Tuberculosis patients with higher levels of poverty face equal or greater costs of illness.

SETTING: Fifty-six public clinics in Limpopo Province, South Africa.OBJECTIVE: To evaluate the association between tuberculosis (TB) patient costs and poverty as measured by a multidimensional poverty index.DESIGN: We performed cross-sectional interviews of consecutive patients with TB. TB episode costs were estimated from self-reported income, travel costs, and care-seeking time. Poverty was assessed using the South African Multidimensional Poverty Index (SAMPI) deprivation score (a 12-item household-level index), with higher scores indicating greater poverty. We used multivariable linear regression to adjust for age, sex, human immunodeficiency virus status and travel time.RESULTS: Among 323 participants, 108 (33%) were 'deprived' (deprivation score >0.33). For each 0.1-unit increase in deprivation score, absolute TB episode costs were 1.11 times greater (95%CI 0.97-1.26). TB episode costs were 1.19 times greater with each quintile of higher deprivation score (95%CI 1.00-1.40), but lower by a factor of 0.54 with each quintile of lower self-reported income (higher poverty, 95%CI 0.46-0.62).CONCLUSION: Individuals experiencing multidimensional poverty and the cost of tuberculosis illness in Limpopo, South Africa faced equal or higher costs of TB than non-impoverished patients. Individuals with lower self-reported income experienced higher costs as a proportion of household income but lower absolute costs. Targeted interventions are needed to reduce the economic burden of TB on patients with multidimensional poverty.

Molecular repair of a defective CFTR protein in cystic fibrosis.

We analyse a paper, which reports an entirely novel approach to the treatment of cystic fibrosis, consisting in "repairing" the defective mutant protein. Patients with cystic fibrosis have a mutation of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel involved in salt and fluid transport in multiple organs, including the lungs and pancreas. The mutations have different effects on the CFTR protein, such as misfolding for the ΔF508 mutation (the most common), or defective opening of the chloride channel for the G551D-CFTR mutation, found in 4 to 5% of the patients. The authors of this work have shown that VX-770, an agent known previously to increase the activity of wild-type and G551D-CFTR cell surface protein in vitro, was able, when given orally to 39 cystic fibrosis patients during 14 and 28 days, to partially restore chloride conductance, as measured by nasal epithelium potential difference. Similarly, the agent partially restored chloride transport in sweat glands, as measured by the sweat chloride concentration. Clinically, VX-770 increased the forced expiratory volume per second (FEVi). Side effects included macular skin rash, elevation of blood glucose concentration and glycosuria. All side effects resolved after discontinuation of the drug. VX-770 has also been shown to increase the activity of ΔF508-CFTR channels in vitro, provided they reach the cell surface. This study appears to be a milestone in the treatment of cystic fibrosis and possibly other genetic diseases.

[Right upper quadrant abdominal pain and fever. Genetic phospholipid deficiency]. / Douleurs de l'hypochondre droit et fièvre.

A 35-year-old woman is referred for right upper quadrant abdominal pain and fever. She had a cholecystectomy for gallstones 4 years previously. An aunt has also had a cholecystectomy. Abdominal ultrasound examination shows numerous hyperechoic foci within the liver and some "comet tail" artifacts. Because of her age (less than 40), the recurrence of biliary symptoms after cholecystectomy, her family history and the intrahepatic hyperechoic foci, the diagnosis of low phospholipid-associated cholelithiasis (LPAC) syndrome is suspected and confirmed by the demonstration of a point mutation of the ABCB4 gene. Therapy by ursodeoxycholic acid (AUDC) is started. Symptoms improve and they disappear completely within a few weeks. The cause, pathophysiology, diagnosis and treatment are reviewed.

A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year (with possible extension for responders). The dose was titrated according to serum calcium levels. The treatment effect was evaluated by regular CT scans. Out of 33 patients evaluable for tumour response, two had complete response (CR), 12 stable disease and 19 progressive disease. The CRs appeared after 6 and 24 months of treatment, and lasted for 29 and at least 36 months (patient still in remission when data censored). Seocalcitol was well tolerated; the most frequent toxicity was hypercalcaemia and related symptoms. Most patients tolerated a daily dose of 10 micro g of Seocalcitol. This is the first study showing activity, by reduction in tumour dimensions, of a differentiating agent in patients with an advanced bulky, solid tumour. Seocalcitol may have an effect in the treatment of HCC, especially in early disease when a prolonged treatment can be instituted. The survival benefit with or without tumour response should be determined in controlled studies.

Hypervariable region 1 quasispecies in hepatitis C virus genotypes 1b and 3 infected patients with normal and abnormal alanine aminotransferase levels.

The role of hepatitis C virus (HCV) heterogeneity in the severity of chronic hepatitis C infection remains unclear. Our aim was to study the hypervariable region 1 (HVR1) heterogeneity in patients with chronic hepatitis C infected with genotype 1b or 3 and with normal or abnormal alanine aminotransferase (ALT). HVR1 quasispecies were assessed by single strand conformational polymorphism (SSCP) in 67 patients with chronic hepatitis C, including 35 with persistently normal ALT and 32 with abnormal ALT. Sixty-two patients underwent a liver biopsy. Among the 67 patients, 40 were infected with genotype 1b and 27 with genotype 3. In univariate analysis, low heterogeneity (

Ectopic hepatocellular carcinoma arising in the left chest wall: a long-term follow-up.

We report the case of a 66-year-old man with chronic hepatitis C and a slowly growing left chest wall mass. Two years after the patient first noticed the mass, it was resected. A diagnosis of hepatocellular carcinoma (HCC) was established. The liver was studied by ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, but no mass was found. Blind liver biopsy showed mild chronic hepatitis without cirrhosis or HCC. Three years after the discovery of the chest wall HCC, no liver mass had appeared at CT and MRI. We conclude that solitary extrahepatic HCC (i) may arise in ectopic liver tissue; (ii) should not be considered as a metastasis of an occult HCC; and (iii) can be amenable to cure through resection.

Haemobilia causing acute pancreatitis after percutaneous liver biopsy: diagnosis by magnetic resonance cholangiopancreatography.

Magnetic resonance cholangiopancreatography (MRCP) has received much attention as a non-invasive alternative to endoscopic retrograde cholangiopancreatography, primarily for investigation of choledocholithiasis, but also for evaluation of less common biliary anomalies. We present a case of haemobilia causing acute pancreatitis after percutaneous liver biopsy in which the diagnosis could be made clearly by MRCP, thus avoiding endoscopic retrograde cholangiopancreatography and sphincterotomy.

Cigarette smoking and hepatic lesions in patients with chronic hepatitis C.

A possible hepatotoxicity of cigarette smoke has been recently suggested by epidemiological and experimental studies. Our aim was to study the possible relationships between smoking and liver fibrosis and activity in patients with chronic hepatitis C. A cross-sectional study was performed in a group of 310 patients with chronic hepatitis C consecutively hospitalized for their first liver biopsy. The relationships between age, gender, alcohol consumption, route of contamination, tobacco consumption, and Knodell fibrosis and activity scores were examined in univariate, age-adjusted, and multivariate analyses. One hundred and seventy-six patients (57%) were current smokers. Smokers were younger (P <.001), more often of male gender (P =.001), more often alcohol consumers (P =.001), and more often had a history of intravenous drug use (P =.0001) than never smokers. Smoking was related to increased fibrosis and activity scores in age-adjusted (P =.009 and P =.005, respectively) and multivariate analyses (P =.03 and P =.04, respectively). Smoking increases the severity of hepatic lesions in patients with chronic hepatitis C.

Hepatic manifestations of hemophagocytic syndrome: a study of 30 cases.

OBJECTIVE: Hemophagocytic syndrome has been defined as the combination of a proliferation of cytologically benign, actively phagocytic macrophages in bone marrow, spleen, or lymph nodes in association with fever, cytopenia, splenomegaly, and hypertriglyceridemia. Hepatic dysfunction is often present but the nature of the hepatic lesions and related manifestations have not been fully characterized. The aim of this study was to ascertain the features of hepatic involvement in hemophagocytic syndrome. METHODS: Thirty patients with hemophagocytic syndrome were retrospectively studied. Inclusion criteria included: 1) bone marrow with hemophagocytic histiocytosis, 2) clinical or biological signs of hepatic involvement, and 3) available liver specimen. RESULTS: The association of fever, jaundice, and hepatomegaly or splenomegaly was present in 50% of the patients. Median value for serum alanine transaminase activity was five times the upper limit of normal values (range, 0.3-125), for serum alkaline phosphatase activity 2.7 upper limit of normal values (range, 0.2-47.7), for total bilirubin 136 micromol/L (range, 4-681 micromol/L), and for factor V 70% (range, 19-145%). Sinusoidal dilatation with hemophagocytic histiocytosis were found in the biopsy specimen in all patients. An underlying condition potentially responsible for altered immune function (lymphoma, leukemia, liver transplantation) was identified in 29 patients. Liver biopsy was diagnostic for the underlying condition in 15 patients (including eight cases with nonspecific bone marrow biopsy findings). High serum bilirubin, elevated serum alkaline phosphatase activity, low factor V level, and lack of treatment for the underlying disease were associated with a poor prognosis. CONCLUSIONS: Hemophagocytic syndrome should be suspected in immunodeficient patients with fever, jaundice, and hepatosplenomegaly. Hepatic lesions are characterized by nonspecific sinusoidal dilatation with hemophagocytic histiocytosis and in 50% of the patients by alterations specific to the underlying condition. Liver biopsy is a useful diagnostic procedure in patients with this clinical presentation.

Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy.

BACKGROUND & AIMS: The outcome of portal vein thrombosis in relation to associated prothrombotic states has not been evaluated. We assessed current outcome and predictors of bleeding and thrombotic events in a cohort of 136 adults with nonmalignant, noncirrhotic portal vein thrombosis, of whom 84 received anticoagulant therapy. METHODS: Multivariate Cox model analysis for event-free survival and analysis taking into account multiple events were used. RESULTS: Median follow-up was 46 months. The incidence rate of gastrointestinal bleeding was 12.5 (95% confidence interval [CI], 10-15) per 100 patient-years. Large varices were an independent predictor for bleeding. Anticoagulant therapy did not increase the risk or the severity of bleeding. The incidence rate of thrombotic events was 5.5 (95% CI, 3.8-7.2) per 100 patient-years. Underlying prothrombotic state and absence of anticoagulant therapy were independent predictors for thrombosis. In patients with underlying prothrombotic state, the incidence rates of splanchnic venous infarction were 0.82 and 5.2 per 100 patient-years in periods with and without anticoagulant therapy, respectively (P = 0.01). Two nonanticoagulated patients died of bleeding and thrombosis, respectively. CONCLUSIONS: In patients with portal vein thrombosis, the risk of thrombosis is currently as clinically significant as the risk of bleeding. The benefit-risk ratio favors anticoagulant therapy.

Factor V Leiden related Budd-Chiari syndrome.

BACKGROUND: The role of factor V Leiden as a cause of Budd-Chiari syndrome has only recently been described. AIMS: To assess the specific features of factor V Leiden related Budd-Chiari syndrome. PATIENTS: Sixty three consecutive patients with hepatic vein or terminal inferior vena cava thrombosis. METHODS: Standardised chart review. RESULTS: Factor V Leiden was found in 20 patients (31% (95% CI 20-43)). In the subgroup of patients with, compared with the subgroup without, factor V Leiden, a combination of prothrombotic states was more common (70% (95% CI 50-90) v 14% (95% CI 3-24)); inferior vena cava thrombosis was more frequent (40% (95% CI 19-61) v 7% (95% CI 0-14)); and distribution of initial alanine aminotransferase values was bimodal (almost normal or extremely increased) versus unimodal (p=0.003). Factor V Leiden accounted for four of five cases of massive ischaemic necrosis (transaminases >50-fold the upper limit of normal values) (p=0.014), and also for all three cases developing during pregnancy. Patients with and without factor V Leiden did not differ with regard to mortality, portosytemic shunting, or listing for liver transplantation. Hepatocellular carcinoma developed in two patients; both had factor V Leiden and indolent obstruction of the inferior vena cava. CONCLUSIONS: In patients with Budd-Chiari syndrome, factor V Leiden (a) is common; (b) precipitates thrombosis mostly when combined with another risk factor; (c) is associated with one of two contrasting clinical pictures: indolent thrombosis-particularly of the inferior vena cava-or massive ischaemic necrosis; and (d) is a major cofactor of Budd-Chiari syndrome developing during pregnancy.

[Natural history of focal nodular hyperplasia. A retrospective study of 44 cases]. / Evolution naturelle de l'hyperplasie nodulaire focale.

AIM: To evaluate the natural course of focal nodular hyperplasia according to hormonal status. METHODS: Forty-four patients were included in this retrospective study. Tumor size was assessed with ultrasound examination. We studied the influence of hormone status on the course of the disease. RESULTS: All patients were women, the median age at diagnosis was 35 years and the median follow-up was 45 months. Ten patients were symptomatic at diagnosis, while none were symptomatic at the end of follow-up. The median size of the lesions was 56 mm. No complications occurred. The size of the tumor remained stable in 19 patients, increased in 12 and decreased in 13. Twenty-one of 37 patients stopped taking oral contraceptives at diagnosis: the lesion remained stable in 11 patients, increased in 3 and decreased in 7. Two patients didn't stop taking oral contraceptives: the lesion increased in one, decreased in the other. Six patients became pregnant and 6 patients went into menopause during follow-up: the lesion remained stable in 3 and 4 patients respectively. CONCLUSION: Focal nodular hyperplasia is a benign lesion. Tumor size remained stable in most cases. It seems that the hormonal status has little or no influence on the course of the disease.

Recurrent cholestatic jaundice associated with generalized pustular psoriasis: evidence for a neutrophilic cholangitis.

Generalized pustular psoriasis can result in systemic complications. We report the case of a woman with relapsing generalized pustular psoriasis and recurring episodes of cholestatic jaundice. Liver biopsy performed during an attack showed a neutrophilic infiltrate surrounding and invading portal triad bile ducts. Ultrasonographic exams and retrograde cholangiography ruled out biliary tract disease. This observation suggests that recurring cholestatic jaundice in pustular psoriasis is related to a neutrophilic cholangitis.