Lymphoma presenting as fulminant hepatic failure; a case report and review of the literature

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Abstracts

patients were compared to 21 patients with AIDS cholangiopathy but normal serum amylase level. Results: For the 19 AIDS cholangiopathy patients with acute pancreatitis, the mean age was 36.6 years. All but two patients had a CD4 counts less than 200 (mean ⫽ 54.3). Mean serum AST, ALT, total bilirubin, alkaline phosphatase, and albumin were 86, 70, 1.55, 824, and 3.3 respectively. None of these values was significantly different from those of the 21 controls. The mean serum amylase level of the 19 cases was 307.11 (standard error ⫽ 281.68) compared to 61.9 (standard error ⫽ 23.9) of the 21 controls. The cases were further stratified by cholangiographic findings: 12 patients had papillary stenosis, one patient had sclerosing cholangitislike lesions, five patients had a mixed type, and one patient had a long extrahepatic bile duct stricture. It appeared that AIDS cholangiopathy patients with acute pancreatitis were more likely to have either papillary stenosis or the mixed type than controls, but it was not statistically significant (p ⫽ 0.086). No difference was found between the two groups with respect to concomitant opportunistic infections and the presence of GI tract Kaposi’s sarcoma. Finally, the mean survival time from the diagnosis of AIDS cholangiopathy to death was 8 months for those with acute pancreatitis and 4 months for those without acute pancreatitis; this was not statistically significant (p ⫽ 0.23). Conclusion: The clinical characteristics were similar for AIDS cholangiopathy patients with or without acute pancreatitis. The survival for AIDS cholangiopathy patients with acute pancreatitis may be slightly better than those without acute pancreatitis but it was not statistically significant.

358 Safety and efficacy of triple therapy (interferon, ribavirin and amantadine) in the treatment of chronic HCV liver disease patients who have previously failed dual therapy Gerond Lake-Bakaar. VAMC, Northport, NY, United States. Purpose: The combination of interferon and ribavirin is currently first line treatment in patients with chronic hepatitis C liver disease. However, a significant number of patients, especially those infected with genotype 1 do not achieve a sustained response with this. There have been a number of reports suggesting that Amantadine, a synthetic antiviral agent with activity against influenza A and C viruses, may have some activity in chronic HCV liver disease. We therefore evaluated the safety and efficacy of triple therapy in chronic HCV liver disease patients who had previously failed treatment with interferon and ribavirin. Methods: We included 13 patients (one female, aged between 32 to 56 years) in the study, on an intention to treat basis. All but one was known to be infected with genotype 1. Six had histological evidence of established cirrhosis. All had failed at least six months of treatment with interferon and ribavirin. Eight were non-responders and the rest had relapsed on treatment discontinuation. Interferon and ribavirin were given at standard or slightly reduced doses. Amantadine was given orally at a dose of 100 mg twice daily. Results: A total of nine patients have completed at least six months of treatment. One discontinued after 2 weeks because of increased malaise; another after one month because of increased weight loss; and a third because of lack of efficacy after three months; a fourth remains on treatment after 3 months and is HCV RNA negative. One initially patient stopped treatment for one week because of a rash; however, the rash did not recur on restarting treatment. In the group of patients who completed six months of treatment, the mean WBC did not differ significantly before, 4.02 ⫹ 1.1 or after 4.0 ⫹ 1.9 treatment (p ⫽ 0.15, t test). Hemoglobin levels also did not change significantly before, 14.12 ⫹ 1.9 or after 13.47 ⫹ 1.8 (p ⫽ 0.81). Three (23 percent) patients, two of whom were relapsers, were HCV RNA negative at the end of six months. Data on sustained responses are not currently available. Conclusions: Triple therapy appears to be safe in patients with chronic HCV liver disease. Efficacy, though low, may still be useful in this group of therapy resistant patients.

AJG – Vol. 95, No. 9, 2000

359 Long-term follow-up of hepatitis A vaccination in patients with chronic liver disease Shou-Dong Lee, M.D., FACG, May-Ing Yu, R.N., Cho-Yu Chan, M.D., Yuan-Jen Wang, M.D., Full-Young Chang, M.D., Kwang-Juei Lo, M.D. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan. The long-term safety and immunogenicity of inactivated hepatitis A was evaluated in a study involving 60 patients with chronic liver disease (CLD) (56 patients with chronic hepatitis B, and 4 patients with chronic hepatitis C). A two-dose schedule, 1,440 ELISA units of the inactivated hepatitis A vaccine was given at 0 and 6 months, which produced 100% antibodies to hepatitis A virus (anti-HAV) seroconversion (Lee et al., J Med Virol 1997;52:215– 8). Patients in the study were followed up annually for 5 years, and in that time, 2 fatalities were reported. One 21-year-old male chronic hepatitis B patient died following liver transplantation at 3 years follow-up, while another 26-year-old chronic hepatitis B patient died in an accident at 4 years follow-up. The geometric mean titers of anti-HAV among these CLD vaccinees were 419, 185, 169, 168 and 158 mIU/ml at 1, 2, 3, 4 and 5 years, respectively. Although 12% and 14% of the CLD vaccinees whose anti-HAV antibodies became undetectable at 4 and 5 years of follow-up, respectively. Approximately 70% of them whose antiHAV levels were still remained over 100 mIU/ml at the 5 years of follow-up. Inactivated hepatitis A vaccine was safe and immunogenic in patients with CLD, but the immune response was inferior to that observed in healthy subjects (Poovorawan et al., Vaccine 1996;14:1092– 4; Chan et al., Vaccine 1999;17:369 –72), indicating it may be recommended that patients with CLD receive a higher dose, and the classic two-dose schedule of hepatitis A vaccination for protection.

360 Lymphoma presenting as fulminant hepatic failure; a case report and review of the literature Christopher J Lettieri, M.D., Matthew Fandre, Darren S Baroni, M.D.*. Tripler Army Medical Center, Honolulu, Hawaii, United States. Purpose: Hematologic malignancies frequently effect the liver, but typically do not result in overt hepatic dysfunction and rarely progress to fulminant hepatic failure (FHF). Rarer still is FHF the presenting manifestation of a hematologic malignancy. The authors present a case of acute hepatitis, which rapidly progressed to FHF. A high-grade lymphoma was found to be the insulting illness. The literature reports only a 19 cases of similar presentations of lymphoma, these will be reviewed. Methods: A 60 year-old Japanese female initially presented with acute hepatitis which rapidly progressed to FHF. Shortly after admission, she was found to have fevers, night sweats, hepatosplenomegaly (HSM) and diffuse lymphadenopathy (LAN). She underwent a lymph node and bone marrow biopsy which confirmed the diagnosis of a HTLV-1 high grade lymphoma. A liver biopsy was done to exclude other etiologies for FHF. Despite early chemotherapy, she deteriorated rapidly and died 6 days after the onset of FHF. Results: See above. Conclusions: Based on our case and a review of the literature four clinical features are present in patients with FHF as a result of lymphoma: 1) Lactic Acidosis (LA), 2) the presence of HSM, 3) a very poor prognosis, and 4) a delay in diagnosis. LA is not commonly seen in patients with most causes of FHF. Of the 7 cases which recorded serum lactate, all had elevated levels. Likewise, HSM suggests an inflammatory or infiltrative process and if associated with FHF suggests a malignancy, especially lymphoma. HSM was commonly seen in the reviewed cases. FHF secondary to lymphoma resulted in death in 81% of the cases with an average survival of 9.7 days following the onset of symptoms, which is drastically higher than the 50% five-year mortality rate of lymphoma in general. The high mortality rate and short survival time of lymphoma associated with FHF makes early

AJG – September, 2000

Abstracts

diagnosis and treatment essential. However, FHF secondary to lymphoma is rare and therefore not commonly considered in the differential diagnosis of acute hepatic dysfunction. This results in a delayed, if not missed diagnosis, which contributes to the poor prognosis of this disease. Supporting this is that in the cited cases, the diagnosis was made only at autopsy in 15/20 patients. Given that the majority of cases are not made until post-mortem, it can be theorized that lymphoma as an etiology for FHF is underdiagnosed and should be considered in any patient who presents with acute liver failure associated with LA and HSM. Early diagnosis may provide the only opportunity for aggressive chemotherapy the chance for remission. 361 Factors associated with steatosis in patients with chronic hepatitis C Petrea Monson, Deanna L Oliver, Annette Pohl, Cynthia Behling, Nina Aronson, Lina Rossetti, Tarek I Hassanein*. University of California, San Diego, CA, United States. Purpose: Steatosis is a common feature of chronic Hepatitis C (HCV). The pathophysiology of steatosis is not clear. Multiple factors may play a role in the degree of steatosis in patients with HCV infection. We investigated the correlation between pre-treatment body mass index (BMI), serum liver injury tests, and HCV viral load (HCV-RNA), and steatosis in patients with HCV. Methods: Seventy-one patients were included in the study (mean age 45 ⫾ 8 yrs, 53M, 18F). Genotype distribution was 73% and 28% for type 1 and non-1, respectively. Mean pre-treatment ALT, AST, and GGT values were 117 ⫾ 85 IU/L, 72 ⫾ 43 IU/L, and 70 ⫾ 64 IU/L, respectively. Percent steatosis was quantified by a single pathologist from pre-treatment liver biopsies. Statistical method used was correlation analysis. Results: There was no correlation between HCV-RNA, serum ALT and AST, and steatosis. Conclusions: 1) Pre-treatment steatosis was positively correlated with BMI, and 2) Abnormal serum GGT correlated with steatosis.

BMI HCV-RNA GGT ALT AST

R

P Value

0.36 0.03 0.05 0.02 0.24

0.01 0.82 ⬍0.001 0.89 0.04

362 Geographic variation of genotype 1 in hepatitis C viral infection in the United States: Non-urban western Pennsylvania contrasted with inner city Baltimore Morry Moskovitz, MD, FACG, Mia Shilobod, PA-C. Valley Gastroenterology Associates, Beaver, PA, and the University of Pittsburgh, Pittsburgh, PA. It has been determined that there is a poorer prognosis and response to anti-viral therapy in patients with chronic hepatitis C virus (HCV) infection who are genotype 1. There is a considerable variation of genotypes around the world, from country to country. There may be a considerable variation between geographic areas within this country. We performed a retrospective analysis of 68 consecutive patients in whom HCV genotyping was done in our community-based gastroenterology practice in Beaver and Lawrence Counties in Western Pennsylvania. Twenty-six were genotype 1a (38%), 11 were 1b (17%), and one was 1e. Three were 2a (4%), 11 were 2b (16%), 2 were 2c (3%), 11 were 3a (16%), and three were 3e (4%). Therefore, there were 38 genotype 1 patients (56%), while 30 were nontype 1 (44%). Ninety-three percent of the patients were Caucasian. This contrasts with pooled data from the USA, where genotype 1 accounted for 79% of all HCV cases (Zein et al., Ann Int Med 1996;125[8]:634 –9). Furthermore, the incidence of genotype 1 in an inner-city clinic at Johns Hopkins University in Baltimore is 96%, where the population is predom-

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inantly African-American (personal communication—Dr. M. Sulkowski). We conclude that there is a considerable variation in the geographic (and racial) distribution of HCV genotype 1, with a lower incidence in nonurban Pennsylvania, containing a predominantly Caucasian population compared with a predominantly inner-city group in Baltimore. Differences in response to therapy may be expected.

363 Patients with hepatitis C infection and normal transaminases have high sustained response rate to combination therapy R Pena, V Kaul, A Suvannasankha, K DiGregorio, L Stein, F Gross, S Peikin, O Perez, G Benson, A Mushnick, C DeAngelo, J Goldfarb, K Rothstein, C Manzarbeitia, D Reich, N Kern, S Munoz. Center for Liver Disease, Albert Einstein Medical Center, Philadelphia, PA. Background: It is not known whether combination antiviral therapy with ribavirin and interferon alpha 2b (IFN) is useful in patients with normal transaminases. Aim: We prospectively evaluated the virologic response to combination therapy in patients with normal transaminases who had previously not achieved a sustained response with IFN alone. Methods: Non-responders (NR) and relapsers (RE) to monotherapy with IFN were stratified according to HCV RNA level, absence/presence of cirrhosis on biopsy, and randomized to receive IFN 3MU tiw plus ribavirin 600 mg qd, or IFN 5 MU tiw plus ribavirin 1,000 mg qd. Twenty-eight patients with normal ALT/AST at baseline (study group), were compared to 102 others, who had elevated transaminases at baseline (control group). Both groups were comparable in terms of age, sex, % cirrhosis (19% and 24%), and baseline HCV RNA levels (3.63⫾1.9 and 3.52⫾1.8⫻108 copies/ml. respect). Virological response (undetectable HCV-RNA) was evaluated at six (initial response), twelve (end of treatment response) and eighteen months (sustained response). Results: Sixteen patients (57%) in the study group had an initial response and 37 (36%) in the control group (p⫽0.053). Fifteen (53.5%) and 26 (25.4%) had end of treatment response (p⫽0.029), and 11 (39.2%) and 18 (17.5%) had sustained virological response (p⫽0.12) in the study and control groups respectively. Conclusion: Re-treatment with interferon alpha 2b and ribavirin results in better initial and end of treatment response rates in patients with normal aminotransferases. However, the sustained virological response rate of patients with normal transaminases is statistically not different compared to patients with abnormal transaminases at baseline. (Supported in part by Schering Pharm. Corp).

364 Response rates to different doses of combination therapy for HCV R Pena, V Kaul, A Suvannasankha, K DiGregorio, L Stein, F Gross, S Peikin, O Perez, G Benson, A Mushnick, C DeAngelo, J Goldfarb, K Rothstein, C Manzarbeitia, D Reich, N Kern, S Munoz. Center for Liver Disease, Albert Einstein Medical Center, Philadelphia, PA. Background: It is known that combination antiviral therapy with ribavirin and interferon alpha 2b (IFN) has many side effects, often dose-related. Using lower doses may improve compliance. However, the response rate to low dose regimens is not known. Aim: We prospectively evaluated the virologic response to combination therapy in patients who had previously not achieved a sustained response with IFN alone using two different dose regimens. Methods: Nonresponders (NR) and relapsers (RE) to monotherapy with IFN were stratifeid according to HCV RNA level, absence/presence of cirrhosis on biopsy, and randomized to receive IFN 3MU tiw plus ribavirin 600 mg qd. (low dose) or IFN 5 MU tiw plus ribavirin 1,000 mg qd (high dose). Patients were treated for one year. Sixty-eight patients in the low dose and sixty-two in the high dose groups were followed for at least six months. Both groups were comparable in terms of age, sex, % cirrhosis