Parenchymal Liver Disease Research Articles

Prior esophageal variceal bleeding does not adversely affect survival after orthotopic liver transplantation

Prior variceal bleeding may adversely affect the prognosis of orthotopic liver transplantation. We studied this question by evaluating all 175 adult patients undergoing orthotopic liver transplantation at our institution to determine risk factors associated with mortality after transplantation. Seventy patients demonstrated prior variceal bleeding, and of those, 32 had a course of sclerotherapy. Thirteen also had portal systemic shunts. Compared with the 105 transplant patients who had no prior bleeding, patients who bled were more likely to have parenchymal liver disease (74% vs. 50%), equally likely to have cholestatic liver disease (19%), and less likely to have malignancy (6% vs. 19%) or fulminant liver failure (1% vs. 12%). Bleeding patients also were more likely to be Child-Pugh class C (46% vs. 35%). By the common closing date of December 31, 1990, 26 patients (37%) with prior bleeding and 48 patients (46%) without bleeding died after transplantation. From survival curves, patients with prior bleeding had improved survival rates at 1 yr (65% vs. 54%), at 3 yr (60% vs. 47%) and at 5 yr (55% vs. 43%), although the differences were not statistically significant. With a proportional hazards model to adjust for confounding effects, the relative risk of mortality among patients with prior bleeding was 0.60 (95% confidence interval, 0.27 to 1.30). Sclerotherapy or portal systemic shunts did not alter survival. Important adverse risk factors for mortality included older age at transplantation, black race, malignant disease and more advanced Child-Pugh class. This study suggests that prior esophageal variceal bleeding did not adversely affect the mortality of patients undergoing orthotopic liver transplantation.

Effect of Portosystemic Shunting on PGI2 and Glucagon Levels in Humans

This study determined if the proposed mediators of splanchnic blood flow, prostacyclin and glucagon, were elevated in patients with portal hypertension undergoing portal systemic shunts. Chronic portal hypertension results in increased portal venous pressure and increased splanchnic blood flow. Animal studies have suggested prostacyclin or glucagon, potent vasodilators, as potential mediators of this increased flow. Correlative clinical studies have been difficult to perform due to the wide variation in degree of portal-systemic shunting and the frequent association of parenchymal liver disease in patients with cirrhosis. The authors measured portal and systemic hemodynamics in PGI2 and glucagon levels in patients with portal hypertension due to cirrhosis (partial portal systemic shunt) and Budd-Chiari syndrome (complete portal systemic shunt) undergoing portal systemic shunts and in porto normotensive patients undergoing exploratory laparotomies. PGI2 levels in portal hypertension were significantly increased over normal, and prostacyclin in Budd-Chiari patients were increased significantly over patients with cirrhosis. Both PGI2 and portal venous pressure decreased significantly after portal systemic shunting, and prostacyclin levels correlated directly with portal venous pressure (R = 0.37, p < 0.05). This is the first evidence in humans supporting the hypothesis that PGI2 is elevated in portal hypertension and is related to both the degree of portal venous obstruction and portal pressure. PGI2 probably has a role in the abnormal splanchnic hemodynamics of human portal hypertension.

Measurement of visceral blood flow with magnetic resonance imaging.

With the increasing application of magnetic resonance imaging (MRI) and MR angiography in parenchymal liver disease, methods are becoming more widely available for noninvasive measurement of visceral blood flow. Amplitude-based (time-of-flight) and phase-based techniques have proved effective for measurement of portal blood flow, and phase-sensitive methods are applicable to arterial flow measurements. Because respiratory motion degrades the quality of examinations in the abdomen, it is desirable to use methods that can generate flow information in a breath-hold period. Although substantial technical difficulties persist for quantitative arterial flow measurements in the abdomen, the technical requirements for venous flow are less stringent, and important clinical information can be derived using straightforward techniques. The authors describe the principles of flow measurement using time-of-flight and phase methods in visceral arteries and veins, and discuss their practical implementation. Clinical applications are discussed, based on the experience of the authors and others working in the field.

Pharmacokinetics of cefotaxime and desacetylcefotaxime in patients with liver disease

The dispositions of cefotaxime and its metabolite desacetylcefotaxime were investigated in patients with different forms of chronic parenchymal liver disease (CPLD). A total of 31 subjects (27 patients and 4 controls) received a single 2-g dose of cefotaxime by infusion, and serial blood samples were drawn. The area under the concentration-time curve ranged from 176 to 241 micrograms.h/ml, the apparent half-life ranged from 1.49 to 2.42 h, and clearance ranged from 2.06 to 3.10 ml/min/kg in patients with four different forms of CPLD. The area under the concentration-time curve and the apparent half-life of desacetylcefotaxime ranged from 72 to 128 micrograms.h/ml and 7.1 to 13.4 h, respectively. Pharmacokinetic parameters were significantly different in patients with CPLD compared with those in control subjects and were related to clinical indices of hepatic impairment. Modest accumulation of cefotaxime in patients with severe hepatic impairment is unlikely to produce toxicity because of its high therapeutic index, and dosing modifications may not be required.

Vitamin K Therapy in Severe Liver Disease

A middle-aged man with parenchymatous liver disease and a decrease in vitamin K-dependent factors was given large doses of intravenous phylloquinone (10 mg/d for 20 days) without improvement in the synthesis of vitamin K-dependent factors. During subsequent liver transplantation, he exsanguinated. Although the exact role of over treatment with phylloquinone in this case is unclear, plasma levels of phylloquinone 300 times normal were attained after 5 days of treatment without effect on factors II, VII, IX, and X. Further therapy with vitamin K was unnecessary.

Computerized ultrasound B-scan texture analysis of experimental diffuse parenchymal liver disease: correlation with histopathology and tissue composition.

By means of statistical pattern recognition procedures, a quantitative description of the ultrasound B-scan images of experimental diffuse liver disease has been carried out. Fatty livers, fatty fibrosis/cirrhosis, and cirrhosis without fatty infiltration of the liver were studied in female Wistar rats. Separation accuracies of more than 80% between the tissue classes "normal" vs "fatty infiltration," or "normal" vs "fatty cirrhosis," using only two statistical image parameters were found. A subclassification of the diffuse parenchymal liver disease was not possible. It is shown by multiple linear regression analysis that the image parameter "mean grey level" correlates better with total lipid content than with the amount of connective tissue. Furthermore it is demonstrated that connective tissue leads only to a weak increase in "mean grey level," whereas the addition of connective tissue to a given tissue lipid can lead to a reduction in image brightness.

Incidence of parenchymal liver diseases in Denmark, 1981 to 1985: Analysis of hospitalization registry data

The sex-specific and age-specific incidence rates of the major parenchymal liver diseases in a North European population were estimated using a computerized registry of all admissions to somatic hospitals in Denmark. The incidence was calculated by counting all incident cases of these diseases reported to the registry in the 5-yr period 1981 to 1985 and dividing the number of cases by the number of person-years at risk in this period. The incidence rates (per million person-years) were for men and women, respectively: infectious hepatitis, 109 and 71; toxic hepatitis, 19 and 22; chronic hepatitis, 27 and 29; alcoholic cirrhosis, 190 and 85; nonalcoholic nonbiliary cirrhosis, 110 and 82; primary biliary cirrhosis, 4 and 14. The pattern of the age-specific incidence rates was similar in men and women in infectious hepatitis, alcoholic cirrhosis, nonalcoholic nonbiliary cirrhosis and primary biliary cirrhosis. Toxic and chronic hepatitis had a higher incidence in women than in men only in older age groups. The incidence of idiopathic hemochromatosis, Wilson's disease, secondary biliary cirrhosis, portal vein thrombosis and Budd-Chiari's syndrome were less than four in both sexes. (HEPATOLOGY 1991;13:650–655.)

Incidence of parenchymal liver diseases in Denmark, 1981 to 1985: Analysis of hospitalization registry data

The sex-specific and age-specific incidence rates of the major parenchymal liver diseases in a North European population were estimated using a computerized registry of all admissions to somatic hospitals in Denmark. The incidence was calculated by counting all incident cases of these diseases reported to the registry in the 5-yr period 1981 to 1985 and dividing the number of cases by the number of person-years at risk in this period. The incidence rates (per million person-years) were for men and women, respectively: infectious hepatitis, 109 and 71; toxic hepatitis, 19 and 22; chronic hepatitis, 27 and 29; alcoholic cirrhosis, 190 and 85; nonalcoholic nonbiliary cirrhosis, 110 and 82; primary biliary cirrhosis, 4 and 14. The pattern of the age-specific incidence rates was similar in men and women in infectious hepatitis, alcoholic cirrhosis, nonalcoholic nonbiliary cirrhosis and primary biliary cirrhosis. Toxic and chronic hepatitis had a higher incidence in women than in men only in older age groups. The incidence of idiopathic hemochromatosis, Wilson's disease, secondary biliary cirrhosis, portal vein thrombosis and Budd-Chiari's syndrome were less than four in both sexes.

Duplex Doppler ultrasound of the ligamentum teres and portal vein: A clinically useful adjunct in the evaluation of patients with known or suspected chronic liver disease or portal hypertension

The prevalence and potential value of the detection of signs of portal hypertension by duplex Doppler ultrasound (DDU) of the ligamentum teres and portal vein in patients with known or suspected chronic liver disease and/or portal hypertension was studied in 136 consecutive patients undergoing clinical assessment including that of liver histopathology. Portal hypertension was considered to be present when any of the following DDU signs, previously demonstrated to be specific for portal hypertension, were present: an enlarged and/or patent para-umbilical vein, portal vein obstruction or hepatofugal flow in the portal vein. Of 123 patients with parenchymal liver disease, eighty-three had cirrhosis and, of these, portal hypertension was detected on DDU criteria in 86% of alcoholic cirrhotics and 67% of non-alcoholic cirrhotics. Of the 42 patients with non-cirrhotic liver disease, 1 of 7 patients with metastatic liver disease and 3 of 5 patients with alcoholic hepatitis had DDU signs of portal hypertension. Thus, in patients with parenchymal liver disease, DDU had a sensitivity of 73%, specificity of 90% and predictive values of 94 and 62% for positive and negative studies respectively for the detection of cirrhosis. In all 14 patients with portal hypertension secondary to vascular occlusive diseases, DDU examination of the ligamentum teres, portal vein and hepatic vein gave an accurate guide to the site of the occluding lesion. The high positive predictive value of DDU and its ability to aid in localizing the site of increased resistance to flow through the liver suggest that DDU of the ligamentum teres and portal vein is a potentially useful non-invasive adjunct in the assessment of patients with suspected or known liver disease or portal hypertension.

Assessment of Portal Hypertension: Understanding Will Improve Treatment

To many people it may be disappointing that many uncertainties remain with respect to the assessment of PHT. Only a few findings such as increased WHVPG and varices prove PHT. However, we have gained considerable knowledge. PHT is the consequence of a number of changes which involve the intrahepatic and extrahepatic circulation. Alcohol, viruses and drugs may disturb parenchymal architecture and cause cellular swelling, collagen and fibrin deposition and invasion with inflammatory cells. These processes finally may evolve into cirrhosis. Although in initial stages the parenchymal disturbance per se may account for PHT, increasingly impaired liver function results in metabolic changes which cause altered haemodynamics. Advanced PHT in parenchymal liver disease is the result of the complex interaction between local and systemic changes. The current techniques for the assessment of PHT are helpful for the qualitative aspects: increase in pressure can be assessed directly or indirectly; the portal venous system can be visualized even without arteriography. Gastroscopy remains a standard procedure for diagnosing PHT. Ultrasound-endoscopy is particularly helpful to confirm fundic varices and to assess changes after sclerotherapy. Increasingly, non-invasive methods to quantify PHT have become available such as the Duplex scanner. However, limitations and pitfalls need to be realized. The quantitative assessment remains (as yet?) a technique for research centres. It is obvious that the clinician in general practice can do without most of the more sophisticated techniques which have been discussed here. For the time being, PHT, and particularly variceal bleeding, is most often treated with endoscopic sclerotherapy. For that reason, only in a minority of the cases very detailed studies are required. However, the increasing knowledge opens new perspectives for the treatment and prevention of PHT on various levels. This may be a rather specific treatment of parenchymal liver disease (antivirals, d-penicillamine for Wilson's disease or venesections for haemochromatosis), drugs which may reduce local tissue damage via more general pathways (colchicine, steroids) and drugs which influence flow. Undoubtedly one of these years a more selective blocker of portal venous pressure will become available. Optimal assessment for that type of therapy makes it mandatory to master at least a few more advanced techniques. With respect to noncirrhotic PHT with causes which may vary from congenital or acquired clotting abnormalities to anatomical malformations (oesophageal web) and 'natural healthy herb tea', measures can be taken. It is clear that before treating any of the more rare causes, a proper diagnostic work-up is required.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease

To establish the accuracy of ultrasonography in assessing diffuse parenchymal liver disease we performed a prospective comparative study with histology in 50 patients with a wide range of liver disease. Liver biopsy was performed within 24 h of the ultrasound examination and ultrasonography was performed by a single operator who was unaware of clinical details of the patients. Histology was reviewed blind and the degree of steatosis graded mild, moderate or severe while increased portal fibrous tissue was graded mild, moderate or established cirrhosis. Thirty-six patients had steatosis and 31 patients had increased fibrous tissue on histology. Ultrasonography correctly identified steatosis in 32/36 (89%) patients including all patients with the severe grade. Increased fibrous tissue was correctly identified in 24/31 (77%) with a sensitivity of 100% in patients with moderate fibrosis and established cirrhosis. Specificity was 93% for steatosis and 89% for increased fibrous tissue. These results show that ultrasonography can provide a non-invasive prediction of liver histology which in moderate and severe steatosis and advanced fibrosis can be both highly sensitive and specific.

A high frequency of hepatobiliary disease and suspected cholangiocarcinoma associated with heavy Opisthorchis viverrini infection in a small community in north-east Thailand

A group of 87 adults from a small village in north-east Thailand was chosen to undergo ultra-sound investigation based on their intensity of infection with the liver fluke, Opisthorchis viverrini, or clinical status (history of jaundice, current hepatomegaly). From this group, 8 cases of suspected early cholangiocarcinoma were found, and the diagnostic features of 6 of the 8 were confirmed by computerized tomography scan and endoscopic retrograde cholangiopancreatography. In addition, several cases of mild gall-bladder disease, chronic cholecystitis, cholelithiasis and parenchymal liver disease were detected. A highly significant positive relationship between the intensity of liver fluke worm burden and the severity of biliary tract disease within individuals is reported. These results indicate that Opisthorchis is associated with moderate to severe hepatobiliary disease in a considerable proportion of infected individuals.

Colonic disease in cirrhosis: An endoscopic evaluation in 412 patients

Colonic disease is relatively uncommon in cirrhosis. To determine the prevalence of colonic lesions in cirrhosis of all types, cirrhotics evaluated for possible liver transplantation underwent combined pan upper endoscopy and colonoscopy. The patients were divided into two main groups, 248 with parenchymal liver disease (nonviral and viral) and 164 with cholestatic liver disease. The prevalence of the various colonic lesions identified was: polyps, 8.4%; nonspecific edema, 19.9%; inflammatory changes, 11.6%; hemorrhoids, 25.2%; and rectal varices, 3.6%. Normal findings were present in 42.4%. Except for an increased prevalence (P < 0.05) of edema and a reduced prevalence (P < 0.001) of inflammatory changes in the parenchymal liver disease group, the prevalence for all other lesions was similar in the two groups. Esophageal varices were present in most patients with hemorrhoids and in all with rectal varices. The degree of portal hypertension and/or disease severity was associated with hemorrhoids but not with rectal varices. The higher prevalence of inflammatory changes in the cholestatic group was because one fourth of this group had an inflammatory bowel disease.

Echographic tissue characterization in diffuse parenchymal liver disease: Correlation of image structure with histology

Seventy livers were examined in vitro using a computerized ultrasound B-mode data acquisition and analysis system. For tissue characterization, statistical parameters from pattern recognition algorithms describing image brightness and image structure were used. Reference classification based on histopathology as well as on chemical/morphometrical analysis led to the diagnostic classes of normal, fatty liver, fibrosis/cirrhosis and fatty fibrosis/cirrhosis. Comparing the two reference methods for ultrasound tissue characterization, reclassification based on chemical/morphometrical analysis resulted in a significant increase in diagnostic accuracy. The strong correlations between statistical ultrasound image parameters and morphometrical features reflect the relevance of our statistical approach to ultrasound tissue characterization.

Echographic Tissue Characterization in Diffuse Parenchymal Liver Disease: Correlation of Image Structure with Histology

Seventy livers were examined in vitro using a computerized ultrasound B-mode data acquisition and analysis system. For tissue characterization, statistical parameters from pattern recognition algorithms describing image brightness and image structure were used. Reference classification based on histopathology as well as on chemical/morphometrical analysis led to the diagnostic classes of normal, fatty liver, fibrosis/cirrhosis and fatty fibrosis/cirrhosis. Comparing the two reference methods for ultrasound tissue characterization, reclassification based on chemical/morphometrical analysis resulted in a significant increase in diagnostic accuracy. The strong correlations between statistical ultrasound image parameters and morphometrical features reflect the relevance of our statistical approach to ultrasound tissue characterization.

Prevalence of endoscopic findings in 510 consecutive individuals with cirrhosis evaluated prospectively

Upper gastrointestinal hemorrhage is one of the more important complications of cirrhosis and a major cause of death in such patients. The main sites of bleeding are esophageal varices, gastritis, and peptic ulcers. In order to determine the prevalence of either potential bleeding lesions or of other endoscopic findings in hemodynamically stable individuals with various etiologies of cirrhosis, 510 consecutive cirrhotic patients, evaluated for possible orthotopic liver transplantation (OLTx) underwent an upper gastrointestinal endoscopy for combined diagnostic and therapeutic purposes. The patients were divided into two main groups: 319 patients with parenchymal liver disease and 191 patients with cholestatic liver disease. Gastritis was found significantly more often in patients with parenchymal liver disease than in those with cholestatic liver disease (49.8% vs 30.9%; P less than 0.001). In contrast, the prevalence of esophagitis, esophageal and gastric varices, gastric ulcer, duodenal ulcer, and duodenitis was similar in both groups. Normal endoscopic findings were present in 5.0% of the parenchymal group and 11.5% of the cholestatic group (P less than 0.02). Ascites and encephalopathy were found significantly more often in subjects with parenchymal liver disease as compared to those with cholestatic liver disease. Portal hypertension and its degree, as assessed by the presence and size of esophageal varices, was similar in both groups, and in both groups there was a statistically significant qualitative trend of increasing prevalence of esophageal varices with increasing severity of disease as estimated using Pugh-Child's criteria.

Abnormal growth hormone dynamics in chronic liver disease do not depend on severe parenchymal disease

Abnormal basal serum levels of growth hormone (GH) and abnormal GH dynamics have been observed in patients with alcoholic cirrhosis (AC). To further characterize these abnormalities, patients with AC or schistosomal hepatic fibrosis (SHF) were evaluated. The former patients have parenchymal liver disease, portal hypertension, and portosystemic shunting. SHF, in contrast, is characterized by periportal fibrosis with minimal or no parenchymal cell disease, portal hypertension, and portosystemic shunting. We studied 20 patients with SHF and normal stature and 15 patients with AC. In these two groups of patients, basal serum GH was higher than normal ( P < .01). A paradoxical increase in GH was observed during the oral glucose tolerance test (OGTT) in 55% of SHF and in 40% of AC patients. Significant GH elevation followed thyrotropin-releasing hormone (TRH) administration in 80% of SHF and 66% of AC patients, but not in normals. Serum nonsuppressible insulin-like activity (NSILA) and serum somatomedin C (Sm-C) levels were reduced significantly in both groups. In SHF patients, the paradoxical increase in GH during OGTT correlated inversely with Sm-C ( r = −.6, P < .05). We conclude that (1) abnormal GH secretion occurs in both SHF and AC, (2) serum Sm-C and NSILA are diminished in both forms of liver disease, and (3) portosystemic shunting of blood appears to be the important pathology shared by both forms of liver disease.

Prevalence of duodenal ulcer in cirrhotic males referred for liver transplantation

The prevalence of symptomatic duodenal ulcer (DU) assessed primarily in alcoholic males with cirrhosis is estimated to be approximately fivefold increased compared to the normal population. Little information is available, however, as to the prevalence of DU in nonbleeding, nonalcoholic subjects with cirrhosis. In order to estimate the prevalence of DU in males with various types of cirrhosis and its relation to the degree of portal hypertension, 216 male cirrhotic patients (165 with parenchymal liver disease and 51 with cholestatic liver disease) being evaluated for liver transplantation at the University of Pittsburgh between January 1985 and June 1987 underwent pan-upper gastrointestinal endoscopy. The prevalence of DU in each group was 7.8%. However, among the various subgroups it was as follows: chronic active hepatitis due to HBV: 9.4%, alcoholic: 12.2%, cryptogenic: 3.5%, autoimmune chronic active hepatitis: 6.6%, primary sclerosing cholangitis (PSC): 9.5%. The reference data for this study consist of data reported in the literature obtained in 355 healthy asymptomatic male volunteers. The prevalence of DU in this group is significantly less than in the study group (2.2% vs 7.8%; P less than 0.005). While the estimated risk for a DU is increased 3.71-fold (95% CI: 8.74, 1.57; P less than 0.005) in cirrhotic males in general as compared to normal males, only the subgroups with CAH due to HBV, alcoholism, and PSC were found to have an increased estimated risk of DU (all at least P less than 0.01). No association between the prevalence of DU and degree of portal hypertension could be demonstrated in either group.

Ultrasound in the diagnosis of granulomatous liver disease

Ultrasound is a widely used method of assessing the liver for space occupying lesions and, more recently, parenchymal liver disease. We have reviewed the ultrasound scans and reports of 11 patients with biopsy proven granulomatous liver disease. Multiple echogenic lesions 3-5 mm in diameter, each surrounded by an hypoechoic halo, were seen in the liver of all the patients and in the spleens of three patients. A specific diagnosis of granulomatous hepatitis was suggested at the time of scanning in seven patients. An abnormal liver was noted in the other four patients but no specific diagnosis was suggested. We believe that granulomata in the liver can be detected using ultrasound and, if the above appearances are seen during an ultrasound scan, a diagnosis of granulomatous hepatitis should be considered.

ULTRASONOGRAPHY AND SCINTIGRAPHY IN LIVER DISEASE IN DEVELOPING COUNTRIES: A Retrospective Survey

In a study of the value of hepatic ultrasonography (US) and scintigraphy (SG) in detecting liver disease in developing countries 425 US scans and 304 SG scans of patients with focal or diffuse liver disease or normal livers were reviewed. The accuracy of both US and SG in distinguishing between normal and diseased livers was low (68% and 74%, respectively). Both techniques did better at detecting focal than diffuse liver disease; the sensitivity of US and SG in focal and diffuse disease was 88% and 92%, and 27% and 54%, respectively. The specificity of both procedures was high for both types of liver disease (91-96%). Overlap between US features of amoebic liver abscess, hepatocellular carcinoma, and metastatic carcinoma resulted in a correct final diagnosis being made in only 81% of patients with amoebic liver abscess, 29% with hepatocellular carcinoma, and 43% of patients with metastatic carcinoma who had a US scan. This study indicates that these techniques are neither accurate in detecting diffuse liver disease nor capable of determining the cause of diffuse liver disease. When diffuse parenchymal liver disease is suspected biopsy would be needed. Although the accuracy of both imaging modalities in detecting focal disease is high, overlap between the US features of the common causes of space-accupying lesions may result in an incorrect final diagnosis in some cases. In consequence, biopsy or aspiration might be required.