The liver in heart failure

Severe congestive heart failure is associated with two distinct forms of liver dysfunction: jaundice that is related to passive congestion and acute hepatocellular necrosis that is caused by impaired perfusion. Cardiac cirrhosis (fibrosis) may result from prolonged recurrent congestive heart failure. Ischemic hepatitis (shock liver) usually manifests as asymptomatic elevation of the serum aminotransferase levels after an episode of hypotension, although the clinical presentation may mimic that of acute viral hepatitis. In most cases, ischemic hepatitis is of little clinical consequence and is self-limited. Acute liver failure may occur in patients with preexisting cirrhosis, severe chronic heart failure, or sustained hepatic ischemia.     

Hypoxic hepatitis. Prospective, clinical and hemodynamic study of 45 cases

The authors report 45 episodes of centrilobular liver cell necrosis, called ischemic hepatitis, in 43 cardiac patients. In 75 percent of the episodes, centrilobular liver cell necrosis was preceded by a period of progressive deterioration of myocardiac function. In 100 percent of the episodes, liver cell necrosis occurred after an acute clinical event inducing a transient fall of cardiac output. Shock was observed in only 47 percent of the episodes. The biological hallmarks of this centrilobular liver cell necrosis were a massive increase in serum aminotransferase levels and in 85 percent of the episodes, a decrease in the prothrombine time below 50 percent of control level. The mortality rate, 15 days after admission, was 42 percent. Prognosis was mainly related to cardiac function. The hemodynamic comparison between the 45 episodes of centrilobular liver cell necrosis and 22 cases of cardiogenic shock without liver cell necrosis showed that, besides hepatic ischemia, passive venous congestion of the liver and arterial hypoxemia were also involved in the onset of liver cell necrosis in these cardiac patients. Among these 45 episodes of liver cell necrosis of cardiac origin, a unique case of hepatic necrosis secondary to major hypoxemia and passive venous congestion, despite an high cardiac output was observed and is reported in detail. Accordingly, the appellation "hypoxic hepatitis" seems to be more appropriate than "ischemic hepatitis".     

Serum Levels of Secretory Immunoglobulin A in Liver Disease

Secretory immunoglobulin A (sIgA) in serum was measured in patients with various liver diseases using enzyme immunoassay specific to sIgA. Marked elevation of the serum sIgA concentrations was found in liver diseases especially in intrahepatic or extrahepatic cholestasis. In chronic hepatitis and liver cirrhosis serum sIgA correlated significantly with leucine aminopeptidase (r = 0.69), GOT (r = 0.66), alkaline phosphatase (r = 0.55), and direct bilirubin (r = 0.42). In acute hepatitis their levels correlated significantly with total bilirubin (r = 0.59) and GPT (r = 0.55). In acute hepatitis and acute exacerbation of chronic hepatitis the major peaks of serum sIgA were observed later than those of liver enzymes. These results suggest two mechanisms working to elevate the serum sIgA levels in liver diseases. In chronic hepatitis, liver cirrhosis, and intrahepatic and extrahepatic cholestasis the raised serum sIgA probably reflects reflux of bile, a rich source of secretory component and sIgA, into circulation. In acute or chronic massive liver necrosis elevation of sIgA may be associated with liver regeneration. Serial measurement of serum sIgA with other conventional parameters will contribute much to the understanding of the pathophysiology of liver diseases.     

Fulminant hepatic failure due to transient circulatory failure in patients with chronic heart disease

Heart failure is a recognized, although uncommon, cause of massive liver cell necrosis, the clinical consequences of which are intermingled with those of cardiac insufficiency in most cases. We report the cases of six patients suffering from chronic heart failure in whom an episode of acute circulatory failure resulted in massive liver cell necrosis and fulminant hepatic failure. The manifestations of fulminant hepatic failure, ie, hepatic encephalology, jaundice, and marked increase in prothrombin time, developed after an interval of one to three days, after the episode of acute circulatory failure, while the patients' hemodynamic condition had returned to the previous basal status.     

Fulminant hepatitis in infants in Taiwan: Strong association with hepatitis B e antigen-negative but antibody-positive maternal hepatitis B surface antigen carriage

This study examined the virologic profiles and pathologic features in 10 infants with fulminant hepatitis and aged 2–7 months. Nine male infants were related to hepatitis B virus infection: as evidenced by positive anti-HBc IgM (4 cases); positive serum HBsAg, and/or liver HBcAg (4 cases); or born to an HBsAg carrier mother (1 case). Only one female infant had presumed non-A non-B fulminant hepatitis, but none had hepatitis A. The mothers of eight infants with HBV-ralated fulminant hepatitis were all positive for serum HBsAg, and most (5/6) were negative for HBeAg but positive for anti-HBe. These findings suggest that infants born to HBsAg carrier mothers, particularly those who are negative for HBeAg, may contract fulminant hepatitis B in infancy in Taiwan. Six infants studied had massive hepatic necrosis and all died, whereas four had submassive or bridging hepatic necrosis and all survived, suggesting a close correlation between the extent of liver necrosis and the patient's outcome. None of the infants had hepatocyte HBsAg, although four had cytoplasmic HBcAg. Anti-HBc IgM was commonly detected (4/6), in sharp contrast to the constant negativity in infants who had contracted an asymptomatic HBV infection. These findings suggest that cytoplasmic HBcAg and anti-HBc IgM may be related to the occurrence of severe liver disease.     

Effects of irsoglandine maleate in an experimentally-induced acute hepatic failure model using mice

When heat-killed Propionibacterium acnes was intravenously injected into mice followed by an intravenous injection of a small amount of Gram-negative lipopolysaccharide seven days later, most of the mice died of massive hepatic cell necrosis within 24 hours. However, when irsoglandine maleate, an anti-ulcer agent, was administered to mice during the period of experimental induction of acute hepatic failure, the survival rate, serum transaminase levels and histological changes of the liver remarkably improved. These results suggested that irsoglandine maleate may have protective effects on the liver in our experimentally-induced acute hepatic failure model using mice. Therefore, in the absence of a definitive therapy for fulminant hepatitis, irsoglandine maleate may be a promising therapeutic agent.     

Atrium-related hepatitis. Report of four cases]

Four patients developed acute hepatitis after receiving Atrium, an association of phenobarbital, febarbamate and difebarbomate, for the treatment of tremor or for the prevention of alcohol withdrawal symptoms. Hepatitis occurred 1 to 3 months after treatment. Asthenia was the unique clinical manifestation. Marked increase in serum aminotransferases and gamma-glutamyltranspeptidase levels were the main biological features. Histological examination showed liver cell necrosis in two cases, prominent in the centrolobular area in one case. There was no case of hepatic failure. Atrium withdrawal was followed by complete recovery within 6 to 12 weeks. The mechanism of Atrium hepatotoxicity remains unknown.     

Effects of irsoglandine maleate in an experimentally-induced acute hepatic failure model using mice

When heat-killedPropionibacterium acnes was intravenously injected into mice followed by an intravenous injection of a small amount of Gram-negative lipopolysaccharide seven days later, most of the mice died of massive hepatic cell necrosis within 24 hours. However, when irsoglandine maleate, an antiulcer agent, was administered to mice during the period of experimental induction of acute hepatic failure, the survival rate, serum transaminase levels and histological changes of the liver remarkably improved. These results suggested that irsoglandine maleate may have protective effects on the liver in our experimentally-induced acute hepatic failure model using mice. Therefore, in the absence of a definitive therapy for fulminant hepatitis, irsoglandine maleate may be a promising therapeutic agent.     

91例慢性乙型重型肝炎肝衰竭患者的临床病理分析

目的 观察慢性乙型重型肝炎(CSHB)肝衰竭的临床和病理形态特点.方法 回顾性分析91例CSHB临床和病理资料,按其发病前基础病情分为慢性HBV携带组(HBC)、慢性乙型肝炎组(CHB)和肝硬化组(LC),分析各组患者出现肝衰竭的类型、临床特点和病理特点.结果 91例CSHB患者中,男性74例,女性17例,平均年龄(40.6±11.2)岁,发生在HBC者9例(9.9%)、CHB者7例(7.7%)、LC者75例(82.4%).平均年龄在HBC组为(25.8±6.6)岁、CHB组为(36.9±9.0)岁、LC组为(42.0±10.5),HBC组平均年龄较CHB组和LC组小,P值分别为0.032和0.001.各组患者肝衰竭类型均以哑急性为主,发生肝衰竭时间为15～150d,平均(42.2±30.6)d,以黄疸深、腹水为突出特点.常见诱因为劳累、重叠感染、病毒变异、应用肝损伤药物及饮酒.各组CSHB患者的凝血酶原时间、活动度和总胆红素差异无统计学意义.白蛋白、胆碱酯酶在LC组分别为(30.3±5.1)g/L和(2926.8±1471.1)U/L、HBC组分别为(35.6±5.1)g/L和(4363.5±2063.2)U/L、CHB组分别为(37.4±5.0)g/L和(5167.1±1522.1)U/L,LC组白蛋白、胆碱酯酶均明显低于HBC组和CHB组,F值分别为9.450和9.297,P值均＜0.01.胆固醇LC组为(1.8±1.0)mmol/L、HBC组为(2.9±1.0)mmol/L,LC组低于HBC组,P=0.034,差异有统计学意义.HBV DNA定量HBC组为(6.8±1.7)log10拷贝/ml、LC组为(4.2±2.6)log10拷贝/ml,HBC组高于LC组,P=0.019,差异有统计学意义.HBC和CHB基础上的CSHB肝脏病理表现主要为大块或亚大块坏死,病变较均匀,与急性/亚急性重型肝炎的病理特点并无显著区别,CHB基础上的CSHB,出现广泛坏死时极易掩盖原有病变,Masson染色可显示汇管区周围纤维化.肝硬化基础上者病变不均一,大块或亚大块坏死的同时总有部分结节保留,不同部位坏死范围及新旧程度不一.结论 我国CSHB多发生于肝硬化基础上,其病理特征与慢加急/亚急性肝衰竭相对应,而发生在HBC和CHB基础上的CSHB,其病理特征与急性或亚急性肝衰竭类似.     

Hypoxic hepatitis

Hypoxic hepatitis (HH), an acute liver injury also known as 'ischaemic hepatitis' or 'shock liver', is frequently observed in intensive care units. HH is heralded by a massive but transient rise in serum aminotransferase activities caused by anoxic necrosis of centrilobular liver cells. Cardiac failure, respiratory failure and toxic-septic shock are the main underlying conditions accounting for more than 90% of cases, but HH may also occur in other circumstances. Until recently, liver ischaemia, i.e. a drop in hepatic blood flow, was considered the leading, and even the sole, hemodynamic mechanism responsible for HH, and it was generally held that a shock state was required. In reality, other hemodynamic mechanisms of hypoxia, such as passive congestion of the liver, arterial hypoxaemia and dysoxia, play an important role while a shock state is observed in only 50% of cases. Accordingly, 'ischaemic hepatitis' and 'shock liver' are misnomers. Therapy of HH depends primarily on the nature of the underlying condition. The prognosis is poor, with more than half of patients dying during the hospital stay.     

Pirprofen-induced fulminant hepatitis

We report the cases of 2 female patients aged 69 and 61 yr, suffering from fulminant hepatitis induced by pirprofen, a new nonsteroidal antiinflammatory drug. The duration of pirprofen administration before the onset of hepatitis was long, 7 and 9 mo, respectively. Hepatitis was not preceded or accompanied by hypersensitivity manifestations. The liver lesion consisted of massive, predominantly centrilobular hepatic cell necrosis and microvesicular steatosis. One patient died of liver failure. Although the risk of fulminant hepatitis is very low, we recommend that, in patients taking pirprofen for more than 2 mo and complaining of asthenia, nausea, or vomiting, serum aminotransferase levels should be measured and administration of the drug should be interrupted as soon as an increased level is noted.     

Ischemic hepatitis: clinical presentation and pathogenesis

BACKGROUND: The pathophysiology of ischemic hepatitis, otherwise known as "shock liver," is poorly understood, although it is believed to be the result of a reduction in systemic blood flow as typically occurs in shock. The aim of this study was to investigate the importance of this phenomenon as well as other clinical features in patients with ischemic hepatitis.METHODS: We identified a cohort of 31 patients (case group) who met the most commonly accepted definition of ischemic hepatitis (an acute reversible elevation in either the serum alanine or aspartate aminotransferase level of at least 20 times the upper limit of normal, excluding known causes of acute hepatitis or hepatocellular injury, in an appropriate clinical setting). We also evaluated the clinical features and serum aminotransferase levels in a cohort (the control group) of 31 previously healthy patients who sustained major nonhepatic trauma at San Francisco General Hospital, a major trauma center. Both groups of patients had documented systolic blood pressures <75 mm Hg for at least 15 minutes. Clinical and hemodynamic (invasive and noninvasive) data were recorded.RESULTS: Despite the marked reduction in blood pressure, no patient in the control group developed ischemic hepatitis. The mean (+/- SD) peak serum aspartate aminotransferase level in the control group was only 78 +/- 72 IU, in contrast with a mean peak of 2,088 +/- 2,165 IU in the case group. All 31 patients with ischemic hepatitis had evidence of underlying organic heart disease, 29 (94%) of whom had right-sided heart failure.CONCLUSIONS: Systemic hypotension or shock alone did not lead to ischemic hepatitis in any patient. The vast majority of patients with ischemic hepatitis had severe underlying cardiac disease that had often led to passive congestion of the liver. These data lead us to propose that right-sided heart failure, with resultant hepatic venous congestion, may predispose the liver to hepatic injury induced by a hypotensive event.     

ISCHEMIC HEPATITIS: CLINICAL FEATURES, DIAGNOSIS AND PROGNOSIS

Nineteen episodes of ischemic hepatitis were diagnosed by hepatitic liver function tests and characteristic liver pathology in 17 patients. All patients had an acute illness associated with a likely fall in cardiac output although only five episodes were associated with documented hypotension. Right ventricular failure was severe in only four, mild in six, and absent in nine whilst left ventricular failure was clinically apparent in 16. The hepatitic illness was usually mild. No patient died as a direct result of hepatic damage, prognosis depending on the underlying cardiac or systemic disease. Liver function tests were characterised by a marked rise in serum transaminase levels with a parallel increase in serum lactic dehydrogenase of hepatic origin and a short time course of the enzyme elevation lasting 3 to 11 days. It is concluded that ischemic hepatitis (a) is' caused by poor hepatic perfusion associated with an acute fall in cardiac output; (b) is usually a subclinical illness with little influence on prognosis, and (c) may be accurately differentiated from viral hepatitis on clinical and biochemical criteria alone.     

Non-invasive evaluation of liver fibrosis using transient elastography

Transient elastography (TE, FibroScan) is a novel non-invasive method that has been proposed for the assessment of hepatic fibrosis in patients with chronic liver diseases, by measuring liver stiffness. TE is a rapid and user-friendly technique that can be easily performed at the bedside or in the outpatient clinic with immediate results and good reproducibility. Limitations include failure in around 5% of cases, mainly in obese patients. So far, TE has been mostly validated in chronic hepatitis C, with diagnostic performance equivalent to that of serum markers for the diagnosis of significant fibrosis. Combining TE with serum markers increases diagnostic accuracy and as a result, liver biopsy could be avoided for initial assessment in most patients with chronic hepatitis C. This strategy warrants further evaluation in other aetiological types of chronic liver diseases. TE appears to be an excellent tool for early detection of cirrhosis and may have prognostic value in this setting. As TE has excellent patient acceptance it could be useful for monitoring fibrosis progression and regression in the individual case, but more data are awaited for this application. Guidelines are needed for the use of TE in clinical practice.     

Acute viral hepatitis B with bridging necrosis: a follow-up study

ABSTRACT— Forty patients with bridging necrosis (BN) on biopsies taken during the course of acute viral hepatitis B were included in a prospective study to assess the prognostic significance of this lesion. Of the 22 patients with complete clinical, biochemical and histological follow-up (histological follow-up 5–33 months), only two failed to eliminate HBs- and HBe-antigen in serum, a finding paralleled by transition to chronic active hepatitis and by the persistence of focal HBc- and HBs-antigen expression in liver tissue. Nineteen of 22 patients showed complete histological healing; one developed inactive cirrhosis. It is concluded that, in the setting of acute viral hepatitis B, the histological lesion of BN is of no particular prognostic significance, and that transition to chronic liver disease is much less frequent than has been assumed from previous studies of etiologically heterogeneous patient populations. Markers of poor prognosis are the failure of serological elimination of HBs- and HBe-antigen and the persistence of spotty expression of HBc- and HBs-antigen on immunofluorescence histology.     

Localization and serum concentration of secretory component during massive necrosis of human liver

The serum concentration of secretory component was monitored in 9 patients with massive liver necrosis. During acute cytolysis, no increase in serum secretory component levels was observed. Later on, patients with fulminant evolution displayed minor elevations. Values as high as those usually found in acute hepatitis were only observed in cases with delayed liver failure. In these patients, levels were elevated before failure, dropped as liver failure developed, and rose again during recovery. This evolution of serum secretory component level cannot be accounted for by a defective liver clearance of circulating secretory component. It rather suggests a release into the blood of secretory component produced in the liver by cells other than damaged hepatocytes, possibly during liver regeneration. In 3 cases, secretory component localization in the liver was demonstrated by immunocytochemistry and was compared with that in normal liver and in obstructive jaundice. In normal liver, it was restricted to portal bile duct cells and lumens. In obstructive jaundice, additional secretory component staining was found in bile canaliculi. After fatal liver necrosis, secretory component was localized to portal ducts and to a variable proportion of the cholangiocytelike cells belonging to the numerous extraportal proliferating ducts. In these structures, 0.1%, 21%, and 4% of the cells were stained 3, 8, and 30 days after maximal cytolysis, respectively. Remaining hepatocytes and bile canaliculi or bile plugs were unstained. Therefore, portal cholangiocytes and extraportal cholangiocytelike cells are probably essential sources of secretory component in human liver. We propose that proliferation of extraportal cholangiocytelike cells, expression of secretory component synthesis by these cells, and their inability to secrete secretory component in a disorganized biliary tree result in the elevated serum concentration of secretory component observed after acute liver necrosis.     

The role of histologic evaluation in the diagnosis and management of autoimmune hepatitis and its variants

The diagnosis of autoimmune hepatitis requires a constellation of clinical, laboratory, and histologic features that exclude other conditions and support the syndrome. Interface hepatitis is the histologic hallmark of the disease, and it may be associated with panacinar hepatitis with or without bridging necrosis or multiacinar necrosis. The liver tissue examination at accession supports the diagnosis and assesses disease severity. It can also suggest the diagnosis in patients with atypical presentations, including those with an acute onset or cryptogenic disease. The liver tissue examination during therapy defines end points of treatment (remission) and evaluates unexpected outcomes (treatment failure, incomplete response). Manifestations of bile duct injury are incompatible with the classic diagnosis of autoimmune hepatitis, and they may be coincidental findings of no or uncertain clinical significance or weak expressions of a variant form. Histologic features of autoimmune hepatitis may intermix with those of PBC, PSC, and chronic hepatitis C infection, or they may occur in autoimmune cholangitis or cryptogenic chronic hepatitis. Conditions in which the histologic findings suggest the overlap of two disorders or are insufficient for designation as classic disease constitute the variant syndromes.     

Fulminant hepatitis caused by hepatitis C virus during treatment for multiple sclerosis

A 55-year-old woman was treated at our hospital for multiple sclerosis. Therapy consisted of glucocorticosteroids and cyclosporin. In the 7th week after these drugs were discontinued the patient developed acute liver failure due to fulminant hepatitis (FH) and died. Post-mortem examination showed massive liver necrosis. Serologic examination was negative for hepatitis B virus-related markers. Anti-hepatitis C virus (anti-HCV) antibody and serum HCV RNA were negative on admission, but HCV RNA appeared concurrently with the onset of FH. Although HCV infection rarely causes FH, it was considered to be the cause of FH in this patient, since there were no other causes of acute liver injury. We suspect that underlying immunologic abnormalities in conjunction with HCV infection may have precipitated the FH.     

Natural history of chronic hepatitis B

Chronic hepatitis B virus (HBV) infection can cause chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Chronic hepatitis B is characterized by an early replicative phase with hepatitis B e antigen (HBeAg) positivity, high serum HBV-DNA levels and disease activity (HBeAgpositive chronic hepatitis), and a late inactive phase with anti-HBe seroconversion, low or undetectable serum HBV-DNA, and liver disease remission (inactive carrier state). Another form is characterized by active disease due to HBV variants not expressing HBeAg (HBeAg-negative chronic hepatitis). Both types of chronic hepatitis B can lead to cirrhosis and its complications. The incidence of cirrhosis is two to five per 100 person-years, but may be as high as eight to 10 in HBeAg-negative cases. The incidence of HCC varies geographically and increases with the duration and severity of liver disease (0.1 to 8 per 100 person-years). The prognosis is reasonably good in compensated cirrhosis, but very poor following decompensation. Viral and environmental factors influence the natural history of chronic hepatitis B and explain the heterogeneity of its clinical outcomes.     

Acute massive hepatic necrosis with fatal liver failure

A review was made of the hospital records of 33 patients who died of massive liver necrosis, which was confirmed at autopsy, from 1946 through 1968, in three hospitals in Richmond, Virginia. Although the etiology is difficult to prove, the clinical picture and time sequence indicated that the offending agent was: drug in 8; serum hepatitis in 11; infectious hepatitis in 11; and halothane in 3. Of 19 cases in which prothrombin time was determined, 17 had values below 23%. Leukocytosis, often marked, was present in 28 of 33. This study suggests, but does not prove, that the incidence of massive necrosis of the liver is increasing.