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Biomedical subjects

T Hassanein

Publications and source records attributed to T Hassanein.

At least 19 recordsLinked to original sources

Albumin dialysis in cirrhosis with superimposed acute liver injury: possible impact of albumin dialysis on hospitalization costs.

Albumin dialysis using the Molecular Adsorbents Recirculating System (MARS) has been found to be beneficial in the treatment of cirrhotic patients with acute decompensation to improve survival as well as reduce associated complications. The present study attempts to analyze the costs involved, and compare it to the benefit as a result of the MARS therapy, thus evaluating its cost-effectiveness. Using the results of a study by Kim et al. describing the effects of complications on the cost of hospitalization in alcoholic liver disease patients, the expenditure incurred in a group of 11 patients treated with standard medical therapy (five survivors) and a group of 12 patients treated with MARS in addition (11 survivors) (Heemann et al., Hepatology 2002) were analyzed. MARS resulted in a reduction of in-hospital deaths, as well as liver disease-related complications. Both these factors led to a substantial reduction of costs in the MARS group, which was enough to counterbalance the extra costs associated with extra-corporeal therapy. In the control group, the total hospitalization cost per survivor were calculated to be at $35,904. In the MARS group, the overall expenditure per survivor including standard medical therapy plus additional MARS liver support therapy were $32,036--a saving of nearly $4000 compared to the control group. Therefore, it appears that the benefits of MARS therapy are enough to justify the cost of treatment and safe hospital costs, at least in the described population. However, further studies are needed to confirm these results.

Albumins↗

Serum aminotransferase levels and platelet counts as predictors of degree of fibrosis in chronic hepatitis C virus infection.

OBJECTIVE: In patients with chronic hepatitis C virus (HCV) infection, liver fibrosis stage is a prognostic factor for therapy outcome. So far, a liver biopsy is necessary to determine disease stage accurately. We sought to develop a simple, noninvasive method of accurately predicting the degree of liver fibrosis in chronic HCV infection. METHODS: We retrospectively studied 211 consecutive patients with chronic HCV, who received a liver biopsy at the Liver Center of the University of California, San Diego. A total of 58 of these patients had a positive history of alcohol abuse, and we analyzed them separately in a sensitivity analysis. AST/ALT ratio and platelet counts were determined in all patients. Fibrosis was staged using the METAVIR score. RESULTS: Both AST/ALT ratio and platelet counts correlated significantly with the disease stage (r = 0.190, p = 0.006, and r = -0.543, p < 0.00, respectively). In a sensitivity analysis, there was no correlation between AST/ALT ratio and disease stage for patients with a history of alcohol abuse. For patients without history of alcohol abuse, the correlation between disease stage, AST/ALT ratio, and platelet counts was r = 0.297, p < 0.00, and r = 0.560, p < 0.00, respectively. In these patients, AST/ALT ratio > or =1 in combination with a platelet count of <150,000/mm3 can identify patients with severe fibrosis or cirrhosis (stages 3 and 4) with a positive predictive value of 93.1%. Sensitivity, specificity, and negative predictive value were 41.2%, 99.1%, and 85.0%, respectively. In patients with ALT/AST ratio of <1 or platelet counts of >150,000/mm3, these laboratory parameters cannot predict liver fibrosis stage. CONCLUSION: AST/ALT ratio in combination with platelet counts may obviate a liver biopsy for fibrosis staging in some patients with chronic HCV infection.

Adult↗

c-Myb modulates transcription of the alpha-smooth muscle actin gene in activated hepatic stellate cells.

Expression of alpha-smooth muscle actin (alpha-SMA) defines the phenotype of activated (myofibroblastic) hepatic stellate cells. These cells, but not quiescent stellate cells, have a high level of alpha-SMA and c-Myb expression, as well as increased c-Myb-binding activities to the proximal alpha-SMA E box. Therefore, we analyzed the role of c-Myb in alpha-SMA transcription and stellate cell activation. Activated primary rat stellate cells displayed a high expression of the -724 and -271 alpha-SMA/luciferase (LUC) chimeric genes, which contain c-Myb binding sites (-223/-216 bp). Alpha-SMA/LUC minigenes with mutation (-219/-217 bp), truncation (-224 bp), or deletion (-191 bp) of the c-Myb binding site were not efficiently transcribed. Transfection of wild-type c-Myb into quiescent stellate cells, which do not express endogenous c-Myb, induced a approximately 10-fold stimulation of -724 alpha-SMA/LUC expression. Conversely, expression of either a dominant-negative c-Myb basic domain mutant (Cys(43) --> Asp) or a c-Myb antisense RNA blocked transcription from the -724 alpha-SMA/LUC or -271 alpha-SMA/LUC in activated cells. Moreover, transfection of c-myb antisense, but not sense, RNA inhibited both expression of the endogenous alpha-SMA gene and stellate cell activation, whereas transfection of c-myb stimulated alpha-SMA expression in quiescent stellate cells. These findings suggest that c-Myb modulates the activation of stellate cells and that integrity of the redox sensor Cys(43) in c-Myb is required for this effect.

Actins↗

A preliminary experience with GM-CSF plus interferon in patients with HBV and HCV resistant to interferon therapy.

An open label trial of GM-CSF plus high-dose interferon (IFN) alpha 2b was performed in eight patients with chronic hepatitis B infection and 16 patients with chronic hepatitis C, who either failed to clear virus with 6 months of daily high-dose IFN (5 MU daily) therapy (n = 22) or were considered untreatable because of advanced disease and leukopenia (n = 2). The dose of GM-CSF used was 500 micrograms subcutaneously twice weekly. The dose of IFN used was 5 MU daily. Both agents were administered for 4 months. Five of the eight hepatitis B patients and five of the 16 hepatitis C virus patients responded to combined therapy having previously failed IFN therapy alone. The hepatitis B virus responders had low entry ALT, AST, and gamma GPT levels as compared to the non-responders. No such differences for responders and non-responders were seen with the hepatitis C virus patients. These data suggest that the combination of GM-CSF and IFN may be more effective at achieving viral clearance than IFN alone.

Adult↗

New approach to HCV treatment. Recognition of disease process as systemic viral infection rather than as liver disease.

Chronic viral hepatitis C is a problem of immense proportions. The only therapy that currently exists and is FDA approved is interferon (IFN). Much controversy exists regarding the dose and duration as well as the effectiveness of IFN therapy. This study was performed to determine whether a new endpoint of successful treatment, HCV-RNA negativity in plasma and liver, would produce a greater number of long-term responders than is achievable with the currently recommended six months of therapy. The 45 patients enrolled in this study were randomized 2 to 1 in a treatment paradigm consisting of 5 MU IFN three times a week for six months or the same dose of IFN daily until HCV-RNA was undetectable in plasma X 3 over 3 consecutive monthly determinations followed by demonstrated HCV-RNA negativity in liver biopsy tissue. No differences in age, initial WBC count, platelet count, or hepatic injury measures were evident between the two treatment groups. At the end of therapy, 43% of those in group 1 vs 100% in group 2 responded to the IFN therapy as defined by the serum ALT level. More importantly, all of those in group 1, but only half of those in group 2, relapsed and became HCV-RNA positive with discontinuation of the IFN therapy. These data suggest that: (1) IFN therapy is more effective when given for a longer rather than a shorter period; (2) virologic response definitions are now possible and are preferred; (3) using longer therapy and a virologic endpoint, the responses achieved are more durable.

Adult↗

Interferon-alpha 2b improves short-term survival in patients transplanted for chronic liver failure caused by hepatitis B.

Liver transplantation for cirrhosis caused by hepatitis B virus (HBV) has a poor prognosis. This is primarily a consequence of the near universal reinfection of the allograft, subsequent accelerated hepatic disease while receiving immunosuppression, and a reduced long-term survival. Because interferon-alpha has been shown to have an antiviral effect on HBV, a study was initiated in 1986 to assess the effect of interferon-alpha therapy on the course of liver transplantation in HBV-positive recipients. Twenty-eight patients with decompensated endstage liver disease caused by HBV were treated with 5, 2.5 or 1.25 million units (MU) of human recombinant interferon-alpha 2b (r-IFN-alpha 2b) daily for a minimum of 14 days prior to transplantation and continuing for 42 days post-transplantation. HBV antigens, HBV antibodies, HBV DNA and serum transaminase levels were measured throughout the treatment and post-treatment period. HBV DNA was eliminated in 10 of 19 patients, who survived 3 months or more post-transplantation, and was associated with a significant flare of hepatitis as detected by symptoms and transaminase levels (P < 0.05). Patients who cleared HBV DNA had lower HBV DNA levels (P < 0.05) at entry compared with those who did not. While four of 10 patients with hepatitis B e antigen (HBeAg) converted to hepatitis B e antibody (HBeAb), no surviving patient cleared hepatitis B surface antigen (HBsAg) on a long-term basis. Nonetheless, post-transplant survival was significantly better (P < 0.0001, median follow-up 42 months) in the IFN-alpha treated patients as compared with historical controls, and was similar to that of patients transplanted for all causes of parenchymal liver disease other than HBV cancer. Hence IFN-alpha therapy in the perioperative liver transplantation period improves short-term survival but does not prevent HBV infection of the allograft.

DNA, Viral↗

Neuropsychological impairment in a patient with a normal liver and long-standing portacaval anastomosis: studies obtained before and after liver transplantation.

A case report of the neuropsychiatric consequence of long-standing portal caval shunting in a man without intrinsic liver disease is described. Because of his neuropsychiatric status he underwent liver transplantation. Over the succeeding 8 months he had progressive improvement in his neuropsychiatric performance. These data document the adverse effects of portal caval shunting on neuropsychiatric performance in the absence of intrinsic liver disease as well as their reversibility with shunt closure.

Humans↗

Primary liver cancer and survival in patients undergoing liver transplantation for hemochromatosis.

Cirrhotic patients with hereditary hemochromatosis (HHC) have an increased risk of primary liver cancer (PLC). The purpose of this study was to determine the prevalence of primary liver cancer in patients with HHC undergoing orthotopic liver transplantation (OLT). Five liver transplant centers were surveyed; clinical and pathological data on 37 patients with HHC undergoing OLT were retrospectively collected and analyzed. The diagnosis of HHC was established by a combination of serum transferrin-iron saturation, hepatic iron index (HII), and/or pattern of liver iron staining. The diagnosis of HHC had been unsuspected before OLT in 13 of 37 (35%). Primary liver cancer was found in the explants of 10 of 37 patients (27%) and was unsuspected in 7 of 10 (70%); 8 were hepatocellular carcinoma, and 2 were cholangiocarcinoma; foci of hepatocyte dysplasia were found in 6 additional patients. Mean (+/- SEM) hepatic iron content and HII in 20 patients without prior phlebotomy or bleeding were 17.2 mg/g dry weight (+/- 2.9) and 5.5 (+/- 0.8), respectively. The overall 1-year survival rate after OLT in the 37 HHC patients was 58% (v 55% for HHC patients with PLC). We draw the following conclusions: (1) the diagnosis of HHC is often unsuspected before OLT, and HHC should be evaluated pretransplantation by direct and indirect markers; (2) HHC patients undergoing OLT have a high prevalence of primary liver cancer, the majority being unsuspected; and (3) HHC patients have poorer than average survival after OLT, which cannot be explained solely by the presence of concomitant PLC.

Female↗

Chronic hepatitis C in patients with normal or near normal alanine aminotransferase levels: the role of interferon alpha 2b therapy.

BACKGROUND/AIMS: Interferon is the only approved therapy for chronic hepatitis occurring as a consequence of an infection with the hepatitis C virus. Because interferon is expensive, has a large number of untoward effects and its efficacy is not guaranteed, many physicians limit their use of this therapy to those with histologically advanced but not end-stage cirrhotic disease. Moreover, most cases are biopsied only after 6 months or more of abnormal alanine aminotransferase levels have been documented. The rationale for this approach to patients with hepatitis C virus infection has not been demonstrated. METHODS: In the present study, a total of 37 patients with alanine aminotransferase levels < 1.5 upper limits of normal (59 IU/l or less) who were HCV-RNA positive by reverse transcriptase polymerase chain reaction, were selected for interferon treatment, having been identified as having hepatitis C virus disease as the result of a screening Ab-HCV test confirmed with a positive radio immune blotting assay. Once identified, each subject underwent a percutaneous liver biopsy and was tested for the presence of HBsAg, Ab-HBs and HBV-DNA. All liver biopsies were read and graded according to the criteria of Knodell et al. Each subject was treated with interferon a2b at a dose of 5 MU administered daily until a response was achieved (a minimum period of 6 months) or until a full year had elapsed. A response was defined as HCV-RNA negativity in serum on three consecutive monthly determinations. The study population consisted of 21 males and 16 females ranging in age from 17 to 72 years (mean 46.7 +/- 2.2 years). Their mean serum alanine aminotransferase level at the initiation of therapy was 37.5 +/- 2.1 IU/l with a range of 10-59 (normal values being 40 IU/l or less). 54% of the subjects were presumed to have acquired their hepatitis C virus infection as a result of a blood transfusion; 32% as a result of prior intravenous drug abuse; and 13% had no identifiable risk factor for hepatitis C virus. Despite having normal or near normal serum alanine aminotransferase levels, 9 subjects had chronic persistent hepatitis, 13 had chronic active hepatitis and 15 had chronic active hepatitis + cirrhosis documented by histopathologic assessment of their liver biopsies. RESULTS: An interferon response was achieved in 5/9 with chronic persistent hepatitis, 11/13 with chronic active hepatitis and 8/15 with chronic active hepatitis + cirrhosis for an overall response rate of 65%. CONCLUSIONS: This study has demonstrated that individuals who: 1) are hepatitis C virus positive with serum alanine aminotransferase levels < 1.5 x upper limits of normal can have histologically advanced liver disease; 2) can respond to interferon therapy defined as clearance of detectable HCV-RNA in serum; and, 3) should be considered for interferon treatment.

Adult↗

Liver transplantation for Wilson's disease.

BACKGROUND/AIMS: As has been the case with other metabolic diseases of the liver in the last decade, orthotopic liver transplantation has been applied to the treatment of Wilson's disease with increasing frequency. The experience at the University of Pittsburg with orthotopic liver transplantation for Wilson's disease is reported. METHODS: Between February 1981 and December 1991, 51 orthotopic liver transplants were performed on 39 patients (16 pediatric, 23 adults) with Wilson's disease. Twenty-two patients were transplanted because of a presentation co-existent with fulminant hepatic failure. Seventeen presented with chronic advanced liver disease with (n=9) or without (n=8) associated neurologic dysfunction. RESULTS: The rate of primary graft survival (n-39) was 73% and patient survival was 79.4%. No patient mortality occurred beyond 3 weeks post-orthotopic liver transplantation. Survival was butter for those with a chronic advanced liver disease presentation (90%) than it was for those with a fulminant hepatic failure (73%) presentation, but the difference was not statistically significant. CONCLUSIONS: 1) Currently, orthotopic liver transplantation is the treatment of choice for Wilson's disease presenting as fulminant hepatic hepatic failure; 2) orthotopic liver transplantation should be considered for patients with Wilson's disease with advanced, chronic liver disease for whom no other therapy is possible; 3)orthotopic liver transplantation only partially corrects the underlying metabolic defect of patients with Wilson's disease and converts the copper kinetics from that characteristic of an individual affected with a homozygous disease to that of an individual who is an obligate heterozygote, thereby effecting a phenotypic cure.

Adolescent↗

Biochemical abnormalities in liver disease.

A wide array of biochemical findings can be seen in patients with liver disease. Depending upon the setting, these findings can either be used to confirm the presence of a liver disease, document its complications or suggest its presence. Thus, physicians need to be aware of them and recognize and use them as the specific case indicates.

Biomarkers↗

Acute relapsing pancreatitis induced with ursodeoxycholic acid therapy.

A case of acute relapsing pancreatitis associated temporarily with the initiation of ursodeoxycholic acid occurring in a young adult woman with a long common channel connecting her biliary and pancreatic systems and Alagille's syndrome is reported. The attacks occurred only during the period she was being treated with ursodeoxycholic acid for her symptoms of pruritus. Liver transplantation with a Roux-en-Y choledochojejunostomy and discontinuation of ursodeoxycholic acid therapy has been followed by no additional attacks of pancreatitis whereas episodes of acute pancreatitis were occurring on a monthly basis prior to transplant.

Acute Disease↗

Panhypopituitarism in two cirrhotics: clinical presentation and liver disease associations.

Two cases of panhypopituitarism occurring in cirrhotic patients with chronic hepatitis C, hemochromatosis and in the second case, alpha 1-antitrypsin deficiency with phenotype SS. The hypopituitarism was most probably a result of pregnancy-associated pituitary infection in Case 1 and spontaneous infection of a somatotrophic pituitary adenoma in Case 2. Both cases experienced complications related to salt and water excretion, cardiac arrhythmia, and encephalopathy related to the pituitary disease that was initially ascribed to their hepatic disease. These two cases demonstrate the difficulty one can have in caring for patients with advanced liver disease with confounding endocrine dysfunction.

Hemochromatosis↗

Major gastrointestinal bleeding occurring after liver transplantation.

The incidence, frequency, and sites of major gastrointestinal bleeding occurring after successful liver transplantation are reported. Only 2.3% of liver transplant recipients experience a major gastrointestinal hemorrhage characterized by clinical hypotension or a need for more than three units of blood over a 12-hour period. Bleeding rarely occurs from a lesion identified pretransplantation. Most bleeding episodes, although clinically significant, can be managed without additional surgery unless liver graft failure occurs, necessitating a second liver graft.

Gastrointestinal Hemorrhage↗

Right diaphragmatic paralysis following orthotopic liver transplantation.

Although most postoperative complications of liver transplantation are well known and their pathophysiology is reasonably understood, right diaphragmatic dysfunction occurring after liver transplantation remains an unappreciated complication. To evaluate the incidence and mechanisms responsible for such injury, a group of 48 liver transplant patients were studied prospectively. Partial right diaphragmatic paralysis was found in 11 (23%), complete paralysis was found in 10 (21%) and the remaining 27 patients had normal diaphragmatic motion (56%). The operative records of these 48 patients were reviewed. Right diaphragmatic injury was found to be a common postoperative complication of liver transplantation. Moreover, it was found to have a clinically significant effect upon the postoperative course of these patients, often necessitating a prolonged ICU stay and prolonged ventilatory support. Although the exact mechanism responsible for its occurrence remains speculative, careful attention to operative technique particularly in the dissection of the upper cava and careful closure of the bare area of the diaphragm, may reduce the frequency of this untoward complication.

Adolescent↗

Simultaneous right-sided volume overload and left-sided hypovolemia in a man with massive ascites and a hydrothorax.

The medical problems presented by an 83-yr-old man with hepatic amyloidosis complicated by massive ascites and a right hydrothorax are described. As a result of right atrial compression limiting right heart filling, the patient simultaneously experienced left-sided hypovolemia with renal and hepatic ischemia while manifesting signs of right-sided congestive failure. Only with a transjugular intrahepatic portosystemic shunt procedure, which eliminated the right atrial compression with resolution of the hydrothorax and ascites, was it possible to improve the other medical condition of this man.

Aged↗