肝硬化病人发热原因的探讨——附172例分析

目的:探讨肝硬化病人发热原因。方法:对组织学和临床诊断的肝硬化发热病人进行回顾性分析。结果:421例肝硬化病人中,172例伴发热,占40.9％。以各种感染为最多,共75例(43.6％),其他原因主要有结核性腹膜炎、慢性活动性肝炎、合并肝癌或其他癌症,消化道出血和未明原因发热(21例、12.2％)。住院期间死亡48例,同期住院不发热的肝硬化249例中死亡41例。结论:肝硬化病人发热原因较多,其中以感染最为常见,伴发热的肝硬化病人预后更差。     

Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of "autoimmune" hepatitis

Sixty-five patients with histologically proven chronic active hepatitis of unknown cause but associated with the antiliver/kidney microsome antibody type 1, confirmed by immunofluorescence and immunoprecipitation, were selected as forming a special entity. This disease was found to be rare with a prevalence of 5/1,000,000. The female to male ratio was 8:1. The condition occurred at all ages but was most common between the ages of 2 and 14 years. In 22 of the 65 cases, the hepatitis was associated with an autoimmune disease, most commonly insulin-dependent diabetes, autoimmune thyroid disease and vitiligo. The same autoimmune diseases were present in first-degree relatives from seven families. In 36 cases, the onset of disease resembled acute viral hepatitis. Serum biochemical tests showed marked elevation in aminotransaminases and hypergammaglobulinemia. Paradoxically, serum and salivary IgA levels were often normal or low. Histologic findings were multifocal hepatic necrosis with bridging in the acute stage, and aggressive hepatitis with mononuclear cell infiltration or macronodular cirrhosis in the late stages. Serologically, apart from the presence of antiliver/kidney microsome antibody type 1, the disease was characterized by the absence of antiactin, antimitochondria and antinucleus antibodies; however, organ-specific autoantibodies were often present. The clinical course was usually severe: six patients in the acute stage presented with fulminant hepatitis, and all, except two, other patients progressed to cirrhosis. Prolonged treatment with corticosteroids and immunosuppressants was usually effective in rendering the cirrhosis inactive. The cumulative survival rate was 51% at 14 years. We propose to call this entity "anti-LKM1 chronic active hepatitis" or "autoimmune hepatitis type II" to differentiate it from classical "lupoid hepatitis" or autoimmune hepatitis type I.     

Muscle hematomas: Uncommon but horrendous complication of cirrhosis liver

Bleeding manifestations, usually cutaneous or gastrointestinal - are common in liver cirrhosis. Spontaneous intracerebral and intramuscular bleeds are reported uncommonly, often associated with gross hepatic dysfunction and severely deranged hemostatic parameters, and are often markers to imminent mortality. Male sex, alcoholic etiology, significant thrombocytopenia, severe coagulopathy, and advanced liver disease are common denominators in patients with spontaneous intramuscular bleed. We here report three cases of spontaneous muscle hematomas complicating hepatic cirrhosis. To the best of our knowledge, this is the largest single center series reporting spontaneous muscle hematomas complicating cirrhosis from the Indian subcontinent.     

Advanced hepatic fibrosis and cirrhosis due to nonalcoholic fatty liver disease in Sri Lankan children: a preliminary report

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and may progress to advanced hepatic fibrosis and cirrhosis in some patients. Cirrhosis due to NAFLD is considered extremely rare in children in the Asia–Pacific region. We report the characteristics of 5 children with advanced hepatic fibrosis and cirrhosis due to NAFLD. Four of them were obese, and all of them had high alanine transaminase levels and ultrasonographic evidence of fatty liver. None had diabetes mellitus or hyperlipidemia. The calculated HOMA-IR was more than two in all five cases. Liver biopsy showed stage III fibrosis in 2 patients and stage IV fibrosis (cirrhosis) in 3.     

Plasma human atrial natriuretic factor in cirrhosis and ascites with and without functional renal failure

Functional renal failure of cirrhosis (FRFC) is a usually fatal syndrome of acute renal failure occurring in patients with advanced liver disease. Although not conclusively proven, most evidence suggests that renal arterial and arteriolar vasoconstriction is the cause of the renal failure in these patients. However, the mediators of the vasoconstriction remain unknown. Human atrial natriuretic factor (hANF) is a hormone with potent natriuretic, diuretic, and vasorelaxant properties. A deficiency of hANF could lead to renal arterial vasoconstriction and avid renal sodium retention as seen in FRFC. This study was undertaken to determine if patients with FRFC are deficient in circulating hANF. Seven patients with advanced alcoholic liver disease and renal failure of unknown cause (FRFC) were compared with 7 patients with advanced alcoholic liver disease, ascites, and normal serum creatinine as well as with 14 healthy volunteers. Plasma hANF was measured by radioimmunoassay. Plasma hANF was 742 +/- 227 pg/ml (mean +/- SEM) in patients with FRFC compared with 360 +/- 70 pg/ml in patients with liver disease and normal serum creatinine (p greater than 0.05) and 28 +/- 5.7 pg/ml in healthy volunteers (p less than 0.005 vs. FRFC and chronic liver disease, ascites, and normal serum creatinine). Thus, FRFC is not caused by a deficiency of circulating hANF. The elevated plasma hANF levels in patients with chronic liver disease and continued sodium retention may suggest a renal insensitivity to the natriuretic effects of hANF.     

Cryptogenic cirrhosis: clinico-biochemical comparison with alcoholic and viral etiologies

Cryptogenic cirrhosis defines a group of undetermined etiology that would either be caused by factors as alcohol, virus and others or be due to still unknown etiological factors. To test these hypotheses we have looked for similarities or differences in clinico-biochemical presentation of 196 cases of alcoholic, viral and cryptogenic cirrhosis. Age, jaundice, spiders, palmar erythema and factor V showed a statistically significant difference of the cryptogenic cirrhosis when compared with both alcoholic and viral etiologies. On clinico-biochemical grounds it could be suggested that cryptogenic cirrhosis would constitute a discrete group, based on the following parameters: predominance of females, a more advanced age, less marked peripheral signs of chronic hepatic failure (jaundice, spiders and palmar erythema) besides milder alterations of laboratory liver function tests.     

Pathology of chronic hepatitis B virus infection in children: with special reference to the intrahepatic expression of hepatitis B virus antigens

The clinical, virologic and pathologic features of chronic hepatitis B virus infection were studied in 66 children, of whom 29 were symptomatic and 37 asymptomatic. The majority (79%) of symptomatic children had histologically aggressive diseases: 11 had chronic active hepatitis and 10 had cirrhosis. In contrast, most asymptomatic children had nonaggressive diseases (35 cases); only 2 had chronic active hepatitis. Nine of the 10 children with cirrhosis were under 6 years of age, and the cirrhosis was often advanced, indicating that hepatitis B virus infection can cause the rapid development of cirrhosis in early life. HBcAg was present in 71% of 62 cases examined and correlated well with the status of HBeAg in serum. Cytoplasmic HBcAg was more frequently associated with aggressive disease than was nuclear HBcAg expression alone or no detectable HBcAg in the liver. A male predominance (75%) was found, particularly in children with aggressive diseases (91%) compared to those with nonaggressive forms of disease (67%). Sera from mothers of 43 of these children were tested for HBsAg, and 51% were positive. HBsAg was particularly common among mothers of children with symptomatic disease (69%) or cirrhosis (100%). These findings suggest that male sex and perinatal infection are important factors in the development of overt chronic hepatitis B and cirrhosis in children.     

Energy expenditure and substrate oxidation in patients with cirrhosis: the impact of cause, clinical staging and nutritional state.

Many clinicians subjectively feel that cirrhotic patients frequently have clinical signs of hypermetabolism. However, it is unknown whether hypermetabolism is a constant feature of chronic liver disease, corresponds to liver destruction and repair or is of prognostic value. This article is about resting energy expenditure and substrate oxidation rates in 123 patients with biopsy-proven cirrhosis differing with respect to cause, duration of the disease, biochemical parameters of parenchymal cell damage, cholestasis, liver function, number of complications, clinical staging and nutritional state. Resting energy expenditure varied between 1,090 and 2,300 kcal/day and differed from the predicted values in 70% of the patients. Resting energy expenditure was closely related to fat-free mass, and 52% of the variability could be explained by fat-free mass, age and sex. Of all the patients, 18% were hypermetabolic and 31% were hypometabolic. Hypermetabolism showed no strict association with the cause of cirrhosis, the duration of the disease, liver function, cholestasis, cell damage, clinical staging, blood hemoglobin, plasma thyroid hormone levels or human leukocyte antigens. An increased resting energy expenditure was associated with significant losses of muscle, body cell mass and extracellular mass at unchanged body fat, whereas fat and fat-free mass were increased in hypometabolic patients when compared with normometabolic patients. Lipid oxidation was increased, but glucose oxidation was reduced in nearly all patients with cirrhosis. This was most pronounced at advanced stages of liver disease. Although similar with respect to liver function and clinical staging, 76.2% of hypermetabolic patients had transplants within the observation period, compared with only 16.7% and 8.1% in the normometabolic group and hypometabolic group, respectively. Posttransplantation mortality was independent of pretransplantation resting energy expenditure, but it increased significantly in patients with losses in body cell mass. In conclusion, hypermetabolism is not a constant feature of cirrhosis and results more from extrahepatic than from hepatic factors. It may cause malnutrition and contributes to the clinical outcome of patients with chronic liver disease.     

31例HBsAg阴性慢性乙型肝炎患者的临床及病理分析

目的了解HBsAg阴性慢性乙型肝炎(隐匿性乙型肝炎)患者的发病情况、临床和病理特点以及可能的发病机制。方法对31例反复肝功能异常、HBsAg阴性HBV感染患者进行临床、肝组织病理及免疫组化分析;采用荧光定量PCR方法对血清HBVDNA进行定量分析,以免疫组化法检测肝组织内HbsAg和HBcAg的表达,按慢性肝炎病理诊断标准进行分级(G)及分期(S)。结果31例HBsAg阴性慢性乙型肝炎患者中,18例肝组织病理和免疫组化检测证实为慢性乙型肝炎,其中7例诊断为肝炎后肝硬化;18例肝组织学检查HBsAg阳性2例,HBcAg阳性16例;病理分级、分期G4S4有7例,G1-3、S2-3有11例。结论HBsAg阴性HBV感染仍是我国原因不明肝病的主要原因之一,低水平HBV感染可导致慢性肝炎,甚至肝硬化或肝癌。     

Hepatitis C: the clinical spectrum of the disease

The hepatitis C virus (HCV) infects nearly 170 million people worldwide and is responsible for approximately 20% of cases of acute hepatitis and 70% of cases of chronic hepatitis. Acute hepatitis is icteric in only 20% of patients and is rarely severe. Eighty-five percent of infected patients develop chronic infection which is generally asymptomatic, resulting in most cases in fortuitous diagnosis, which may be made at a late stage. Twenty-five percent of the HCV chronic carriers have persistently normal serum alanine aminotransferase (ALT) levels despite having detectable HCV RNA in serum; 75% have elevated ALT levels. The former patients usually have mild histologic lesions, probably with a good long-term prognosis. In the latter patients, a liver biopsy is the most accurate way to distinguish patients with mild chronic hepatitis from those with moderate or severe chronic hepatitis. While most patients with mild chronic hepatitis have a slowly progressive liver disease, the patients with moderate or severe chronic hepatitis may develop cirrhosis within a few years. In patients with HCV-related cirrhosis, the incidence of hepatocellular carcinoma is 2-5% per year. At presently, HCV-related end-stage cirrhosis is the first cause of liver transplantation.     

Advanced hepatocellular carcinoma associated with cystic fibrosis

Advances in the treatment of the respiratory complications of cystic fibrosis, including the availability of lung transplantation have led to a greater awareness of the manifestations of liver disease in up to 40% of patients with Cystic Fibrosis (CF). We report the case of an 18 year old female with CF who presented with advanced hepatocellular carcinoma and no prior clinical evidence of chronic liver disease. Hepatocellular carcinoma is usually the most severe manifestation of advanced cirrhosis although its development in non-cirrhotic cases of chronic liver disease has been reported. With the increasing life expectancy of CF patients it is likely that more unusual hepatic complications of this disease may be identified. Greater awareness may perhaps lead to earlier diagnosis in those at risk.     

A case of partial autotransplantation of the liver in advanced hepatocellular carcinoma.

Hepatocellular carcinoma in Japan is frequently complicated by chronic hepatic disease such as chronic hepatitis and liver cirrhosis, and it is often impossible to decide the range to be resected only based on clinical stage and other tumor factors. We experienced a case with advanced hepatocellular carcinoma complicated by liver cirrhosis that directly infiltrated into the right and middle hepatic vein. Right trisegmentectomy was performed, the tumor site was extracorporeally removed and the hepatic posterior segment was autotransplanted. An anastomosis of the right hepatic vein and the inferior vena cava was performed with a vascular prosthesis. The patencies of the anastomosed vessels in the vascular reconstructions were confirmed by Doppler sonography, which was very useful, providing an easy and exact evaluation of hepatic blood flow at the patient's bedside. Throughout the post-operative course before the patient's discharge, no abnormal hepatic function was found. Though cases for which partial hepatic autotransplantation is appropriate may be few, this operation procedure, which applies hepatic transplantation techniques, is significant in that it increases the resectability and achieves curative resection of hepatocellular carcinoma.     

Hepatic sarcoidosis

Sarcoidosis is a multisystem disease of unknown aetiology. Histological evidence of non-caseating granulomas represents the main finding. It affects mostly young people, targeting primary the lung and hilar lymph nodes although liver involvement is often encountered. Hepatic sarcoidosis covers a broad spectrum from asymptomatic hepatic granulomas formation and slightly deranged liver function tests to clinically evident disease with cholestasis or, in advanced cases, cirrhosis and portal hypertension. Other granulomatous diseases (mainly systemic infections like tuberculosis) should be excluded prior to treatment, as longstanding corticosteroid administration is the main stem of therapy. In advanced cases, liver transplantation represents the ultimate therapeutic option.     

Serum levels of C3 and cholinesterase in various diseases of the liver.

The levels of C3, cholinesterase, albumin and prothrombin were determined in 46 patients (27 males and 19 females) - 26 with cirrhosis of the liver, 9 with acute hepatitis, 6 with chronic aggressive hepatitis, 1 with chronic persistent hepatitis and 4 with fatty liver. In all patients and, particularly in those with cirrhotic liver, it was shown that the normal or pathological level of serum C 3 is related both qualitatively and quantitatively to the normal or pathological levels of cholinesterase, albumin, and prothrombin. The percentage in which the levels of these four parameters were pathological was considerably higher in the cases with hepatic coma than in the cases without hepatic coma. The determination of the range of confidence for the 4 parameters showed that, in the patients with hepatic coma, cholinesterase reacted most sensitively to liver damage (0.5 - 0.94) followed by C3 and prothrombin (0.33 - 0.81). Also in the cases without hepatic coma, cholinesterase was the most sensitive indicator (0.05 - 0.29), followed by prothrombin (0.03 - 0.24), albumin and C3 (0.00-0.16).     

The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years

Forty-two patients with nonalcoholic steatohepatitis were followed for a median of 4.5 yr (range = 1.5 to 21.5 yr). Except for two patients with lipodystrophy, all were obese; 35 of 42 were women, 26 of 32 were hyperlipidemic and 15 were hyperglycemic. Upper abdominal pain was the most common reason for presentation. Initial liver biopsy specimens showed the presence of macrovesicular fatty infiltration, lobular (acinar) inflammation, apoptosis, Mallory bodies (in four cases) and fibrosis (in 18 cases). Cirrhosis was present at initial diagnosis in one subject and in another two subjects liver biopsy showed marked fibrosis with disturbed architecture. Serial liver biopsy specimens revealed minimal or no apparent progression of the disorder in most of the patients, in keeping with their benign clinical course. However, one patient showed progression from fibrosis to cirrhosis during the 5-yr observation period, and in the patients with extensive fibrosis the liver disease evolved from one of active inflammation to one of inactive cirrhosis without fat or inflammation. The patient with cirrhosis later died of hepatocellular carcinoma. The severity or type of hepatic change did not correlate with the degree of obesity, hyperlipidemia or hyperglycemia. However, in individual patients, poorly controlled diabetes and rapid weight loss preceded the onset of steatohepatitis. We conclude that nonalcoholic steatohepatitis is a cause of hepatic inflammation histologically resembling that of alcohol-induced liver disease but usually slowly progressive and of low-grade severity. However, the disorder may ultimately result in cirrhosis. Nonalcoholic steatohepatitis should be distinguished from alcoholic steatohepatitis and recognized as a further cause of "cryptogenic cirrhosis."     

The clinical features of hepatic angiosarcoma: a report of four cases and a review of the English literature.

Four cases of hepatic angiosarcoma are reported with a review of 99 other cases in the English literature. Angiosarcoma of the liver is associated with chronic exposure to thorotrast, vinyl chloride, arsenicals, radium and possibly copper and with chronic idiopathic hemochromatosis. Although 40% of patients have hepatic fibrosis or cirrhosis at autopsy, the nature of the association between chronic liver disease and hepatic angiosarcoma is unknown. The clinical presentation of hepatic angiosarcoma is nonspecific with abdominal pain, weakness and weight loss common complaints and with hepatomegaly, ascites and jaundice common findings. Liver function tests are usually abnormal but there is no one liver function test or set of tests specific for the tumor. The occurrence of thrombocytopenia and disseminated intravascular coagulation is characteristic of hepatic angiosarcoma and may be related to local consumption of clotting factors and formed blood elements in the tumor. Catastrophic intraabdominal bleeding is also characteristic and occurs in one-fourth of all cases. This complication is likely related to the high incidence of clotting abnormalities and the vascular nature of the neoplasm. Selective hepatic arteriogram and open liver biopsy are the foundations of diagnostic evaluation. Percutaneous liver biopsy should be avoided. Failure to appreciate the possibility of hepatic angiosarcoma in the proper clinical setting, leading to blind percutaneous biopsy, may result in failure to make the diagnosis at the cost of significant morbidity and mortality. Survival of patients with hepatic angiosarcoma is brief; only 3% live longer than 2 years. Treatment of the tumor to date is empirical. There are probably a few patients who might benefit from radical surgery with curative intent. For all others chemotherapy is indicated. Adriamycin is active against hepatic angiosarcoma, but optimal dose and mode of administration require further investigation. Further study is also required to delineate the cause of hepatic angiosarcoma in the 60% of cases without definite epidemiologic association.     

肝病与乙型、丙型肝炎病毒感染关系的探讨

本文采用ELISA法对25例慢性肝炎，105例肝硬化，64例肝癌，以及8例急性黄疸型肝炎进行了HBV标志物及抗－HCV的检测，结果：HBV感染率为80．6％，抗－HCV检测阳性率为46％，二者均阳性的双重感染率为32％。其中肝癌组双重感染明显高于肝硬化组，P＜0．001。单纯抗-HCV检出率为10．8％，说明HBV是引起肝炎，肝硬化，肝癌的主要原因，而CV感染也是其致病因素。本文对有输血史的慢性肝炎，肝硬化，肝癌100例进行抗－HCV检测其阳性率为59％，而02例无输血史的肝病患者抗－HCV检出率为25％，输血组抗－HCV检出率明显高于无输血组，P＜0．001。其中慢性肝炎，肝硬化，肝癌病人输血组抗－HCV检出率亦明显高于无输血组，各组P＜0．001，故提示，HCV感染与输血有密切关系。50例HBV标志物阴性的健康献血员抗－HCV阳性率为6％。     

The blood and bone marrow in patients with cirrhosis of the liver

The peripheral blood and bone marrow findings in patients with cirrhosis ofthe liver have been analyzed on the basis of a review of the literature and theauthors’ study of 25 patients with diagnoses verified by biopsy of the liver.

The principal blood findings are macrocytic or normocytic anemia with normalor elevated mean corpuscular hemoglobin values, lymphopenia and thrombocytopenia in the majority of cases.

Anemia may be independent of bleeding, and the severity of anemia or macrocytosis does not appear to be related to the severity of the liver lesion.

The consistent change in the bone marrow is extension of the marrow organ sothat active hematopoiesis is found in the shafts of the long bones.

Regardless of the presence or absence of bleeding or anemia, the marrow of thesternum is of normal or increased cellularity, with normal or increased erythrocytogenesis and megakaryocytogenesis in most cases.

Hypocellularity of the marrow is an unusual finding, even in patients with advanced liver lesions.

Macronormoblastic erythropoiesis is seen in patients with macrocytic anemia,but megaloblastic erythropoiesis dces not result from cirrhosis of the liver.

The presence of peripheral cytopenias (anemia and thrombocytopenia) in spiteof normal or increased formation of erythroblasts and megakaryocytes in the marrow is suggestive of hypersplenism in patients with hepatic cirrhosis.

In patients with chronic hemorrhage the blood and bone marrow pictures arethose of iron deficiency anemia, although other changes such as lymphopenia andthrombocytopenia tend to persist.

The combined peripheral blood and sternal marrow examination is often of valuein establishing the diagnosis of cirrhosis of the liver.

     

Accelerated hepatic fibrosis in patients with combined hereditary hemochromatosis and chronic hepatitis C infection

BACKGROUND/AIMS: Hereditary hemochromatosis (HH) and chronic hepatitis C virus (HCV) infection can both result in hepatic fibrosis and cirrhosis. It has been proposed that iron overload and HCV may have potentiating effects on hepatic fibrogenesis. This study determined if HH patients with HCV would present with hepatic fibrosis/cirrhosis at a younger age and at a lower hepatic iron concentration compared to patients with HH or HCV alone. METHODS: Ten patients with combined HCV and HH were compared to 13 patients who had HH alone and 24 patients who had HCV alone. All patients had advanced fibrosis/cirrhosis on liver biopsy. All HH patients were homozygous for the C282Y mutation. RESULTS: At presentation with advanced fibrosis/cirrhosis, the mean age of the HH/HCV group was significantly lower than that of the HH group and the HCV group. The mean hepatic iron concentration was lower in the combined HH/HCV group compared to that of the HH group. CONCLUSIONS: HH patients with HCV present with advanced fibrosis/cirrhosis at a younger age and at a lower hepatic iron concentration compared to HH patients without HCV. These findings support the concept that the combination of HH-induced iron overload and HCV has a potentiating effect on hepatic fibrogenesis.     

Liver fibrosis in hepatitis B: a dynamic process

Liver fibrosis is a common complication of chronic hepatitis B leading to the progressive destruction of normal tissue architecture or the replacement of hepatocytic tissue with fibrous tissue. The final outcome of this process is liver cirrhosis, which is the major cause of morbidity and mortality in chronic viral hepatitis. Fibrogenesis is closely related to activation of the main type of fibrocompetent cells in the liver: hepatic stellate cells. Experimental models have allowed a better understanding of the dynamics of fibrosis, the biological processes related to its progression and regression and the development of new anti-fibrotic drugs. Nevertheless, it is universally accepted that such an anti-fibrotic treatment will be efficient only after hepatitis B virus eradication. Furthermore, early fibrosis is more amenable to regression than more advanced and highly organized liver cirrhosis.