Portal hypertension and neutrocytic ascites in POEMS syndrome

We report a case of portal hypertension and neutrocytic ascites in a 52 year old man with POEMS syndrome. POEMS syndrome is an association of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy and skin changes. Portal hypertension is rare in POEMS syndrome and this is the first time that culture negative neutrocytic ascites has been described with this syndrome.     

Electrocardiographic and hemodynamic correlations in primary pulmonary hypertension

In order to evaluate the pulmonary hemodynamics in primary pulmonary hypertension, the relation between the standard 12-lead electrocardiogram (ECG) and pulmonary hemodynamics as determined by right-heart catheterization was analyzed. Significant positive correlations were noted between amplitude of the R in V1, the R/S ratio in V1, and the pulmonary artery systolic pressure (r = 0.46 and 0.50, respectively, p less than 0.01). An amplitude of the R in V1 of more than 1.2 mV indicated a pulmonary artery systolic pressure of more than 90 mmHg with a sensitivity of 94% and a specificity of 47%. The cardiac index showed a significant positive relationship with amplitude of the R in V5 and V6 and the R/S ratio in V5 and V6 (r = 0.46, 0.46, 0.39, and 0.48, respectively; each with a p less than 0.01). Moreover, an AQRS greater than or equal to 100 degrees, and either an SV6 greater than or equal to 0.7 mV, or R/SV6 less than or equal to 2 indicated a cardiac index of less than 2.8L/min/m2 with a sensitivity of 82% and 84% and a specificity of 86% and 100% respectively. This study suggests, therefore, that the 12-lead ECG is useful for the evaluation of the severity of pulmonary hypertension by its ability to predict pulmonary artery systolic pressure and cardiac index with clinically useful accuracy.     

Cardiac hepatopathy: clinical,hemodynamic, and histologic characteristics and correlations

Cardiac hepatopathy, hepatic injury caused by cardiac dysfunction, is a common entity but has been characterized incompletely, particularly the relationship between hemodynamics and histology. We aimed to describe the clinical, biochemical, hemodynamic, and histologic characteristics of this disorder. Eighty-three patients from 2 tertiary referral centers were studied. Patients were divided into 3 groups based on the duration of cardiac dysfunction: (1) acute (n = 12); (2) chronic (n = 53); and (3) acute on chronic (n = 18). Results showed that serum aminotransferase levels were increased typically, particularly in the acute group (median aspartate aminotransferase level was 30.2 times the upper limit of normal [range, 1-100]; P <.0001 vs. the chronic group). The most salient hemodynamic features were elevated right atrial (14 mm Hg [range, 1-29]), and hepatic venous pressures (wedged: 18 mm Hg [range, 5-35]; free: 15 mm Hg [range, 2-30]). The hepatic venous pressure gradient was normal in most (81%), correlated moderately with the aminotransferase levels (aspartate aminotransferase level: r =.59; P <.0001), and associated with the presence of centrilobular necrosis and inflammation, periportal necrosis, and stainable hepatic iron (P <.05 for all comparisons), but not fibrosis. Sinusoidal dilatation was associated with higher right atrial (P =.047) and free hepatic venous pressures (P =.06). Although cirrhosis was rare (n = 1), centrilobular fibrosis was common (74%) and not associated with any hemodynamic measurement. In conclusion, cardiac hepatopathy has diverse clinical, hemodynamic, and histologic manifestations that vary with the temporal course of cardiac dysfunction. Hepatic fibrosis is common, but does not correlate with systemic or hepatic hemodynamics.     

Portal pressure in patients with exudative ascites in the course of acute hepatitis B

ABSTRACT— We describe three patients who developed ascites during the course of acute viral hepatitis B. Two of them had exudative ascites, with a high protein and cell content, and the other transudative ascites, with low protein and cell content. Both patients with exudative ascites had a benign clinical course, and their liver disease was milder than in the patient with transudative ascites, who had signs of severe liver failure and a submassive hepatic necrosis on liver biopsy. Moreover, the patient with transudative ascites had evidence of portal hypertension (as indicated by a hepatic vein pressure gradient of 12.5 mmHg, normal 1–6 mmHg), whereas patients with exudative ascites did not (hepatic vein pressure gradient of 5 and 5.5 mmHg, respectively). These data support our previous suggestion that “exudative” ascites during acute viral hepatitis B represents a self-limited immunopathic sign that is not related to portal hypertension or severe hepatic disease.     

Lymphocyte cytotoxicity in chronic active hepatitis: effect of therapy and correlations with clinical and histological changes

A study of lymphocyte cytotoxicity for rabbit hepatocyte cultures in 15 patients with untreated chronic active hepatitis showed positive results in all cases, both HBsAg positive and negative. After immunosuppressive therapy cytotoxicity became negative and remained negative, in four of nine patients followed serially. In 51 patients established on therapy for periods from three months to 12 years, cytotoxicity was negative in 19 and all patients are currently alive. However, in the remaining 32 patients in whom cytotoxicity was positive there has been a 34% mortality. Cytotoxicity remained persistently positive in 12 of 15 patients followed serially, and persistently negative in seven of nine. Cytotoxicity showed a significant association with histological disease activity, especially the extent of piecemeal necrosis, but not with biochemical tests of liver function, immunoglobulins, or autoantibodies. The basis of this cytotoxicity test is an antibody dependent cell-mediated autoimmune reaction directed against a liver specific protein, and the results suggest that in some cases immunosuppressive therapy is followed by control of this reaction. It may be possible to stop therapy in these patients, but in those in whom the reaction continues, as shown by continuing cytotoxicity, the prognosis is not as good and the use of other drug schedules would seem worthy of trial.     

Portal blood flow in acute hepatitis with and without ascites: A non-invasive measurement using an ultrasonic Doppler

Abstract To evaluate the role of portal blood flow in severe acute hepatitis leading to the formation of ascites, we studied the portal blood flow of 30 patients with severe acute hepatitis (20 without ascites and 10 with ascites), 20 patients with mild acute hepatitis and 20 healthy normal volunteers using duplex sonography. The portal blood flow of patients with severe acute hepatitis and ascites (421 ± 94 mL/min) was lower than that of the volunteers (725 ± 131 mL/min), the mild acute hepatitis (658 ± 148 mL/min), and the severe acute hepatitis (633 ± 108mL/min) without ascites ( P < 0.001). The congestion index of severe acute hepatitis and ascites (0.16 ± 0.04 cm · s) was higher than that of the volunteers (0.09 ± 0.03 cm · s, P < 0.001), the mild acute hepatitis (0.09 ± 0.02 cm · s, P < 0.001), and the severe acute hepatitis (0.12 ± 0.04 cm · s, P < 0.02) without ascites. Portal blood flow was negatively correlated with prolonged prothrombin time ( P < 0.001) and serum total bilirubin level ( P = 0.002) and congestion index was positively correlated with heart rate ( P = 0.006), prolonged prothrombin time ( P < 0.001). and serum total bilirubin level ( P = 0.001). Our study shows that in severe acute hepatitis, portal blood flow was reduced in patients with ascites. The non-invasive ultrasonic Doppler is a safe and helpful method in the clinical evaluation of portal hypertension in severe acute hepatitis.     

Portal hypertension in primary biliary cirrhosis: Relationship with histological features

The prevalence and type of portal hypertension (PH) in primary biliary cirrhosis (PBC) and their relationship with liver lesions have been investigated in 32 patients with the disease. Portal hypertension was considered when oesophageal or gastric varices were observed by endoscopy and/or when hepatic venous pressure gradient measured by hepatic vein catheterization was greater than 6 mmHg. Within 3 days of endoscopy, a liver biopsy was performed for histological staging and semiquantitative grading (0 to 3+) of portal and sinusoidal fibrosis, portal inflammation, piecemeal necrosis, lobular necrosis, cholestasis, as well as the presence of granulomas and Mallory's hyaline. Twenty patients (62.5%) had portal hypertension, five of them showing presinusoidal PH (15.5%) and the remaining 15 (47%) with sinusoidal component. The four patients in stage IV had sinusoidal PH and the only patient in stage I had no PH. The prevalence of portal hypertension was similar in patients in stage II (57%) and stage III (55%), but presinusoidal PH was only observed in patients in stage II. Patients with PH showed significantly higher portal inflammation and piecemeal necrosis than patients without PH. By contrast, there were no differences in portal and sinusoidal fibrosis, nor in the other histologic features. These results indicate that portal hypertension is common in PBC and it may be present in the early stages of the disease. The fact that presinusoidal PH was only observed in patients in stage II suggests that portal hypertension is initially of presinusoidal type, and then as the disease progresses is joined by a sinusoidal component.     

Chronic hepatitis B virus infection: Viral replication and patterns of inflammatory activity: Serological, clinical and histological correlations

We have studied serum and tissue markers of viral replication in 39 patients with chronic hepatitis B virus (HBV) infection and correlated these with periportal and lobular activity in liver biopsies. HBV DNA positivity correlated with the presence of hepatitis B e antigen (HBeAg, P less than 0.001) and aspartate transaminase (AST) levels (P less than 0.005). The lobular but not the periportal inflammatory activity was significantly associated with the presence of HBV DNA (P less than 0.02) and HBeAg (P less than 0.001) and with higher AST levels. The periportal activity correlated with the periportal and lobular display of beta 2-microglobulin on hepatocytes (P less than 0.001 and P less than 0.002, respectively). In patients with chronic HBV infection therefore, the lobular rather than the periportal component of activity was related to viral replication. The association of display of beta 2-microglobulin on hepatocytes with the inflammatory process, in patients with active viral replication, is consistent with the hypothesis that increased display of HLA type I enhances recognition of hepatocytes bearing viral proteins and allows lysis of immune cells.     

Portal hypertension in fulminant viral hepatitis.

The gradient between wedged and free hepatic venous pressures were measured in 10 unselected adult patients suffering from fulminant viral hepatitis. The gradient was increased in all the studied patients, ranging from 0.9 to 2.1 kPa; this finding indicates that portal hypertension was present in all these cases. Ascites was present in all the five patients having a gradient about 1.5 kPa and affected only two of the five patients having a gradient below 1.5 kPa; this observation suggests that portal hypertension plays a role in the mechanism of ascites in fulminant viral hepatitis. Portal hypertension in fulminant viral hepatitis is likely to be the consequence of an intrahepatic block due to massive necrosis of the liver cells.     

Serum lipid pattern in chronic hepatitis C: histological and virological correlations

Lipoproteins are closely connected to the process of hepatitis C virus (HCV) infection. The aim of this study was to evaluate the lipaemic profile in patients with chronic HCV infection, and to identify any association between serum lipid levels and viral load, HCV genotype or liver histology. Total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) were measured in the sera of 155 patients with chronic HCV infection and 138 normal subjects, matched for age and sex. Viral parameters and liver histology were evaluated in HCV-infected patients. Serum TC (P < 0.0005), HDL-C (P < 0.0005) and LDL-C (P < 0.0005) were lower in chronic hepatitis C patients compared with controls. Grading score was positively correlated with TC and LDL-C. Patients with HCV genotype 3a had significantly lower levels of TC, HDL-C, LDL-C, higher viral load and higher frequency of hepatic steatosis than those with other genotypes. Logistic regression analysis identified genotype 3a (OR, 6.96; 95% CI, 2.17-22.32, P = 0.0011) as the only significant predictive variable associated with low serum cholesterol concentration. HCV infection is associated with clinically significant lower cholesterol levels (TC, LDL and HDL) when compared with those of normal subjects. This finding is more pronounced in patients infected with HCV genotype 3a. Further studies are necessary to define the pathophysiology of the relationship between lipid metabolism and HCV infection.     

Portopulmonary hypertension: distinctive hemodynamic and clinical manifestations

Portopulmonary hypertension is now recognized as one of the pulmonary complications of chronic liver disease. However, previous studies reported that the incidence ranged from 0.25% to 2%, excluding fortuitous coincidence. In this study, we aimed to determine the variant hemodynamic and clinical features of portopulmonary hypertension in an area with a high prevalence of viral cirrhosis. After reviewing the hemodynamic data of 322 patients with portal hypertension admitted to the Taipei Veterans General Hospital between 1987 and 1999, we found 10 with portopulmonary hypertension. The overall incidence was, therefore, 3.1% in all patients with portal hypertension. Most of the patients with portopulmonary hypertension experienced exertional dyspnea. The survival times ranged from 2 to 86 months. In our series, most of the patients who died, died of complications related to cirrhosis and portal hypertension, but not of complications related to pulmonary hypertension. This study suggested that portopulmonary hypertension was not a frequent complication in cirrhotic patients and was not associated with an adverse outcome. Received: June 15, 2000 / Accepted: September 8, 2000     

Echocardiographic ejection fraction in patients with acute heart failure: correlations with hemodynamic, clinical, and neurohormonal measures and short-term outcome

BACKGROUND: Although echocardiographic ejection fraction (EF) is frequently used for the estimation of left ventricular contractility in patients with acute heart failure, its exact role and correlations with clinical, hemodynamic, and neurohormonal variables of cardiac contractility is not known. METHODS: Patients (343) with acute heart failure, enrolled into two prospective placebo-controlled hemodynamic studies of tezosentan, and in whom EF was available at baseline, were included. Outcome was evaluated in a subset of 94 patients who were enrolled in the placebo arms of the studies. RESULTS: Higher echocardiographic EF was correlated with older age, increased incidence of hypertension and atrial fibrillation, and female gender. We observed weak correlation between EF and cardiac output or cardiac power and no correlation with wedge pressure, and the change in hemodynamic variables over time. Higher EF was correlated with more baseline leukocytosis and higher plasma levels of endothelin-1 and blood urea nitrogen, while lower EF was related to higher baseline B-type natriuretic peptide (BNP). We observed no overall correlations between EF and outcome. CONCLUSIONS: In patients with acute heart failure, echocardiographic EF is weakly correlated with hemodynamic measures of left ventricular contractility and outcome; hence, it should be interpreted cautiously when evaluating patients admitted due to acute heart failure.     

Portal hypertension in acute liver failure.

Twenty five patients with acute liver failure were measured for hepatic venous pressure gradient as an index of portal pressure during the course of a transjugular liver biopsy. Hepatic venous pressure gradient ranged from 4 to 24.5 mm Hg with a mean of 12.8 (5.3) mm Hg (normal values less than 5 mm Hg). All patients but one had increased portal pressure gradient. Portal hypertension correlated with the degree of architectural distortion of the liver, as suggested by a direct correlation between hepatic venous pressure gradient and the area of reticulin collapse, evaluated by means of a morphometric analysis on Sirius red stained liver slides (r = 0.43, p less than 0.05). Hepatic venous pressure gradient was significantly higher in patients with ascites (15.1 (5) mm Hg, n = 15) or renal failure (14.4 (5.3) mm Hg, n = 16) than in those without (9.3 (3.4) mm Hg and 10.1 (4) mm Hg, respectively; p less than 0.05). Portal hypertension was associated with systemic vasodilation and a hyperkinetic circulatory state, with decreased arterial pressure, and peripheral resistance and increased cardiac output.