Response to article by Formann et Al. (2003).
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Alanine Transaminase↗
Biomedical subjects
I M Jacobson
Publications and source records attributed to I M Jacobson.
CD56(+dim) and CD56(+bright) cell activation and apoptosis in hepatitis C virus infection.
CD3- CD56(+dim) natural killer (NK) cells, which are cytotoxic against virally infected cells, may be important in hepatitis C virus (HCV)-infected patients who are successfully treated with pegylated interferon (PEG-IFN)-alpha. We used flow cytometry to enumerate activated (CD69+) and apoptotic (annexin-V+) dim (CD3- CD56(+dim)) and bright (CD3- CD56(+bright)) NK cells obtained from HCV-infected patients before treatment (n=16) and healthy controls (n=15) in the absence and presence of pegylated interferon (PEG-IFN)-alpha-2b. A subset of HCV-infected patients, subsequently treated with PEG-IFN-alpha-2b in vivo, was determined to have a sustained virological response (SVR, n=6) or to not respond (NR) to treatment (n=5). In the absence of IFN, activated dim (CD3- CD56(+dim) CD69+) NK cells were significantly decreased (P=0.04) while activated apoptotic dim (CD3- CD56(+dim)CD69+ annexin-V+) NK cells tended to be increased (P=0.07) in SVR patients compared with NR patients. Activated bright (CD3-CD56(+bright)CD69+) and activated apoptotic bright (CD3- CD56(+bright)CD69+ annexin-V+) NK cells were significantly correlated (P=0.02 and P=0.01, respectively) with increasing hepatic inflammation. These findings suggest that in the absence of PEG-IFN, activated dim (CD3- CD56(+dim)CD69+) NK cell turnover may be enhanced in SVR compared with NR patients and that activated bright (CD3- CD56(+bright)CD69+) NK cells may play a role in liver inflammation.
Adult↗
Efficacy of high-dose interferon in combination with ribavirin in patients with chronic hepatitis C resistant to interferon alone.
OBJECTIVE: Interferon combined with ribavirin has efficacy in the treatment of patients with chronic hepatitis C virus (HCV) infection. However, its utility in patients who have not responded to prior interferon therapy is not clear. Furthermore, the effect of using an increased dose of interferon in combination with ribavirin in patients with chronic hepatitis C resistant to conventional doses of interferon is not known. The aim of our study was to evaluate the effect of high-dose interferon in combination with ribavirin on the efficacy of treating patients with chronic hepatitis C resistant to interferon monotherapy in a large multicenter trial. METHODS: We randomized 154 patients with chronic hepatitis C who failed to achieve a sustained response with prior interferon therapy to receive either 3 or 5 MU of interferon alpha-2b and ribavirin (1000-1200 mg/day) for 12 months. There were 119 patients who had not responded and 35 who initially responded but relapsed after prior interferon monotherapy. Serum HCV RNA levels were measured at entry, 6, and 12 months of treatment and at the end of a 6-month follow-up period. RESULTS: The mean age of the subjects was 47 yr (range 28-68 yr), and 110 (71.4%) were men. One hundred thirty-two patients (86%) had HCV genotype 1, whereas 21 (14%) had cirrhosis. Eighty-one subjects (53%) were randomized to receive 3 MU of interferon alpha-2b. Fifteen of 35 relapse subjects (43%) and 12 of 119 prior nonresponder entrants (10%) achieved a sustained virological response to the 12-month course of treatment. Overall, 11 of 81 patients (14%) receiving 3 MU, and 16 of 73 patients (22%) receiving 5 MU of interferon maintained an undetectable HCV RNA level after cessation of therapy. The difference in sustained response rates between the two interferon dosage groups did not reach statistical significance (p = 0.09). However, among the nonresponder patients alone, there was an increased sustained response in the high-dose interferon group compared with the standard interferon dose group (15.5% vs 4.9%, p = 0.055). Twenty-six patients discontinued therapy before 6 months, including 10 patients (12.3%) in the 3-MU and 16 patients (21.9%) in the 5-MU groups (p = 0.17). CONCLUSIONS: Sustained virological response to combined interferon alpha-2b and ribavirin was significantly higher in relapse patients than those who did not respond to prior interferon monotherapy. Although, when all treated patients were analyzed, there was no significant difference in sustained response between subjects receiving 3 and 5 MU of interferon, among the prior nonresponder patients, treatment with 5 MU of interferon with ribavirin resulted in a slightly increased response compared with treatment with the standard interferon dosage. The tolerability of the treatment regimens was comparable.
Adult↗
An unusual case of acute colitis.
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Acute Disease↗
Evaluation of the pattern of liver tests and yield of cholangiography in symptomatic choledocholithiasis: a prospective study.
BACKGROUND: The role of ERCP in the management of choledocholithiasis in an era of minimally invasive therapy continues to be defined. METHODS: We evaluated prospectively the pattern of liver test abnormalities and yield of cholangiography after presentation with illnesses suggesting choledocholithiasis. Ninety-four consecutive patients, all with liver test abnormalities (total bilirubin, alkaline phosphatase, AST, and ALT) at presentation, had serial determinations to within 24 hours of cholangiography and were divided into four groups based on their patterns of rise or fall of liver test results as well as presenting clinical syndrome. Group I: normalized liver tests; Group II: falling liver tests, and alkaline phosphatase falling greater than 50% of the difference between presentation value and upper limit of normal; Group III: alkaline phosphatase falling less than 50%; and Group IV: any liver test with increasing levels. Clinical syndromes included cholangitis, pancreatitis, combined cholangitis and pancreatitis, and biliary pain with abnormal liver tests. RESULTS: Yields of choledocholithiasis were 13% (Group I), 50% (Group II), 67% (Group III), and 94% (Group IV). Yield by syndromes were 36% (biliary pancreatitis), 72% (biliary pain and abnormal liver tests), 87% (cholangitis), and 100% (cholangitis and pancreatitis). CONCLUSION: The degree of decline in liver test levels is inversely related to the yield of cholangiography in symptomatic choledocholithiasis; the yield of ERCP in these patients (with normalized liver tests) is low and they do not require ERCP. Pre-ERCP estimates of the likelihood of choledocholithiasis can be made on the basis of the pattern of liver tests, and biliary pancreatitis patients with normalized liver tests do not require ERCP.
Adult↗
Recurrent acute pancreatitis: an additional manifestation of the "wandering spleen" syndrome".
A case of "wandering spleen" associated with recurrent pancreatitis and diagnosed with computed tomography (CT), is reported. The entity was also associated with a rotated, distended stomach, gastric outlet obstruction secondary to extrinsic compression of the duodenum, and partial small bowel obstruction secondary to extrinsic compression of a mobile, distended cecum that lay under the right diaphragm.
Acute Disease↗
Safety of ERCP during an acute MI.
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Aged↗
ERCP for symptomatic choledocholithiasis in pregnancy.
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Adolescent↗
A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group.
BACKGROUND AND METHODS: Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. RESULTS: Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P less than 0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P less than 0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03). CONCLUSIONS: In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum.
Adult↗
Treatment of chronic hepatitis C with recombinant alpha-interferon. A multicentre randomized, controlled trial. The Hepatitis Interventional Therapy Group.
To assess the efficacy of therapy with the antiviral agent interferon in chronic hepatitis C (non-A, non-B hepatitis), we randomly assigned 166 chronic hepatitis C patients to treatment with either 3 million or 1 million units of recombinant interferon alfa-2b three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after 6 months of interferon therapy was 46% in patients treated with 3 million units of interferon (p less than 0.001) and 28% in those treated with 1 million units (p less than 0.02), but only 8% in untreated patients. Serum alanine aminotransferase levels became completely normal in 22 of the 26 patients (85%) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56%) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histological improvement because of the regression of lobular and periportal inflammation. Relapse within 6 months after the completion of treatment occurred in 51% of the patients treated with 3 million units of interferon and 44% of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common.
Chronic Disease↗
Biliary and pancreatic disease in the elderly.
Cholelithiasis and its complications, along with malignancy, account for the majority of biliary and pancreatic diseases in the elderly and increase in frequency with advancing age. The presentation is often subtle and requires a high index of suspicion on the part of the clinician. Surgical management of pancreaticobiliary disease usually is associated with an increased morbidity and mortality relative to younger patients, although in some cases surgery still remains the best treatment modality. A major advance has been the development of nonsurgical therapeutic techniques, such as endoscopic sphincterotomy and biliary endoprostheses.
Administration, Oral↗
Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial.
Chronic hepatitis C (non-A, non-B hepatitis) is a common and often progressive viral liver disease. To assess the efficacy of therapy with the antiviral agent interferon alfa, we randomly assigned 166 patients with chronic hepatitis C to treatment with either 3 million or 1 million units of recombinant interferon alfa three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after six months of interferon therapy was 46 percent in patients treated with 3 million units of interferon (P less than 0.001) and 28 percent in those treated with 1 million units (P less than 0.02), but only 8 percent in untreated patients. The serum alanine aminotransferase level became completely normal in 22 of the 26 patients (85 percent) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56 percent) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histologic improvement because of the regression of lobular and periportal inflammation. Relapse within six months after the completion of treatment occurred in 51 percent of the patients treated with 3 million units of interferon and 44 percent of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common.
Alanine Transaminase↗
Biliary tract obstruction in the acquired immunodeficiency syndrome.
Three patients with the acquired immunodeficiency syndrome had biliary obstruction resulting from benign strictures of the biliary tract. Stenosis of the distal common bile duct with differing degrees of irregularity of the smaller intrahepatic and extrahepatic ducts was seen in association with either cryptosporidial or cytomegaloviral infection of the biliary tree. We review cytomegaloviral and cryptosporidial infections of the biliary system, as well as possible relationships with idiopathic primary sclerosing cholangitis. Stenotic biliary tract disease appears to be yet another complication of the acquired immunodeficiency syndrome.
Acquired Immunodeficiency Syndrome↗
Late-onset Wilson's disease with neurological involvement in the absence of Kayser-Fleischer rings.
We report a patient with Wilson's disease whose case is unusual in two respects. First, the patient was 58 years of age when the diagnosis was made based on urinary, serum, and hepatic copper studies, as well as liver histological investigation. Second, despite the patient's neurological impairment, Kayser-Fleischer rings had not developed. We conclude that in patients with chronic, degenerative neurological disease, particularly when associated with hepatic dysfunction, the diagnosis of Wilson's disease should be considered regardless of age at onset or the absence of Kayser-Fleischer rings on slit lamp examination.
Age Factors↗
Relapsing viral hepatitis type A.
Three patients with a relapsing course of serologically confirmed viral hepatitis type A are presented. In addition, one patient had aminotransferase elevations for over 6 mo. In all three, hepatitis ultimately resolved. A relapsing or protracted course does not appear to alter the benign prognosis of hepatitis A.
Adult↗
Gastric and duodenal fistulas in Crohn's disease.
We report gastric or duodenal fistulas in 6 patients with Crohn's colitis or ileocolitis. Two patients had duodenocolic fistulas, 1 had a duodenoileal fistula, 2 had gastrocolic fistulas, and 1 had gastric and duodenal fistulas from an ileocolic anastomosis. In each case the fistula originated from the lower bowel segment, and no patient in this series had primary gastroduodenal Crohn's disease. These cases illustrate the range of manifestations of fistulas to the stomach and duodenum in Crohn's disease, and emphasize that the predominant symptoms determining surgical intervention usually arise from the diseased ileum and colon, rather than from the fistula. Our experience demonstrates the simplicity and safety of excision of the fistula with primary closure of the stomach or duodenum when the stomach and duodenum are otherwise normal by endoscopic examination.
Adult↗
Immunogenicity of hepatitis B vaccine in renal transplant recipients.
To evaluate the immunogenicity of hepatitis B vaccine in renal transplant recipients, we administered three 40-microgram doses of vaccine to 17 patients who had previously undergone transplantation and were on immunosuppressive therapy. Life-table analysis revealed a cumulative antibody response rate of only 17.6% at 12 months, and the three responders had low titers of antibody to hepatitis B surface antigen. There were no serious adverse effects and no episodes of graft rejection in responders or nonresponders. In addition, the ratio of helper/inducer (T4) to suppressor/cytotoxic (T8) T cells in vaccinees bore no relationship to the immunogenicity of the vaccine. These data indicate that hepatitis B vaccine is weakly immunogenic in renal transplant recipients and illustrate the need for vaccination prior to transplantation for maximal protection against hepatitis B virus infection.
Adult↗