Not so sweet: autoimmune diabetes mellitus on triple therapy for chronic hepatitis C infection.

BACKGROUND: Triple therapy with pegylated interferon, ribavirin and a protease inhibitor has proven efficacy in hepatitis C infection and is currently the standard of care. Interferon-based therapies have been, rarely, associated with the development of Type 1 diabetes mellitus, but few cases have yet been reported in triple therapy for hepatitis C. CASE REPORT: We describe a case of autoimmune Type 1 diabetes developing in a 23-year-old woman after initiation of triple therapy for chronic hepatitis C virus infection. The patient had the IL-28B gene polymorphism rs12979860 CT genotype, which is associated not only with antiviral therapy response but also with diabetes risk after liver transplantation for hepatitis C. CONCLUSION: Further studies are required to determine which individual characteristics may identify patients who are at risk of developing Type 1 diabetes when treated with interferon-based regimens for hepatitis C infection.

Transmission of hepatitis C virus to recipients of parenteral vitamin therapy in a primary care facility.

BACKGROUND AND OBJECTIVES: The Australian prevalence of hepatitis C virus (HCV) is approximately 1%, with the majority of cases acquired through injecting drug use. However, occasionally HCV infection occurs in healthcare settings. Three new HCV infections were identified amongst patients attending a general practice in Sydney, Australia, specialising in parenteral vitamin therapy. STUDY DESIGN: An investigation was conducted to identify the source of infection and mechanism of transmission. Molecular analysis was conducted by sequencing the HCV NS5A, Core and NS5B regions. RESULTS: Two sources were identified using molecular epidemiology - a genotype 3a case was the source for a case acquired in late 2004 and a genotype 1b case the source for one case acquired in late 2006 and another in early 2007. The common risk factor was parenteral vitamin C therapy. CONCLUSIONS: Inadequate infection control was apparent and likely to have resulted in blood contamination of the healthcare workers, their equipment, the clinic environment and parenteral medications. Molecular and clinical epidemiology clearly identified parenteral transmission of HCV, highlighting the risks of blood contamination of parenteral equipment and use of multi-dose flasks on more than one patient.

Pruritus and cholestasis: therapeutic options.

The pathogenesis of pruritus of cholestasis remains unclear. Bile salts do not appear to be the sole prurogens in cholestasis. Histaminergic pathways may be involved, and central opiate receptor processes seem much more important than has previously been recognized. The therapeutic options for relief of cholestatic pruritus are summarized in Table 2. Resins such as cholestyramine are the first line of therapy. In cases where cholestyramine has failed, rifampicin and antihistamines may be beneficial. Opiate antagonists hold great potential if opioid withdrawal-like syndromes can be avoided. Ursodeoxycholic acid and methotrexate have an advantage in not only relieving pruritus but also potentially retarding disease progression in PBC and PSC, respectively, although this remains to be proved. Other agents such as EPO and SAMe remain experimental and require further study to clarify their effectiveness before they can be recommended.

Regression of gastric T cell lymphoma with eradication of Helicobacter pylori.

Helicobacter pylori is thought to be important in the pathogenesis of chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric B cell lymphoma of mucosa associated lymphoid tissue. The mechanism of evolution from chronic gastritis to monoclonal B cell proliferation is not known but is thought to be dependent on antigen specific T cells to H pylori and its products. Here, we report a case of gastric T cell lymphoma associated with chronic H pylori gastritis which regressed with eradication of the organism. This is the first report of a gastric T cell lymphoma regressing with H pylori eradication, and suggests a causal link between primary gastric T cell lymphoma and this organism.

Portal hypertension secondary to sigmoid colon arteriovenous malformation.

A case of portal hypertension secondary to an arteriovenous malformation of the sigmoid colon is presented. The importance of mesenteric angiography in the diagnosis of this condition is discussed. The dramatic clinical improvement in this case following surgery emphasizes that arteriovenous malformations of the gastrointestinal tract represent a potentially curable cause of portal hypertension.

Cyclosporin, a new treatment for autoimmune chronic active hepatitis.

A 51-year-old man whose aggressive autoimmune chronic active hepatitis had been treated with prednisone for five years, was treated with cyclosporin for 12 months. The disease had become unresponsive to high doses of prednisone and the side-effects had become disabling. Azathioprine could not be used because of drug hypersensitivity. With cyclosporin therapy the patient's symptoms disappeared for the first time since the onset of his illness, his liver enzyme levels fell almost to normal values and virtually no side-effects occurred. We suggest that cyclosporin be used on a clinical trial basis in patients with autoimmune chronic active hepatitis that is resistant to prednisone and azathioprine therapy.

Hepatic vein webs and resistant ascites. Diagnosis, management and implications.

Webs of hepatic veins have been rarely described. Two patients presented with intractable ascites in whom hepatic venography demonstrated this unusual finding. Liver biopsies from both patients showed variable patterns of perivenular fibrosis. Transvenous balloon dilatation of the web was effective in abolishing the pressure gradient across the obstruction and improving hepatic venous outflow. Both patients showed a dramatic clinical improvement following the procedure, with complete resolution of ascites in one patient and considerable improvement in the other with symptoms not recurring over 18 months of follow-up. The histological features that help to distinguish hepatic venous outflow obstruction from other causes of perivenular fibrosis are described.

High incidence of poor sulfoxidation in patients with primary biliary cirrhosis.

An impaired sulfoxidation pathway has been implicated in the pathogenesis of chlorpromazine-induced hepatotoxicity. Since some patients with chronic chlorpromazine-induced cholestasis may have features of primary biliary cirrhosis, we studied the ability to sulfoxidate the amino acid analogue S-carboxymethyl-cysteine in 44 patients with primary biliary cirrhosis and in two control groups--one without liver disease and one with a variety of liver diseases other than primary biliary cirrhosis. Poor sulfoxidation was observed in 84 percent of the patients with primary biliary cirrhosis, as compared with 24 percent of patients with other liver diseases and 22 percent of normal controls (P less than 0.0005 for both comparisons). Poor sulfoxidation did not correlate with the degree of hyperbilirubinemia or histologic severity of liver disease in any of the groups studied. There was an inverse correlation with age only in the patients with primary biliary cirrhosis (r = -0.44, P less than 0.001). Liver transplantation was performed in six of the patients and improved sulfoxidation in five; in the four with primary biliary cirrhosis, sulfoxidation improved from poor to good or intermediate. We conclude that poor sulfoxidation is closely associated with primary biliary cirrhosis but not with the other liver diseases we studied.

Sulphoxidation and sulphation capacity in patients with primary biliary cirrhosis.

We have previously reported an association of impaired S-oxidation with primary biliary cirrhosis. In order to confirm and further define this relationship, we retested S-oxidation capacity via three metabolic pathways and sulphation capacity via a fourth pathway. Metabolism of S-carboxymethyl-L-cysteine is polymorphic -20% of healthy individuals being poor S-oxidisers. We found 26% with primary biliary cirrhosis were poor S-oxidisers, compared with 36% with other liver disease and 25% of healthy controls. Differences were not statistically significant. S-oxidation of ranitidine is dependent upon flavin mono-oxygenases. We showed a non-significant trend toward less S-oxide in primary biliary cirrhosis and other liver disease, compared with healthy controls, with no significant difference between disease groups. Conversion of cysteine to sulphate depends predominantly on cysteine dioxygenase. Impaired activity may be reflected by decreased plasma sulphate and elevated cysteine. We found that the plasma cysteine: sulphate ratio was significantly elevated not only in primary biliary cirrhosis (p < 0.0001), but also in other liver disease (p < 0.0001), compared with healthy individuals. Sulphation capacity was studied by analysing paracetamol metabolism. Paracetamol sulphate and sulphate: glucuronide ratio were reduced in primary biliary cirrhosis compared with normal individuals, (p < 0.05). A trend towards less sulphate in primary biliary cirrhosis compared other liver disease was not significant (p = 0.42). We conclude that although sulphation and some sulphoxidation pathways are impaired in primary biliary cirrhosis, we can currently find no evidence to substantiate the hypothesis that primary biliary cirrhosis is a disease specifically associated with poor S-oxidation, as assessed via these metabolic pathways.

Role of endoscopic retrograde cholangiopancreatography after orthotopic liver transplantation.

Twelve of 178 (7%) liver transplant patients underwent endoscopic retrograde cholangiopancreatography (ERCP) after transplantation. The indications for ERCP were persistent or late onset cholestasis, recurrent cholangitis, and suspected biliary leaks or strictures. The time between transplantation and ERCP ranged from 44 to 330 days (median 153 days). Biliary complications diagnosed by ERCP included biliary sludge in the form of casts, calculi, or debris (n = 7); bile leaks (n = 2); a biliary stricture (n = 1), and complete biliary obstruction (n = 1). One patient had a normal cholangiogram after transplantation. Biliary sludge was detected by ultrasound before ERCP in only one of six patients. Eight patients underwent endoscopic papillotomy, followed by clearance of biliary sludge in four and dilatation of a biliary stricture in one. Two patients bled after papillotomy but neither required surgical intervention. At a median follow up of 1.2 years (range 0.5-2.8 years), nine patients are well and three have died. ERCP provides both accurate diagnosis of biliary complications after liver transplantation and treatment that obviates the need for additional surgery in selected patients.