Laparoscopic transgastric endoscopic retrograde cholangiopancreatography for benign common bile duct stricture after Roux-en-Y gastric bypass.

Access to the gastric remnant and duodenum is lost after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Traditionally, a percutaneous transhepatic access to the common bile duct has been used to manage choledocholithiasis and duct strictures. We present a novel method of laparoscopic transgastric endoscopic retrograde cholangiopancreatography for managing a benign biliary stricture after a Roux-en-Y gastric bypass.

Combined interferon, famciclovir and GM-CSF treatment of HBV infection in an individual with periarteritis nodosa.

Treatment of chronic hepatitis B virus (HBV) infection in an individual with periarteritis nodosum is described. A combination of famciclovir, granulocyte macrophage colony stimulating factor (GM-CSF) and interferon alpha 2b was utilized. The periarteritis, but not the HBV infection, responded to immunosuppressive therapy consisting of cyclophosphamide and glucocorticoids. Moreover, the patient failed to clear this HBV infection, despite a full year of interferon therapy at 5 MU daily. With the addition of famciclovir and GM-CSF, the HBV infection rapidly resolved and he converted from HBsAg and eAg positive to HBsAb and eAb positive. No exacerbation of his periarteritis nodosum occurred during the course of his antiviral therapy.

Treatment of chronic hepatitis C in individuals with pre-existing or confounding neuropsychiatric disease.

The problems associated with the recognition and management of chronic hepatitis C in a population of individuals with confounding psychiatric disease are identified. The experience of treating such patients and the psychotropic medication required during treatment are reviewed.

Lamivudine treatment of advanced and decompensated liver disease due to hepatitis B.

The purpose of this study was to evaluate the effectiveness and safety of lamivudine treatment in patients with advanced and end-stage liver disease caused by hepatitis B. Nine cases of advanced or end-stage liver disease due to hepatitis B infection were treated with lamivudine. Four received liver transplants while receiving lamivudine. Moreover, each of these four has been maintained on lamivudine therapy post-transplantation while receiving immunosuppression. No cases of HBV reactivation have been seen. More importantly, the allograft liver tissue has been HBc and HBs antigen negative as well as HBV-DNA negative by PCR. This report suggests that: 1) lamivudine can be given safely to liver transplant candidates; 2) lamivudine suppresses HBV replication, so much so that HBV-DNA becomes undetectable in the serum; 3) despite powerful immunosuppression associated with transplantation, HBV reactivation does not occur under lamivudine therapy; and 4) the observations should cause transplant physicians, surgeons and third-party payers to reconsider their positions relative to transplantation of individuals with HBV-associated cirrhosis.

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.

Retreatment of hepatitis C interferon non-responders with larger doses of interferon with and without phlebotomy.

BACKGROUND/AIMS: Interferon a (IFN) is the only agent currently approved by the FDA for the treatment of chronic viral hepatitis due to hepatitis C (HCV). Unfortunately, less than half the patients with HCV treated with IFN respond. Worse yet, half or more of those who do respond relapse when the agent is withdrawn. MATERIALS AND METHODS: In this prospective randomized study, 30 individuals who had failed to respond to a standard course of IFN therapy consisting of 3 MU IFN administered 3 x week for 6 months were randomized to receive a second 6 month course of either 5 MU IFN daily or 5 MU IFN plus regular phlebotomies at weekly intervals to achieve a hemoglobin level of between 10-11 g/dl. The response rates defined as HCV-RNA negativity after 6 months of therapy and after 6 months of follow-up without IFN were determined. RESULTS: Both groups experienced a significant reduction in their serum ALT levels (p < 0.01) and Knodell scores with treatment. A greater number of responders were found in the phlebotomy plus IFN group than in the IFN alone group whether the response was defined by the serum ALT level or presence or absence of HCV-RNA in serum at the end of treatment and follow-up. CONCLUSIONS: The results of this study suggest that both an increased IFN dose coupled with more frequent dosing of IFN alone and combined with phlebotomy treatment are effective at obtaining a response to IFN in individuals with HCV disease who previously have failed to respond to a standard treatment regimen.

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.

Treatment of hepatitis C virus in elderly persons with interferon alpha.

BACKGROUND: Hepatitis C virus (HCV) is a health problem that is common in adults. Because screening of blood and blood products for HCV has only been possible recently, older adults are more likely than younger adults to have HCV. Despite the higher prevalence of HCV in older adults, few are treated. This failure to treat is a result of the concern that the untoward effects of Interferon alpha (IFN) may not be tolerable in older individuals. METHODS: Twenty-five subjects age > 65 years who were Ab-HCV positive and desired IFN therapy were treated with 5 MU Interferon administered TIW for 6 months. Twenty-five adults (mean age 44 +/- 1 years) matched for gender and histologic disease were utilized as a control population. Responses were classified as full if the ALT level was normal, and partial if the ALT fell by > 50% but was still abnormal after 6 months of therapy. All other responses were defined as failures. RESULTS: At the end of treatment, no biochemical difference between the elderly and younger adults was evident for any parameter. Moreover, the response rates (48% and 41%, respectively) were nearly identical. None of the elderly discontinued IFN therapy during the treatment period. The rate of untoward events reported by the elderly was similar to that reported by the younger controls. CONCLUSIONS: These data demonstrate that: (a) the elderly with HCV infections can be treated with IFN; (b) the response rate is similar in elderly and younger adults; and, (c) the rate and type of untoward IFN effects experienced by the elderly do not differ from that reported by younger adults.

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.

Interferon alpha treatment of chronic hepatitis C in patients with evidence for co-existent autoimmune dysregulation.

BACKGROUND/AIMS: We performed a prospective nonrandomized clinical trial to demonstrate that Interferon (IFN) treatment of individuals with chronic hepatitis C virus (HCV) positive hepatitis (CH-C) and serologic and/or histologic evidence of autoimmune dysregulation is feasible and whether the benefits of successfully treating CH-C are outweighed by the risk of exacerbating Autoimmune Chronic Active Hepatitis (ACAH). PATIENTS AND METHODS: 23 patients with positive autoimmune dysregulation markers underwent a 6 month course of IFN treatment for chronic HCV hepatitis and were followed for a total of 12 months. Patients were treated with 5 MU of a2b IFN administered subcutaneously 7 days a week for 6 months. Complete blood counts and a panel of liver enzymes were monitored weekly for 4 weeks and then monthly for an additional 11 months (6 months of therapy and 6 months of follow-up). Serum auto-antibodies titers were determined prior to treatment, at the end of the treatment and again after 6 months of follow-up. A liver biopsy was performed prior to, and at the end of treatment and again at 12 months. RESULTS: Using the standard ALT criteria for defining a response to IFN therapy, 14 (61%) patients experienced a full response and 3 (13%) experienced a partial response. Forty-three percent of the full responders and 33% of the partial responders experienced a relapse during the follow-up. The titer of each of the previously positive autoantibodies either remained unchanged or increased by 1 or 2 dilutions. No clinical exacerbations of a co-existent ACAH were observed. CONCLUSIONS: Individuals with combined CH-C and one or more markers of autoimmune dysregulation can be treated successfully with IFN. Such treatment does not necessarily increase or exacerbate co-existent ACAH and elevate the serum ALT level. In those who clear HCV-RNA as a result of IFN, the liver histology shifts from one consistent with CH-C to resembling ACAH.

Combination treatment of advanced HCV associated liver disease with interferon and G-CSF.

BACKGROUND/AIMS: Interferon (IFN) is the only therapy currently approved for chronic hepatitis C treatment. Unfortunately, not all patients respond to IFN therapy with a disease remission. Some people consider advanced histologic disease to be either a contraindication for treatment or a predictor of a poor response to treatment. To assess the validity of the two preceding widely held views, a total of 30 consecutive patients with advanced histologic disease associated with hepatitis C were studied. MATERIALS AND METHODS: Patients were treated with 5 million units of IFN administered SQ daily either alone or in combination with G-CSF (300 micrograms SQ on Mondays and Thursdays). RESULTS: Both groups responded to the IFN therapy with 53 and 60% respectively being HCV-RNA negative after 6 months of therapy and 40 and 53% respectively continuing as HCV-RNA negative after 6 months of follow-up after IFN. The mean white blood cell (WBC) count and peak WBC counts of those receiving G-CSF were greater than those not receiving G-CSF therapy. The nadir values for both groups, however, were similar. CONCLUSIONS: Based upon this study, utilizing daily high dose IFN (5 MU) therapy, it can be concluded that individuals with advanced histologic disease can be treated successfully with IFN and obtain a prolonged remission. The addition of G-CSF during IFN therapy of patients with histologically advanced disease increases the mean WBC and peak WBC count levels achieved during the course of IFN therapy but without significantly increasing the response rate defined as clearance of HCV-RNA at the end of treatment and follow-up.

The Oklahoma-Pittsburgh experience with interferon alpha in the treatment of HCV disease.

Interferon alpha (IFN) is the only Food and Drug Administration (FDA)-approved therapy available for the treatment of chronic hepatitis C. The ideal dose and frequency of IFN administration that produces the greatest number of patient responders with the least number of relapses following drug withdrawal remains unclear. METHODS. One hundred seventeen patients recruited over a five-year period with chronic hepatitis C were divided into four groups and treated with progressively larger doses. The rate of clinical responses defined as a loss of detectable hepatitis C virus-ribonucleic acid (HCV-RNA) in serum by polymerase chain reaction (PCR) and normalization of the serum ALT (abnormal alanine aminotransferase) for each group was calculated. RESULTS. As the dose of IFN administration increased, the response rate defined by the absence of HCV-RNA in the patient's serum after six months of follow-up increased from 7.7% to 26.6%. If the end point utilized was HCV-RNA negativity after six months of treatment, the response rate varied from 19.2% to 30%. Using the less difficult end point of a normal ALT level, the response rates varied from 32.1% to 63.3% after six months of therapy and from 10.7% to 26.7% after six months of follow-up. CONCLUSIONS. This experience demonstrates that both the response rate at the end of therapy and after six months of follow-up improves with an increase in dose of IFN administered over a six-month period.

Interferon-alpha can be used successfully in patients with hepatitis C virus-positive chronic hepatitis who have a psychiatric illness.

OBJECTIVE: To determine whether individuals with concurrent active psychiatric disease and chronic hepatitis C virus (HCV) can be treated safely and effectively with interferon-alpha. DESIGN: Prospective, open label study. SETTING: Tertiary referral hospital. PATIENTS: Thirty-one consecutive patients with co-existent chronic HCV and a psychiatric illness. INTERVENTIONS: Interferon-alpha was administered at doses of either 5 MU three times per week for 6 months (n = 17) or 5 MU daily for 6 months (n = 14). METHODS: HCV-RNA in serum was measured using reverse transcriptase polymerase chain reaction. Serum alanine aminotransferase levels were assessed and liver biopsy was performed before and after 6 months of treatment and again after 6 months of follow-up. RESULTS: Twenty-nine of the 31 patients completed 6 months of therapy. Two patients discontinued therapy after 2 and 3 months of treatment. Serum alanine aminotransferase levels returned to normal in 22 (71%) patients. Fifteen (48%) of the 31 patients cleared HCV-RNA from their serum. Only four patients experienced a worsening of their psychiatric illness during treatment. Interferon therapy was discontinued in two of these patients. CONCLUSIONS: Patients with a co-existent psychiatric illness and chronic HCV can be treated successfully with interferon-alpha with the active participation of a psychiatrist and the maintenance of psychotropic drug therapy during interferon treatment.