Diagnostic features of tuberculous peritonitis in the absence and presence of chronic liver disease: a case control study.

PURPOSE: To determine diagnostic features of tuberculous peritonitis (TBP) in the absence and presence of chronic liver disease. PATIENTS AND METHODS: Thirty-four patients with TBP (13 without [Group I] and 21 with chronic liver disease [Group II] and 26 controls with cirrhosis and uninfected ascites (Group III) were studied. RESULTS: The clinical features in Groups I and II were similar and all patients had elevated ascitic fluid total mononuclear cell count. In Groups I, II, and III, respectively, ascitic fluid protein was > 25 g/L in 100% (13/13), 70% (14/20), and 0% (0/26); serum-ascites albumin gradient (SAAG) was > 11 g/L in 0% (0/13), 52% (11/21), and 96% (25/26), (0% [0/13], 71% [15/21], and 96% [25/26] after correction for serum globulin); and ascitic fluid lactate dehydrogenase (LDH) level was > 90 U/L in 100% (12/12), 84% (16/19), and 0% (0/20), respectively. In Groups I and II combined, ascitic fluid acid-fast stain was negative in all but Mycobacterium tuberculosis culture was positive in 45% (10/22); peritoneal nodules occurred in 94% (31/33), granulomas in 93% (28/30), and positive peritoneal M tuberculosis culture in 63% (10/16). CONCLUSIONS: In patients with suspected TBP, ascitic fluid protein of > 25 g/L, SAAG of < 11 g/L and LDH of > 90 U/L have high sensitivity for the disease. With coexistent chronic liver disease, a lower protein level and higher SAAG are usually not helpful but LDH > 90 U/L is a useful parameter for screening. Diagnosis is best confirmed by laparoscopy with peritoneal biopsy and M tuberculosis culture.

Sex and strain differences in response to cocaine.

After pretreatment with phenobarbital, female B6AF1 mice showed considerably higher serum glutamic oxaloacetic transaminase (SGOT) elevations and more periportal necrosis from a single injection of cocaine than males. This sex difference was androgen dependent. Castration or treatment with flutamide made males respond like females, while testosterone made females behave like males. There was no significant sex difference in enzymes of cocaine metabolism. When the mice were induced by exposure to pine bedding, males showed higher SGOT elevations and more centrilobular necrosis after cocaine than females. In this case, the sex difference could be attributed to increased levels of cytochrome P-450 and cocaine N-demethylase in liver microsomes. BALB/cBy mice on pine bedding showed much less liver damage from cocaine than B6AF1 mice, but they were more sensitive to norcocaine and N-hydroxynorcocaine. This difference was correlated with low levels of cocaine N-demethylase in the BALB/cBy mice. Liver microsomes from phenobarbital-induced BALB/cBy mice had less norcocaine N-hydroxylase activity than those from B6AF1 mice. These studies demonstrate that the pattern of sex and strain differences in liver damage from cocaine depends on the inducing agent and can be related to a large extent to the microsomal enzymes induced by that agent.

Control of ventilation, respiratory muscle strength, and granulomatous involvement of skeletal muscle in patients with sarcoidosis.

Granulomatous involvement of skeletal muscle occurs in 50 to 80 percent of patients with sarcoidosis. How this may affect respiratory muscle function in sarcoidosis is not known. To attempt to answer this question, we compared respiratory function and muscle force generation, and control of ventilation in 12 untreated patients with 12 healthy, nonsmoking subjects. While seated, room air breathing, measurements included expiratory reserve volume (ERV), components of breathing pattern, and occlusion pressure at 1 s (P0.1). Three of nine patients who consented to muscle biopsy demonstrated granulomatous involvement on histologic examination, and Pmax values less than the group mean; however, some patients without muscle granulomas also demonstrated low Pmax values. Breathing pattern in the sarcoid patients was rapid and shallow, but not related to the degree of radiographic infiltration or respiratory elastance. Mean inspiratory flow (VT/TI), minute ventilation, and P0.1 were, in general, greater than in the control subjects, indicating an increase in central drive. There was a significant inverse correlation between FVC and P0.1, and a weak inverse relationship between ERV and P0.1. With no significant difference between group "effective impedances" (P0.1/(VT/TI)), findings indicate that in the sarcoidosis group, decreased muscle force generation was compensated for by an increase in central drive. Granulomatous infiltration may be one of many factors contributing to respiratory muscle weakness in sarcoidosis.

A distinctive perivenular hepatic lesion associated with heart failure.

Hepatic morphologic changes in seven patients in heart failure who were initially thought to have hepatitis are reported. In each instance, percutaneous liver biopsy or post mortem tissue examination disclosed a striking lesion involving all perivenular areas, with replacement of hepatocytes by erythrocytes. Four patients were in pure left-heart failure, while three were in biventricular failure. Upon treatment of the heart failure, the conditions of all patients improved clinically, and liver-function tests returned to normal or near normal. In two patients who later had refractory heart failure and died, there was no evidence of hepatic-vein thrombosis or occlusion post-mortem. A hypothesis is offered for the pathogenesis of this lesion, and its clinico-pathologic differential is discussed.

Risk lesions in cirrhosis and development of hepatocellular carcinoma: an autopsy study.

Non-neoplastic morphologic changes in various types of cirrhosis were evaluated in relationship to the presence or absence of hepatocellular carcinoma (HCC), using autopsy livers from Hokuriku (Japan) and Los Angeles (USA). Macronodular cirrhosis was closely related to HCC in B-viral cirrhosis, alcoholic cirrhosis and cirrhosis of uncertain type. Liver cell dysplasia was most frequently seen in cases with and without HCC in B-viral cirrhosis but was significantly more frequent with HCC in cases of alcoholic cirrhosis and cirrhosis of uncertain type. Nodular bulging activity within regenerative nodules was closely related to HCC in alcoholic cirrhosis. A positive relationship between HCC and Mallory bodies was found in non-alcoholic cirrhosis. These data suggest that patients with macronodular cirrhosis, liver cell dysplasia, nodular bulging activity and Mallory bodies may have an increased risk of developing, or having HCC dependent on the etiology of cirrhosis. The geography and race differences had some relationship to the incidence of HCC.

Delta agent superinfection. Rapidly progressive liver disease in a hepatitis B virus carrier.

We report a case of rapidly progressive chronic active hepatitis (CAH) following acute delta infection in a previously asymptomatic hepatitis B virus carrier. Serologic evidence of delta superinfection coincided with an acute icteric hepatitis, and was followed by the development of clinically evident chronic liver disease. The liver biopsy specimens documented the acute hepatitis and subsequent progression of severe CAH. This case illustrates the clinical and pathologic changes that may follow acute delta infection in chronic hepatitis B carriers.

Hepatic lesions resembling alcoholic liver disease.

Patients who do not consume alcohol may have hepatic lesions that are characteristic of those of alcoholic liver disease: portal fibrosis, sinusoidal collagen deposition, fatty change, parenchymal neutrophilic exudate, and Mallory body deposition. Here, the author discusses entities that mimic alcoholic liver disease on biopsy and disorders that have morphologic features also seen in alcoholic liver disease.

Glomerular tubular reflux--a morphologic renal lesion associated with the hepatorenal syndrome.

The hepatorenal syndrome, a primary cause of death from acute and chronic liver disease, consists of a functional renal failure whereby examination of the kidney has previously shown no distinct or specific morphologic change. We describe an unusual renal lesion consisting of the reflux of proximal convoluted tubular epithelium into Bowman's space. An autopsy series shows this glomerular change to be present in 71.4% of cases with the hepatorenal syndrome, while only present in 0 to 27.3% in other autopsy categories (p less than 0.001). Since this lesion has been previously described with experimental renal ischemic change and terminal hypotension, it is possible that it is caused in part by the decreased or altered renal blood flow known to be associated with the hepatorenal syndrome.

Twenty isoniazid-associated deaths in one state.

Twenty deaths from isoniazid-associated hepatitis are known to have occurred in California over a 14-yr period in persons ranging in age from 5 to 73 yr. Because no comprehensive survey was carried out, more such deaths probably occurred. With one exception, the patients were not seen or contacted monthly throughout the course of treatment. However, in 16 patients where the information was known, eight were seen by a member of the group giving the isoniazid (INH) within 30 days prior to the patients presenting with hepatitis. In 12 of 17 cases, symptoms were present for 7 days or more before the patient presented for medical care. In at least 35% of cases where the information was known, a management error occurred, usually failing to immediately stop INH when the patient presented with symptoms. The duration of treatment before hepatitis developed varied from 9 to 53 wk. Four of the 20 patients had cholelithiasis or a history of cholelithiasis. With one possible exception, no excessive alcohol use was noted. Concomitant acetaminophen, barbiturate, and tetracycline use occurred in several cases. There were no deaths in Orientals. Sixteen of the 20 deaths occurred in women who had started to receive INH between the ages of 15 and 55. Four of these women began receiving INH during pregnancy and continued it postpartum. Eight deaths occurred in persons starting INH before 35 yr of age. The continued occurrence of INH-associated deaths suggests that indications and precautions for INH preventive treatment be carefully reconsidered.

Portal vein thrombosis complicating endoscopic variceal sclerotherapy. Convincing further evidence.

Portal vein thrombosis occurred in a patient who bled from gastric varices that developed after obliteration of esophageal varices by endoscopic sclerotherapy. This complication was recognized only at surgery when thrombectomy and endovenectomy preceded the successful placement of an end-to-side portocaval shunt. At histopathology, the presence of an amorphous, eosinophilic material staining negatively for fibrin and similar to sclerosant injected at sclerotherapy was observed within the clot. This latter finding, previously unreported, provides convincing evidence for the causal relationship of portal vein thrombosis to endoscopic sclerotherapy.

Support of sinusoidal endothelial cell glutathione prevents hepatic veno-occlusive disease in the rat.

Depletion of sinusoidal endothelial cell glutathione (GSH) has been proposed as a common mechanism leading to hepatic veno-occlusive disease (HVOD). This study examines whether intraportal infusion of GSH can prevent HVOD in the monocrotaline rat model. HVOD was induced in rats with monocrotaline 160 mg/kg i.g. on day 0. GSH was infused intraportally by mini-osmotic pump. Monocrotaline decreased GSH in sinusoidal endothelial cells, but not in liver homogenate. Infusion of GSH, 2 micromol/hr starting day - 1, prevented the decrease in sinusoidal endothelial cell GSH and protected against histological and clinical evidence of HVOD. Protection by GSH was dose-dependent (0.5-2 micromol/hr). In rats receiving continuous GSH infusion, treatment with buthionine sulfoximine starting day - 2 decreased sinusoidal endothelial cell GSH and attenuated the protective effect of GSH against monocrotaline. GSH infusion starting 24 hours after monocrotaline ("glutathione rescue") offered substantial protection to most rats. N-acetyl-L-cysteine conferred protection, but N-acetyl-D-cysteine (an antioxidant that is not a precursor for GSH) had little or no protective effect, and 4-hydroxy TEMPO, a free radical scavenger, was not protective. Discontinuation of the GSH infusion 5 days after monocrotaline administration led to severe hepatic veno-occlusive disease on day 6. In conclusion, monocrotaline selectively depletes sinusoidal endothelial cell GSH. Intraportal infusion of GSH protects against monocrotaline toxicity, at least partially by maintaining sinusoidal endothelial cell GSH levels. Glutathione infusion started after monocrotaline is partially protective. Monocrotaline induces prolonged changes in the liver that remain suppressed as long as GSH is infused.

High-density lipoprotein cholesterol and liver disease.

To establish whether there is any significant relationship between high-density lipoprotein cholesterol (HDLC) concentrations and biopsy-documented liver disease, 169 patients had needle biopsies, serum cholesterol, and HDLC evaluated. Twenty-four patients had serial cholesterol, HDLC, prothrombin, and aminotransferase levels and activities examined. In both men and women, HDLC decreased strikingly and significantly in acute alcoholic hepatitis and in acute viral hepatitis, compared to controls (p less than 0.001). Men and women with inactive alcoholic liver disease and chronic active hepatitis showed moderate decreased in HDLC (p less than 0.001). Patients with primary and metastatic hepatic neoplasms also had strikingly decreased HDLC (p less than 0.001). Serial testing showed an excellent direct correlation between HDLC and prothrombin activity, r values ranging from 0.71 to 0.98. Although alcohol intake is known to correlate positively with HDLC concentrations, our data shows that this association is not absolute, and in most cases is reversed once liver disease becomes apparent.

Prevalence of delta-antibody among chronic hepatitis B virus infected patients in the Los Angeles area: its correlation with liver biopsy diagnosis.

The overall prevalence of delta-antibody among 80 patients with chronic infection of hepatitis B virus in the Los Angeles area was found to be 24%. Twenty-three patients had a histologic diagnosis of persistent hepatitis and 57 had chronic active hepatitis with or without cirrhosis. Only 1 patient among those with persistent viral hepatitis had delta-antibody, whereas 18 with chronic active hepatitis had delta-antibody in their sera (p less than 0.05).

Globular hepatic amyloid--an unusual morphologic presentation.

Hepatic amyloid, when identified, is usually located in the sinusoids, portal tracts, and arterioles. We report 14 cases of hepatic amyloidosis where eosinophilic globules having the histochemical and electron microscopic features of classic amyloid were found. The globules were round to oval, 5 to 40 micrometer in diameter, and were found within the space of Disse as well as aggregated within the portal tracts. There were no distinctive clinical or laboratory features distinguishing this type of amyloidosis from classic hepatic amyloidosis. However, there were no cases of multiple myeloma and only one of benign monoclonal gammopathy. All seven patients who were studied at postmortem examination had systemic (nonglobular) amyloidosis. This form of hepatic amyloidosis is probably not an early form of the disease but is an original but rare presentation of hepatic amyloid deposition.

"Naturally-occurring" anti-K1: possible association with mycobacterium infection.

We report a case of "naturally-occurring" (nonred blood cell stimulated) anti-K1. The patient had never received a blood transfusion. Red blood cell antibody screening panels showed agglutination with K:1 red blood cells at room temperature and not in the anti-globulin test. Testing with 2-mercaptoethanol showed the antibody to be IgM. The antibody is "naturally-occurring" and may be associated with pulmonary tuberculosis.

Chronic delta infection and liver biopsy changes in chronic active hepatitis B.

The delta agent consists of particles of RNA nucleoprotein and is probably a defective virus present only in the livers of patients with B-viral acute or chronic liver disease. Its frequency is significantly greater in patients with chronic active hepatitis B than in those with persistent viral hepatitis B, suggesting that chronic delta infection may increase the severity of liver disease. We studied biopsy or autopsy tissue samples from 57 patients with chronic active hepatitis B for morphologic differences between chronic delta-positive and delta-negative cases. The delta-positive cases had significantly greater portal and parenchymal inflammatory change, parenchymal necrosis, and nuclear dysplastic and polyploid change than did the delta-negative cases. These findings suggest that chronic delta infection, with ongoing delta replication, may increase the degree of hepatic damage, and possibly hasten the progression of liver disease, in patients with chronic active hepatitis B.

Tubular dysfunction in the deeply jaundiced patient with hepatorenal syndrome.

We examined beta 2-microglobulin (B2MG) excretion, an index of tubular function, in patients with hepatorenal syndrome, in whom tubular function is generally regarded as normal. Urine B2MG was significantly higher in these patients than in control patients with normal serum creatinine concentration. Patients with high urine B2MG concentration had markedly higher serum bilirubin than did patients with normal values (31 +/- 3 vs. 10 +/- 8 mg%, p less than 0.001), whereas prothrombin activity, serum albumin and serum B2MG concentration were similar. A "threshold" serum bilirubin concentration of about 23 mg% differentiated patients with normal and high urine B2MG values. Renal morphology at autopsy was unremarkable in both groups. Tubular dysfunction, manifested by increased urinary excretion of B2MG, occurs in patients with hepatorenal syndrome and deep jaundice. This measurement cannot, therefore, be used to make a diagnosis of acute tubular injury, as due to aminoglycosides, in such patients.

Ultrasonographic diagnosis of acute alcoholic hepatitis 'pseudoparallel channel sign' of intrahepatic artery dilatation.

BACKGROUND: In an ultrasound pilot study of acute alcoholic hepatitis (AAH), parallel tubular structures within the liver subsegments were observed. Pulse-Doppler flowmetry revealed that these structures were formed by a dilated hepatic arterial branch and an adjacent portal venous branch. This finding was termed the "pseudoparallel channel sign" (PPCS). The aims of this study were to assess the significance of this sign and show the characteristic ultrasound findings of AAH. METHODS: PPCS was specifically searched for on ultrasonography by two physician operators in consecutive patients (77 AAH, 119 other alcoholic liver disease, 49 nonalcoholic liver disease, and 15 healthy patients). RESULTS: PPCS was observed in 90% of patients with AAH and in 23% of patients with other alcoholic liver disease. This sign was not detected in nonalcoholic liver disease or healthy patients. Biopsy specimens were available in 100 patients, 51 of whom were patients with alcoholism. In those 51 patients, PPCS gave a sensitivity of 82%, a specificity of 87%, and an accuracy of 84% in diagnosing AAH. Patients with criteria of AAH had more segments involved with PPCS than patients without. CONCLUSIONS: PPCS may be an important diagnostic finding in AAH.

Cocaine-induced liver cell injury: comparison of morphological features in man and in experimental models.

Although investigative research of animal models in cocaine metabolism and associated liver cell injury has been fairly extensive during the past 10 yr, little evidence of hepatotoxicity has been documented in man. We report a case of fulminant hepatic failure and acute rhabdomyolysis resulting from cocaine use. Coagulative-type perivenular and midzonal necrosis and periportal microvesicular fatty change were the predominant morphological features throughout all lobules of the liver, in contrast to periportal necrosis described in the only previous case report with biopsy. Differences in zonal necrosis caused by the same drug are not typically seen in man experiencing direct or indirect intrinsic hepatotoxicity. However, experimental models have shown cocaine to have this ability, dependent on enzyme induction or inhibition, sex and dose. Therapeutic approaches for prevention of possible liver cell injury by cocaine toxicity are discussed.