M. Coltorti

Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies

This paper reviews the complications that arose after 68 276 percutaneous liver biopsies performed from 1973 to 1983. The complications are analyzed in relation to the underlying liver disease and to the type of needle used. Death was infrequent (9/100 000); it was always due to haemoperitoneum and occurred only in patients with malignant diseases or cirrhosis. Complications were less frequent in AVH (44/100 000) than in other liver diseases (from 125 to 278/100 000). Death, serious haemorrhagic complications, pneumothorax and biliary peritonitis were more frequent after biopsy with the Trucut needle than after biopsy with Menghinis needle (3/1000 against 1/1000). Sixty-one percent of complications were discovered within two hours of biopsy and 96% within one day. The data indicate a post biopsy observation period of at least 24 hours. The day-case procedure should be reserved for patients not presenting liver tumour or cirrhosis.

Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1–2 hepatic encephalopathy

In 40 patients with cirrhosis on a dietary protein regimen of 1 g/kg b.w., we determined the effect on chronic hepatic encephalopathy of long-term administration of Enterococcus faecium (SF68) versus lactulose. The patients received one of the two treatments for three periods of 4 weeks, each separated by drug-free 2-week intervals. The efficacy of treatment was assessed by arterial blood ammonia concentration, mental status, number connection (Reitans part A) test and flash-evoked visual potentials. At the end of the third period the reduction in both blood ammonia concentrations and Reitans test times was more enhanced in patients on SF68 than in patients on lactulose. Furthermore, while patients on lactulose tended to return to basal values during drug-free intervals, responders in the SF68 group maintained improvement throughout the study. In conclusion, SF68 is at least as useful as lactulose for the chronic treatment of chronic hepatic encephalopathy; it has no adverse effects, and treatment can be interrupted for 2 weeks without losing the beneficial effects.

Hepatitis C virus infection is an additive risk factor for development of hepatocellular carcinoma in patients with cirrhosis.

The aim of the present study was to evaluate whether hepatitis C virus plays any role in the development of hepatocellular carcinoma in cirrhotic patients. The role of age, sex, alcohol abuse, and infection by other hepatitic viruses, such as hepatitis B and Delta viruses, was also assessed. We found that mean age and male/female ratio were significantly higher in patients with HCC plus liver cirrhosis than in those with liver cirrhosis alone. Also, the prevalence of HCV infection was found to be higher in HCC patients compared to cirrhotics. Further, by means of multiple logistic regression, we evaluated the independent role of each variable in the development of HCC. Age, male sex, and to a lesser degree, HCV infection, as assessed by anti-HCV positivity, were the only risk factors which significantly correlated with the development of HCC. Moreover, when age and sex were excluded from the statistical model, HCV infection, but not HBV, HDV, and alcohol abuse, appeared to be associated with HCC. In conclusion, based on these data, age and male sex are the most important factors for the development of hepatocellular carcinoma in cirrhotic patients. Hepatitis C virus, at least in the Mediterranean area, may play a role as an additive risk factor of HCC in patients suffering from liver cirrhosis.

Enterococcus Lactic Acid Bacteria Strain SF68 and Lactulose in Hepatic Encephalopathy: a Controlled Study

Forty cirrhotic patients with non-advanced hepatic encephalopathy were randomly allocated into groups which were given orally either two capsules three times daily of a preparation of Enterococcus lactic acid bacteria strain SF68 or 30 ml lactulose four times daily. The patients were evaluated over a 10-day course of treatment and for 10 days post-treatment. The Enterococcus SF68 preparation proved to be as effective as lactulose in lowering blood ammonia, and in improving mental state and psychometric performance. Moreover, the effects of Enterococcus SF68, contrary to that of lactulose, persisted longer after treatment withdrawal. Some patients reported diarrhoea and abdominal pain with lactulose. Lactulose is a standard therapy in the treatment of patients with hepatic encephalopathy. In this study, however, the use of the Enterococcus SF68 preparation was shown to offer advantages over lactulose in these patients.

Alterations of glucose metabolism in chronic liver disease

The prevalence of glucose intolerance has been studied by oral glucose tolerance test in 670 patients affected by chronic liver disease. The glycometabolic status was evaluated by criteria given by WHO in 1980. Sixty-nine subjects appeared to be affected by chronic persistent hepatitis and 140 by chronic active hepatitis. In these patients the prevalence of diabetic responses (DR) did not differ much from that of the general population in our geographic area. In contrast, a markedly higher frequency of DR appeared in a cirrhotic group of 401 patients compared to non-cirrhotic subjects. The cirrhotics, divided according to different disease stages, showed a higher DR frequency in decompensated patients than in well compensated patients, the prevalence reaching 63% in the former subgroup. The coincident presence of hepatocarcinoma - documented in 60 other cirrhotic patients - does not modify the prevalence of diabetes. Other risk factors for diabetes such as age, sex, and family history have been considered. Our results suggest that: (1) all these factors seem not to play a major role in the pathogenesis of alterations of glucose metabolism in patients suffering from chronic liver disease, and therefore (2) liver cirrhosis by itself might be a risk factor in the disturbance of glucose tolerance.

Alteration of erythrocyte glutathione, cysteine and glutathione synthetase in alcoholic and non-alcoholic cirrhosis

Glutathione (GSH) and cysteine were determined in the plasma and the erythrocytes of alcoholic and non-alcoholic cirrhotics as fluorescent monobromobimane derivatives by high-performance liquid chromatography (HPLC). Cirrhotic patients displayed a significant decrease of plasma GSH, as well as of plasma cysteine, that was related to the degree of liver disease but not to the nutritional conditions. On the contrary, erythrocyte cysteine was found to increase significantly in all cirrhotics, particularly in alcoholics, regardless of the severity of disease. In an attempt to find a possible explanation of these alterations, the GSH synthesizing enzymes, gamma-glutamylcysteine synthetase (GC-s) and GSH synthetase (GSH-s) activities were determined in the erythrocytes. GSH-s activity was significantly lower in cirrhotic patients, whereas GC-s activity did not differ in the three groups.

Hepatitis C virus RNA in serum and liver histology in asymptomatic anti-HCV positive subjects

SummaryThis study was designed to evaluate serum HCV-RNA, liver histology, and RIBA-II pattern in asymptomatic anti-HCV positive subjects with persistently normal or slightly (i.e. ≤1.5 times the upper limit of the normal range) elevated serum ALT levels. To this purpose, 22 asymptomatic anti-HCV positive subjects (11 men and 11 women, median age 40, range 21–70 years) underwent liver biopsy and determination of serum HCV-RNA. Positivity for anti-HCV was determined by ELISA-2 and by RIBA-II. Serum HCV-RNA was determined by PCR. Our data show that: 1) 9/22 symptom-free, anti-HCV positive subjects had histological features of chronic liver disease associated with ongoing HCV infection; 2) four subjects had no histological signs of chronic hepatitis and normal serum ALT levels despite positivity for serum HCV-RNA; 3) serum ALT levels did not discriminate HCV-RNA positive subjects with from those without chronic hepatitis; 4) in anti-HCV positive subjects with normal serum ALT levels, a positive RIBA-II pattern was not always predictive of HCV viraemia or chronic hepatitis while an indeterminate RIBA-II pattern was frequently associated with nonspecific liver changes or normal histology. In conclusion, based on these findings, “true” healthy carriers of HCV (i.e. subjects with normal serum ALT levels and no histological features of chronic hepatitis despite HCV viraemia) may exist.ZusammenfassungBei asymptomatischen, anti-HCV positiven Personen mit andauernd normalen oder leicht (das heißt ≤1,5 fach über der oberen Normgrenze) liegenden Serum ALT-Spiegeln wurden die HCV-RNA im Serum, Leberhistologie und das RIBA-II-Muster untersucht. Bei 22 asymptomatischen, anti-HCV positiven Personen (11 Männern und 11 Frauen im mittleren Alter von 40; Bereich 21–70 Jahren) wurde eine Leberbiopsie durchgeführt und HCV-RNA im Serum bestimmt. Der Nachweis von anti-HCV wurde mit ELISA-2 und RIBA-II-Tests geführt. Die HCV-RNA im Serum wurde mittels PCR bestimmt. Unsere Untersuchungen zeigten, 1.) daß 9/22 asymptomatischen, anti-HCV-positiven Personen histologische Zeichen einer chronischen Lebererkrankung mit fortbestehender HCV-Infektion hatten. 2.) Vier Personen hatten keine histologischen Zeichen einer chronischen Hepatitis und normale Serum-ALT-Spiegel trotz Nachweises von HCV-RNA im Serum. 3.) Die ALT-Spiegel im Serum unterschieden HCV-RNA positive Personen mit chronischer Hepatitis nicht von denjenigen ohne chronische Hepatitis. 4.) Bei anti-HCV positiven Personen mit normalen ALT-Spiegeln ist ein positiver RIBA-II Test nicht immer mit einer HCV-Virämie oder einer chronischen Hepatitis assoziiert. Bei unklarem RIBA-II-Muster bestanden häufig unspezifische Leberveränderungen oder ein normaler histologischer Befund. „Wirklich“ gesunde Träger von HCV (das heißt, Personen mit normalem Serum ALT-Spiegel, ohne histologische Zeichen einer chronischen Hepatitis trotz HCV Virämie) können folglich vorkommen.This study was designed to evaluate serum HCV-RNA, liver histology, and RIBA-II pattern in asymptomatic anti-HCV positive subjects with persistently normal or slightly (i.e. ≤1.5 times the upper limit of the normal range) elevated serum ALT levels. To this purpose, 22 asymptomatic anti-HCV positive subjects (11 men and 11 women, median age 40, range 21–70 years) underwent liver biopsy and determination of serum HCV-RNA. Positivity for anti-HCV was determined by ELISA-2 and by RIBA-II. Serum HCV-RNA was determined by PCR. Our data show that: 1) 9/22 symptom-free, anti-HCV positive subjects had histological features of chronic liver disease associated with ongoing HCV infection; 2) four subjects had no histological signs of chronic hepatitis and normal serum ALT levels despite positivity for serum HCV-RNA; 3) serum ALT levels did not discriminate HCV-RNA positive subjects with from those without chronic hepatitis; 4) in anti-HCV positive subjects with normal serum ALT levels, a positive RIBA-II pattern was not always predictive of HCV viraemia or chronic hepatitis while an indeterminate RIBA-II pattern was frequently associated with nonspecific liver changes or normal histology. In conclusion, based on these findings, “true” healthy carriers of HCV (i.e. subjects with normal serum ALT levels and no histological features of chronic hepatitis despite HCV viraemia) may exist. Bei asymptomatischen, anti-HCV positiven Personen mit andauernd normalen oder leicht (das heißt ≤1,5 fach über der oberen Normgrenze) liegenden Serum ALT-Spiegeln wurden die HCV-RNA im Serum, Leberhistologie und das RIBA-II-Muster untersucht. Bei 22 asymptomatischen, anti-HCV positiven Personen (11 Männern und 11 Frauen im mittleren Alter von 40; Bereich 21–70 Jahren) wurde eine Leberbiopsie durchgeführt und HCV-RNA im Serum bestimmt. Der Nachweis von anti-HCV wurde mit ELISA-2 und RIBA-II-Tests geführt. Die HCV-RNA im Serum wurde mittels PCR bestimmt. Unsere Untersuchungen zeigten, 1.) daß 9/22 asymptomatischen, anti-HCV-positiven Personen histologische Zeichen einer chronischen Lebererkrankung mit fortbestehender HCV-Infektion hatten. 2.) Vier Personen hatten keine histologischen Zeichen einer chronischen Hepatitis und normale Serum-ALT-Spiegel trotz Nachweises von HCV-RNA im Serum. 3.) Die ALT-Spiegel im Serum unterschieden HCV-RNA positive Personen mit chronischer Hepatitis nicht von denjenigen ohne chronische Hepatitis. 4.) Bei anti-HCV positiven Personen mit normalen ALT-Spiegeln ist ein positiver RIBA-II Test nicht immer mit einer HCV-Virämie oder einer chronischen Hepatitis assoziiert. Bei unklarem RIBA-II-Muster bestanden häufig unspezifische Leberveränderungen oder ein normaler histologischer Befund. „Wirklich“ gesunde Träger von HCV (das heißt, Personen mit normalem Serum ALT-Spiegel, ohne histologische Zeichen einer chronischen Hepatitis trotz HCV Virämie) können folglich vorkommen.

Prevalence of hepatitis C virus infection in the household contacts of patients with HCV-related chronic liver disease.

SummaryIt is still controversial whether the familial environment plays a role in the diffusion of HCV infection. The aim of this study was to evaluate the prevalence of anti-HCV positivity in the household contacts of patients with HCV-related chronic hepatitis. Nearly all the household contacts of 113 subjects with anti-HCV+ chronic hepatitis (100/113 spouses and 260/290 children) were investigated. Anti-HCV was determined by means of ELISA II and was confirmed by RIBA II. Anti-HCV positivity was found in 27% of the spouses and in 1.9% of the children. Prevalence of anti-HCV positivity in spouses correlated positively with the duration of the marital status. Seventeen/32 (53.1%) of anti-HCV-positive subjects were found to have chronic hepatitis. This study indicates that intrafamilial diffusion of HCV infection is mostly accounted for by horizontal, in particular spouse to spouse, transmission and that spouse to spouse transmission of HCV infection correlates positively with the duration of marital status.ZusammenfassungDie Bedeutung der Familie als Faktor für die Ausbreitung der HCV-Infektion wird immer noch kontrovers diskutiert. In der vorliegenden Studie wurde versucht, die Prävalenz anti-HCV-positiver Fälle unter den häuslichen Kontaktpersonen von Patienten mit HCV-assoziierter chronischer Hepatitis zu bestimmen. Nahezu alle Kontaktpersonen von 113 Personen mit anti-HCV-positiver Hepatitis (100/113 Ehegatten, 260/290 Kinder) wurden untersucht. Für die Bestimmung von anti-HCV wurde ELISA-II mit Bestätigung durch RIBA II eingesetzt. 27% der Ehegatten und 1,9% der Kinder erwiesen sich als anti-HCV-positiv. Bei den Gatten korrelierte die Prävalenz der anti-HCV-Positivität mit der Dauer der Ehe. Bei 17/32 (53,1%) der anti-HCV-positiven Personen wurde eine chronische Hepatitis aufgedeckt. Diese Studie gibt Hinweise auf eine vorwiegend horizontale Übertragung der HCV-Infektion zwischen Ehegatten und eine positive Korrelation zwischen Übertragung und Dauer der Ehe.

Gastric Endoscopic Features in Patients with Liver Cirrhosis: Correlation with Esophageal Varices, Intravariceal Pressure, and Liver Dysfunction

This study was aimed at evaluating the gastric endoscopic features in patients with liver cirrhosis and at assessing whether endoscopic findings correlated with the severity of portal hypertension and of the underlying liver disease. We studied 394 cirrhotic patients and 110 controls. Prevalence of a mosaic-like pattern of the gastric mucosa was significantly higher in cirrhotics than controls (80.5 vs. 0.9%; p < 0.001). Red spots of the gastric mucosa were found in 8.1% of cirrhotic patients and in none of the control subjects. Erosions and petechiae were found in 14.5 and 5.4% of the control population, but their prevalence was significantly higher in cirrhotics (28.7 and 12.7%, respectively; p < 0.05). Severity of the mosaic-like pattern as well as the presence of red spots were closely related to the size and hemorrhagic risk of esophageal varices and to the presence of fundic varices. Also, severe mosaic-like patterns were found more frequently in patients with severe impairment of liver function, as assessed by the Child-Pughs criteria. Furthermore, the mosaic-like pattern was more severe in cirrhotic patients with a higher degree of portal hypertension as indirectly assessed by measurement of esophageal intravariceal pressure. In conclusion, (1) a mosaic-like pattern and red spots of the gastric mucosa are the only specific signs of congestive gastropathy in liver cirrhosis, and (2) the severity of the mosaic-like pattern correlates with the severity of liver dysfunction and of portal hypertension.

Effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients.

This study was undertaken to evaluate the effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients. Sixteen cirrhotics were randomly assigned to metoclopramide (10 mg i.v.) or saline. Metoclopramide significantly decreased transmural variceal pressure (15.7% decrease, p less than 0.05 vs. basal value). In order to evaluate if the metoclopramide-induced drop in transmural variceal pressure was due to an effect on portal haemodynamics, we also measured, by means of real time and pulsed Doppler ultrasonography, portal vein diameter, mean velocity of portal flow, and portal venous flow. No significant change was observed before and after metoclopramide. In conclusion, metoclopramide, which increases lower oesophageal sphincter pressure, significantly decreases transmural variceal pressure in cirrhotic patients. However, it does not have any effect on portal haemodynamics.