Parenchymal Liver Disease Research Articles

Is ultrasonography useful in the assessment of diffuse parenchymal liver disease?

One hundred twenty-five patients investigated at the Royal Brisbane Hospital, who underwent both hepatic ultrasonography and liver biopsy between 1980 and 1983, were scored quantitatively for ultrasound features of loss of detail, echogenicity, and attenuation, as well as for histologic features of fat, fibrosis, and inflammation. Strong correlations were found between the score for fat content and each of the three ultrasound features, and between the score for hepatic fibrosis and loss of detail and echogenicity, but there was no strong correlation with attenuation. Hepatic inflammation did not correlate with any of the ultrasound features. The correlations for fat were strongest when the interval between ultrasonography and liver biopsy was ≤7 days. Although ultrasonography had a positive predictive value of 98% in the diagnosis of diffuse parenchymal abnormality, it did not distinguish fat from fibrosis nor reliably diagnose cirrhosis. Ultrasonography gave false-positive results in only 2 patients, but in 17 patients, false-negative ultrasound examinations were encountered. These findings indicate that ultrasound is not a useful screening investigation for parenchymal liver disease, nor is it useful in gauging hepatic pathology. However, abnormal hepatic ultrasonography in patients with suspected liver disease strongly suggests the presence of diffuse liver disease.

Diagnostic accuracy of computerized B-scan texture analysis and conventional ultrasonography in diffuse parenchymal and malignant liver disease.

The use of a diagnostic system for ultrasonic liver tissue characterization based on computerized B-mode image analysis is clinically tested and compared with the results of conventional realtime and static grey scale liver ultrasound as independently assessed by three experienced observers. The diagnostic classes, normal, diffuse parenchymal and malignant disease, are clearly differentiated by computerized image analysis which is superior to subjective evaluation of liver echograms. Computerized analysis also renders a reliable and clinically useful diagnostic subclassification of diffuse parenchymal disease into echopattern changes prevalent in chronic hepatitis, cirrhosis/fibrosis, fatty infiltration and a mixed state of cirrhosis/fibrosis with fatty infiltration which cannot be achieved by conventional liver ultrasound.

Postprandial serum cholyl-glycine/SCG/ levels in hospitalised patients without parenchymal liver disease

Postprandial serum cholyl-glycine/SCG/ levels in hospitalised patients without parenchymal liver disease

Lipid and lipoprotein response to a high carbohydrate diet in parenchymal liver disease

Lipid and lipoprotein response to a high carbohydrate diet in parenchymal liver disease

Liver Transplantation: The Cambridge— King's College Hospital Experience

Replacement therapy, either with transplants or artificial prosthetic devices, offers a gift of life to those with end-stage debilitating diseases. For the many with primary liver cancer, congenital metabolic deficiency, or acquired parenchymatous liver disease, a liver transplant is the only hope. With the advent of cyclosporine immunosuppression, Roy Y. Calne reports that there is now obviously a worldwide need for liver grafting, which has been developed and performed in only four centers until recently. For those interested in the development of new programs, Professor Calne has edited, in classic British style, Liver Transplantation , the first and currently only such extensive work to my knowledge devoted to liver grafting. The material presented is a compilation of the broad experiences and research from four pioneering centers—Addenbrooke's Hospital, Cambridge, England, with the Liver Unit, Kings College Hospital, London; Groningen in Sweden; Hannover in West Germany; and our own unit under Tom Starzl,

Antithrombin III, plasminogen and alpha 2 antiplasmin in jaundice. Clinical usefulness and prognostic significance.

In this prospective study, antithrombin III, plasminogen and alpha 2 antiplasmin which are synthetised by the liver were measured and compared with the Normotest, Thrombotest and fibrinogen concentrations in 92 consecutive jaundiced patients. Antithrombin III appeared to be the most discriminant coagulation test in differentiating hepatocellular from cholestatic jaundice. A high correlation was observed between antithrombin III, plasminogen and alpha 2 antiplasmin values suggesting that the liver synthesis of these parameters was closely linked. The prognostic significance of the blood coagulation tests in patients with jaundice has been studied. In parenchymatous liver disease, antithrombin III, plasminogen and alpha 2 antiplasmin were superior to the Normotest, Thrombotest and fibrinogen concentrations in predicting the prognosis of the patients at the time of admission. In cholestatic jaundice, however, none of the blood coagulation tests studied had a prognostic significance.

UDP-glucuronyltransferase-catalyzed deconjugation of bilirubin monoglucuronide.

Bilirubin monoglucuronide is rapidly deconjugated when incubated with UDP and rat liver microsomal preparations at pH 5.1. The following evidence was found that this reaction is catalyzed by UDP-glucuronyltransferase: (i) unconjugated bilirubin and UDP-glucuronic acid were identified as the reaction products; (ii) Gunn rat microsomal preparations lack bilirubin UDP-glucuronyltransferase deficiency and do not catalyze the deconjugation reaction, and (iii) neither saccharo-1,4-lactone, a beta-glucuronidase inhibitor, nor butylated hydroxytoluene, an inhibitor of spontaneous isomerisation, affect the rate of the deconjugation reaction. Deconjugation appears to be the reverse of UDP-glucuronyltransferase-catalyzed glucuronidation. The conditions for the reverse reaction differ in the following aspects from those of the forward reaction: (i) nucleotide triphosphates stimulate the reverse reaction probably allosterically; (ii) UDP-N-acetylglucosamine stimulates the forward reaction but has no effect on the reverse reaction; (iii) the optimal pH for the reverse reaction is pH 5.1 and for the forward reaction is pH 7.8, and (iv) Mg++ ion is not required for the reverse reaction but stimulates the forward reaction. Detergents stimulate both reactions. Stimulation of the reverse reaction by nucleotide triphosphates and detergents is mutually independent and additive which suggests different mechanisms of action. Deconjugation reactions may become important during parenchymatous liver disease when, as a result of anaerobic glycolysis, intracellular pH decreases. Elevated levels of unconjugated bilirubin in the serum of patients with parenchymatous liver disease may be a sign of sick liver cells rather than decreased UDP-glucuronyltransferase activity.

PROCEEDINGS OF THE AUSTRALASIAN SOCIETY OF CLINICAL AND EXPERIMENTAL PHARMACOLOGISTS

PROCEEDINGS OF THE AUSTRALASIAN SOCIETY OF CLINICAL AND EXPERIMENTAL PHARMACOLOGISTS

Sonographic features of hepatocellular disease in neonates and infants.

The sonograms of 12 neonates and infants with documented nonneoplastic parenchymal liver diseases, including cytomegalovirus infection, biliary atresia, alpha 1-antitrypsin deficiency, nesidioblastosis, Alagille association, microabscesses, and idiopathic neonatal jaundice, were analyzed by various sonographic criteria. Nine (75%) of the hepatic sonograms were abnormal; however, most showed only one sonographic abnormality. Although it was not possible to distinguish one condition from another sonographically, focal areas of heterogeneity simulating mass lesions and accentuated periportal brightness were the most notable abnormal features. The prime indication for hepatic sonography in this age group continues to be the differentiation of obstructive from nonobstructive jaundice. Nonetheless, when obstruction has been excluded, sonography may demonstrate the presence of hepatic parenchymal disease and provide a noninvasive means for following its course over time.

The Detection and Differentiation of Parenchymal Liver Disease by Ultrasound

The Detection and Differentiation of Parenchymal Liver Disease by Ultrasound

Ranking of liver tests for differential diagnosis of liver parenchymal diseases.

Liver function tests were ranked in the order useful to differentiate 8 liver parenchymal diseases in combination of tests by forward selection and backward elimination procedures in the likelihood method using a microcomputer. The orders were almost same in both procedures: indocyanine green plasma disappearance rate, glutamic pyruvic transaminase (GPT), zinc turbidity test, alkaline phosphatase, age, HBsAg, RA test, glutamic oxaloacetic transaminase (GOT)/GPT ratio, GOT, cholesterol, total protein, total bilirubin, albumin/globulin ratio and gamma-globulin. The first 9 tests had almost all informations of all tests. The first likelihood diagnosis using the 9 tests was correct in 53% and the first or the second diagnosis was correct in 71% of 444 cases of 8 liver parenchymal diseases. A score table of likelihood diagnosis using the 9 tests was presented for manual application to new cases.

Changes in high density lipoproteins in patients with hepatobiliary diseases

Lipids of HDL (high density lipoproteins) and their subfractions (HDL2 and HDL3), and LCAT activity (lecithin: cholesterol acyltransferase) were determined in hepatobiliary diseases without severe hyperbilirubinemia (less than 10 mg/dl). The decrease in major lipid constituents (cholesterol and phospholipids) of HDL was mainly attributable to the decrease in those of HDL3, except in some liver diseases of acute or severe stage (acute hepatitis in an acute stage and hepatoma) which were accompanied with a simultaneous moderate decrease in those of HDL2 and in fatty liver which showed a preferential decrease in those of HDL2. The LCAT activity also decreased in several diseases. Some of the hepatobiliary diseases, on the contrary, showed an increase in HDL-triglycerides (mostly in HDL3 and in some diseases also in HDL2) which might participate to some extent in secondary hyperlipidemia in the liver parenchymal diseases, although they were the minor lipid constituents of HDL. From results that HDL3- but not HDL2-cholesterol levels significantly correlated with serum total protein, albumin and choline esterase, it was suggested that the decrease in large constituents of HDL, particularly of HDL3, is caused by hepatocellular dysfunction which causes inhibition of protein and lipid syntheses in the liver in most of the hepatobiliary diseases except for fatty liver which has a preferential decrease in HDL2 lipids.

Ultrasonic and scintigraphic imaging for malignant liver tumours in heavy drinkers

One hundred and ninetynine patients (111 with and 88 without malignant tumours) living in north east Italy, a region with a high alcohol consumption (21 litres of pure alcohol per capita), had scintigraphic and echographic liver examinations. Focal coloid defect(s) were seen in 57.6% of those with neoplasm and 47.7% of those with parenchymal non-malignant liver diseases either alone or with other changes on radioisotopic scan. Echogenic lesions on ultrasonography were confirmed in 46.2% of the livers with focal defect(s). In 80 livers histologically examined, radio-colloid imaging showed relatively good sensitivity (77%) but a bad specificity (33%) in the overall population studied and also (74% and 35% respectively) in the cancer patient group. On the contrary, echography demonstrated an excellent specificity in detecting malignancy (98%–100%) and echogenic lesions were predominantly seen in patients with neoplasm. Ultrasonography produced, however, an elevated number of false negatives primarily in cancer patients (38%). A suitable diagnostic accuracy for malignant liver tumours was achieved when scintigraphic and echographic data were simultaneously interpreted.

Differential diagnosis of liver parenchymal diseases by likelihood method using 12 laboratory data and age.

Liver parenchymal diseases were statistically diagnosed by likelihood method using 12 routine liver function tests and age. 444 cases of liver diseases were classified into 8 groups by histological diagnosis. A score diagnosis table was made from the data of these cases. For the likelihood diagnosis, data of each case were adapted to the score table and the probable diagnosis was calculated. Correct diagnosis rate of the first probable diagnosis was 50% in all cases and that of the first and the second was 71%. Descending order of the correct diagnosis rate of the first diagnosis was fatty liver (76%), liver cirrhosis (67%), slight histological changes (61%), acute hepatitis (51%), alcoholic liver injury (48%), chronic aggressive hepatitis 2A (43%), chronic persistent hepatitis (40%) and chronic aggressive hepatitis 2B (26%). In conclusion, differential diagnosis of liver parenchymal diseases was made easily with the score table of 13 informations with a considerable success.

Lipoprotein Abnormalities Associated With a Viral Syndrome

HERITABLE disorders causing profound high-density lipoprotein (HDL) deficiency include Tangier disease¹and familial lecithin-cholesterol acyltransferase (LCAT) dificiency.²Acquired HDL deficiency of comparable severity is usually associated with obstructive or parenchymal liver disease.³We describe a patient with fever, transient leukopenia, and evidence of mild hepatic dysfunction who nevertheless exhibited a striking reduction of serum HDL. An LCAT deficiency in association with a viral syndrome appeared to be the most likely origin. <h3>Report of a Case</h3> A 25-year-old woman was in good health until one week before presentation, when she experienced a flulike illness. Three days before admission she noted a severe sore throat and gingival ulcers, fever, weakness, and cervical lymphadenopathy. No other significant history was available except for possible exposure to acrylic paints and amphetaminelike compounds. Physical examination demonstrated aphthous ulcers on her gingivae, pharyngitis with a right tonsillary exudate, and bilateral large, tender, anterior cervical

Amino acid imbalance and hepatic encephalopathy.

Hepatic encephalopathy is one of the most frequent terminal episodes of primary liver disease. It was already known at the time of Hippocrates, and it was well described by Johanne Baptista Margagni, teacher at the Padua Medical School, in the 18th century. Hepatic encephalopathy is a neuropsychiatric syndrome seen in the pres­ ence of hepatic functional impairment secondary to acute liver failure or chronic parenchymal liver disease with or without spontaneous or surgi­ cally induced portalsystemic shunting of portal blood. The neuropsychiatric symptoms of liver failure are varied and range from subtle alterations, including mild personality change and disturbance in sleep rhythm, to confusion, drowsiness, stupor, and finally deep coma. In acute liver failure the progression of events may be extremely rapid, taking place in only a few hours. In chronic encephalopathy, in contrast, consciousness may be slowly altered over months, and may occasionally present as progressive and irre­ versible neurological symptomatology with dementia, parkinsonism, or other extrapyramidal signs suggesting involvement of the cerebellum or basal ganglia (170). Most often in the chronic situation, however, episodes of mental impairment are episodic, the result of defined stresses, and recov­ ery to the premorbid state is the rule. Other symptoms of hepatic encephalopathy are not specific for liver disease. Asterixis (flapping tremor of the extremities) is probably the most characteristic neurological sign of hepatic encephalopathy, is more common

High serum levels of secretory IgA in liver disease: possible liver origin of the circulating secretory component.

Patients with liver disease frequently display unexplained elevations of serum secretory IgA (sIgA). The sIgA levels in various liver diseases were compared to various biochemical or clinical parameters. Patients with primary biliary cirrhosis, biliary tract obstruction, or acute hepatitis displayed highest sIgA levels. In chronic parenchymal liver disease sIgA levels correlated strongly with serum alkaline phosphatase (r = 0.79), leucine aminopeptidase (r = 0.83), and direct bilirubin levels (r = 0.63), but not with prothrombin time, aminopyrine breath test, or presence of portacaval shunting. In acute hepatitis sIgA correlated best with serum glutamic oxaloacetic transaminase (r = 0.69) but not with bilirubin; in four patients with fulminant hepatitis, sIgA fell rapidly together with all liver enzymes and prothrombin time; it rose quickly again in one patient when parenchymal regeneration occurred. These results suggest a hepatobiliary origin of the serum sIgA in liver disease. In acute hepatitis the persistence of hepatocytes seems necessary for maintaining high serum sIgA levels, suggesting a possible hepatocyte origin of the secretory component.

Radiological patterns of cortical bone modelling in women with chronic liver disease

The pattern of cortical bone modelling in healthy and diseased populations can be derived from simple measurements taken from radiographs of tubular bones. To determine the pattern of bone modelling in women with chronic cholestatic and parenchymal liver diseases, these parameters have been measured in 83 women with primary biliary cirrhosis (PBC), 34 with steroid-treated chronic active hepatitis (CAH) and 27 with parenchymal liver disease (PLD) not treated with corticosteroids. Bone modelling profiles have been compared in these groups with expected pattern in healthy females. Abnormal bone modelling occurs in all three groups. In PBC, cortical thinning is progressive from the fourth decade onwards. In steroid-treated CAH, an initial increase in cortical thickness is observed in the third and fourth decades, after which cortical thinning occurs. In the PLD group, progressive loss of bone cortex is present from the fourth decade onwards. In all forms of liver disease, cortical thinning results from widening of the medullary cavity rather than resorption of the cortical surface.

Saliva and plasma clearance of antipyrine as reflectors of liver function.

Antipyrine kinetics, after oral administration to patients with changes in liver function were determined from data obtained by measuring drug concentration in saliva and plasma. Antipyrine kinetics calculated from saliva concentrations did not diverge from values obtained from plasma antipyrine measurements. The saliva and plasma clearance rates were reduced in parallel in subjects with liver parenchymal disease, and showed similar increases in subjects with normal liver treated with enzyme inducing drugs as compared to values in subjects with normal liver and no inducing treatment. The clearance values were related to changes in liver histology. The area under the concentration/time curve was increased in subjects with altered liver histology, and reduced in subjects with normal liver and therapy with enzyme inducing drugs. Antipyrine saliva clearance seems to be a useful method for assessing hepatic drug metabolism and liver microsomal function in vivo in subjects with varying degrees of liver function damage.

The quest for a clearer understanding of ovarian carcinoma

Ovarian cancer is usually a virulent malignancy. Most patients present with extension beyond the ovary, often in the upper abdomen; cures are rare in such patients. Despite gains from contemporary chemotherapy regimens and whole abdominal radiation techniques, the overall impact on survival has been minimal: One out of every 100 women will die from ovarian malignancy, which is the fourth leading cause of all female cancer deaths. lmproved survival in ovarian cancer will probably result from two factors-improved therapy and earlier detection. Modeling systems should provide a stronger scientific basis for radiation and chemotherapy testing. while further research on tumor-associated antigens and the host-tumor relationship may pave the way for the serologic diagnosis of early disease. Ovarian carcinoma is not a single entity, since malignant cells arise from stromal tissue as well as the surface mesothelium. In most discussions, however, “ovarian cancer” is considered synonymous with the epithelial type of ovarian malignancy which arises from the surface mesothelial, or epithelial, cells. Although stromal tumors, functioning hormonal lesions and sex cord malignancies are fascinating and often curable, they do not represent the public health menace of epithelial ovarian malignancy. and will not be considered in the remainder of this discussion. Little is known regarding hormonal relationships of this cancer, and receptor studies are in their infancy. Nothing postulated as an etiologic agent has had meaningful scientific support to date. Epidemiologic data, however, has provided a few clues. Relative infertility4 may be more common in patients with ovarian cancer. although this has been disputed.” Early pregnancy may play a protective role’ as it does with breast cancer. Scandinavian. Swiss and North American women have a high incidence of ovarian carcinoma. while Latin Americans do not.” Some authors, reviewing the extremely IOU incidence of carcinoma in ovariotomies published from the 1800’s. have concluded that ovarian carcinoma may primarily be a disease of the 20th century.lx The macroscopic and microscopic growth patterns of this cancer are unique. Clinical observations suggest that advanced ovarian disease frequently occurs in conjunction with small, often non-palpable ovaries.’ (Kolstad, P., oral communication, April, 1980). It has a characteristic surface-spreading pattern of growth: the cancer cells will rarely, if ever, invade viscous structures. Death is caused by inanition secondary to small bowel obstruction, or respiratory compromise from pleural and abdominal effusions. Hematogenous metastases to the brain, lung parenchyma, skin or bone is very rare, and parenchymal liver disease is uncommon. Such a pattern of growth has led some authors to postulate that epithelial ovarian cancer shares many growth characteristics with mesotheliomas.” As such, abdominal and pleural disease in this malignancy may not represent geographic “spread” as we normally think of it, but rather a cancerous change developing on mesothelial surfaces. most likely derived from multiple foci of premalignant atypia. Histologically, these malignancies are fascinating in their recapitulation of other gynecobogic and pelvic tissues. Serous tumors, often with visible cilia, resemble fallopian tube mucosa, while mutinous tumors are similar to endocervical or colonic tissue, and have high levels of carcino-embryonic antigen.15 Endometrioid tumors, as the name suggests, are often identical to endometrial carcinoma, and in fact, frequently co-exist with them. Mesonephroid tumors have a clear cell architecture similar to genito-urinary malignancies and those adenocarcinomas seen in fetuses exposed to diethylstilbestroL6 A reasonably large percentage of the remaining cancers are either undifferentiated or possess an admixture of these