Harvey Solomon

Positron emission tomography scanning in the evaluation of hepatocellular carcinoma

BACKGROUND/AIMS 18F-fluorodeoxyglucose uptake allows estimation of glucose metabolism by tumor cells using positron emission tomography (PET). We evaluated the role of PET imaging in the diagnosis of hepatocellular carcinoma. METHODS PET images were collected after intravenous injection of 8-12 mCi of 18F-FDG in 20 patients with hepatocellular carcinoma (HCC). PET tumor activity level was assessed on a scale of 1 to 4 compared to normal liver tissue. The PET score was compared with abdominal computerized tomography (CT) scan results and between tumors of different grades and differentiation. RESULTS Of the 20 patients studied, 11 (55%) had positive PET scans (PET score: 3 or 4) while nine (45%) were negative (PET score: 1 or 2). CT scan was positive in 18 patients (90%) and negative in two (10%). PET, however, revealed metastases in three patients that were not seen on CT. On pathological review, well-differentiated and low-grade tumors had lower PET scores. Comparison of the well-differentiated with the moderately- and poorly-differentiated tumors revealed a statistically significant difference. No statistical significance was observed between the moderately- and poorly-differentiated tumors or between different tumor grades and PET scores. CONCLUSIONS The sensitivity of PET in diagnosis of HCC was 55% compared to 90% for CT scanning, although only PET detected some tumors (including distant metastases). Well-differentiated and low tumor grades had lower activity on PET and correspondingly lower PET scores. PET imaging may help assess tumor differentiation and may be useful in the diagnosis and staging and prognostication of HCC as an adjunct to CT.

Studies of Pediatric Liver Transplantation (SPLIT) : Year 2000 outcomes

Background. Initiated in 1995, the Studies of Pediatric Liver Transplantation (SPLIT) registry database is a cooperative research network of pediatric transplantation centers in the United States and Canada. The primary objectives are to characterize and follow trends in transplant indications, transplantation techniques, and outcomes (e.g., patient/graft survival, rejection, growth parameters, and immunosuppressive therapy.) Methods. As of June 15, 2000, 29 centers registered 1144 patients, 640 of whom received their first liver-only transplant while registered in SPLIT. Patients are followed every 6 months for 2 years and yearly thereafter. Data are submitted to a central coordinating center. Results. One/two-year patient survival and graft loss estimates are 0.85/0.82 and 0.77/0.72, respectively. Risk factors for death include: in ICU at transplant (relative risk (RR)=2.63, P <0.05) and height/weight deficits of two or more standard deviations (RR=1.67, P <0.05). Risk factors for graft loss include: in ICU at transplant (RR=1.77, P <0.05) and receiving a cadaveric split organ compared with a whole organ (RR=2.3, P <0.05). The percentage of patients diagnosed with hepatic a. and portal v. thrombosis were 9.7% and 7%, respectively; 15% had biliary complications within 30 days. At least one re-operation was required in 45%. One/two-year rejection probability estimates are 0.60/0.66. Tacrolimus, as primary therapy posttransplant, reduces first rejection risk (RR=0.70, P <0.05). Eighty-nine percent of school-aged children are in school full-time, 18 months posttransplant. Conclusions. This report provides one of the first descriptions of characteristics and clinical courses of a multicenter pediatric transplant population. Observations are subject to patient selection biases but are useful for generating hypothesis for future studies.

Disease- and cell-specific expression of GP73 in human liver disease.

OBJECTIVES:GP73, a Golgi membrane protein, is expressed at high levels in hepatocytes of patients with decompensated cirrhosis. Its expression in other forms of liver disease has not been investigated. Therefore, we studied GP73 expression in patients with noncirrhotic liver disease.METHODS:GP73 expression was detected immunohistochemically and by immunofluorescence microscopy in patients with acute hepatitis of various etiologies, autoimmune hepatitis, chronic HCV infection, and alcoholic liver disease. In order to quantitate hepatocyte GP73 expression, an immunohistochemical scoring system was developed, and validated by a direct comparison with GP73 protein levels as determined by Western blotting.RESULTS:GP73 immunostaining and Western blotting data were highly correlated, demonstrating the suitability of the immunohistochemical scoring system to quantitate hepatocyte GP73 expression. Hepatocyte GP73 expression was increased in patients with acute and autoimmune hepatitis. Treatment of autoimmune hepatitis was associated with a normalization of GP73 expression, indicating that the initial upregulation was reversible. Increased levels of GP73 expression were also noted in chronic HCV infection and alcoholic liver disease. Under these conditions, GP73 levels were correlated with disease stage but not grade. GP73 immunoreactivity was occasionally detected in α-SMA-positive, sinusoidal lining cells, suggesting activated stellate cells as a potential source of GP73.CONCLUSIONS:Hepatocyte GP73 levels are upregulated in acute hepatitis and during the progression of liver disease to cirrhosis. This expression pattern suggests the presence of two regulatory mechanisms, the first triggered during acute hepatocellular injury, the second during the progression of chronic liver disease.

OKT3 rescue for steroid-resistant rejection in adult liver transplantation

The results of OKT3 use for steroid-resistant rejection rescue in adult liver transplantation were analyzed retrospectively from a single transplant center. Comparison was made with concurrent patients who had no rejection (NR) or steroid-responsive rejections (SR). The records of 290 patients who underwent 323 liver transplants from April 1985 to December 1989 were examined. The first technically successful grafts were used for this analysis (265 grafts). Follow-up was a minimum of 1 year, or until death or loss of graft. All patients received triple-drug induction immunosuppression (CsA, Aza, steroids). Initial rejection was treated with 1 g methylprednisolone bolus i.v., followed by a 5-day taper of steroids from 200 mg to 20 mg. No rejection occurred in 108 (40.8%) and SR in 86 (32.4%), and OKT3 was given for persistent rejection in 71 (26.8%). The age, sex distribution, mean follow-up, and preoperative status were similar in all three groups. The preoperative diagnoses were similar, except for fulminant liver failure, in which 19 of 20 patients experienced rejection (P < 0.0001). The median hospitalization stay was 37 days for OKT3, 27 days for SR, and 21 days for NR (P < 0.0001). The median ICU stay was similar in the three groups (OKT3, 4; SR, 4; NR, 3). Infections in the first 6 weeks, and in the period of 6 weeks to 1 year posttransplant, were of similar frequency for all three groups. By the Kaplan-Meier estimation, the graft and patient actuarial survival rates were comparable. At 1 year, the graft survival rate was 79.6% for NR, 79.8% for SR, and 67.6% for OKT3. The 1-year patient survival rate was 85.2% for NR, 83.7% for SR, and 84.5% for OKT3. Following treatment by OKT3, rejection was permanently reversed in 42 patients. A temporary response occurred in 12 patients, 16 patients failed to respond to OKT3, 2 patients died during therapy, and 6 of the nonresponders died within 12 months. Additional OKT3 treatment was attempted in 6 patients for persistent rejection within a 1-month interval from the previous OKT3 course. Of these 6, 4 developed lymphoproliferative disorder, and only 1 survived in response to drastic reduction of immunosuppression. In conclusion, OKT3 was effective as rescue therapy for adult liver transplant steroid-resistant rejection. Because of the associated morbidity and expense, OKT3 should be used in a selective fashion. Failure to respond to OKT3 is a serious complication, and should not be managed by prolonged or repeated courses, but rather by alternative means.

Comparison of genetic heterogeneity of hepatitis C viral RNA in liver tissue and serum.

Objective:Hepatitis C virus (HCV) is known to be heterogeneous and to circulate as a group of closely related quasispecies in individual patients, although hepatic viral genetic characteristics have not been well documented.Methods:Matched serum and liver samples were tested by reverse transcription polymerase chain reaction amplification and single stranded conformation polymorphism analysis of the hypervariable portion of the E2/NS1 region of the HCV genome. The number of quasispecies was compared with the amount of HCV RNA, HCV genotyping, and infection with the hepatitis G virus.Results:Sixteen of 40 patients had HCV RNA detectable in serum and liver. The HCV genotype was identical in serum and liver of all but one case. HCV RNA levels were approximately 10-fold higher in liver than serum. The number of HCV quasispecies in serum ranged between two and six (median 3.0) and in the liver between 2 and 19 (median 3.5, mean liver/serum ratio 1 to 6.3, median 1.8). The number of quasispecies in liver was equal to or greater than that in serum in all cases. HGV infection was found in 14 cases and did not influence serum or hepatic levels of HCV RNA.Conclusions:The number of hepatic HCV quasispecies usually exceeds that in serum, independent of the amount of HCV RNA and HCV genotype. This finding is compatible with clearance of some quasispecies from serum, but not liver, by putative neutralizing antibodies.

Biliary-Venous Fistula Complicating Transjugular Intrahepatic Portosystemic Shunt Presenting With Recurrent Bacteremia, Jaundice, Anemia and Fever

A 50‐year‐old White man with noncirrhotic portal hypertension presented with bleeding from gastric varices. Bleeding was initially managed with band ligation and subsequent transjugular intrahepatic portosystemic shunt (TIPS). Over the next few months, the patient had recurrent episodes of anemia, jaundice, fever and polymicrobial bacteremia. Computed tomography (CT) of the abdomen and chest, upper and lower endoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and echocardiography failed to explain the bacteremia and anemia. Follow‐up CT scan and Doppler sonography 9 months after placement showed TIPS was occluded. Repeat ERCP showed a bile leak with free run‐off of contrast from the left hepatic duct into a vascular structure. The patients status was upgraded for liver transplantation with Regional Review Board agreement and subsequently received a liver transplant. Gross examination of the native liver demonstrated a fistula between the left bile duct and the middle hepatic vein. Pathologic evaluation confirmed focal necrosis of the left hepatic duct communicating with an occluded TIPS and nodular regenerative hyperplasia consistent with noncirrhotic portal hypertension. Infection is rarely reported in a totally occluded TIPS. Biliary fistulas in patent TIPS have been treated by endoluminal stent graft and endoscopic sphincterotomy with biliary stent placement. Liver transplantation may be the preferred treatment if TIPS becomes infected following its complete occlusion.

Is hepatitis G/GB virus-C virus hepatotropic? Detection of hepatitis G/GB virus-C viral RNA in liver and serum.

The recently identified hepatitis G virus (HGV, also named GB virus‐C, GBV‐C) appears to have similarities to hepatitis C virus and other flaviviridae. To better understand its clinical significance and hepatotropism, we collected liver tissue and matched serum samples from 56 patients undergoing liver transplantation. HGV/GBV‐C RNA was detected by reverse transcription–nested PCR, using primers from the relatively conserved 5′ noncoding region of the genome to detect HGV/GBV‐C RNA and the amount was semiquantitatively estimated by serial 10‐fold endpoint dilution. The presence and amount of HCV RNA was estimated by the same methodology. Seventeen patients (30%) had HGV/GBV‐C RNA detectable either in liver or in serum, including two of three with cryptogenic liver disease. Interestingly, 5 of 17 (29%) patients had HGV/GBV‐C RNA in serum but not liver, even with repeated testing of hepatic RNA from different portions of the liver. Furthermore, the titer of HGV/GBV‐C RNA was significantly lower in liver than in serum in most samples (mean log titer, 1.33 vs. 2.56, P < 0.05). In contrast, all 21 patients with HCV RNA in serum also had the virus detectable in liver. In five patients coinfected with HCV and HGV/GBV‐C, the mean titer of HCV RNA in liver was higher than that in serum (log titer, 2.8 vs. 3.0, P > 0.05). Thus, our results suggest that HGV/GBV‐C is probably not hepatotropic and may replicate predominantly in sites other than the liver. These findings brings into question the role of HGV in causing significant liver disease. J. Med. Virol. 58:160–164, 1999.

Rapid development of hepatic alpha1-antitrypsin globules after liver transplantation for chronic hepatitis C

A 37-year-old man undergoing liver transplantation for cirrhosis caused by chronic hepatitis C and alcoholism developed large numbers of alpha1-antitrypsin (AAT) globules within hepatocytes of the transplanted liver during a 5-month period. This finding occurred simultaneously with severe recurrent hepatitis C. The AAT phenotype of this patient changed from MM before transplantation to MZ after transplantation; AAT levels in serum did not change significantly. After a second liver transplantation 6 months after the first, the AAT phenotype reverted to MM and globules were not detectable in the second transplanted liver. Severe recurrent hepatitis C and the appearance of AAT globules within the liver allograft of a heterozygous donor may be related. The recurrent infection may have induced accumulation of AAT protein, or, alternatively, the MZ liver may have been more susceptible to injury from recurrent viral infection.

A prospective randomized trial between Euro-Collins and university of Wisconsin solutions as the initial flush in hepatic allograft procurement

University of Wisconsin solution is currently recognized as the best solution for long-term organ preservation. It is recommended that UW solution be used as the in situ flush prior to organ explantation. The purpose of our study was to determine if hepatic allograft function was impaired by flushing the graft in situ with Euro-Collins and later flushing the graft ex vivo with UW solution, prior to cold storage. Fifty-six donors were randomly assigned to either an EC (n=24) or UW (n=32) in situ flush. The livers flushed with EC in situ were later flushed with 1 L of UW on the back table and stored in UW solution. Livers flushed with UW in vivo were similarly flushed and stored in UW on the back table. Concerning the donor allograft, there was no statistical difference (P<0.05) between groups in sex, race, blood type, arterial anatomy, age, prothrombin time (PT), partial thromboplastin time (PTT), total bilirubin (TBR), direct bilirubin (DBR), aspartate amino transferase (AST), or alanine amino transferase (ALT). In addition, the recipients were compared for differences in sex, race, blood type, preoperative status, number of rejections, recipient age, length of surgery, and ischemia time and patient survival. There was no significant difference between groups (P < 0.05). There was no significant difference in patient survival (P = 0.238). Values for TBR, AST, ALT, PT, PTT, and AP were collected immediately preoperatively and post-operatively and on postoperative days 1, 3, 7, 14, and 28. There was no difference between groups in these values (P < 0.05). In our study there was no difference between the groups with respect to graft performance. This would justify the use of EC as an in situ flush during solid organ procurement and flushing with UW solution on the back table with an estimated savings of 400 to 1200 per procurement.

Small bowel perforation from a migrated biliary stent

Gastric outlet obstruction secondary to benign or malignant disease can be treated with self-expanding metallic stents. This obviates the need for surgical bypass procedures and returns most patients to a normal diet. Prosthesis displacement is described as a late complication. A case of stent migration to the rectum, presenting with the symptoms and signs of incomplete large bowel obstruction, is described.