Lone Galmstrup Madsen

The Value of Alarm Features in Identifying Organic Causes of Dyspepsia

The unaided clinical diagnosis of dyspepsia is of limited value in separating functional dyspepsia from clinically relevant organic causes of dyspepsia (gastric and esophageal malignancies, peptic ulcer disease and complicated esophagitis). The identification of one or more alarm features, such as weight loss, dysphagia, signs of gastrointestinal bleeding, an abdominal mass or age over 45 years may help identify patients with a higher risk of organic disease. This review summarizes the frequency of alarm symptoms in dyspeptic patients in different settings (such as the community, primary care and specialist clinics). The prevalence of alarm features in patients diagnosed with upper gastrointestinal malignancy or peptic ulcer disease is described. The probability of diagnosing clinically relevant upper gastrointestinal disease in patients presenting with alarm features and other risk factors is discussed. Alarm features such as age, significant weight loss, use of nonsteroidal anti-inflammatory drugs, signs of bleeding and dysphagia may help stratify dyspeptic patients and help optimize the use of endoscopy resources.

Menetrier's Disease and Helicobacter pylori (Normalization of Gastrointestinal Protein Loss After Eradication Therapy)

Me ne trier’ s disease is a poorly de ® ned condition of unknown origin, characte rized by giant folds in the fundus and corpus of the stomach, and with a histologic feature of foveolar hype rplasia, atrophy of the glands, and a marked overall increase in mucosal thickne ss (1). The condition is often associate d with prote in loss from the stomach, seen as hypoalbum inemia, and hypoor achlorhydria can be expected when the process involve s most of the oxyntic gland mucosa. Apart from the characteristic ® ndings of foveolar hyperplasia, standard histological criteria for Me ne trier’ s disease have not been establishe d. The clinical spectrum is broad. The most common features are epigastric pain, weight loss, anemia due to gastric blood loss, diarrhe a, and peripheral edema. The most characte ristic laboratory abnormalitie s are low serum albumin and prote in levels (2). The etiology and pathoge nesis of Me ne trier’s disease are unknown. A possible etiologic role of Helicobacter pylori infection has been sugge sted, as healing of the prote in-losing hype rtrophic gastropathy by eradication therapy has been reported (3± 7). We report the ® rst case with direct documentation of a normalization of gastrointe stinal protein loss after eradication of Helicobacter pylori in a patient with prote in-losing hypertrophic gastropathy.

Primary (AL) amyloidosis with gastrointestinal involvement

Objective. Immunoglobulin light-chain (AL) amyloidosis is a rare disease that can affect several organs. The aim of this study was to characterize patients with gastrointestinal manifestations of AL amyloidosis, in terms of symptoms, biochemistry, and outcome. Material and methods. Retrospectively, patients with AL amyloidosis admitted for evaluation of malabsorption in a Department of Gastroenterology between January 2000 and December 2006 were identified. Results. A total of 11 patients (4 F, age 60 years, median (range) 50–69) were included in the study. Gastrointestinal amyloidosis was histologically verified in all patients. All patients had gastrointestinal symptoms, 8 of them prior to establishment of diagnosis. Median (range) delay from initial symptoms to diagnosis was 7 (0–24) months. The most prominent symptom was weight loss (n=10) averaging 7 (0–25) kg, followed by diarrhea (n=5). Steatorrhea (2 mild, 1 moderate, 1 severe) was found in 4 of 7 patients examined. At presentation, 9 patients had hypoalbuminemia and 6 patients had anemia. Three patients were treated with home parenteral nutrition. Five patients received conventional chemotherapy (oral melphalan and prednisone) and 5 patients underwent high-dose melphalan and autologous stem-cell transplantation. Five patients died within the observation period, at a median of 10 (3–36) months after the diagnosis was established. Non-survivors tended to have lower albumin levels on admission and more involvement of other organs compared to survivors. Conclusions. Most patients with gastrointestinal AL amyloidosis experience weight loss and all have signs of malabsorption. Despite treatment the prognosis is grave.

A Doppler waveform index to characterize hepatic vein velocity pattern and evaluate hepatic fibrosis.

To describe a Doppler waveform index representing the hepatic vein flow velocity pattern and to examine its relationship to the degree of hepatic fibrosis.

Hepatic Transit Time of Ultrasound Contrast in Biopsy Characterized Liver Disease

Purpose: To study the hepatic transit time of an ultrasound contrast agent in patients with liver disease, and to evaluate the mechanism(s) of the well-established shorter cubital vein to hepatic vein transit time in cirrhosis. Material and Methods: Thirty-four patients scheduled for Menghini liver biopsy were studied by ultrasound after injection of 2.5u2005g Levovist (Schering, Berlin, Germany) into an arm vein. The time from injection until the first appearance of contrast echoes in the hepatic artery and hepatic veins was registered. Hepatic transit time was the difference between the two. Results: Biopsy showed cirrhosis in 9 patients, other diffuse hepatic pathology in 23 patients, and normal liver in 2 patients. Mean hepatic vein arrival time was earlier in cirrhosis than in other liver disease (19.4u2005s versus 26.0u2005s; P = 0.013), and hepatic transit time was shorter (6.6u2005s versus 11.6u2005s; P = 0.024). A hepatic transit time <10u2005s was found in all patients with cirrhosis, but also in 10 of 23 patients with other liver pathology. Conclusion: Hepatic transit time measurement could not be used to distinguish between cirrhosis and other hepatic pathology, but a transit time = 10u2005s excluded cirrhosis. The earlier hepatic vein arrival time in cirrhosis is apparently mainly caused by intrahepatic shunting rather than by early arrival of contrast to the liver.

Nationwide Experience of Treatment with Protease Inhibitors in Chronic Hepatitis C Patients in Denmark: Identification of Viral Resistance Mutations

Background and Aims The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting. Methods 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy. Results 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively. Conclusions The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.

Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark

Abstract Objective: In Denmark, pregnant women have been screened for hepatitis B virus (HBV) since 2005, and children born to HBV-infected mothers offered hepatitis B immunoglobulin at birth, vaccination against HBV at birth and after 1, 2 and 12 months. The purpose of this study was to determine the risk of vertical HBV transmission in children born to mothers with chronic HBV infection, to investigate the antibody response in the children and to investigate possible maternal predictive risk factors for HBV transmission. Materials and methods: Through the Danish Database for Hepatitis B and C, we identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. 132 (36%) children, born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc. Results: We found vertical HBV transmission in Denmark to be 2.3% [95% CI: 0.5, 6.5], a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission. Conclusion: In a HBV low prevalence setting as Denmark, despite a national vaccination program, vertical HBV transmission occurred in 2.3% of children born to HBV-infected mothers. In addition, a high proportion of the children had insufficient anti-HBs levels and a high proportion had serological signs of resolved HBV infection.

Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections: A Scandinavian real-life study

Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12–24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-α) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12–16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment. Results We included 316 patients with a mean age of 55 years (range 24–79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). Conclusion We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.

Mortality in patients with Chronic Hepatitis C and cirrhosis compared to the general population: a Danish cohort study

Background Knowledge of mortality in patients with Chronic Hepatitis C (CHC) with cirrhosis is limited. This study aimed to estimate all-cause mortality among CHC patients with and without cirrhosis in Denmark compared to the general population. Methods Patients registered in The Danish Database for Hepatitis B and C with CHC and a liver fibrosis assessment were eligible for inclusion. Liver fibrosis was based on liver biopsy, transient elastography, and clinical cirrhosis. Up to 20 sex- and age-matched individuals per patient were identified in the general population. Data were extracted from nationwide registries. Results 3,410 CHC patients (1,014 with cirrhosis), and 67,315 matched individuals were included. Adjusted mortality rate ratios (MRR) between patients with and without cirrhosis and their comparison cohorts were 5.64 [CI95% 4.76; 6.67] and 1.94 [1.55; 2.42], respectively. Cirrhosis among patients was associated with a MRR of 4.03 [3.43; 4.72]. A cure for CHC was associated with a MRR of 0.64 [0.40; 1.01] among cirrhotic patients and 2.33 [1.47; 3.67] compared to the general population. Conclusions Mortality was high among CHC patients with and without cirrhosis compared to the general population. Curing CHC was associated with reduced mortality among cirrhotic patients but remained higher than the general population.

Liver-related morbidity and mortality in patients with chronic hepatitis C and cirrhosis with and without sustained virologic response

Background Chronic hepatitis C (CHC) causes liver cirrhosis in 5%–20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained virologic response (SVR). Furthermore we aimed to estimate the rate of hepatocellular carcinoma (HCC) and decompensation associated with certain prognostic factors. Materials and methods Patients with CHC and cirrhosis registered in the Danish Database for Hepatitis B and C were eligible. Cirrhosis was based on liver biopsy, transient elastography, and clinical cirrhosis. Data were extracted from nationwide registries. The study period was from 2002 until 2013. Results Of 1,038 patients included, 716 (69%) were male and the median age was 52 years. Median follow-up was 3.8 years, 360 patients died, and 233 of 519 treated patients achieved SVR. Alcohol overuse and hepatitis C virus genotype 3 were associated with an increased incidence rate (IR) of HCC, whereas diabetes and alcohol overuse were associated with increased IRs of decompensation. Achieving SVR reduced all-cause mortality (adjusted mortality rate ratio 0.68 [95% CI 0.43–1.09]) and liver-related mortality (mortality rate ratio 0.6 [95% CI 0.36–1]), as well as liver-related morbidity with adjusted IR ratios of 0.37 (95% CI 0.22–0.62) for HCC and 0.31 (95% CI 0.17–0.57) for decompensation. The IRs of HCC and decompensation remained elevated in patients with alcohol overuse after SVR. Conclusion Alcohol overuse, hepatitis C genotype 3, and diabetes were associated with liver-related morbidity in patients with CHC and cirrhosis. SVR markedly reduced liver-related morbidity and mortality; however, special attention to patients with alcohol overuse should continue after SVR.