Patients with cirrhosis and ascites have false values of bone density: implications for the diagnosis of osteoporosis.

UNLABELLED: The effect of ascites on bone densitometry has been assessed in 25 patients with advanced cirrhosis, and it was concluded that ascites over 4 l causes inaccuracy of BMD measurements, particularly at the lumbar spine. This fact must be considered when assessing bone mass in patients with decompensated cirrhosis. INTRODUCTION: Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) is the best procedure for assessment of osteoporosis and fracture risk, but BMD values at the central skeleton may be influenced by changes in soft tissues. Therefore, we have studied the effect of ascites on BMD. METHODS: BMD was measured by DXA at the lumbar spine, femoral neck and total hip, just before and shortly after therapeutic paracentesis in 25 patients with advanced liver cirrhosis. Changes in BMD, lean and fat mass, abdominal diameter and weight, as well as the amount of removed ascites were measured. RESULTS: The amount of drained ascites was 6.6 ± 0.5 l (range: 3.0 to 12.7 l). After paracentesis, BMD increased at the lumbar spine (from 0.944 ± 0.035 to 0.997 ± 0.038 g/cm(2), p < 0.001) and at the total hip (from 0.913 ± 0.036 to 0.926 ± 0.036 g/cm(2), p < 0.01). Patients with a volume of drained ascites higher than 4 l showed a significant increase in lumbar BMD (7.0%), compared with patients with a lower amount (1.5%) (p < 0.03). The decrease in total soft tissue mass correlated with the amount of removed ascites (r = 0.951, p < 0.001). Diagnosis of osteoporosis or osteopenia changed after paracentesis in 12% of patients. CONCLUSION: Ascites over 4 l causes inaccuracy of BMD measurements, particularly at the lumbar spine. This fact must be considered when assessing bone mass in patients with advanced cirrhosis.

Lithocholic acid downregulates vitamin D effects in human osteoblasts.

BACKGROUND: Osteoporosis is a common complication in chronic cholestasis. It has been proposed that retained substances such as bile acids may produce a damaging effect on bone cells. This study analyses the effects of lithocholic acid (LCA) on cell survival and vitamin D metabolism in human osteoblasts (hOB). MATERIALS AND METHODS: Human osteoblasts cultures were performed with or without foetal bovine serum (FBS) or human albumin (HA) at different LCA concentrations and times with or without vitamin D. RESULTS: Lithocholic acid at concentrations higher than 10(-5 )M decreased cell survival. This effect was partially prevented by the presence of FBS or HA. Vitamin D stimulated CYP24A, BGLAP and TNFSF11 expression in hOB and these effects were modified by nontoxic LCA concentrations. LCA significantly decreased vitamin D stimulation of CYP24A, BGLAP and TNFSF11 gene expression at 72%, 79% and 56% (respectively). LCA alone has an agonistic effect, as has vitamin D, thus partially increasing CYP24A and BGLAP expression, but with no changes on TNFRSF11B expression. Equivalent effects of the LCA were observed by performing gene reporter assays using MG-63 cells transfected with constructs containing CYP24A1 promoter regions. CONCLUSIONS: Lithocholic acid decreases the stimulatory effect of vitamin D on CYP24A, BGLAP and TNFSF11 expression in hOB. This effect is produced through vitamin D response elements (VDREs), located in the promoter regions of these genes, suggesting that LCA acts as a mild analogous of vitamin D, interacting with the vitamin D receptor. These results may explain the potential deleterious effects of retained bile acids on hOB.

Clinical and economic burden of community-onset multidrug-resistant infections requiring hospitalization.

OBJECTIVES: To analyze the clinical and economic burden of community-acquired (CA) or community-onset healthcare-associated (COHCA) multidrug-resistant (MDR) infections requiring hospitalization. METHODS: Case-control study. Adults admitted with CA or COHCA MDR infections were considered cases, while those admitted in the same period with non-MDR infections were controls. The matching criteria were source of infection and/or microorganism. Primary outcome was 30-day clinical failure. Secondary outcomes were 90-day and 1-year mortality, hospitalization costs and resource consumption. RESULTS: 194 patients (97 cases and 97 controls) were included. Multivariate analysis identified age (odds ratio [OR], 1.07, 95% confidence interval [CI], 1.01-1.14) and SOFA score (OR, 1.45, CI95%, 1.15-1.84) as independent predictors of 30-day clinical failure. Age (hazard ratio [HR] 1.09, 95%CI, 1.03-1.16) was the only factor associated with 90-day mortality, whereas age (HR 1.06, 95%CI, 1.03-1.09) and Charlson Index (HR 1.2, 95%CI, 1.07-1.34) were associated with 1-year mortality. MDR group showed longer hospitalization (p<0.001) and MDR hospitalization costs almost doubled those in the non-MDR group. MDR infections were associated with higher antimicrobial costs. CONCLUSIONS: Worse economic outcomes were identified with community-onset MDR infections. MDR was associated with worse clinical outcomes but mainly due to higher comorbidity of patients in MDR group, rather than multidrug resistance.

Bone mass improves in alcoholics after 2 years of abstinence.

To evaluate the effect of abstinence on bone mass and bone mineral metabolism in chronic alcoholics, a 2 year longitudinal follow-up study was carried out in a group of 30 chronic alcoholic males who started a rehabilitation program. Lumbar and femoral bone mineral density (BMD) and serum levels of osteocalcin and 25-hydroxyvitamin D were measured at entry and after 1 and 2 years in all patients. Circulating cortisol and parathyroid hormone were measured in 14 and 6 patients, respectively, at entry and every year. Testosterone was measured in 18 patients at entry and after 1 year. At entry, lumbar BMD was significantly lower in alcoholics (1.06 +/- 0.03 g/cm2) than in age-matched healthy men (1.22 +/- 0.03 g/cm2; p < 0.001). Circulating osteocalcin and vitamin D levels were also significantly lower in alcoholics than in controls. Lumbar and femoral neck BMD increased in alcoholics after 2 years of abstinence (lumbar BMD, mean +/- SEM, 1.06 +/- 0.03 to 1.10 +/- 0.04 g/cm2, p < 0.05; femoral BMD, 0.82 +/- 0.02 to 0.84 +/- 0.02 g/cm2; p < 0.02). Moreover, lumbar BMD increased in alcoholics (2.9 +/- 1.4%) and decreased in controls (-1.1 +/- 0.2%; p < 0.02). Femoral BMD also increased in alcoholics (2.8 +/- 1.0%) but the expected mean decrease of -0.92% was found in healthy age-matched males. Baseline low osteocalcin levels (5.1 +/- 0.6 ng/ml) increased after 1 year (8.6 +/- 0.5 ng/ml, p < 0.001) and 2 years of abstinence (9.5 +/- 0.7 ng/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Collagen-related markers of bone turnover reflect the severity of liver fibrosis in patients with primary biliary cirrhosis.

The influence of a nonskeletal disease with increased connective tissue synthesis or degradation in the collagen-related markers of bone turnover has been evaluated in 34 women with primary biliary cirrhosis (PBC; age range 41-81 years), a disease with increased hepatic fibrosis, often associated with osteoporosis. Serum osteocalcin (BGP), and carboxy-terminal (PICP) and amino-terminal (PINP) propeptides of type I collagen were assessed as indexes of bone formation, whereas serum tartrate-resistant acid phosphatase (TRAP), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), and type I collagen cross-linked N- (NTX) and C-telopeptide (CTX) were measured as markers of bone resorption. The histologic stage of the disease and serum amino-terminal propeptide of type III collagen (PIIINP) as an index of liver fibrogenesis were also evaluated. BGP levels were significantly lower, whereas PICP and PINP levels were higher in patients than in controls. Among the bone resorption markers, serum ICTP and urinary PYR, DPYR, HYP, NTX, and CTX levels were significantly higher in patients than in controls. Serum PIIINP levels were also increased in PBC patients. BGP did not correlate with PICP and PINP, but these markers of bone formation as well as ICTP, PYR, DPYR, and NTX correlated with serum PIIINP levels. Serum TRAP did not correlate with collagen-related markers of bone resorption. Moreover, patients with PIIINP and bilirubin above normal levels had higher PICP, PINP, ICTP PYR, DPYR, CTX, and NTX. These markers correlated with the histologic stage of the disease, but not with osteopenia measured by densitometric procedures in 22 patients. In conclusion, collagen-related markers of bone turnover do not reflect bone remodeling in PBC. The close association of these markers with PIIINP and the clinical and histologic stage of the liver disease suggests that they are influenced by liver collagen metabolism.

FRAXA premutation associated with premature ovarian failure.

A family is described in which six females in three generations experienced premature ovarian failure (POF). In three of them a FRAXA premutation was documented and the carrier status of a fourth female could be inferred, because her son had the fragile X syndrome. These findings provide further evidence for a nonrandom association between POF and the FRAXA premutation.

Serum amino-terminal propeptide of type III procollagen levels in chronic pancreatitis.

The severity of pancreatic fibrosis, a characteristic feature of patients with chronic pancreatitis (CP), can be assessed only by direct histologic analysis of pancreatic tissue. Since serum levels of the amino-terminal type III procollagen propeptide (PIIIP) can reflect the degree of fibrogenic activity in several diseases associated with fibrosis, the current study was aimed at investigating whether PIIIP are increased in chronic pancreatitis, the relationship between PIIIP and pancreatic fibrogenic activity, and the influence of pancreatectomy, pancreatic exocrine function, and duration of disease on PIIIP levels. Serum PIIIP was measured in 18 patients with CP (15 without liver disease and three with cholestasis) and in 21 healthy controls. The effect of pancreatectomy on PIIIP was evaluated in seven patients, in whom PIIIP was measured immediately before and 2 months after surgery. Prolylhydroxylase (PHase) activity as an index of pancreatic fibrogenesis was evaluated in pancreatic tissue from 11 patients who had undergone subtotal pancreatectomy and from 11 organ donors. The bentiromide (BT)-PABA test as an index of exocrine pancreatic function was measured in all patients. PIIIP was significantly higher in patients who had or had not undergone pancreatectomy (17.3 +/- 4.0 and 25 +/- 11.4 ng/ml, respectively) than in controls (12.3 +/- 3.1 ng/ml) (p < 0.001). PIIIP decreased significantly after pancreatectomy (before, 32.0 +/- 9.3 ng/ml; after, 18.4 +/- 4.8 ng/ml; p = 0.005). PHase was significantly higher in patients (773 +/- 250 cpm/mg protein) than in controls (405 +/- 121 cpm/mg protein) (p < 0.001). PIIIP was correlated with pancreatic PHase (r = 0.7, p = 0.001) but not with BT-PABA or with the duration of the disease. In conclusion, serum PIIIP levels are increased in patients with CP and reflect the severity of pancreatic fibrogenic activity. No relationship between the serum PIIIP levels and the pancreatic exocrine function and duration of disease was found.

Role of zinc in the process of pancreatic fibrosis in chronic alcoholic pancreatitis.

Zinc acts as a cofactor in many enzymatic processes, including collagen synthesis. The observation of increased activity of prolylhydroxylase (PHase), an enzyme that takes part in the synthesis of collagen, in zinc-depleted liver tissue suggests that zinc deficiency is associated with hepatic collagen deposition. The pancreatic zinc content in chronic alcoholic pancreatitis (CAP) is still unknown. The objectives of this study were (a) To assess zinc concentrations in the pancreatic tissue in CAP; (b) to establish a possible relation between pancreatic zinc content, fibrosis, and PHase activity; and (c) to evaluate the relation between serum and pancreatic zinc levels. Sixteen surgical specimens of pancreatic tissue from patients with CAP were analyzed; control pancreatic samples from 11 organ donors were also studied. Zinc concentration, PHase activity, and the amount of fibrous tissue were assessed in the pancreatic tissue of each individual. The amount of fiber deposited in the pancreas in CAP was 68.4 +/- 19.8%, and that of the control group, 5 +/- 2% (p < 0.001). PHase activity in CAP was 754 +/- 230 cpm/mg of protein and that of the control group was 405 +/- 151 cpm/mg of protein (p < 0.001). The amount of pancreatic zinc in the former was 15.0 +/- 9.7 micrograms/g of tissue and that of the latter was 28.1 +/- 18.1 micrograms/g of tissue (p = 0.023). Serum zinc levels were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis and degradation of collagen in pancreatic fibrogenesis.

The mechanism of fibrogenesis in the pancreas is not well known. We analyzed the role of prolylhydroxylase and collagenase activities in the development of fibrosis in chronic alcoholic pancreatitis (CAP). Nineteen patients with CAP and 11 controls (organ donors) with normal pancreatic histology were included in the study. Pancreatic tissue was obtained from all subjects to measure (a) area of fibrosis (histomorphometric method); (b) prolylhydroxylase activity (PHase), which reflects the intracellular synthesis of collagen (Hutton's method); and (c) collagenase activity, which reflects the degradation of collagen (collagenase assay system, 3H). The percentage of the fibrosis area in relation to the total area of pancreatic tissue was significantly higher in CAP than in the control group (70.6+/-20.2% vs. 4.6+/-1.8%; p<0.001). Mean pancreatic PHase activity was also significantly higher in CAP than in the control group (775+/-258 cpm/mg protein/h vs. 405+/-151 cpm/mg protein/h; p<0.001). The collagenase activity was significantly lower in CAP than in the control group (8.7+/-3.5 cpm/cpm added/mg protein vs. 18.0+/-3.9 cpm/cpm added/mg protein; p<0.001). A significant correlation was observed between percentage fibrosis evaluated histomorphometrically and PHase activity in all patients (r = 0.72; p<0.001), and between PHase and collagenase activities in controls (r = 0.70; p = 0.024), but not in CAP. Pancreatic tissue in CAP has an increased fibrogenic activity and an impaired collagen-degradation capacity. These findings might explain the excessive development of fibrosis in CAP.

Hepatic fibrogenic activity in chronic alcoholic pancreatitis.

The prevalence and the mechanisms of hepatic fibrosis in chronic alcoholic pancreatitis remain uncertain. The aim of this study was to investigate the fibrogenic activity of the liver in patients with chronic pancreatitis and its relation with either the alcohol or cholestasis. Liver biopsies were obtained from 16 patients with chronic pancreatitis at the time of surgery and from 10 organ donors. Samples were processed for histologic examination to assess the presence and extent of fibrosis, inflammatory reactions, and cholestasis- and alcohol-related lesions. In other samples, the collagen content was measured by morphometry, and prolylhydroxylase activity was determined. Liver-function tests, ultrasonography, and endoscopic retrograde cholangiopancreatography were performed before surgery in all the patients. Of patients with chronic pancreatitis, 75% had significantly greater hepatic fibrosis and prolylhydroxylase activity than the control group. Moreover, prolylhydroxylase activity in patients with chronic pancreatitis was higher in those with cholestasis or partial obstruction of the common bile duct than in those without cholestasis or partial obstruction of the common bile duct. Both the fibrogenic activity and the collagen content in the livers of patients with chronic alcoholic pancreatitis are significantly increased, even in those without histologic lesions, and these alterations may be secondary to a partial occlusion of the common bile duct.

Drinking patterns and problems: a comparison of emergency room populations in the United States and Spain.

The association of alcohol consumption and casualties is compared in probability samples of two culturally diverse emergency room populations: Barcelona, Spain (N = 2972) and Contra Costa County, California (N = 3609). Similar methods and data collection instruments were used to breathalyze and interview patients regarding self-reported alcohol consumption 6 h prior to the injury, usual drinking patterns and alcohol-related problems. Breathalyzer reading was positively associated with injury in both Contra Costa and Barcelona, but at the legal level only in Barcelona. Self-reported alcohol intake within 6 h prior to the event was positively associated with injury only among females in Contra Costa. Frequent light drinking was associated with injuries in Barcelona while heavier drinking was associated with injuries in Contra Costa. Little association was found between social consequences of drinking and injuries in either sample, however, the Contra Costa sample reported significantly higher rates of these problems than Barcelona, among moderate and high quantity drinkers. Although few differences were found between the two samples, findings suggest that usual drinking patterns within a culture may influence the association of alcohol and casualties, and future studies should explore these differences by type and cause of injury.

Effects of ethanol feeding and malnutrition on collagen synthesizing and degrading enzymes in rat pancreas.

This study was performed to delineate the combined effects of a low-fat diet and chronic ethanol ingestion on collagen metabolism in rat pancreas. Rats fed a very low-fat diet (5% of total calories as lipid) for 12 weeks developed malnutrition as judged by weight loss (-33% of the initial body weight) and low serum albumin and amylase levels. The pancreas of malnourished rats showed increased collagenase activity with respect to animals fed a 35% lipid diet (p < 0.05). Hydroxyproline content was higher in the pancreas of malnourished rats and collagenase activity correlated well with hydroxyproline content (r = 0.57, p = 0.0013). Ethanol feeding for 12 weeks, regardless of the nutritional state of the rats, did not change the synthesis and degradation rates of collagen in the pancreas. The present study suggests that malnutrition may have profound effects on collagen metabolism.

Prediction of alcohol-related casualties in the emergency room: a U.S.-Spain comparison.

Alcohol consumption variables predictive of casualties are compared in probability samples of emergency room (ER) patients in two countries with different drinking patterns; (1) Spain, where frequent light drinking is the typical pattern (N = 2,072), and (2) the U.S. (i.e., California), where less frequent heavier drinking is more typical (N = 1,756). Logistic regression was used to evaluate the predictive value of breath-analyzer readings, drinking patterns and problems, time and place of injury, and demographic characteristics on ER admission for injuries vs noninjuries and for alcohol-related injuries vs non-alcohol-related injuries. Quantity and frequency of drinking, time and place of injury, and feeling drunk at the time of the event were predictive of casualties in California. Drinking patterns were less predictive of injury occurrence and of alcohol-related injury in Spain. One possible explanation for this difference may be that drinking is integrated into society as part of the wine drinking culture in Spain, while in the U.S. drinking occasions are more circumscribed by appropriateness of time and place.

Validity of self-reported alcohol consumption in the emergency room: data from the United States, Mexico and Spain.

The validity of self-reported alcohol consumption within 6 hours prior to injury based on breath-analyzer readings obtained at the time of emergency room (ER) admission is compared among probability samples of ER patients in Contra Costa County, California (n = 450), Mexico City (n = 500) and Barcelona, Spain (n = 864). The same questionnaire, study design and methods were used in all three countries to maintain comparability for comparative analyses. The analysis was restricted to those breath analyzed within 6 hours of injury occurrence who reported no drinking following the event. Validity of self-reports was high in all three samples. The proportion of those reporting not drinking prior to injury who had positive breath-analyzer readings was .5% in the U.S., 1.5% in Spain and 3.3% in Mexico. Validity of self-reports was not associated with cause of injury in the United States. In Mexico those injured in motor vehicle accidents or by violence were most likely to deny drinking, while in Spain those injured in violent situations were most likely to report not drinking. Validity of self-reports in these studies is much higher than that found in other U.S. studies, but this may be partly due to the fact that self-reports were obtained after the patient had been breath analyzed.

Influence of zinc intake on hepatic lipid peroxidation and metallothioneins in alcoholic rats: relationship to collagen synthesis.

Hepatic lipid peroxidation, metallothioneins, collagen and proline hydroxylase activity were investigated in 16 ethanol-fed rats and in 16 control animals. The rats were further divided into three groups to receive either a standard diet, a zinc-deficient diet or a zinc-supplemented diet. The animals were sacrificed at week 12 of the experiment for histological and biochemical assessments. Hepatic tissue examination indicated that oral zinc supplementation was associated with a decrease in lipid peroxidation, collagen deposition and proline hydroxylase activity together with an increase in metallothionein concentration in alcoholic rats. There were no significant differences in lipid peroxidation in the control group in relation to the diet. Zinc supplementation was associated with increased concentrations of hepatic metallothioneins together with decreased concentrations of proline-hydroxylase and collagen but to a lesser degree than in alcoholic animals. These results indicate that zinc is an efficient hepato-protective agent against lipid peroxidation in alcoholic rats and its effect may be, in part, mediated by the activation of metallothionein synthesis. Also, lipid peroxidation may be related to changes in hepatic collagen synthesis.

Treatment of primary biliary cirrhosis.

Primary biliary cirrhosis is a chronic liver disease of unknown etiology, characterized by inflammation and destruction of the intrahepatic biliary ducts, resulting in chronic cholestasis and eventually cirrhosis. The main clinical manifestations consists of pruritus, jaundice, xanthomas, and the consequences of intestinal malabsorption, including vitamin deficiencies and osteodystrophy. Treatment of PBC is addressed at preventing or relieving the symptoms and clinical consequences of chronic cholestasis, and also at correcting the bile duct abnormalities by specific treatments. Pruritus is treated with cholestyramine, but in some cases other drugs, such as rifampicin or opioid antagonists are needed. Bisphosphanates are effective for increasing bone mass in osteopenic patients. Vitamin D and cAlcium supplements are also recommended, particularly in patients with severe cholestasis. Ursodeoxycholic acid (UDCA) has become the standard treatment (13-15 mg/kg/day), resulting in marked relieving of cholestasis. UDCA also prevents the histological progression of the disease, although the effects on survival are less apparent. Small trials of combination therapy using UDCA with methotrexate, colchicine, or prednisone, have been reported but have not shown any increased efficacy over UDCA therapy. Liver transplantation is the only treatment available when cholestasis progresses, with very good survival rates.

[Oliguric and non-oliguric renal failure in high risk patient in intensive care units (author's transl)]. / Insuficiencia renal aguda oligúrica y no oligúrica en enfermos de alto riesgo ingresados en unidades de cuidados intensivos.

Oliguric and non-oliguric acute renal failure was studied in a group of 28 high risk patients in an intensive care unit. Of these, 15 (53.5%) presented oliguric and 13 (46.4%) non oliguric acute renal failure. Causal agents of the renal failure were postoperative in 14 cases, mainly peritonitis; medical in 10 and posttraumatic in 4. Oliguric renal failure was most commonly medical, while non-oliguric renal failure was predominantly postoperative in origin (p less than 0.05). Results of urinalysis indicative of renal failure were similar in both groups: NAO, osmolarity, FeNa, BUN o/p and creatinine o/p, as were degree and course of renal failure, and the appearance of complications and indications for dialysis. There was no significant difference in mortality rate between oliguric (93%) and non-oliguric (85%) patients; total mortality was 89%. The results of this study clearly show that non-oliguric acute renal failure carries the same poor prognosis in high risk patients in intensive care units as do the oliguric forms of the entity.

[Prevalence and factors associated to the presence of fatty liver in apparently healthy adult men]. / Prevalencia y factores asociados a la presencia de esteatosis hepática en varones adultos aparentemente sanos.

BACKGROUND: Alcohol intake in one of the factors associated with fatty liver, although its contribution as well as other factors have not been completely established. Therefore the aim of this study was to assess the prevalence and associated factors for fatty liver diagnosed by ultrasonography. SUBJECTS AND METHODS: 1,801 presumably healthy male workers (age range 18-60 years). A complete physical and laboratory investigations, including HBsAg and anti-HCV antibodies, a detailed interview on alcohol intake, and an abdominal ultrasound examination were performed in all cases. Diagnosis of fatty liver was based on defined ultrasonographic criteria. RESULTS: Eighty eight cases were excluded because of the HBsAg or anti-HCV positivity or incomplete ultrasonography. Among the remaining 1,713 cases, 236 (13.8%; 12.2-15.4) had fatty liver. Logistic regression analysis disclosed age (RR: 1.04; CI 95%; 1.03-1.05), ethanol intake > 40 g/d (2.19; 1.81-2.65), gamma-glutamyl-transferase > 40 U/l (3.51; 2.95-4.18), body mass index > 30 (3.87; 3.22-4.66) and glycemia > 120 mg/dl (2.69; 1.85-3.90) as the risk factors for fatty liver. Fatty liver was present in 8.8% of cases who did not have obesity, diabetes or hypercholesterolemia. When the subjects with obesity, hyperglycemia or hypercholesterolemia were excluded, regression analysis confirmed age, ethanol intake and gamma-glutamyl-transferase as independent factors associated with fatty liver. CONCLUSIONS: Age, alcohol intake, obesity, and increased serum levels of glucose, cholesterol and gammaglutamyl transferase are the main factors associated with fatty liver in presumably healthy adult men.

[Autoimmune hepatitis. Clinical characteristics and response to treatment in a series of 49 spanish patients]. / Hepatitis autoinmune. Características clínicas y respuesta al tratamiento de una serie de 49 pacientes españoles.

The clinical and evolutive characteristics and the response to treatment of a series of 49 patients with autoimmune hepatitis (AIH) diagnosed in the Liver Unit of a tertiary hospital from 1979 to 1996 and followed over 5.6 +/- 0.7 years were reviewed. Forty cases (80.4%) were AIH type 1 (ANA/AML positive), 7 (14%) type 2 (ALKM positive) and 2 (5%) of an undetermined type (absence of detectable antibodies). In 13 (26.6%) the disease presented as acute hepatitis and 16 (32%) presented extrahepatic manifestations. The AIH type 2 was observed in younger patients with the debut being more acute than in AIH type 1, but no significant differences were observed between the two groups with regard to the results of laboratory tests, frequency of a systemic manifestations and histologic lesions. Immunosuppressive treatment was effective in 90% of the cases, but 11 (30%) out of 37 relapsed on suppression of prednisone or reduction of the dosis. All showed response on reinitiation or an increase in the dosis of prednisone. Progression to cirrhosis was observed in 17% of the patients without cirrhosis at the time of diagnosis despite biochemical remission induced by treatment. No patient died during the follow up but 4 required liver transplantation.