Parenchymal Liver Disease Research Articles

Medicine in Ethiopia.

The medical school in Addis Ababa is situated 9° N of the Equator at an altitude of about 2500 m, the average for the greater part of Central Ethiopian plateau. This altitude corresponds to an inspired oxygen tension of 14.2 kPa (107 mmHg) and an alveolar oxygen tension of around 9.3 kPa (70 mmHg). Clinical practice in Addis Ababa is conducted therefore at medium altitude and within the tropics. To date, no clinical studies have been made of altitude effects on health and disease. This paper will present the personal experience of the author of ten years and of approximately 30 000 patients presenting with ‘medical’ disorders at the Princess Tsehai Memorial Hospital, which has been throughout the principal teaching hospital in Addis Ababa. The diseases encountered have been above all those of poverty and to a lesser extent of tropical parasitisms. A unique feature has been an overwhelming burden of parenchymal liver disease of uncertain pathogenesis. The influence of altitude on heart and lung disease is considered, but the consideration is necessarily speculative rather than factual.

Serum Bile Acid Concentrations in Patients with Liver Disease

An enzymatic-fluorimetric method using a highly purified 3alpha-hydroxysteroid dehydrogenase (Sterognost-3alpha, Nyco) was used to determine fasting serum bile acid concentrations on 49 occasions in 43 patients with various liver diseases. A two-hour postprandial bile acid determination was carried out on 29 occasions in 27 of the patients. Fasting bile acid concentration correlated significantly both in cholestatic hepatobiliary and in parenchymatous liver disease to serum bilirubin and aspartate aminotransferase (ASAT) but not to alanine aminotransferase (ALAT), alkaline phosphatase, or albumin. The two-hour postprandial bile acid concentration was above normal in all patients with biochemical and/or histological signs of hepatobiliary disease, also when fasting concentration was within normal limits. In parenchymatous liver disease correlations existed between the two-hour postprandial bile acid concentration and bilirubin, ASAT, and ALAT. The sensitivity of serum bile acid estimation was compared to other liver function tests. Both the fasting and the postprandial serum bile acid concentrations tended to be more sensitive tests of hepatobiliary disease than bilirubin, ASAT and ALAT.

Clinical significance of serum glutathione reductase in various clinical conditions, especially in liver diseases.

Serum glutathione reductase activity was measured in various conditions including acute hepatitis, chronic hepatitis, liver cirrhosis, malignant neoplastic diseases, and obstructive jaundice. A statistically significant elevation of the enzyme activity was found in all of these clinical conditions above normal value, especially in patients with acute hepatitis, some liver cancer, and malignant biliary obstruction. Comparison with other liver function tests showed the existence of statistically significant correlations of serum glutathione reductase with SGOT, SGPT and alkaline phosphatase in acute hepatitis, and with alkaline phosphatase in cirrhosis. In parenchymatous liver disease, serial determination was found to be important. High values in obstructive jaundice suggest the malignant obstruction.

False-Positive Liver Scan Following Colectomy

To the Editor.— The purpose of this letter is to report an interestingly abnormal liver scan in a normal liver. A falsely abnormal liver scan was obtained in a patient following total colectomy. True normalcy of the liver in this case was confirmed by liver function tests, liver biopsy, and, finally, laparotomy. To our knowledge, this type of observation has not previously been reported in the literature. A 27-year-old man with Crohn disease and carcinoma of the colon underwent total colectomy. His preoperative liver scan (Figure, top) was within normal limits. The postoperative liver scan (Figure, bottom) was apparently abnormal, characterized by heterogeneous colloid uptake and focal defects in the liver and increased splenic uptake. This may erroneously be attributed to parenchymal liver disease with possible portal hypertension. In this patient, however, there was no disease in the liver, as evidenced by normal liver function tests, liver biopsy, and laparotomy.

PERCUTANEOUS TRANSHEPATIC CHOLANGIOGRAPHY

The patient who presents with jaundice, regardless of the etiology, cannot be adequately examined by a gallbladder series and intravenous cholangiography. Clinical evaluation aided by laboratory analysis will not always differentiate between primary liver parenchymal disease and biliary tract obstruction. Percutaneous transhepatic cholangiography, when successfully performed, answers the question of whether the jaundice is due to primary liver parenchymal disease or due to biliary tract obstruction. The point to emphasize is that under no circumstances is it appropriate to presume any information if the biliary system is not entered and visualized successfully. The proper interpretation of the level of block can fall prey to the mistake of incomplete aspiration of the thick, inspissated bile in the obstructed biliary tree before injection of contrast material. The problem will be worsened by a peripheral entrance into the biliary system rather than a more central one. Gastrointestinal series should always be available to aid in identifying pathology at the entrace of the common bile duct into the duodenum. Lastly, identifying the etiology at the site of the block will require additional procedures. Selective visceral angiography has contributed greatly in this area. During the 20 years of clinical usage of percutaneous transhepatic cholangiography, we feel it has become the single examination capable of preventing unnecessary exploration of the jaundiced patient with primary liver parenchymal disease and the most useful potential source of practical information if laparotomy is necessary to correct biliary tract obstruction.

The Effect of Parenchymal Liver Disease on the Disposition and Elimination of Sedatives and Analgesics

The Effect of Parenchymal Liver Disease on the Disposition and Elimination of Sedatives and Analgesics

Hepatitis-B antigen and cirrhosis in Bantu patients with primary liver cancer.

Hepatitis-B antigen (HBAg) was found in the serum of 30 of 75 (40%) Bantu patients with primary liver cancer (PLC), but in only 7% of 18,377 apparently healthy rural Bantu, confirming an association between this tumor and persistence of the hepatitis-B virus. No relationship could be demonstrated between hepatitis-B antigenemia and alpha-fetoprotein, which was present in 77% of the patients. HBAg was not more common in the younger patients. In 60% of the patients, PLC coexisted with „posthepatitic” or postnecrotic cirrhosis. HBAg was found in 45.6% of the patients with cirrhosis, but also in 31% of those without, an insignificant difference. Our findings may be interpreted as meaning that persistence of the hepatitis-B virus is the cause or result of PLC, or that some immunologic defect is responsible for both. If the former, the virus must be directly oncogenic, in addition to having the potential to induce neoplasia indirectly via chronic parenchymal liver disease.

Serum Cholesterol Esterification in Human Liver Disease: Role of Lecithin-Cholesterol Acyltransferase and Cholesterol Ester Hydrolase

Serum cholesterol esters in man are largely formed intravascularly by lecithin-cholesterol acyltransferase (LCAT), a circulating enzyme of hepatic origin. Esterification of serum cholesterol in vitro is normally equatable with LCAT activity, but in patients with liver disease it has been suggested that the damaged liver releases cholesterol ester hydrolase into the circulation, so that serum net cholesterol-esterifying activity reflects a balance between LCAT and hydrolase activities rather than LCAT alone. To assess the validity of this hypothesis, we simultaneously assayed net cholesterol-esterifying activity and LCAT in sera from 25 patients with parenchymal liver disease, the former by a colorimetric method and the latter by a 14 C-isotopic assay. There was close agreement between the two esterification rates ( r = 0.89, P P r ≅ 0.7, P 14 C cholesterol linoleate into autologous serum substrate. Electrophoretic and radiochromatographic analysis of substrate sera suggested that most of the 14 C-ester was incorporated into lipoproteins, and validity of the assay was confirmed by its ability to detect known cholesterol ester hydrolase activity in dog serum and hog pancreatic extract. Serum hydrolytic activity was sought in 13 of the patients, but none was detected even in those with severe hepatic disease. These studies, therefore, revealed neither direct nor indirect evidence of circulating cholesterol ester hydrolase in patients with parenchymal liver disease, although its rare occurrence has not been completely excluded. Low LCAT activity can entirely account for the impaired in vitro cholesterol esterification of hepatic disease and probably contributes to the cholesterol ester derangements seen in vivo.

Lecithin: Cholesterol Acyltransferase in Human Liver Disease

Serum cholesterol esterification in vitro is usually impaired in patients with parenchymal liver disease. This abnormality roughly parallels the severity of the hepatic disorder and appears due to decreased synthesis or release of LCAT by the damaged liver. The extent to which this explains the cholesterol ester derangements observed in vivo is still unclear. but it probably plays a significant role. In contrast, cholesterol esterification in patients with cholestatic hepatobiliary disease has been variably reported as low, normal. or high. Conflicting data may partly be due to the influence of substrate on apparent LCAT activity. Further studies are needed to sort out complex interactions among LCAT, lipoprotein-X, and other factors which probably contribute to the serum lipid abnormalities of cholestasis.

Lipid and Lipoprotein Abnormalities in Liver Disease: The Possible Role of Lecithin: Cholesterol Acyltransferase Deficiency

Abnormalities of plasma lipids are common in patients with diseases of the liver. Plasma cholesterol levels are usually high with obstructive jaundice and low with severe parenchymal liver disease. In both situations free cholesterol tends to be elevated; the ester: free ratio is low. Lecithin levels may be high and lysolecithin low. These changes are similar to those found in patients suffering from a familial deficiency of the plasma enzyme lecithin: cholesterol acyltransferase (LCAT). Detailed examination of plasma lipoproteins reveals other similarities between the effects of liver disease and those of familial LCAT deficiency. Decreased activity of LCAT would explain many of the lipid changes of liver disease but it is unlikely that it could account for all of them.

Hepatic Venous Obstruction and Bile Flow-Reply

To the Editor. —Donovan et al are, of course, justified in pointing out that the experimental methods employed by them 1 and by us 2 were entirely different. Perhaps, as they suggest, there is no reason for comparing them at all. One cannot quibble with the markedly increased bile flows measured by Lenthall et al 3 in seven patients with severe, parenchymal liver disease. This suggests increased bile flow in liver disease with presumed hepatic congestion, although only one of these seven patients exhibited ascites at laparotomy, and then only a minimal amount (300 ml). We maintain that, in their animal study, Donovan and his colleagues failed to document one important proof of hepatic congestion—ascites. We have personally made the error of estimating constriction of the vena cava to 50% of original diameter, only to find later that the constriction was too little (no ascites) or too much (the dog

Increased skeletal uptake of radiocolloid due to metastatic liver disease.

The reticuloendothelial system may be visualized by the injection of 99Tcm colloid at an activity level of 12 mCi/70 kg bodyweight (De Land and Wagner, 1972a). At the much radiolower activities used for liver and spleen scintigraphy the uptake in the skeletal component of the RES is not significant except in certain cases of parenchymal liver disease when bone marrow uptake may be observed on the liver scan (Wagner and Mishkin, 1969; De Land and Wagner, 1972b).

Hepatobiliary diseases associated with serum antimitochondrial antibody (AMA)

In an attempt to define the clinical spectrum of hepatobiliary disease associated with antimitochondrial antibody (AMA), 41 female and four male patients with AMA were investigated. On the basis of clinical criteria, 22 patients had primary biliary cirrhosis (group I), seven had extrahepatic biliary obstruction (group II) and 16 had other liver diseases including chronic active hepatitis, cryptogenic cirrhosis and minor abnormalities of liver function (group III). Elevations of serum cholesterol, alkaline phosphatase and bile acid levels separated the patients with primary biliary cirrhosis from those with miscellaneous liver disease, whereas in those with extrahepatic biliary obstruction results were intermediate. The cholestatic syndrome of primary biliary cirrhosis was further defined by a cholic to chenodoxycholic acid ratio > 1.0 which was found in 75 per cent of the patients with primary biliary cirrhosis but in none of those with miscellaneous liver disease. No significant differences in AMA titers or immunoglobulin M (IgM) levels were found between the groups, indicating that these tests are not correlated with cholestatic liver disease. Examination of liver tissue revealed features which were compatible with the clinical impression in the majority of cases. Cholelithiasis was present in 33 per cent of the patients. Common bile duct obstruction due to stones and/or stricture was found in six cases and carcinoma in one. Since four had fully developed cirrhosis at the time of presentation, extrahepatic biliary obstruction was probably a result of gallstone disease complicating AMA positive parenchymal liver disease. AMA seems to be a marker for idiopathic parenchymal liver disease, primarily in middle-aged women, but in itself gives no. further diagnostic information and does not exclude extrahepatic biliary obstruction.

Benign familial recurrent intrahepatic cholestasis.

Three new cases of benign familial recurrent intrahepatic cholestasis in a brother, sister, and mother are reported. These cases emphasize the familial nature of the disorder and the characteristic clinical findings of recurrent attacks, cholestatic jaundice, pruritus with increases in the serum bilirubin, and increased alkaline phosphatase. A normal extrahepatic biliary tree was shown by dye studies, and liver biopsy showed central lobular cholestasis without any inflammation or necrosis. Liver function tests were normal between attacks. This condition must be differentiated from extrahepatic obstruction, parenchymal liver disease, drug-induced cholestatic disease, and other familial types of jaundice.

Lecithin-cholesterol acyltransferase and serum cholesterol esterification in obstructive jaundice.

Abstract Lecithin-cholesterol acyltransferase (LCAT), an enzyme produced by the liver, catalyzes the intravascular formation of cholesterol esters from free cholesterol. Impaired LCAT activity may be largely responsible for the low ratio of esterified-to-free serum cholesterol found in patients with parenchymal liver disease, but whether this is also the case in obstructive jaundice remains uncertain. To clarify this point we studied 8 patients with biliary obstruction and 8 normal subjects. Cholesterol esterifying activity of serum was determined in vitro both by a radioisotopic LCAT assay and by a colorimetric method. Despite having an abnormally low ratio of of esterified-to-free serum cholesterol, the patients had a higher mean serum LCAT activity than the normal subjects, 44.5 ± 15.7 S.D. as opposed to 31.0 ± 6.5 S.D. micrograms cholesterol esterified per milliliter per hour, respectively (p

Antibody neutralization in hypoprothrombinaemic plasma.

The technique of antibody neutralization has been used to study the plasma of a large group of patients with hypoprothrombinaemia of diverse causes. The associated disorders included obstructive jaundice, acute infective hepatitis and chronic parenchymal liver disease. A number of patients were receiving warfarin and salicylate therapy. Irrespective of the aetiology of the prolonged prothrombin time, patients were demonstrated with an excess of clotting protein over clotting activity for factors II, VII, IX and X. In general, this discrepancy paralleled the prolongation of the prothrombin time.

Local 'Schwartzman equivalent' reaction in active chronic hepatitis.

The development of a purpura-fulminans-like disorder which is a human equivalent of a local Shwartzman reaction in a woman with active chronic hepatitis is described. The cyclical appearance of blue-black, well circumscribed, haemorrhagic, acutely painful lesions in the buttocks, over the lateral aspects of the thighs, and on the arms suggested the diagnosis. Evidence of increased intravascular coagulation was obtained although interpretation of clotting factor deficiencies in the presence of parenchymal liver disease was difficult. Treatment with heparin arrested the disorder on three separate occasions. The reasons for the development of the syndrome are not clear and even more surprising was the occurrence of such a disorder in the presence of increased fibrinolysis. While disseminated intravascular coagulation has been described in association with liver disease, the development of features of purpura fulminans in such patients does not appear to have been noted.

47 Calcium abosrption in parenchymatous and biliary liver disease.

As measured by whole body retention of isotopic calcium given in milk, absorption of calcium was impaired in 10 patients with chronic parenchymal non-biliary liver disease who were icteric. Mean absorption was normal in 15 patients with parenchymal liver disease who were anicteric although some individual patients absorbed less than any of the controls. Depressed absorption of calcium was seen in 10 patients with primary biliary cirrhosis and seven patients with intra- or extra-hepatic biliary obstructive disease. The most likely cause for this malabsorption is reduced bile salt secretion into the intestinal lumen which impairs vitamin D and fat absorption. The finding that parenteral vitamin D increased calcium absorption to normal levels in five patients with primary biliary cirrhosis suggests that deficiency of this vitamin is a major and correctable factor leading to calcium malabsorption in such patients. Precipitation of calcium salts by excess intraluminal fat appears to be a further possible factor reducing calcium absorption in these patients. These findings emphasize the importance of parenteral vitamin D therapy in patients with chronic obstructive biliary diseases. They also suggest that certain patients with chronic parenchymatous liver disease, particularly those who are icteric, may also occasionally require therapy with vitamin D.

Normal or "negative" percutaneous cholangiogram.

Percutaneous transhepatic cholangiography has been attempted in 104 patients with jaundice due to a variety of causes. Biliary tract visualization was accomplished in 57, the majority having extrahepatic obstruction due to malignancy or calculi. Nonvisualization (a "negative" study) or a normal cholangiogram, was commonly associated with parenchymal liver disease which was confirmed by percutaneous needle liver biopsy. With an injection technique and television roentgen monitoring, false negative studies have been eliminated in patients with dilated intrahepatic bile ducts, and even normal ducts can be visualized. Needle liver biopsy has become an alternative to unproductive biliary tract exploration.

Reciprocal relation between plasma albumin level and hepatic sulfobromophthalein removal.

Abstract In four patients with hypoalbuminemia due to the nephrotic syndrome, the removal rate of sulfobromophthalein (BSP) was rapid with less than 1 per cent dye retention at 45 minutes. After partial correction of the hypoalbuminemia by intravenous infusion of salt-poor human albumin, dye retention was 4 to 9 per cent at 45 minutes. This reciprocal relation between BSP removal rate and plasma albumin level appears to reflect the degree of dye binding in the plasma that governs the rate of BSP extraction by the liver. The accelerated dye disappearance associated with hypoalbuminemia may have clinical implications in patients with chronic parenchymal liver disease, in whom a low plasma albumin may tend to minimize the extent of BSP retention that would prevail if the albumin level were normal.