Spontaneous clearance of hepatitis C after liver and renal transplantation.

Spontaneous clearance of hepatitis C virus (HCV) is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.

Re-treatment with peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have relapsed or not responded to a first course of pegylated interferon-based therapy.

BACKGROUND: Pegylated interferon (pegIFN) and ribavirin combination therapy remains the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the wealth of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegIFN-based therapy is largely unreported. AIM: To assess the effectiveness of the retreatment of patients who have previously failed an initial course of pegIFN-based therapy with pegIFNalpha-2a and ribavirin. METHODS: A post-hoc analysis of a multicentre open-label study was performed. Patients received pegIFNalpha-2a and ribavirin at a dose of 800 mg/day and later 1000 mg/day to 1200 mg/day for 24 to 48 weeks at the discretion of the investigator. Outcomes at week 12 (early virological response [EVR]) and week 24 (sustained virological response [SVR]) were analyzed. RESULTS: Eighty-seven patients who had relapsed after previous pegIFN-based therapy (n=28; 78% genotype 1) or were nonresponders (n=59; 71% genotype 1) were analyzed. Of the relapsers, 86% achieved an EVR and 68% achieved an SVR. In relapsers to pegIFN monotherapy (n=15) or pegIFN plus ribavirin (n=13), 60% and 77% achieved an SVR, respectively. Fibrosis and genotype did not affect the likelihood of SVR in relapsers although this may be the result of the relatively small number of patients. In previous nonresponders, an EVR was achieved in 53% but an SVR occurred in only 17%. In nonresponders to pegIFN monotherapy (n=9) and pegIFN plus ribavirin (n=50), 33% and 14% achieved an SVR, respectively. Genotype did not affect SVR in nonresponders. Only 10% with a METAVIR score of F3 or F4 on liver biopsy achieved an SVR. CONCLUSIONS: Relapse after previous pegIFN-based therapy is associated with a strong probability of treatment success whereas retreatment of those with previous nonresponse does not.

Multiple focal nodular hyperplasia and steatosis: Atypical imaging characteristics.

Focal nodular hyperplasia is a rare, benign condition of the liver. A 28-year-old woman with malignant melanoma, mild liver enzyme abnormalities, steatohepatitis and newly documented hepatic lesions is described. Ultrasound, computed tomography and magnetic resonance imaging suggested only areas of focal fatty sparing but could not eliminate the concern for metastases. A (99m)technetium-labelled sulphur colloid scan, however, revealed areas of increased uptake consistent with multiple focal nodular hyperplasia. This diagnosis was ultimately confirmed with a liver biopsy. The investigation of a patient with a malignancy and expanding hepatic lesions is challenging. This case illustrates the usefulness of the (99m)technetium-labelled sulphur colloid scan in the evaluation of patients with hepatic lesions.

Muscle cramps: a 'complication' of cirrhosis.

Muscle cramps are a common complaint in clinical practice. They are associated with various metabolic, endocrine, neurological and electrolyte abnormalities. A variety of hypotheses have been generated to explain the cause of muscle cramping, yet none has been able to support a consistent pathophysiological mechanism. Muscle cramps are painful, involuntary contractions of skeletal muscle. They occur frequently in individuals with cirrhosis, regardless of the etiology, and are thought to be a symptom of cirrhotic-stage liver disease. The pathophysiology of these cramps remains elusive; hence, a specific therapy has not been identified. Many therapeutic approaches have been offered, yet their efficacy, safety and mechanism of action remain poorly defined. This review defines muscle cramps and illuminates its prevalence in the cirrhotic individual. Current theories relating to the pathogenesis of muscle cramps are reviewed, and an overview of the various pharmacological agents that have had therapeutic success for this distressing and frustrating symptom is provided.

Surgery and transplantation for hepatocellular cancer.

1. Curative treatment of hepatocellular carcinoma (HCC) depends on early diagnosis. 2. The cure rate for operable HCC occurring in the absence of cirrhosis is only 10% to 25%. 3. Features of HCC in patients with cirrhosis that are associated with a 5-year survival rate of 75% after liver transplantation include (1) solitary tumor less than 5 cm; (2) 3 or fewer tumors, each less than 3 cm; and (3) absence of vascular invasion. 4. Advanced cirrhosis limits the widespread application of partial hepatectomy to patients with HCC. 5. Neoadjuvant therapy has not yet been proven to improve patient outcome for early-stage HCC that is promptly treated by transplantation.

The cost-effectiveness of hepatitis A vaccination in patients with chronic hepatitis C.

Infection with hepatitis A virus (HAV) occasionally leads to acute liver failure and has a higher fatality rate in patients with chronic hepatitis C virus (HCV). Vaccination of patients with HCV against HAV is effective and well tolerated. This study examines the cost-effectiveness of HAV vaccination in North American patients with chronic HCV. A decision analysis model was constructed to compare 3 HAV vaccination strategies in adult patients with chronic HCV over a period of 5 years: (1) vaccinate no patients (treat none); (2) vaccinate only susceptible (anti-HAV negative) patients (selective); or (3) vaccinate all patients without prior testing of immune status (universal). Probabilities and direct costs were estimated from hospital data and the literature. The cost per patient for the 3 vaccination strategies were: treat none, $2.00; selective, $56.00; and universal, $82.00. For every 1,000,000 patients with HCV vaccinated over a 5-year period, the selective strategy prevented 128 symptomatic cases of HAV, 3 liver transplantations, and 3 deaths owing directly to HAV compared with the treat none strategy. In addition, the selective strategy costs an additional $427,000 per patient with HAV prevented, and $23 million per HAV-related death averted, compared with the treat none strategy. The results were most sensitive to the incidence of HAV infection; vaccination increased costs if the annual rate of infection was less than 0.56% (baseline, 0.01%). Vaccination of North American patients with chronic HCV against HAV infection is not a cost-effective therapy.

Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis.

Liver transplantation is the only effective therapeutic option for patients with end-stage liver disease due to primary sclerosing cholangitis (PSC). In this study, we analyzed a single center's experience with 150 consecutive PSC patients who received 174 liver allografts. Mean follow-up was 55 months. Actuarial patient survival at 1, 2, 5, and 10 years was 93.7%, 92.2%, 86.4%, and 69.8%, respectively, whereas graft survival was 83.4%, 83.4%, 79.0%, and 60. 5%, respectively. The main indication for retransplantation was hepatic artery thrombosis, and the major cause of death was severe infection. Patients with PSC had a higher incidence of acute cellular and chronic ductopenic rejection compared to a non-PSC control group. Chronic ductopenic rejection adversely affected patient and graft survival. Biliary strictures, both anastomotic and nonanastomotic, were frequent and occurred in 16.2% and 27.2% of patients, respectively. The incidence of recurrent PSC was 20%. A negative impact on patient survival was not seen in patients with either postoperative biliary strictures or recurrence of PSC. Six patients (4%) had cholangiocarcinoma and 1 patient died related to recurrence of malignant disease. Seventy-eight percent of PSC patients had associated inflammatory bowel disease, most commonly chronic ulcerative colitis, which did not adversely impact patient outcome posttransplantation. Nine patients required proctocolectomy after liver transplantation; 5 because of intractable symptoms related to inflammatory bowel disease and 4 due to the development of colorectal carcinoma/high-grade dysplasia. Our data show that liver transplantation provides excellent long-term patient and graft survival for patients with end-stage PSC.

Recurrence of primary sclerosing cholangitis following liver transplantation.

Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been suggested; however, it has not been fully defined because of numerous complicating factors and the lack of diagnostic criteria. In the present study, we investigated the recurrence of PSC by developing strict criteria and applying them to a large cohort of PSC patients who underwent liver transplantation. Between March 1985 and June 1996, 150 PSC patients underwent liver transplantation at the Mayo Clinic; mean follow up was 55 months. The incidence of nonanastomotic biliary strictures and hepatic histologic findings suggestive of PSC were compared between patients transplanted for PSC and a non-PSC transplant control group. Our definition of recurrent PSC was based on characteristic cholangiographic and histologic findings that occur in nontransplant PSC patients. By using strict criteria, 30 patients with other known causes of posttransplant nonanastomotic biliary strictures were excluded leaving 120 patients for analysis of recurrence of PSC. We found evidence of PSC recurrence after liver transplantation in 24 patients (20%). Of these, 22 out of 24 patients showed characteristic features of PSC on cholangiography and 11 out of 24 had compatible hepatic histologic abnormalities with a mean time to diagnosis of 360 and 1,350 days, respectively. Both cholangiographic and hepatic histologic findings suggestive of PSC recurrence were seen in nine patients. The higher incidence and later onset of nonanastomotic biliary strictures in patients with PSC compared with a non-PSC control group is supportive of the fact that PSC does recur following liver transplantation. We were unable to identify specific clinical risk factors for recurrent PSC, and the overall patient and graft survival in patients with recurrent PSC was similar to those without evidence of recurrence. Our observations provide convincing evidence that PSC frequently recurs in the hepatic allograft using strict inclusion and exclusion criteria.

Pemoline hepatotoxicity in children.

Pemoline hepatotoxicity ranges from asymptomatic elevations in levels of serum aminotransferases to fulminant liver failure. We report five cases of pemoline hepatotoxicity in children (four boys, one girl), including the only reported case resulting in orthotopic liver transplantation. We conclude that pemoline causes toxic liver damage in children. The severity of the damage is highly variable, and its onset may be late in the course of treatment. Pemoline and methylphenidate may act synergistically to cause liver damage. The levels of serum aminotransferases should be monitored throughout treatment with these agents.

Neoral compared to Sandimmune is associated with a decrease in histologic severity of rejection in patients undergoing primary liver transplantation.

BACKGROUND: In a randomized, controlled study we investigated the clinical efficacy of the microemulsion formulation of cyclosporine (Neoral) in comparison with Sandimmune (SIM) in the treatment of patients who underwent primary orthotopic liver transplantation (OLT). METHODS: In total, 33 patients were randomized in a double-blind fashion before undergoing primary OLT to receive either Neoral or SIM. All 33 patients initially received intravenous cyclosporine, but as soon as it was tolerated, the oral study drug was initiated (median time, 3.6 days) and 17 patients received Neoral and 16 SIM (for both drugs, 10 mg/kg/day). Both groups were comparable with regard to age, sex, etiology of chronic liver disease, and hepatic biochemical profile. Episodes of rejection were diagnosed histologically and characterized as mild, moderate, or severe using criteria from the National Institute of Diabetes and Digestive and Kidney Diseases. RESULTS: Patients were followed for 1 year. Four patients in each group were discontinued prematurely. The reason for discontinuation of cyclosporine was drug-related complications in two of the NEO patients and in three of the SIM group; the other three were non-drug-related. Rejection episodes occurred in 9 of 17 patients (52.90%) in the Neoral group and in 9 of 16 patients (56.3%) in the SIM group. The total number of rejection episodes in each group was 14. However, in evaluating the severity of rejection histologically, nine episodes of rejection were characterized as moderate/ severe in the SIM group compared with only three in the Neoral group (P=0.027). Five of the nine moderate/severe rejection episodes in the SIM group occurred within the first 2 weeks after transplant. In contrast, moderate/severe rejection did not occur in the Neoral group in this early period. Two patients in the SIM group and no patients in the Neoral group required treatment with OKT3 for steroid-resistant rejection. There were no differences in mean doses or trough levels when comparing the two study groups. The incidence of adverse effects was similar in the two groups. CONCLUSIONS: Neoral is a safe and efficacious drug in the treatment of primary OLT patients. Given comparable doses of cyclosporine in each group over 1 year, there was no significant difference in the total number of rejection episodes between study groups. However, patients treated with Neoral had a lower incidence of moderate/severe histologic rejection and were free of steroid-resistant rejection when compared with SIM-treated patients.

Sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease whose aetiopathogenesis is unknown. PSC is frequently associated with inflammatory bowel disease, in particular chronic ulcerative colitis, is most commonly observed in young males and is clinically characterized by fatigue, pruritus and jaundice. The diagnosis is supported by a cholestatic biochemical profile and histological abnormalities, and confirmed by visualization of an abnormal biliary tree. The natural history of the disease is currently being evaluated but is generally recognized to be slowly progressive, leading to complications of chronic cholestasis, portal hypertension and biliary cirrhosis. There is no specific medical treatment, and orthotopic liver transplantation remains the only definitive treatment for patients with end-stage PSC. A more rational approach to medical therapy will ensue upon a better understanding of the aetiopathogenesis of this disease.

Biliary sludge: a risk factor for 'idiopathic' pancreatitis?

Idiopathic acute pancreatitis is common. Recent evidence suggests that biliary sludge may be the etiology in many patients with this disorder. In this case-control study, admission ultrasound examinations of patients with idiopathic pancreatitis, patients with acute alcohol-associated pancreatitis and a control group were compared. Biliary sludge was found in seven of 21 patients (33%) with idiopathic pancreatitis, two of 25 (8%) with acute alcohol-associated pancreatitis and one of 63 controls (1.6%). Comparison of idiopathic pancreatitis patients with both acute alcohol-associated pancreatitis patients and controls for the presence of sludge revealed odds ratios of 31.0 (95% CI 3.5 to 273) and 5.8 (95% CI 1.1 to 32.0), respectively. Also observed was a trend towards higher levels of liver enzymes, bilirubin and amylase in patients with idiopathic pancreatitis who had sludge identified. This study provides further evidence linking biliary sludge with a significant proportion of patients with idiopathic acute pancreatitis.

Metastatic Crohn's disease.

The case of a 25-yr-old female with Crohn's disease who developed recurrent erythematous nodules on her lower extremities is described. These modules enlarged and ulcerated. Repeated bacterial, fungal, and acid-fast cultures remained negative. A skin biopsy revealed non-caseating granulomata, confirming the diagnosis of cutaneous "metastatic" Crohn's disease. The lesions completely resolved with systemic corticosteroid therapy. Although cutaneous metastatic Crohn's disease is uncommon, patients with Crohn's disease who develop unusual skin lesions that persist should have them biopsied.