Changes in Utilization and Discard of Hepatitis C-Infected Donor Livers in the Recent Era.

The impact of interferon (IFN)-free direct-acting antiviral (DAA) hepatitis C virus (HCV) treatments on utilization and outcomes associated with HCV-positive deceased donor liver transplantation (DDLT) is largely unknown. Using the Scientific Registry of Transplant Recipients, we identified 25 566 HCV-positive DDLT recipients from 2005 to 2015 and compared practices according to the introduction of DAA therapies using modified Poisson regression. The proportion of HCV-positive recipients who received HCV-positive livers increased from 6.9% in 2010 to 16.9% in 2015. HCV-positive recipients were 61% more likely to receive an HCV-positive liver after 2010 (early DAA/IFN era) (aRR:1.45 1.611.79 , p < 0.001) and almost three times more likely to receive one after 2013 (IFN-free DAA era) (aRR:2.58 2.853.16 , p < 0.001). Compared to HCV-negative livers, HCV-positive livers were 3 times more likely to be discarded from 2005 to 2010 (aRR:2.69 2.993.34 , p < 0.001), 2.2 times more likely after 2010 (aRR:1.80 2.162.58 , p < 0.001) and 1.7 times more likely after 2013 (aRR:1.37 1.682.04 , p < 0.001). Donor HCV status was not associated with increased risk of all-cause graft loss (p = 0.1), and this did not change over time (p = 0.8). Use of HCV-positive livers has increased dramatically, coinciding with the advent of DAAs. However, the discard rate remains nearly double that of HCV-negative livers. Further optimization of HCV-positive liver utilization is necessary to improve access for all candidates.

Human Herpesvirus 8-Related Primary Effusion Lymphoma After Liver Transplantation.

Primary effusion lymphoma is a rare subclass of non-Hodgkin lymphoma associated with human herpesvirus 8 infection and principally seen in human immunodeficiency virus-positive patients. We report on the case of a 72-year-old human immunodeficiency virus-negative male with a hepatic transplant 10 years prior, who presented with a symptomatic right-sided pleural effusion and was found to have primary effusion lymphoma by flow cytometric and cytopathologic examination. Immunohistochemistry of his lymphoma cells was positive for human herpesvirus 8. Both he and his donor had no identifiable risk factors for human herpesvirus 8 infection. The patient was intolerant of antiviral therapy and chemotherapy, dying 7 months after diagnosis. Posttransplant primary effusion lymphoma is exceedingly rare and carries a very poor prognosis. Individualized treatment strategies are necessary given the scant body of published literature with guidance based solely on case reports.

Management of hepatitis C infection among patients with renal failure.

Hepatitis C virus (HCV) infection is a rising global public health burden with an estimated 130-150 million infected people worldwide and 350,000 to 500,000 HCV-related deaths each year. Chronic kidney disease (CKD) is also a highly prevalent public health issue as the escalating numbers of patients worldwide are developing type 2 diabetes mellitus and hypertension due to high fat diets and a growing obesity epidemic. The high incidence and prevalence of HCV infection leads to substantial morbidity and mortality among renal dialysis patients. Recommendations are to screen for HCV infection among all patients with renal failure especially prior to initiation of hemodialysis and renal transplant evaluation. HCV-antibody enzyme immunoassay (EIA) followed by confirmation with HCV RNA nucleic acid test (NAT) is recommended for low prevalence regions, but in dialysis centers with a high prevalence of HCV, initial testing with NAT is recommended due to higher false positive EIA rates. Liver biopsy is used to assess of liver disease severity. Transjugular liver biopsy, as an effective and safe technique in patients with ESRD can be considered instead of percutaneous approach. Non-invasive approaches to staging fibrosis, including liver stiffness measurement by transient elastography and panels of serum fibrosis biomarkers, are also widely used. Although difficult to manage, combined pegylated- interferon (PEG IFN) and ribavirin therapy was the only treatment modality available for HCV-positive patients until the recently introduced new direct-acting antiviral agents. However, except boceprevir, there are no currently available data to suggest that these new anti-viral drugs are safe and effective among end-stage renal failure patients. IFN-containing regimens were also associated with high rates of renal graft loss in post-renal transplant patients. Therefore, management of HCV infection in renal failure patients is unique and should be tailored individually with calculated risk/benefit ratio. New studies are immediately warranted to determine the safety profile and efficacy of newer anti-HCV drugs not only in patients with end-stage renal failure prior to kidney transplantation but also among kidney transplant recipients.

Impact of a single-day multidisciplinary clinic on the management of patients with liver tumours.

PURPOSE: Multidisciplinary cancer clinics may improve patient care. We examined how a single-day multidisciplinary liver clinic (mdlc) affected care recommendations for patients compared with the recommendations provided before presentation to the mdlc. METHODS: We analyzed the demographic and clinicopathologic data of 343 patients assessed in the Johns Hopkins Liver Tumor Center from 2009 to 2012, comparing imaging and pathology interpretation, diagnosis, and management plan between the outside provider (osp) and the mdlc. RESULTS: Most patients were white (n = 259, 76%); median age was 60 years; and 146 were women (43%). Outside providers referred 182 patients (53%); the rest were self-referred. Patients travelled median of 83.4 miles (interquartile range: 42.7-247 miles). Most had already undergone imaging (n = 338, 99%) and biopsy (n = 194, 57%) at the osp, and a formal management plan had been formulated for about half (n = 168, 49%). Alterations in the interpretation of imaging occurred for 49 patients (18%) and of biopsy for 14 patients (10%). Referral to the mdlc resulted in a change of diagnosis in 26 patients (8%), of management plan in 70 patients (42%), and of tumour resectability in 7 patients (5%). Roughly half the patients (n = 174, 51%) returned for a follow-up, and 154 of the returnees (89%) received treatment, primarily intraarterial therapy (n = 88, 57%), systemic chemotherapy (n = 60, 39%), or liver resection (n = 32, 21%). Enrollment in a clinical trial was proposed to 34 patients (10%), and 21 of the 34 (62%) were accrued. CONCLUSIONS: Patient assessment by our multidisciplinary liver clinic had a significant impact on management, resulting in alterations to imaging and pathology interpretation, diagnosis, and management plan. The mdlc is an effective and convenient means of delivering expert opinion about the diagnosis and management of liver tumours.

Is post-Lipiodol CT better than i.v. contrast CT scan for early detection of HCC? A single liver transplant center experience.

Hepatocellular carcinoma is a highly vascular neoplasm usually arising from a cirrhotic liver. Delayed, noncontrast, computed tomography (CT) imaging after 7 to 14 days reveals an oil-based contrast agent to be concentrated in the tumor but not in normal hepatic parenchyma. The aim of this study was to retrospectively correlate the post Lipiodol CT scan findings with respect to tumor size in the explanted liver. We retrospectively reviewed adult patients who had undergone orthotopic liver transplantation between November 1995 and December 2004 and also had an hepatic arteriogram with Lipiodol injection as part of their pretransplant workup. We calculated sensitivity, specificity, false-negativity, false-positivity, and accuracy of the test, as well as positive and negative predictive values. Lipiodol CT exam had sensitivity of 1.0; specificity of 0.6 with a calculated positive predictive value of 0.89 and a negative predictive value of 1.0. Overall accuracy of Lipiodol CT scan test was found to be 0.91, which was superior to an intravenous contrast CT alone. In conclusion, because of the higher sensitivity and accuracy values, hepatic arterial Lipiodol injection can be considered during the pretransplantation workup of high-risk cirrhotic patients, since the current model for End-stage Liver Disease scoring system for hepatocellular carcinoma is built on the ultimate bulk of the tumor. Further multicenter, controlled, large-volume prospective studies are warranted to verify this observation.

Liver transplantation for hepatitis B in the United States.

AIM: To evaluate the impact of hepatitis B virus (HBV) on US health care system, we reviewed the Organ Procurement and Transplantation (OPTN, formerly UNOS) HBV database. METHOD: We reviewed records of liver transplantations (LTx) performed in the United States listed for the diagnoses of HBV between 1993 and mid-October 2004. Both acute as well as chronic cases were included. Coinfection with hepatitis C virus was excluded from study. The specific states selected for review were chosen from those areas that are receiving large numbers of new immigrants from high HBV endemic areas (ie, Texas, Pennsylvania, California, New York, and Florida). One-, 3-, and 5-year patient survival rates for both cadaveric and living related donors were analyzed. Survival rates were obtained from OPTN database as Kaplan-Meyer survival test. RESULTS: Between 1993 and mid-October 2004, 53,312 LTx had been performed nationwide. Of these, 2314 (4.34%) were performed for the diagnosis of HBV; 1816 cases (78%) were due to chronic HBV infection (45 of them were living donor LTx) and 498 cases (22%) were due to HBV-induced acute liver failure (seven of them were living donor LTx). Three- and 5-year survival rates of chronic HBV-related LTx patients were better than acute HBV-related and overall LTx patients. CONCLUSION: HBV is generally considered to have a minor health significance by many community gastroenterologists. With growing immigration from overseas, it may eventually have a higher impact on LTx. Therefore, it is crucial to further educate gastroenterologists and primary care physicians caring for this specific group of patients.

Disseminated Cryptococcus neoformans in a cirrhotic patient.

Disseminated cryptococcal infection often occurs in the setting of an immuncompromised patient. We report a case of disseminated Cryptococcus neoformans in a cirrhotic patient, referred for Orthotopic Liver Transplantation evaluation due to acute hepatic decompensation.

Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment.

Total and low density lipoprotein cholesterol concentration reduction in patients with markedly increased levels of these substances, leads to a decline in the incidence of myocardial infarction and death. A unique cholesterol-rich lipoprotein, lipoprotein Lp(a), has been identified which not only can be confused with low density lipoproteins, but has also been associated with premature cardiovascular disease. Using the cholesterol-lowering drugs neomycin and niacin in 14 type II hyperlipoproteinemic subjects, we determined the effect of lipid-lowering therapy on lipoprotein Lp(a) concentrations. Neomycin (2g/day) reduced low density lipoprotein cholesterol and lipoprotein Lp(a) concentrations by 23% and 24%, respectively. Combination therapy with neomycin (2 g/day) and niacin (3 g/day) induced a 48% decline in low density lipoprotein cholesterol levels and a 45% reduction in the concentration of lipoprotein Lp(a). These changes in lipoprotein Lp(a) levels were associated with a striking decline in the intensity of the slow pre-beta-lipoprotein fraction determined Lp(a) by lipoprotein electrophoresis. This slow pre-beta-lipoprotein fraction contained Lp(a) determined by immunofixation. These observations indicate that lipoprotein Lp(a) concentrations can be altered pharmacologically and that the progression of cardiovascular disease may be altered through changes in lipoprotein (a) levels.

NK activity during graft-versus-host disease and graft rejection in rats following intestinal semiallogenic and allogenic transplantation with or without mesenteric lymphadenectomy.

Graft-versus-host disease (GVHD) and graft rejection are major problems following intestinal transplantation (IT). Natural killer (NK) cells may be important effector cells in both conditions. In this study, Sprague-Dawley (SD) or SD-Brown Norway (BN) F1 rat intestine was transplanted into BN recipients with and without associated graft mesenteric lymphadenectomy (GML). Cyclosporine (15 mg/kg day) was administered to all animals. Pieces of the intestinal graft were examined 4 days posttransplant and again at death. NK activity calculated using intestinal intraepithelial lymphocytes (IL) was determined utilizing an 18-hr cytotoxic assay assessing 51Cr release and the results are reported as lytic units. YAC-1 cells were used as the target. NK activity was reduced 4 days after IT both in native (8.02 +/- 0.64) and in grafted bowel (3.14 +/- 1.51), with histological evidence of rejection as compared with that of control bowel in ungrafted rats (21.1 +/- 2.14). Survival was increased, on mean, a total of 6 days with the addition of GML in both semiallogenic and allogenic transplanted rats. At the time of death, the NK activity in the native bowel had increased (17.1 +/- 3.02) and histologic evidence of GVHD was present. These data suggest that: (1) NK cells are important in GVHD and (2) both semiallogenic and allogenic transplants survive longer if they are combined with GML (P < or = 0.05 and P < or = 0.01, respectively).

Hypertension, erectile dysfunction, and occult sleep apnea.

Sleep-related respiratory pattern was evaluated in 175 hypertensive and 110 normotensive men, none of whom reported difficulties in initiating or maintaining sleep. Patients were grouped according to sexual status (complaint of erectile problems), hypertension treatment status (treated or untreated), and blood pressure (diastolic less than 90 or greater than or equal to 90). The prevalence of sleep apnea, apnea index, duration of the longest episode of apnea, and penile rigidity were tabulated. The group with elevated blood pressure, persistent even with antihypertensive drug therapy, had the most sleep apnea. The treated hypertensive men with controlled blood pressure had significantly less apnea than those whose blood pressure remained high. Untreated hypertensive groups, however, did not differ from normotensive groups with respect to apnea. Evidence of abnormal sleep-related respiratory activity was found in both hypertensive and normotensive groups with erectile problems. Interestingly, penile rigidity was significantly lower for hypertensive men with erectile complaints than for normotensive men with erectile complaints. There was also a small, but significant, negative correlation between apnea index and penile rigidity among men with erectile complaints. These results indicate that sexual status is an important consideration in the diagnosis of hypertension and sleep apnea. Moreover, these data suggest an interrelationship among hypertension, erectile dysfunction, and sleep apnea.

The effect of fatty acid chain length on the rate of arylester hydrolysis by various albumins.

A series of synthetic chromogenic and fluorogenic substrates for monitoring the arylesterase-like activity of albumins from various sources has been studied. Except for ovalbumin, all displayed enzyme-like activity. The acetate, butyrate, caprylate, laurate, and palmitate esters of a coumarin dye were found to be efficiently hydrolyzed within the pH range 8.8-9.8, with the non-enzymatic rate being highest for acetate and lowest for laurate. The latter is considered to be the substrate of choice because it is cleaved most quickly by the proteins tested. A considerable increase in hydrolytic activity was observed upon addition of detergents, but not of Ca and Mg ions, while addition of 1 equivalent of lauric acid to BSA resulted in a 30% decrease in its activity. The results are interpreted in terms of the well-known affinity of albumins for long chain fatty acids and provide the basis for a sensitive determination of small amounts of albumins.

A sensitive kinetic assay of serum albumin based on its enzyme-like hydrolytic activity, using a new chromogenic and fluorogenic substrate.

A new albumin assay, based on the unusual enzyme-like activity of the protein that promotes hydrolysis of ester bonds in fatty acid arylesters was designed for clinical routine use. The substrate introduced shows improved analytical wavelengths and is suitable for both photometric and fluorimetric assay. Experiments have been performed with a conventional photometer, a fluorimeter and a Cobas Fara autoanalyzer. Detection limits are as low as 10 micrograms/ml photometrically and 20 ng/ml fluorimetrically. The method provides a sensitive quantitative determination of even minute amounts of albumin in liquid solution, and a simple semiquantitative test may be performed by fixing the dye on a test strip which then is immersed into a sample solution and observing the development of yellow color intensity.

Prostate-specific antigen levels among cirrhotic patients.

PURPOSE: The aim of this study was to determine serum prostate-specific antigen (PSA) levels in patients with liver cirrhosis. PATIENTS AND METHODS: Between January 1995 and August 2001, 216 men with cirrhosis were evaluated. The extent of their liver disease was classified according to the Child-Pugh classification. Serum PSA levels were measured with the Hybritech Tandem-R RIA method and matched with age-related reference PSA levels. Digital rectal examination (DRE) was performed in all patients. Patients with elevated PSA levels and/or abnormal DRE were recommended to undergo further assessment including transrectal ultrasonography (TRUS) and biopsy performed by an urologist. RESULTS: Two hundred and sixteen men (mean age 54.09 +/- 9.09 years, range 25-76) with cirrhosis were examined. Their mean PSA value was 0.57 +/- 0.84 ng/mL and tended to be lower than in the normal population. The degree of PSA decrease was found to parallel the severity of the liver disease (p=0.002). The mean serum PSA level increased with each age decade in a statistically significant manner (p<0.001). Four patients (three with elevated PSA values) underwent prostate biopsy. Three biopsies were positive for prostate cancer, the other showed evidence of benign prostatic hyperplasia (BPH). CONCLUSION: Serum PSA is influenced by the severity of liver disease and its levels tend to be lower in cirrhotic patients than in the normal population. However, serum PSA can still be considered a reliable marker in the clinical management of prostatic disease in patients with cirrhosis.

A liver transplant center experience with liver dialysis in the management of patients with fulminant hepatic failure: a preliminary report.

Among extracorporeal liver support devices, liver dialysis is cleared by the U.S. Food and Drug Administration to be used for the management of fulminant hepatic failure (FHF). The outcomes of patients following liver dialysis need to be clearly evaluated. Among the 25 patients with FHF admitted to the Liver ICU between May 2000 and November 2002, 12 underwent liver dialysis, including 6 men and 6 women, of mean age 32 years. The causes of FHF were identified as acetaminophen (n = 10), herbal medications (n = 1) and autoimmune disease (n = 1). At presentation, the mean total bilirubin was 9.35 mg/dL (range, 0 to 1.3), mean ALT 3015 U/L (range, 0 to 48), mean AST 3457 (range, 0 to 42), mean ammonia 98 micromol/L (range, 10 to 60) and mean INR 1.88. A control group including 13 patients (2 men and 11 women), of mean age 27.8 years mean total bilirubin 5.66, mean ALT 3494, mean AST 3528, mean ammonia 113 and mean INR 3, were not treated with liver dialysis, due to the lack of machine availability or physician's choice. The causes of FHF were acute hepatitis B (n = 1), acetaminophen (n = 10) or unknown (n = 2). There was no statistically significant difference in the baseline characteristics of the two groups (P >.05). Among the liver dialysis group, 1 patient died, 2 underwent OLTx, and 9 were discharged home. Among the control group; 4 patients died, 2 underwent OLTx, and 7 were discharged home. Preliminary results seem to support survival benefit among patients who underwent liver dialysis compared to non-liver dialysis; however, further randomized control trials are warranted to verify this observation.

The impact of total plasma exchange on early allograft dysfunction.

INTRODUCTION: Early allograft dysfunction (EAD) is a rare but serious complication encountered among patients undergoing liver transplant surgery. Total plasma exchange (TPE) in EAD has been suggested, but its role is still considered investigational. We retrospectively assessed the efficacy of TPE in EAD and its impact on other parameters of liver function. MATERIALS AND METHODS: Between 1995 and 2001, 25 orthotopic liver transplant recipients developed EAD, which was defined as early postoperative prothrombin time (PT) >17 seconds, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2500 IU/L, and/or the presence of hepatic encephalopathy, and development of renal failure. Daily TPE was performed using the Cobe Spectra TPE (Gambro) for 4 hours until an adequate clinical response, the patient underwent retransplantation, or the patient died. International normalizing ratio (INR), partial thromboplastin time (PTT), fibrinogen, ALT, AST, gamma-glutanyl transpeptidase (GGT), blood urea nitrogen (BUN), ammonia, and total bilirubin were analyzed before and after TPE. Student t and chi-square tests were used for statistical analysis. RESULTS: Twenty-five patients with EAD included 13 females, 12 males of mean age 42.3 years (range, 1-63 years). Coagulopathy and hyperbilirubinemia significantly improved with TPE. Nineteen patients (76%) survived and 2 required retransplantation. Mean number of TPE sessions was 4.3. CONCLUSION: TPE was effective to correct coagulopathy and improve liver function. These results suggest the benefit of potential temporary liver support until recovery or retransplantation, in the absence of sepsis or multi-system organ failure.

Hepatitis C and the controversies it creates relative to liver transplantation and autoimmune hepatitis.

The paradox of hepatitis C. An agent that persists in tissue for years by escaping the immune system and not killing but only damaging its host while simultaneously being associated with autoimmune hepatitis as well as other putative autoimmune diseases is presented. Liver transplantation necessitates immune suppression and is associated with progressive HCV disease albeit at a rather slow rate. Diagnosis and treatment concerns are raised and discussed.

A comparison of the prevalence of autoantibodies in individuals with chronic hepatitis C and those with autoimmune hepatitis: the role of interferon in the development of autoimmune diseases.

BACKGROUND AND OBJECTIVES: Viral hepatitis due to hepatitis C virus results in chronic liver disease in more than 70% of individuals infected with the virus. Hepatitis C virus is also thought to be the cause of autoimmune chronic hepatitis, type II. The only treatment for chronic hepatitis C is interferon (IFN). IFN is both an antiviral agent and an up regulator of the cellular immune system. The latter effect is non-specific. Thus, IFN diffusely activates the cellular immune system and can initiate new autoimmune diseases in patients treated with it. To determine the prevalence of autoantibodies in patients with chronic hepatitis C and in patients with autoimmune hepatitis and to determine the incidence of new onset autoimmune disease in IFN-treated subjects with chronic hepatitis C, the records of 323 unselected patients with chronic hepatitis were reviewed. MATERIAL AND METHODS: A total of 203 patients with a mean age of 45.7 +/- 0.8, ranging 18-81 with either HCV disease or autoimmune hepatitis, were identified and studied. One hundred sixty-two patients with chronic hepatitis C defined by elevations of serum alanine aminotransferase (ALT) for at least 6 months, the presence of detectable anti-HCV (HCV; second generation enzyme immunoassay [EIA2], a positive recombinant immunoblot assay [RIBA], the presence of HCV-RNA by PCR in serum and an abnormal biopsy consistent with chronic hepatitis C) were identified. Each was also negative for HbsAg, HbeAg and anti-Delta. Forty-one patients with a putative autoimmune chronic hepatitis (AIH) diagnosed on the basis of serologic positivity for classical autoantibodies (ANA and anti-smooth muscle antibodies), tissue typing (B8, Dr3 positive), characteristic liver biopsy findings and the absence of anti-HCV and HCV-RNA in serum were identified. The records of both of these groups of patients were reviewed for the following antibodies: anti-nuclear antibodies (ANA), antimitochondrial antibodies (AMA), anti-liver-kidney microsomal antibody (LKM), anti-smooth muscle antibodies (SMA), anti-microsomal antibodies (MSA). RESULTS: The rate of ANA positivity was 63% in both groups; the rate of SMA positivity was 65% in patients with HCV infection (group I) and 63% in patients with AIH (group II). AMA was positive in 4% of the subjects in group I and 50% of the subjects in group II; anti-LKM antibodies were absent in all 91 HCV cases and were present in 4% of the cases in group II; MSA positivity was present in 17% of group I and 10% of group II. Eighty-one of the one hundred sixty-two patients (50%) with chronic hepatitis C received IFN treatment at a dose of 5 MU SQ daily for 6 months. Thirty-two of these eighty-one patients (42 females and 39 males with a mean age of 45.0 +/- 1.3, ranging from 18 to 81 yr.) had at least two autoantibodies detectable prior to the IFN therapy (subgroup 1) and 49 had one or no identifiable autoantibodies (subgroup 2) present prior to IFN therapy. No significant differences in the interferon response rate defined by HCV-RNA negativity and normalization of serum ALT levels at the end of therapy was noted between those with autoantibodies and those without autoantibodies. Fifteen of the interferon-treated patients developed a clinical manifestation of a new onset autoimmune disease during the course of their interferon treatment. Six of the fifteen patients belonged to subgroup 1 (n = 32) and the remaining 9 patients to subgroup 2 (n = 49) (p > 0.05). None were managed by discontinuing the interferon. Most required some form of specific treatment.(ABSTRACT TRUNCATED)

Liver transplantation after an acute episode of spontaneous bacterial peritonitis.

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is a common complication of advanced cirrhosis. Thus many potential transplant recipients will experience this problem while waiting for a liver donor. The minimal amount of time with the use of appropriate antibiotics after which a potential recipient can be transplanted safely is not currently known. We examined the effect of pretransplant SBP on subsequent post-transplant outcome. MATERIALS AND METHODS: A retrospective review of the records of 100 liver transplant recipients having an episode of spontaneous bacterial peritonitis within 30 days of their transplant was performed. The records of transplant controls without an episode of spontaneous bacterial peritonitis were reviewed to compare the outcome between the two groups in terms of sepsis during the initial 30 post-transplant days. RESULTS: Post-transplant sepsis occurred in 8.8% of the cases and 10% of the controls (NSO). Only one episode in the study group could be ascribed to the pre-transplant episode of spontaneous bacterial peritonitis and it occurred in an IgA deficient recipient. CONCLUSIONS: These data suggest that SBP prior to liver transplantation does not lead to an increased rate of postoperative sepsis if 4 or more days of appropriate treatment for SBP are administered prior to liver transplantation.

A comparison of chemoembolization with conventional chemotherapy and symptomatic treatment in cirrhotic patients with hepatocellular carcinoma.

BACKGROUND/AIMS: The results of transcatheter arterial chemoembolization (TACE) in 28 cirrhotic patients with advanced hepatocellular carcinoma (HCC) were compared to those obtained in 15 cirrhotic patients with HCC treated with systemic chemotherapy, and 14 patients with HCC receiving no specific anti-cancer treatment. MATERIALS AND METHODS: From November, 1986 through May 1994, 235 patients with HCC were seen by the investigators. Twenty eight of these patients actually received TACE. The chemotherapeutic agent used was mitomycin C mixed with Lipiodol and arterial embolization was achieved using Gelfoam. In 19 of 28 cases treated with TACE, the embolization was limited to an artery feeding the tumor, thereby avoiding liver cell injury in non-tumor tissue. In 9 others, the main left or right hepatic artery was embolized. The results obtained in these 28 cases were compared to those obtained in 15 patients with HCC larger than 5 cm. who received systemic mitomycin C and doxorubicin chemotherapy and with those obtained in 14 patients who received no specific anti-tumor therapy. RESULTS: One patient died of liver failure related to the TACE and three patients died of bleeding from esophageal varices within weeks of the TACE procedure. Two of the remaining 24 patients are alive with a follow-up of 6 and 22 months. Twenty-six of the 28 patients treated with TACE died within 1 and 28 months of the initiation of the TACE therapy. The mean survival of those receiving TACE was 13.0 months. Chemotherapy without embolization yielded a mean survival of 7.2 months. The mean survival of the patients receiving no specific anti-cancer treatment was only 6.9 months. There was no statistical differences between the survival of those receiving systemic chemotherapy and those receiving no specific treatment. In contrast, the mean survival of the group receiving TACE was significantly greater than that of either of the other two groups (p < 0.005). CONCLUSIONS: These data suggest that TACE provides the best survival for individuals with larger hepatocellular carcinomas (> 5 cm) not eligible for surgery or percutaneous ethanol injection (PEI).

gamma-Glutamyl transpeptidase as a response predictor when using alpha-interferon to treat hepatitis C.

BACKGROUND/AIMS: This study was performed to identify response predictors for Interferon therapy given to patients with chronic hepatitis C. MATERIALS AND METHODS: The biochemical measures of liver injury that characterize viral hepatitis due to hepatitis C were followed prospectively in 84 individuals treated with alpha-Interferon. In addition, the liver histology and the hepatic iron content of these same individuals, prior to the initiation of Interferon therapy, were determined. RESULTS: Patients not responding to the interferon therapy showed an increase in liver iron content from an average of 337 micrograms/g wet weight. In responder to a value of 1075 micrograms/g wet weight in non responders. gamma-glutamyl transpeptidase levels in responders were significantly lower than in partial or non-responders. CONCLUSIONS: Both the hepatic iron content of the liver and the gamma-glutamyl transpeptidase value prior to treatment were able to predict a clinical response to Interferon therapy. More importantly, the gamma-glutamyl transpeptidase level measured in serum could be used to monitor the IFN response during treatment and was found to predict clinical exacerbations of hepatitis following withdrawal of Interferon therapy.