Archie H. Baggenstoss

Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared.

Among 120 consecutive patients with chronic active liver disease (CALD) randomized to different treatments, those receiving maintenance doses of prednisone 20 mg daily (Pred), prednisone in doses given on alternate days and titrated to secure resolution of clinical and biochemical abnormalities (Pred-Titrad), or a combination of prednisone 10 mg and azathioprine 50 mg daily (Comb) survived and underwent resolution of clinical and biochemical features of disease more often than a control group receiving placebo or azathioprine 100 mg daily. Histological remission occurred significantly more often with Pred and Comb than with other regimens. Major side-effects of therapy were commoner with Pred than with Comb or Pred-Titrad, which did not differ. We conclude that Comb is the initial treatment of choice for CALD, since clinical, biochemical, and histological resolution of disease activity occurs as often as with Pred, whereas early side-effects are significantly less frequent.

Observer error and sampling variability tested in evaluation of hepatitis and cirrhosis by liver biopsy

In 50 patients with chronic active liver disease, observer and sampling error in histologically evaluating hepatitis and cirrhosis after blind-needle biopsy of the liver was assessed from coded tissue. This was done by repeated readings of the same specimens by the same pathologist, by sequential biopsies from the same patients with cirrhosis, and by multiple simultaneous biopsies from adjacent areas of the liver. Observer error was small. The consistency of grading the individual histologic characteristics of hepatitis was 90%, and the reproducibility of the degree of either hepatitis or cirrhosis was 94%. Sampling error was also trivial in hepatitis, indicating that a single needle biopsy accurately reflects the type and degree of inflammation and necrosis in adjacent areas of the liver. By contrast, sampling error was of considerable magnitude when the presence of cirrhosis in patients known to have the lesion was sought, since confirmation by simultaneous or sequential biopsies was made in only 33% of the cases.

THE RELATIONSHIP OF THERAPY WITH CORTISONE TO THE INCIDENCE OF VASCULAR LESIONS IN RHEUMATOID ARTHRITIS

Excerpt In the last six years polyarteritis nodosa has been seen clinically, and proved histologically by biopsies, in patients who had had classic rheumatoid arthritis for many years. This associa...

Chronic active liver disease: The range of histologic lesions, their response to treatment, and evolution

Abstract Histologic study of serial biopsy specimens in a prospective, controlled, double blind, randomized trial of treatment involving 63 patients with predefined clinical and biochemical criteria of severe chronic active liver disease revealed five different histologic patterns of hepatic injury on initial biopsy: chronic persistent hepatitis, chronic aggressive hepatitis, subacute hepatitis with bridging, subacute hepatitis with multilobular necrosis, and cirrhosis. The initial biopsies in the fatal cases revealed cirrhosis, subacute hepatitis with multilobular necrosis, or subacute hepatitis with bridging. Patients with subacute hepatitis with bridging and with multilobular necrosis more frequently revealed stigmata of viral hepatitis and more frequently developed cirrhosis than chronic aggressive hepatitis, regardless of treatment. The severe forms of hepatitis more frequently remitted to the histologic features of chronic persistent hepatitis in patients treated with prednisone and a combination of prednisone and azathio-prine than with azathioprine or placebo alone. Serial biopsy specimens frequently revealed changes in the histologic pattern before remission to chronic persistent hepatitis. Histologic progression to cirrhosis may occur by bouts of intralobular and multilobular necrosis as well as by piecemeal necrosis. Sampling error in needle biopsy of cirrhosis is so great that the condition either may be missed or may be impossible to accurately classify into portal and postnecrotic cirrhosis. Observations at autopsy always revealed postnecrotic cirrhosis characterized by extensive parenchymal loss and incomplete regeneration. We conclude that the evolution of any lesion is influenced by at least two factors: the original histologic pattern and the therapy applied.

Corticosteroid-treated chronic active hepatitis in remission: uncertain prognosis of chronic persistent hepatitis.

To assess the prognosis of patients with severe chronic hepatitis after histologic examination had shown an improvement to chronic persistent hepatitis, we followed 52 such patients regularly for 54 +/- 4 months after the cessation of corticosteroid therapy. In 24 patients, the condition deteriorated 7 +/- 1 months after therapy and required further treatment with prednisone. Histologic features of chronic active hepatitis, including bridging and multilobular necrosis, were documented in all 14 patients in whom biopsies were performed. In 20 of 24 patients, the disease responded to retreatment, but 13 again had relapses, and cirrhosis developed in two. Of 28 patients who remained asymptomatic for 48 +/- 6 months, 17 retained features of chronic persistent hepatitis, and nine had improvement to normal histologic features. Cirrhosis developed in two patients without clinical manifestations of active inflammation. Findings before and after treatment did not predict outcome. We conclude that severe chronic active hepatitis that has been treated with prednisone and converted to chronic persistent hepatitis will often and unpredictably deteriorate after treatment has been stopped. Cirrhosis develops rarely but may occur with or without clinically overt chronic active hepatitis.

Severe chronic active liver disease

To determine the usefulness of recognizing the different morphologic patterns of chronic active liver disease (CALD), we compared clinical and biochemical features as well as responses to treatment in 32 patients with chronic active hepatitis (CAH); 36 with subacute hepatitis and bridging necrosis (SHB); 30 with subacute hepatitis and multilobular necrosis (SHMN); and 30 with cirrhosis and active hepatitis (Cirrh). The morphological lesions did not correlate with clinical or etiologic features. Patients with CAH had less severe biochemical abnormalities, entered remission more often, and failed to respond to treatment less frequently than those with SHMN or Cirrh. SHB and SHMN resembled each other in many regards and showed greater functional changes than CAH. Cirrhosis developed more often after SHMN than CAH and was associated with a poorer prognosis than CAH. Serial liver biopsies revealed all possible histologic transitions, with reduction of inflammation usually occurring in patients treated with steroids and extension of inflammation being more frequent in those not receiving these drugs. CAH, SHB, SHMN, and Cirrh, therefore, reflect the degree and extent of disease activity at any given time in CALD, rather than representing different conditions. Identification of the initial morphologic lesion is helpful because of differences in prognosis.

PULMONARY LESIONS IN DISSEMINATED LUPUS ERYTHEMATOSUS

Excerpt Pathologists and clinicians have been aware for many years that pulmonary and renal complications are often terminal events in the life history of the patient suffering from disseminated lu...

Effect of d-Penicillamine on Copper Retention in Patients with Primary Biliary Cirrhosis

As part of a double blind, randomized trial evaluating D-penicillamine in primary biliary cirrhosis, we monitored urinary copper excretion and hepatic copper concentration during the 1st year of therapy in 46 patients with this disease. The retention of copper in primary biliary cirrhosis was confirmed by finding abnormally high levels of standard copper measurements in almost all patients before treatment. The hepatic copper was elevated in 43 of 45 patients, the urinary copper in 42 of 46, and the ceruloplasmin in 46 of 46. Urinary copper excretion correlated with the hepatic copper concentration (r = 0.68, P less than or equal to 0.001). No significant correlation occurred between hepatic copper and ceruloplasmin. Hepatic copper concentrations greater than 400 microng per g of dry weight were found almost exclusively in patients with advanced histological disease (P less than or equal to 0.01). Therapy with D-penicillamine and a low copper diet sustained increased urinary copper excretion for 1 year in almost all patients (P less than or equal to 0.001). Among patients taking placebo, the median hepatic copper concentration increased 13 microng per g of dry weight after 1 year. In contrast, among the patients taking D-penicillamine, the median hepatic copper concentration decreased 99 microng per g of dry weight (P less than or equal to 0.02). Continued observation of this therapeutic trial may help to clarify the relationship of copper retention and liver injury in primary biliary cirrhosis.

Primary Malignant Neoplasms of the Duodenum. Excluding the Papilla of Vater: A Clinicopathologic Study of 31 Cases

Summary Primary malignant neoplasms of the duodenum, excluding the papilla of Vater, are rare. Thirty-one cases were found at necropsy at the Mayo Clinic from 1910 through 1953, an incidence of 0.12 per cent. Twenty-seven of the 31 tumors were adenocarcinomas; the remaining 4 were sarcomas of various types. There was no evidence in this series that a benign ulcer had undergone neoplastic change. Metastasis had occurred in 20 of the 31 cases. The commonest sites of metastasis were the regional lymph nodes and the liver. The commonest clinical features in this series were pain, loss of weight, vomiting and anemia. Melena, jaundice and an abdominal mass were also prominent findings. A lesion was found by roentgenologic examination in 15 of 22 cases. In no case was a correct diagnosis made without positive roentgenologic evidence of the lesion.

RHEUMATOID GRANULOMATOUS NODULES AS DESTRUCTIVE LESIONS OF VERTEBRAE

In a case of rheumatoid arthritis, granulomatous nodules were observed clinically in the subcutaneous tissue and at necropsy in the synovial membranes, pericardium, myocardium, subchrondral bone, and vertebrae. The granulomatous process in the vertebrae in this case caused compression fracture of the twelfth thoracic vertebra and appeared similar roentgenographically to such other destructive lesions as multiple myeloma, metastatic carcinoma, and tuberculosis. This case, together with three others reported briefly, emphasizes the fact that the granulomatous inflammation which is so commonly observed in the subcutaneous tissues and occasionally in the viscera of patients with rheumatoid arthritis may also involve the vertebrae. This fact is important in the consideration of the differential diagnosis of destructive lesions of vertebrae in patients with rheumatoid arthritis.