight patients (0.3 kg/month +/- 0.3), whereas weight appeared to stabilize in the nonoverweight ones. We conclude that excessive weight gain after liver transplant is common and occurs early. Since obesity may contribute to, as well as be a separate cause, of hepatic abnormalities, confusion may result when interpreting abnormal results of hepatic tests. Obesity prior to transplant predicts excessive weight gain posttransplant, although all patients may be at risk.
Adult↗
Hepatocellular carcinoma in a long-term survivor of intrahepatic biliary duct hypoplasia.
We describe the development of hepatocellular carcinoma (HCC) in a 46-yr-old woman with intrahepatic biliary duct hypoplasia. Her underlying liver disease was quiescent for many years until a dramatic rise in serum bilirubin was seen. Orthotopic liver transplantation was performed, and a large tumor was found during surgery. A bile-producing HCC was identified, infiltrating about 50% of an otherwise noncirrhotic liver which had a paucity of intrahepatic ducts. The findings of HCC in this long-term survivor of intrahepatic biliary duct hypoplasia indicates HCC may occur in patients with long-standing disease.
Bile Ducts, Intrahepatic↗
Sexual function and testosterone levels in men with nonalcoholic liver disease.
The effects of nonalcoholic liver disease on sexual desire, arousal, activity, orgasmic function and satisfaction and serum testosterone levels were studied in 75 men with nonalcoholic liver disease. Each man was interviewed about his sexual behavior and problems and was asked to comment on whether he felt liver disease affected his sexual function. The average age of the patients was 49 yr, and a wide variety of liver diseases was represented. Child-Pugh grading was A in 51 patients, B in 18 and C in 6; the mean duration of liver disease was 8 yr. Sexual desire, arousal and activity of patients with grade A disease were within the ranges observed in studies of healthy men of comparable age. Diminished sexual desire was reported by 2% of grade A patients and 35% of grade B and C patients (p less than 0.005). Arousal problems were noted by 16% of grade A patients, 60% of grade B patients and 67% of C patients (p less than 0.005). Loss of erection and inability to regain erection were noted by 7%, 40% and 67% of grade A, B and C patients, respectively (p less than 0.01). Premature and retarded ejaculation were more frequent in patients classed in Child-Pugh grades B and C. Frequency of coitus and orgasm were significantly higher in grade A patients than in grade B and C patients. Total and free testosterone levels were (in nanograms per milliliter) A, 677/1.78; B, 416/1.06; and C, 178/0.43 (p less than 0.002). We concluded that Child-Pugh grade A nonalcoholic liver disease in men does not affect sexual desire, function or performance. Men with disease grades B and C have significant sexual dysfunction and significant reduction of both total and free testosterone levels.
Adult↗
Long-term follow-up of patients with primary biliary cirrhosis on colchicine therapy.
We followed up a group of patients with primary biliary cirrhosis who participated in a 4-yr prospective, double-blind controlled trial of colchicine therapy for 4 additional years. All were placed on open label colchicine (0.6 mg twice daily) after the trial was concluded. Of the original group of 28 patients treated with colchicine, 8 died and 5 received transplants (3 of the 5 died). Of the original placebo control group eight patients died and six received transplants (1 of the 6 died). Surviving patients on long-term colchicine therapy (mean period = 8.1 yr, range = 5.3 to 9.1) showed reduction of mean serum alkaline phosphatase from 5.1 times the upper limit of normal values to 1.9 times (p less than 0.01). Mean ALT fell from 1.8 to 1.2 times the upper limit of normal (p = 0.05), and mean serum total bilirubin remained stable (1.6 mg/dl vs. 1.5 mg/dl). Major complications of cirrhosis developed in four patients in the colchicine group and five patients in the original control group. The only side effect of colchicine was diarrhea, which was noted in three patients. The diarrhea resolved with reduction in the dose of colchicine. Colchicine is a safe and inexpensive drug for the long-term treatment of primary biliary cirrhosis. The biochemical parameters of disease activity (alkaline phosphatase and ALT) remain improved after long-term follow-up, and bilirubin values remain stable. However, complications of cirrhosis, deaths and transplantations were not prevented. The clinical usefulness of colchicine in the treatment of primary biliary cirrhosis seems to be limited.
Alanine Transaminase↗
Effect of weight reduction on hepatic abnormalities in overweight patients.
The effects of weight reduction on hepatic test results and physical findings related to the liver were retrospectively evaluated in 39 overweight patients screened to exclude other factors affecting the liver. An additional 11 overweight patients with primary liver disease were retrospectively evaluated to compare the effect of weight reduction in patients with liver disease with its effect in those without primary liver disease. This study showed that in overweight adults without primary liver disease, a weight reduction of greater than or equal to 10% corrected abnormal hepatic test results, decreased hepatosplenomegaly, and resolved some stigmata of liver disease. In similarly studied overweight patients with primary liver disease, some findings improved, but the changes did not correlate with a greater than or equal to 10% weight loss. Increased alanine aminotransferase activity was the most frequent hepatic enzyme abnormality in this population. For every 1% reduction in body weight, alanine aminotransferase activity improved by 8.1%. After other causes of liver disease are eliminated by clinical and biochemical parameters, weight reduction should be tried for overweight patients with abnormal hepatic test results in the absence of obvious primary liver disease as judged by clinical and biochemical parameters before extensive and expensive studies are undertaken.
Alanine Transaminase↗
The liver in HIV infection.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Hepatocellular carcinoma associated with autoimmune chronic active hepatitis.
Primary hepatocellular carcinoma, one of the most common malignancies in the world, develops in chronic liver diseases of different etiologies. Hepatitis B and non-A, non-B infections, alcoholic cirrhosis, hemochromatosis, contamination with aflatoxins, and oral contraceptives are just a few of the conditions that have been associated with this carcinoma. To our knowledge, few cases of autoimmune chronic active hepatitis and hepatocellular carcinoma have been reported in the literature. We describe a patient who developed hepatocellular carcinoma 21 years after the onset of the autoimmune hepatitis.
Autoimmune Diseases↗
High-dose recombinant interleukin-2 for chronic viral hepatitis.
Explore the source record for details and available documents.
Adult↗
Sexual behavior in women with nonalcoholic liver disease.
Sexual behavior in women with liver disease was examined in 150 women to determine whether liver disease influenced sexual desire, frequency or performance. The average age of women studied was 53 years (range: 26 to 76 years), and a wide variety of liver diseases were represented. Sexual desire was reduced in 33%. Difficulty in becoming sexually aroused was noted by 18%. Orgasm during intercourse was not experienced by 25%. The frequency of sexual intercourse decreased since onset of disease in 27%. Dyspareunia was a complaint by 21%, most often attributed to decreased vaginal lubrication. Liver disease was considered a significant factor interfering with sexual function in 17%. No statistical difference was found between sexual desire or function in our study and in large studies of sexual behavior in women. Each category was subdivided by presence or absence of cirrhosis, pre- or postmenopausal state, laboratory values and duration of disease. Except for a greater number of postmenopausal women with complaints of painful intercourse, no statistical differences or trends were found. Nonalcoholic liver disease does not affect sexual desire, function or performance. Variables other than liver disease influence sexuality. Women with liver disease can thus be reassured that they can maintain normal sexual relations.
Adult↗