Portal Hemodynamics in Fulminant Hepatic Failure as Assessed by Duplex Doppler Ultrasonography

Portal hypertension usually occurs in patients with fulminant hepatic failure (FHF). There is, however, no information on portal venous hemodynamics in patients with FHF. Therefore, we studied the portal venous hemodynamics in patients with FHF using duplex Doppler ultrasonography. We measured the portal vein diameter, flow velocity, and volume flow with duplex Doppler ultrasonography in 29 patients with FHF and 15 patients with uncomplicated acute viral hepatitis. No significant difference was observed in the portal vein parameters in the two groups. Nineteen patients with FHF survived. No difference in portal flow velocity and flow rate was observed between survivors and nonsurvivors. A significantly lower portal flow velocity was observed in nine patients of FHF with ascites compared with those without ascites (12.29 ± 2.81 vs 16.26 ± 4.87 cm/sec; P < 0.01). Portal hemodynamics do not significantly change in fulminant hepatic failure; therefore, it has no prognostic significance.     

Fulminant Hepatic Failure in an African Setting: Etiology, Clinical Course, and Predictors of Mortality

This is prospective cross-sectional study on 37 patients presenting to different hospitals in Khartoum state, Sudan, sought to determine the etiology, clinical course, and predictors of mortality in patients presenting with fulminant hepatic failure (FHF). Patients were subclassified into hyperacute, acute, and subacute FHF; all sera were tested for hepatitis A, B, C, and E; negative samples were tested for antinuclear antibodies and anti-smooth muscle antibodies. The commonest etiologic factors included seronegative hepatitis (38%), hepatitis B virus (22%), severe Plasmodium falciparum malaria (8%), autoimmune hepatitis (8%), hepatitis E virus (5%), anti-tuberculous drugs (5%), and lymphomatous infiltration of the liver (5%). The mortality rate was high at 84%. Poor prognostic factors included presentation with grade III/IV encephalopathy, evidence of bacterial infection, and a prolonged prothrombin time of >25 seconds over the controls.     

Liver Transplantation Avoided in Patients With Fulminant Hepatic Failure Who Received Albumin Dialysis With the Molecular Adsorbent Recirculating System While on the Waiting List: Impact of the Duration of Therapy

Eighteen patients with fulminant hepatic failure due to various medical causes were listed for emergency liver transplantation and treated with extracorporeal albumin dialysis sessions using the molecular adsorbent recirculating system (MARS) at our center over a 74‐month period. Due to improvement of liver function, transplantation could be avoided in 9 patients (50%, 95% confidence interval 29% to 71%) who fully recovered afterwards. This improvement rate was higher than the rate of improvement in the French cohort of fulminant hepatic failure patients with similar etiologies (19.3%, 95% confidence interval 14.9% to 24.6%, P = 0.002). In our 18 patients, there were no statistically significant differences in any baseline characteristics or in the time with liver failure meeting transplant criteria between the patients who improved while waiting and those who did not. However, the patients who improved received a greater number of sessions and a longer total duration of MARS therapy (all P < 0.001). In the whole study population, a MARS therapy duration ≥15 h was significantly associated with improvement of liver function without transplantation (adjusted adds ratio [OR] 65.76, 2.48–1743.11, P = 0.01). Tolerance of therapy was acceptable. These results suggest that MARS therapy could contribute to native liver recovery and is safe in patients on the waiting list for fulminant hepatic failure. A minimum duration of therapy (≥15 h) could be necessary to expect significant liver function improvement.     

CASE REPORT: Troglitazone-Induced Fulminant Hepatic Failure

The three reported cases demonstrate that troglitazone is an idiosyncratic hepatotoxin that can lead to irreversible liver injury. Thus, troglitazone should be prescribed with caution and should not be used as a first-line agent in the treatment of type II DM when potentially less toxic alternatives are available. It remains to be seen whether the hepatotoxicity associated with troglitazone is a drug-class effect or specific to troglitazone. Other thiazolidinediones currently in clinical trials may be able to provide the therapeutic benefits of troglitazone without significant hepatotoxicity. If troglitazone is used, frequent monitoring of serum aminotransferases and symptoms is mandatory. However, as illustrated by these and other cases reported to date, the onset of troglitazone-induced liver injury is insidious and temporally variable. Thus, the value of close monitoring and when, if ever, it is safe to stop such monitoring are currently unclear.     

微囊化肝细胞移植治疗暴发性肝衰竭大鼠的疗效观察

目的观察微囊化肝细胞腹腔移植对暴发性肝衰竭大鼠的疗效。方法气流法制备含肝细胞的微囊。D-氨基半乳糖诱导大鼠急性肝功能衰竭模型,设模型组、裸肝细胞腹腔移植组、微囊化肝细胞移植组,每组8只测定ALT、AST、TBil水平。样本比较采用重复测量的多元方差分析或单因素方差分析,组间比较采用t检验。结果肝衰竭模型建立后ALT、AST、TBil迅速升高（P〈0．05）,并于24h～72h达高峰。同一时间点两两比较发现,Ⅱ、Ⅲ组在48h、72h、120h均明显低于Ⅰ组（P〈0．05）,Ⅲ组在48h、72h均低于Ⅱ组（P〈0．05）。Ⅲ组峰值较Ⅰ组前移。模型组、裸肝组和微囊组大鼠生存率分别是26．7％（4／15）、40．0％（6／15）、73．3％（11／15）,微囊组较模型组、裸肝组大鼠生存率有显著性提高（P〈0．05）。结论HCT能降低FHF大鼠ALT、AST和TBil水平,减轻肝损伤程度,可能改善FHF预后。     

用肝细胞生长因子治疗25例重症肝炎的临床观察

本文用肝细胞生长因子（HSS）加综合治疗方法对25例重症肝炎患者进行了治疗，并对20例重症肝炎病人仅用综合疗法进行对照观察。结果提示：经2个疗程治疗后，治疗组血清转氨酶，胆红素及凝血酶原时间好转例数及恢复正常例数均明显高于对照组（P＜0．05）。但在两个疗程时间内，其白，球蛋白比例改善例数在二组间未见有差异（P＞0．05）。对照分析还显示，治疗组病人的总体治疗有效率（100％）明显高于对照组（45％）（P＜0．05）。提示肝细胞生长因子治疗重症肝炎病人有较好疗效，是一种较好的治疗药物。     

Pig Liver Perfusion in the Treatment of Fulminant Hepatic Necrosis

This paper describes 4 patients with hepatic coma resulting from presumed viral hepatitis with massive liver cell necrosis, who were treated with pig liver perfusion alternating with exchange transfusion. None of the patients survived, but two showed a response to the program of treatment employed, in that there was an improvement in the level of consciousness. All patients died of haemorrhagic complications. The contribution of the oxygenator used in the circuit to the development of thrombocytopoenia is discussed, with reference to other circuits with and without oxygenators. Thrombocytopoenia may also result from disseminated intravascular coagulation in the patient, and from sequestration of platelets in the liver perfused with heterologous blood.     

Fulminant hepatitis and the new G/GBV-C flavivirus

A new virus within the family Flaviviridae, 'hepatitis' G/GBV-C, has been incriminated by several authors as a causative factor of idiopathic or cryptogenic fulminant hepatitis, a syndrome of presumed viral aetiology. Review of worldwide data from 22 studies on 364 cases indicates that G/GBV-C infection is present in approximately 20% of idiopathic cases but a similar or even higher prevalence is detected in fulminant hepatitis of viral B, D or C aetiology, reflecting a high rate of parenteral viral exposure rather than a specific aetiology of fulminant hepatic failure. An aetiopathogenic role of G/GBV-C in fulminant hepatitis seems to be further refuted by the analysis of other data in the literature. The presence of G/GBV-C infection in fulminant hepatic failure is largely a result of secondary infection or coinfection. The aetiopathogenetic mystery of cryptogenic or idiopathic fulminant hepatitis remains unsolved.     

Fulminant hepatic failure resulting from small-cell lung cancer and dramatic response of chemotherapy

Prompt treatment in tumor-associated encephalopathy may prolong survival. We describe a 69-year-old male patient who was presented with fulminant hepatic failure, secondary to small-cell lung carcinoma with rapidly progressing encephalopathy. Both symptoms remitted following chemotherapy, suggesting swift diagnosis and administration of chemotherapy to be effective in treatment of fulminant hepatic failure and encephalopathy.     

Elevated Resistive Index in the Hepatic Artery as a Predictor of Fulminant Hepatic Failure in Patients with Acute Viral Hepatitis: A Prospective Study Using Doppler Ultrasound

To assess the sensitivity and specificity of the resistive index of the hepatic artery, which is related to the vascular resistance of the artery, for the prediction of fulminant hepatic failure, we performed Doppler ultrasonography examinations on the hepatic arteries of 72 patients with acute viral hepatitis (25 of whom developed fulminant hepatic failure and 47 of whom recovered without developing fulminant hepatic failure) as well as the hepatic arteries of age- and sex-matched controls. The mean resistive index of the hepatic arteries in patients who developed fulminant hepatic failure was significantly larger than that of patients who recovered without developing fulminant hepatic failure (P < 0.01). When a resistive index cutoff level of 0.74 was used, an 84% sensitivity and a 94% specificity were obtained for the prediction of fulminant hepatic failure. An elevated resistive index of the hepatic artery may be useful for predicting the patient's clinical outcome and determining the need for a liver transplantation in patients with acute viral hepatitis.     

Granulocyte-Colony Stimulating Factor Administration Ameliorates Liver Regeneration in Animal Model of Fulminant Hepatic Failure and Encephalopathy

It has previously been shown that recombinant granulocyte-colony stimulating factor (rG-CSF) accelerates and enhances hepatocyte proliferation in partially hepatectomized rats. In the present study, we examined the effect of rG-CSF administration on liver injury, regeneration, and survival outcome in an experimental rat model of fulminant hepatic failure (FHF) and encephalopathy induced by repeated injections of thioacetamide (TAA). FHF was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA, at intervals of 24 hr. The animals were also injected with either saline or rG-CSF. Serum biochemical parameters and blood ammonia levels, liver histology, stage of hepatic encephalopathy, and survival were statistically significantly improved in TAA-intoxicated and rG-CSF-treated rats compared to TAA-intoxicated and saline-treated ones. Furthermore, rG-CSF not only ameliorated the histologically evident liver injury in a statistically significant manner but also enhanced the proliferative capacity of the hepatocytes. Our data confirm the beneficial effect of rG-CSF administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of rG-CSF as supportive therapy in the management of FHF.     

Fulminant Adenoviral-Induced Hepatitis in Immunosuppressed Patients

Human adenovirus (HAdV) can often lead to fulminant hepatitis in immunocompromised patients, mostly after reactivation of HAdV. Different risk factors, e.g., transplantation and chemotherapy, increase the risk of developing a HAdV hepatitis. We retrospectively analyzed three patients who showed the characteristics of a HAdV hepatitis observed in disseminated disease. In addition to PCR, diagnosis could be proven by pathology, CT scan, and markedly elevated transaminases. All patients had a hemato-oncologic underlying disease. Two had received a stem-cell transplant, and one was under chemotherapy including rituximab. Despite therapy with cidofovir, all patients died. As the incidence of HAdV hepatitis is low, diagnosis may be easily overlooked. No treatment approaches have yet been established. HAdV hepatitis should be considered as a differential diagnosis, especially when risk factors are present. To avoid dissemination, treatment should be initiated as soon as possible.     

Prognostic Value of Abdominal CT Scanning and Hepatic Histopathology in Patients with Acute Liver Failure

Acute liver failure has extremely high mortality without liver transplantation. We attempted to determine the value of abdominal CT scanning and liver biopsy in its management. A retrospective analysis of patients with acute liver failure was performed; demographic, clinical, radiologic and histopathologic features were noted. Over a period of 13 years, 177 patients were evaluated. The mean age was 39 years and 63% were females. The patients were divided into three groups. Fourteen percent survived with medical management (group I), 37% died (group II), and 49% had liver transplantation (group III). Most patients showed diffuse low density of the liver on CT scanning and the proportions were similar in the three groups. Moderate to large ascites was not present in group I but occurred in 31% of patients in group II and in 15% in group III. Mean hepatic volumes were similar in the three groups; however, 97% of the patients with a liver volume of less than 1000 ml either died or required liver transplantation. Liver biopsies among patients with spontaneous recovery (group I) were distinguished by the presence of regenerative changes and a hepatic parenchymal necrosis of less than 50%. These results suggest that in patients with acute liver failure a liver volume of less than 1000 ml and/or hepatic parenchymal necrosis of greater than 50% is indicative of a poor prognosis. This information may assist decision making in such patients, in particular, regarding the need for liver transplantation.     

Hepatitis E virus is a leading cause of acute-on-chronic liver disease:experience from a tertiary centre in Bangladesh

BACKGROUND:Acute-on-chronic liver failure(ACLF) is common in Bangladesh.Acute viral E hepatitis is sporadically encountered in this country each year,with a rising incidence in the rainy season.This study aimed to identify the etiology of ACLF in Bangladesh. METHODS:In this retrospective study,69 ACLF patients were included.They presented to our department at the Bangabandhu Sheikh Mujib Medical University in Dhaka.History of diseases was recorded and appropriate investigations were conducted in all patient...     

Clinical course and duration of viremia in vertically transmitted hepatitis E virus (HEV) infection in babies born to HEV-infected mothers

Summary.  Infection with the hepatitis E virus (HEV) causes a self-limiting acute hepatitis. However, prolonged viremia and chronic hepatitis has been reported in organ transplant recipients. Vertically transmitted HEV infection is known to cause acute hepatitis in newborn babies. The clinical course and duration of viremia in vertically transmitted HEV infection in neonates in not known. We studied 19 babies born to HEV infected mothers. Babies were studied at birth and on a monthly basis to evaluate clinical profile, pattern of antibody response and duration of viremia in those infected with HEV. Fifteen (78.9%) babies had evidence of vertically transmitted HEV infection at birth (IgM anti-HEV positive in 12 and HEV RNA reactive in 10) and three had short-lasting IgG anti-HEV positivity because of trans-placental antibody transmission. Seven HEV-infected babies had icteric hepatitis, five had anicteric hepatitis and three had high serum bilirubin with normal liver enzymes. Seven babies died in first week of birth (prematurity 1, icteric HEV 3, anicteric HEV 2 and hyperbilirubinemia 1). Nine babies survived and were followed up for clinical, biochemical, serological course and duration of viremia. Five of 9 babies who survived were HEV RNA positive. HEV RNA was not detectable by 4 weeks of birth in three babies, by 8 weeks in one and by 32 weeks in one. All surviving babies had self-limiting disease and none had prolonged viremia. Thus HEV infection is commonly transmitted from mother-to-foetus and causes high neonatal mortality. HEV infection in survivors is self-limiting with short lasting viremia.