Drug-induced mononucleosis-like hepatic injury in a patient with systemic lupus erythematosus

A case of systemic lupus erythematosus (SLE) with mononucleosis-like hepatic injury was described. An emergent cesarean section was performed in a 25 yr-old house wife at 34 weeks gestation, followed by administration of several antibiotics. After the surgery she complained of high fever, hepatomegaly and dull right hypochondralgia, and mild liver dysfunction was also found. The liver biopsy showed prominent mononuclear cell infiltration in the sinusoids with minimum hepatocellular necrosis and mild triaditis, resembling hepatic lesion in infectious mononucleosis (mononucleosis-like injury). There were no clinical and serological features suggestive of infectious mononucleosis. This hepatic lesion was thought to be a manifestation of allergic reaction to drugs to which the lymphocyte stimulation test was found to be positive. Immunological abnormalities inherent in SLE might be related to occurrence of such allergic drug reaction.     

Significant liver injury with dual positive IgM antibody to Epstein-Barr virus and cytomegalovirus as a puzzling initial manifestation of infectious mononucleosis

A 35-year-old man was admitted because of significant hepatic dysfunction with mild splenomegaly and intra-abdominal lymphadenopathy of unknown cause. Infectious mononucleosis was suggested by subsequently detected high fever, pharyngotonsillitis and cervical lymphadenopathy, but IgM to Epstein-Barr virus (EBV) and cytomegalovirus (CMV) showed dual positivity. A definite diagnosis of EBV-induced infectious mononucleosis was established 3 months later on the basis of seroconversion to Epstein-Barr nuclear antigen (EBNA)-IgG positivity and reduced CMV-IgM titer with persistently negative CMV-IgG. This case highlights the initial diagnostic difficulties of EBV-induced infectious mononucleosis particularly in older patients, due to concomitant abnormal humoral immunity and unusual initial manifestations such as significant liver injury and extensive intra-abdominal lymphadenopathy.     

Hepatic encephalopathy in primary human immunodeficiency virus type 1 (HIV-1) infection

Primary infection of human immunodeficiency virus type 1 (HIV-1) is occasionally associated with common cold-like symptoms, and rarely with a self-limited illness resembling infectious mononucleosis. We report a 32-year-old man who presented with infectious mononucleosis-like blood picture on admission. Five days after admission he developed hepatic encephalopathy, which was ameliorated by administration of bolus corticosteroid. Based on the results of serologic studies, we diagnosed that he had primary HIV-1 infection. To our knowledge, this is the first published report of hepatic encephalopathy as a clinical manifestation of primary HIV-1 infection.     

Hepatic involvement in infectious mononucleosis

Summary A case of infectious mononucleosis complicated by hepatic involvement is reported. Serial liver biopsy studies revealed a lesion indistinguishable from viral hepatitis. The suggestion is made that though mononucleosis hepatitis is milder than infectious hepatitis, the pathologic changes occurring in the liver in these diseases may be the same and differ only in extent depending solely upon the severity of the illness.The opinions or assertions contained herein are those of the authors and are not to be construed as official or reflecting the views of the Navy Department or of the Naval Service at large.     

Hepatic vasculitis presenting with multiple sterile liver abscesses in a patient with systemic lupus erythematosus

Although biochemical evidence of liver disease is common in patients with systemic lupus erythematosus (SLE), clinical liver disease is uncommon. We report on a 26‐year‐old woman who presented with acute febrile illness, right upper abdominal pain and multiple hypo‐dense lesions in the liver in a computed tomographic study that mimicked multiple liver abscesses. Multiple necrotizing hepatic granulomas and old occlusive hepatic arteritis were observed in the surgical liver specimen. She was later found to have SLE. This patient represented a rare case of SLE that had hepatic vasculitis with hepatic infarction mimicking multiple liver abscesses as an initial manifestation.     

Diagnostic evaluation of mononucleosis-like illnesses

Clinicians face a diagnostic challenge when a patient with the classic fever, pharyngitis, and lymphadenopathy triad of infectious mononucleosis has a negative “spot” heterophile antibody test. This screening test, although commonly considered sensitive for the presence of Epstein-Barr virus (EBV) infection, may be negative early after infection. A growing number of pathogens have been reported to cause heterophile-negative mononucleosis-like illnesses, including cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), human immunodeficiency virus (HIV), adenovirus, herpes simplex virus (HSV), Streptococcus pyogenes, and Toxoplasma gondii. Other infectious and noninfectious disorders also may present in ways that mimic mononucleosis, but fail to generate EBV’s archetypal triad of clinical findings. A systematic approach to the diagnosis of mononucleosis-like illnesses ensures that conditions warranting specific therapy are distinguished from others requiring only supportive care.     

101例慢性布鲁氏菌病患者的肝功及菌苗治疗的影响

本文报告了101例慢性布病患者的肝功测定结果,肝功异常者占48.5％。肝功异常与皮内变态反应强度有关,即随着皮试红肿面积的增大,其肝功异常者增多。19例肝功异常病人经菌苗治疗后有7例(36.8%)恢复正常。     

Bone Marrow Findings in Infectious Mononucleosis and Mononucleosis-Like Diseases in the Older Adult

The bone marrow findings in 5 older adults with infectious mononucleosis or mononucleosis-like illnesses are presented. These individuals were initially considered to have lymphoproliferative disorders which often have similar constitutional signs and symptoms. All had atypical lymphocytosis of the peripheral blood. In addition, there were also abnormalities in the bone marrow. The most common findings included focal collections of lymphocytes and the presence of granulomas. The granulomas were small without caseous necrosis and giant cells were infrequent. This is in contrast to the idea that the bone marrow is normal in infectious monoculeosis and gives support to performing core biopsies as the aspirate smears in these individuals did not demonstrate the focal lymphocytosis or granulomas. Whereas, infectious mononucleosis and mononucleosis-like illness may be uncommon in the older individual, they certainly are not rare and it is important to differentiate these benign disorders from the more serious lymphoproliferative diseases. Heterophil test and/or Epstein Barr titers are important confirmatory tests.     

Transcatheter arterial embolization for hemorrhage caused by injury of the hepatic artery

BACKGROUND: The aims of the study were to compare (i) the effects of transcatheter arterial embolization on initial hemostasis and the control of rebleeding in the treatment of hemorrhage due to hepatic artery injury; and (ii) the outcomes of embolization by different locations. METHODS: Subjects were 32 patients with suspected hepatic artery injury who were transferred to Chi-Mei Foundation Medical Center for hepatic angiography and embolization. The causes of arterial injury included liver trauma (n = 15) and iatrogenic injury (n = 17). The sites of embolization were classified into four groups: group 1 (n = 8) was classified as 'combined outlet, target and inlet control' with embolization of the vascular lesion (target) and hepatic artery distal (outlet) and proximal (inlet) to the vascular lesion simultaneously; group 2 (n = 11) as 'combined target and inlet control'; group 3 (n = 8) as 'combined outlet and inlet control'; group 4 (n = 5) as 'inlet control' only. RESULTS: Successful initial hemostasis was achieved in 30 of the 32 patients (93.8%), with two failures, both of which were caused by liver injury and occurred in subjects in group 4. Rebleeding was seen in three patients who had successful initial hemostasis: two of them in group 4 (66.7%) and one in group 1 (12.5%). All rebleedings were successfully managed by repeat embolization. Abscess formation was found in two group 1 patients, and both were successfully managed by percutaneous drainage. CONCLUSIONS: Transcatheter arterial embolization is an effective method for hemostasis in hepatic artery hemorrhage for both patients with liver trauma and patients with iatrogenic injuries to the hepatic artery. Based on this experience, embolization of the vascular lesion and/or the arterial lumen distal to the vascular lesion combined with inlet control is recommended for preventing recurrent hemorrhage, but studies with larger sample sizes will be required to validate this conclusion.     

An analytical review of vasculobiliary injury in laparoscopic and open cholecystectomy

Objectives

Biliary injuries are frequently accompanied by vascular injuries, which may worsen the bile duct injury and cause liver ischemia. We performed an analytical review with the aim of defining vasculobiliary injury and setting out the important issues in this area.

Methods

A literature search of relevant terms was peformed using OvidSP. Bibliographies of papers were also searched to obtain older literature.

Results

Vasculobiliary injury was defined as: an injury to both a bile duct and a hepatic artery and/or portal vein; the bile duct injury may be caused by operative trauma, be ischaemic in origin or both, and may or may not be accompanied by various degrees of hepatic ischaemia. Right hepatic artery (RHA) vasculobiliary injury (VBI) is the most common variant. Injury to the RHA likely extends the biliary injury to a higher level than the gross observed mechanical injury. VBI results in slow hepatic infarction in about 10% of patients. Repair of the artery is rarely possible and the overall benefit unclear. Injuries involving the portal vein or common or proper hepatic arteries are much less common, but have more serious effects including rapid infarction of the liver.

Conclusions

Routine arteriography is recommended in patients with a biliary injury if early repair is contemplated. Consideration should be given to delaying repair of a biliary injury in patients with occlusion of the RHA. Patients with injuries to the portal vein or proper or common hepatic should be emergently referred to tertiary care centers.     

Inhibition of Inducible Nitric Oxide Synthase Prevents Hepatic, but Not Pulmonary, Injury Following Ischemia-Reperfusion of Rat Liver

The aim of this study was to investigate the contribution of inducible nitric oxide synthase (iNOS)-derived nitric oxide on the liver and lung injury following hepatic ischemia-reperfusion (I/R) using a novel and potent iNOS inhibitor, ONO-1714. Rats were subjected to 90 min of partial hepatic ischemia followed by 3, 6, 12, and 24 hr of reperfusion. Expression of iNOS mRNA peaked at 3 hr of reperfusion in the liver and lung. Plasma nitric oxide levels were increased fourfold at 24 hr of reperfusion and plasma ALT was increased, reaching a peak at 12 hr of reperfusion; both were significantly inhibited by ONO-1714. Histological examination revealed extensive liver damage, whereas this was not seen in the ONO-1714 group. Lung injury was not significantly changed in groups with versus without ONO-1714. Nitrotyrosine expression was seen in regions similar to those of the histological injuries of the liver, while this staining was absent in the ONO-1714 group. These data show that generation of peroxynitrite could be involved in the pathogenesis of liver injury but not lung injury after hepatic I/R. Inhibition of iNOS could be applied for attenuation of liver injury following hepatic I/R.     

肝功指标判断汉坦病毒所致肝损害的临床价值

目的探讨常用肝功能指标判断汉坦病毒所致肝损害的临床价值。方法回顾性分析367例肾综合征出血热(HFRS)患者肝功能指标、病情及治疗结局的关系。结果HFRS患者ALT、AST、TBIL及白蛋白异常分别占73.84%(271/367)、79.84%(293/367)、13.35%(49/367)和44.41%(163/367)。HFRS不同临床型间ALT、AST和TBIL差异有统计学意义(P<0.001),而白蛋白各型间差异无统计学意义(P>0.05)。结论汉坦病毒易于引起肝脏损害,肝损害程度与病情、预后有关;ALT、AST及TBIL是反映肝脏损害程度的重要指标;而白蛋白不能作为汉坦病毒肝损害程度的判断指标。     

Modulation of ischemia-reperfusion-induced hepatic injury by kupffer cells

To elucidate the role of Kupffer cells in ischemia-reperfusion-induced hepatic injury, hepatic injury induced by ischemia-reperfusion was analyzed after modulation of Kupffer cell function. Ischemia of the liver was performed by occlusion of both the portal vein and hepatic artery, which enter into the left lateral and median lobes of the liver. Blood flow in the ischemic lobe was reduced, in contrast to an increased blood flow in the nonischemic lobe during occlusion of the veins. Although hepatocyte damage was not demonstrated by ischemia for <60 min, hepatic injury was found after reperfusion of the liver, and activation of Kupffer cells was morphologically demonstrated by electron microscopies. Suppression of Kupffer cells, induced by previous administration of gadolinium chloride or latex particles, reduced the grade of hepatic injury induced by ischemia-reperfusion. On the other hand, stimulation of Kupffer cell phagocytosis, induced by administration of latex particles at the time of reperfusion, aggravated the ischemia-reperfusion-induced hepatotoxicity, which was then reduced by simultaneous administration of superoxide dismutase. Kupffer cells, isolated from the rats treated with the ischemia-reperfusion procedure, have been found to release increased amounts of oxygen radical intermediates. These results suggest that hepatic injury induced by ischemia-reperfusion is modulated by the function of Kupffer cells and that superoxide anion released from Kupffer cells cound play an important role in ischemia-reperfusion hepatic injury.     

活络舒肝胶囊对急性肝损伤细胞保护作用的实验研究

目的 :研究活络舒肝胶囊对急性肝损伤的肝细胞保护作用。方法 :SD大鼠 30只均分为 3组 :模型组采用四氯化碳腹腔注射制作急性肝损伤模型 ;治疗组首先予以活络舒肝水溶液 6 m l/ d,分 3次灌胃 ,1周后造模 ,造模后继续给予此药灌胃 ;另设正常组比较。造模 1周后取肝组织行组织病理学检查 ,同时采集静脉血进行血浆肝酶学和血蛋白质含量的测定。结果 :模型组大鼠出现明显的肝细胞坏死 ,而治疗组大鼠坏死范围明显缩小 ,程度明显减轻 ,此外 ,电镜检查结果两组亦有差异。模型组大鼠丙氨酸氨基转移酶、门冬氨酸氨基转移酶、碱性磷酸酶值升高 ,总蛋白下降 ,与治疗组相比差异有显著性意义 (P <0 .0 5 )。结论 :活络舒肝胶囊对急性肝损伤时肝细胞具有保护作用     

Flucloxacillin-associated hepatic injury

Eleven cases of hepatic injury attributed to the intake of flucloxacillin were reported to the Netherlands Center for Monitoring of Adverse Reactions to Drugs between 1982 and 1992. They concerned four men and seven women, with a mean age of 57 years, treated for 2–28 days with an oral dose varying from 1500–4000 mg per day. Symptoms mostly appeared 10 to 30 days after starting treatment with flucloxacillin. Biochemically, the pattern was compatible with cholestatic hepatitis in seven cases, with a mixed cholestatic-hepatocellular type of injury in one case, a hepatocellular pattern in two cases, and mild liver enzyme elevations in one patient. Two patients died, one due to fatal bleeding from the liver after biopsy, and the second patient to a combination of hepatic and cardiac failure. The other patients recovered, on average 72 days after peaking of serum aminotransferase values. Histology in seven cases showed cholestatic hepatitis in five, with cholangitis or cholangiolitis in four of these patients. In the other two patients, there was centrilobular cholestasis with extensive bridging fibrosis and portal-central bridging necrosis, respectively.     

Late persistence of serum gamma-glutamyl transpeptidase activity after mononucleosis. Report of 3 cases.

gamma-Glutamyl transpeptidase (GGTP) is a sensitive but nonspecific index hepatobiliary disease. In infectious mononucleosis (IM) or the mononucleosis-like disease attributable to cytomegalovirus (cytomegalovirus-induced IM), GGTP reverted to normal later than aspartate aminotransferase and alkaline phosphatase. In three cases elevated serum GGTP activity persisted for up to 24 months -- raising the question of persistent 'post-IM' hepatitis. Such prolonged GGTP activity was unusual in other late IM specimens. Possible, but unlikely, causes for such persistent GGTP activity are an unusual degree of hepatic damage during acute IM, excessive induction of microsomal enzyme system activity by drugs, or unusual Epstein-Barr virus carrier state activation that might contribute to ongoing hepatic structural damage. Other markers of chronic hepatocellular disease including aspartate aminotrasferase, alkaline phosphatase, and bilirubin were normal in late specimens from these 3 patients. The cause of their persistent elevated GGTP activities remains unknown.     

Primary infection with Epstein-Barr virus in infants in the United States: clinical and serologic observations.

Previous studies in Ghana had shown that primary infections with Epstein-Barr virus in infants under the age of two years remain silent and evoke antibody responses different from those seen in infectious mononucleosis. In order to determine whether or not these observations were limited to Africa, 80 American infants presenting with minor infectious complaints were studied serologically; 14 (17.5%) showed evidence of recent or current primary infections with Epstein-Barr virus. The clinical features of these 14 infants were similar to those of the other 66 and did not suggest a diagnosis of infectious mononucleosis, nor were there histories of a recent infectious mononucleosis-like illness. Ten (72%) had antibodies to the early antigen complex induced by Epstein-Barr virus; however, these antibodies were directed, as in the Ghanaian infants, against the restricted rather than the diffuse components, in contrast to the pattern generally observed in infectious mononucleosis. Possible reasons for the differences between the responses of infants and those of older individuals to primary infection with Epstein-Barr virus and to the early antigen complex are discussed.     

Cold agglutinins in infectious mononucleosis and heterophil-antibody-negative mononucleosis-like syndromes.

Cold agglutinins (CA) were evaluated prospectively in patients with various mononucleosis syndromes and in a large control group. Cold agglutinins with anti-i specificity were seen mainly in heterophil-positive or -negative Epstein-Barr virus (EBV)-induced infectious mononucleosis (31.8% of cases). Unclassified CA with equal reactivity against cord and adult erythrocytes were seen in 56 of 150 (37.3%) cases of heterophil-antibody-positive infectious mononucleosis (IM), in 1 of 7 (14.3%) cases of heterophil-negative EBV-induced IM, and in 12 of 31 (38.7%) cases of the heterophil-negative mononucleosis-like syndrome due to cytomegalovirus or other unspecified agents. One patient with heterophil-positive IM had a persistent, partially papain sensitive CA with anti-Pr-like activity. Anti-i CA were seen in less than 1.0% of healthy young adults (500) or patients without mononucleosis (500) submitted for heterophil studies. Unclassified CA were noted in 3.2% of the latter 1000 samples.     

Heterophil-negative infectious mononucleosis and mononucleosis-like illnesses. Laboratory confirmation of 43 cases.

During a 50-month period the diagnosis of heterophil antibody negative infectious mononucleosis or of a mononucleosis-like illness was made in 43 patients with a variable clinical picture and significant numbers of atypical lymphocytes. Epstein-Barr virus (EBV)-related serologic tests revealed that seven patients had primary EBV infections based on the detection of immunoglobulin M (IgM) antibodies to EB-viral capsid antigens (IgM-VCA) and the absence of anti-Epstein-Barr virus associated nuclear antigen (EBNA) on most initial specimens (six of seven cases). Thirty cases were due to active cytomegalovirus (CMV) infections and both detectable CMV-macroglobulins (≧1:32) and significant anti-CMV titers were present by a complement fixation technic. Abnormalities in liver function were less marked in CMV than in EBV infections in age-matched subjects. Of the remaining six cases, one was due to rubella and one to toxoplasmosis. Four cases were of undetermined etiology. Serums from 38.1 per cent of the patients with heterophil-antibody positive infectious mononucleosis were found to “cross react” in the IgM-CMV test, but serums from patients with acute CMV infection did not cross react in the VCA-specific IgM test. In nine of 36 cases without heterophil antibody (six due to CMV, one due to toxoplasmosis and one apparent infectious hepatitis), anti-D or -R of the early-antigen (EA) complex was detected (1:10 to 1:40), raising the question of reactivation of the EBV-carrier state by intervening infections mainly of viral origin.     

The liver in infectious mononucleosis

Summary 1. Twenty-two patients with infectious mononucleosis were studied by liver biopsy and paper electrophoresis of the serum proteins. The findings were compared with a similar group of 30 patients with infectious hepatitis.2. The essential histologic features of infectious mononucleosis were the presence in the hepatic sinusoids and portal tracts of chronic inflammatory cells resembling small lymphocytes, with essentially no parenchymal cell damage. Admixed with this lymphocytic infiltrate, but in relatively minimal numbers, were a few plasma cells and polymorphonuclear leukocytes. In addition, in infectious mononucleosis there were, with rare exceptions, no lipochrome-containing Kupffer cells. Thus, in the majority of cases, the histologic picture was distinct from that seen in infectious hepatitis. Only in comparing a few of the more severe infectious mononucleosis cases with subsiding infectious hepatitis cases was there any tendency for the two pictures to merge, and the distinction on histologic grounds between the two entities could be made in the great majority of cases.3. The most commonly seen abnormalities in the paper electrophoretic patterns of sera obtained from patients with infectious mononucleosis were decreased albumin, increased gamma globulin, not infrequent but variable changes in alpha₂ globulin, and the presence of abnormal proteins migrating with mobilities intermediate to alpha₂ and beta, and beta and gamma globulins. The abnormalities observed in infectious hepatitis were similar to those of infectious mononucleosis, except that in hepatitis alpha₂ globulin was decreased more consistently, gamma globulin increased less frequently, and beta globulin, which was normal in practically all the cases of infectious mononucleosis, was increased in a considerable number of cases.4. Treatment of patients with infectious mononucleosis need not include prolonged bed rest and restriction of activity in an effort to avoid the development of chronic liver disease.