Cause-specific mortality in patients with alcohol-related liver disease in Denmark: a population-based study.

BACKGROUND: Increased knowledge of the causes of death will be essential to prevent premature death in alcohol-related liver disease. We examined cause-specific mortality, including death due to specific cancers, in the 15 years after diagnosis of alcohol-related liver disease. METHODS: We used nationwide health registries to identify patients (aged ≥18 years) with a first diagnosis of alcohol-related liver disease between Jan 1, 2002, and Dec 31, 2017, in Denmark and followed up patients for their underlying cause of death up to Dec 31, 2019. We estimated the cause-specific mortality and investigated whether the cause-specific mortality differed by sex, age (<50, 50-59, and ≥60 years), alcohol-related liver disease severity at diagnosis (decompensated cirrhosis, compensated cirrhosis, alcoholic hepatitis, and steatosis or unspecified liver disease), and presence of diabetes. FINDINGS: The study included 23 385 patients with incident alcohol-related liver disease. Patients had a median age of 58 years (IQR 51-65), 15 819 (68%) were men and 7566 (32%) were women, and 15 358 (66%) had cirrhosis. During 111 532 person-years of follow-up, 15 692 (67%) patients died. Liver disease was the leading cause of death. In the first 5 years after alcohol-related liver disease diagnosis, liver disease caused almost half of all deaths, and the 5-year risk of death due to liver disease was 25·8% (95% CI 25·3-26·4). Beyond 5 years, causes other than liver disease combined became more common; of these extrahepatic causes, cancer, cardiovascular disease, and alcohol use disorder were the most common. Hepatocellular carcinoma was the dominant cause of cancer death (10-year risk of 2·5%, 95% CI 2·3-2·7), followed by lung cancer (1·9%, 1·7-2·1). The 10-year risk of death due to liver disease (around 30%) was similar for patients in all age groups and independent of sex and diabetes but was three times higher for those with decompensated cirrhosis (46·7%, 44·8-48·4) than steatosis or unspecified liver disease (16·2%, 15·3-17·2). INTERPRETATION: Patients diagnosed with alcohol-related liver disease were at high risk of dying from liver disease many years after diagnosis, irrespective of age and sex. Death due to specific cancers, including hepatocellular carcinoma, each contributed minimally to the total mortality in patients with alcohol-related liver disease. FUNDING: TrygFonden and the Novo Nordisk Foundation.

Social support and risk of mortality in cirrhosis: A cohort study.

Background & Aims: The function and structure of social relationships influence mortality in individuals within the general population. We compared aspects of social relationships in individuals with cirrhosis and a matched comparison cohort and studied their association with health-related quality of life (HRQoL) and mortality in cirrhosis. Methods: Individuals with cirrhosis and comparators were identified among participants of the Danish National Health Surveys 2010-2017. The surveys included questions on functional (social support and loneliness) and structural (living alone/cohabitating and frequency of contacts with relatives and friends) aspects of social relationships and HRQoL (Short Form-12). We estimated associations of aspects of social relationships with HRQoL and all-cause mortality in individuals with cirrhosis through 2020. Results: Of 541 individuals with cirrhosis and 2,157 comparators, low social support (22% in cirrhosis vs. 13% in comparators), loneliness (35% vs. 20%), and living alone (48% vs. 22%) were more frequent in individuals with cirrhosis than comparators, whereas the frequency of contacts with relatives and friends was similar. Except for living alone, weak functional and structural social relationships were associated with lower mental HRQoL in those with cirrhosis. Physical HRQoL was only marginally associated with social relationships. During 2,795 person-years of follow-up, 269 individuals with cirrhosis died. Functional and not structural aspects of social relationships were associated with risk of mortality in cirrhosis. Specifically, the adjusted hazard ratio was 1.4 (95% CI 1.1-1.9), p = 0.011, for low vs. moderate-to-high social support (functional aspect), and 1.0 (95% CI 0.8-1.3), p = 0.85 for living alone vs. cohabitating (structural aspect). Conclusions: Individuals with cirrhosis have weaker functional and structural social relationships than matched comparators. Weak functional relationships are associated with lower mental HRQoL and increased risk of mortality in individuals with cirrhosis. Impact and implications: This study investigated the prevalence of weak social relationships in individuals with cirrhosis and their influence on health-related quality of life and risk of mortality. Individuals with cirrhosis were nearly twice as likely to report low social support, loneliness, and to live alone than a matched comparison cohort. Low social support and loneliness (functional measures of social relationships) were associated with lower mental health-related quality of life and increased risk of mortality risk in cirrhosis, when adjusting for known confounders. We hope that these results will make healthcare providers aware of the functional aspects of the social relationships of individuals with cirrhosis, in addition to the traditional clinical management, and motivate further research of interventions to strengthen the social support of individuals with cirrhosis.

Ischemic Heart Disease in Chronic Hepatitis B: A Danish Nationwide Cohort Study.

Objective: Data on the risk of ischemic heart disease (IHD) in patients with chronic hepatitis B virus (CHB) are conflicting. Our objective was to address the rate of IHD in patients with CHB compared with individuals without CHB (control-persons) from the general population. Study Design and Setting: We conducted a cohort study of prospectively obtained data from Danish nationwide registries. We produced cumulative incidence curves and calculated the unadjusted incidence rate ratio (IRR) of IHD in persons with and without CHB. The adjusted association between having CHB and developing IHD was examined using a cause-specific Cox regression model. Results: In total, 6472 persons with CHB and 62,251 age- and sex-matched individuals from the general population were followed for 48,840 and 567,456 person-years, respectively, during which 103 (1,59%) with CHB and 1058 (1,70%) control-persons developed IHD. The crude IRR was 1.13 (95% CI: 0.91-1.39). CHB did not have a statistically significant effect on the rate of IHD after adjusting for several confounding factors (adjusted hazard ratio: 0.96, 95% CI: 0.76-1.21). Conclusion: In this nationwide cohort study, we did not find any difference between rate of IHD in persons with CHB in comparison with the general population.

Motivation to Reduce Drinking and Engagement in Alcohol Misuse Treatment in Alcohol-Related Liver Disease: A National Health Survey.

INTRODUCTION: The study aim was to identify predictors of motivation to reduce alcohol consumption and whether motivation predicts engagement in alcohol misuse treatment in alcohol-related liver disease (ALD). METHODS: Data from health surveys and health-care registries were combined. RESULTS: Of 674 patients with ALD, 65% consumed alcohol. Recent hospital admission and severe alcohol problems were associated with motivation to reduce alcohol consumption. Two-year probability for engagement in misuse treatment was 29% for patients with motivation to reduce alcohol consumption versus 6.5% for patients without motivation. DISCUSSION: ALD patients with recent hospital admission were more motivated to cut down alcohol consumption, and motivation predicted engagement in alcohol misuse treatment. This insight can help us target brief interventions.

Tunneled Peritoneal Catheter for Refractory Ascites in Cirrhosis: A Randomized Case-Series.

BACKGROUND AND OBJECTIVES: Refractory ascites markedly worsens prognosis in cirrhosis. Large volume paracentesis (LVP) is standard treatment, but complications are common. In a randomized controlled case-series, we assessed a permanent tunneled peritoneal catheter versus LVP in patients with cirrhosis and ascites. MATERIALS AND METHODS: Random allocation was computer-generated, and concealment used opaque envelopes. Patients were included from January 2017 to December 2018. Inclusion criteria were cirrhosis and recurrent ascites and expected survival of more than 3 months. RESULTS: Thirteen patients were enrolled (PleurX =6 versus LVP = 7). Seven were female, ranging in age from 51 to 80 years. No procedure-related complications occurred. Two patients died due to variceal bleeding (PleurX-group) and sepsis (LVP-group). One patient was withdrawn due to hyponatremia (PleurX-group). Two patients were withdrawn due to bacterial peritonitis and infection of unknown origin (control-group). In the PleurX-group, all patients colonized the catheter, two developed bacterial peritonitis. The most common bacterial colonization was Staph. Epidermidis (n = 4). CONCLUSIONS: In selected patients, the PleurX catheter mobilizes ascites and may be an alternative to LVP. The risk of infection should be considered in each case. The impact of colonization and risk of infections needs further investigation. The present trial does not allow for statistical conclusions.

Implementation of treatment recommendations for chronic hepatitis B in patients attending specialized hospital care in Denmark - a region wide study.

Objective: To evaluate implementation of national guideline recommendations on treatment initiation for chronic hepatitis B (CHB) in Denmark.Methods: Using DANHEP, a nationwide cohort of chronic hepatitis B and C patients attending specialized hospital care in Denmark, we performed a descriptive cohort study from January 2002 through December 2017. We identified patients with CHB in 3 of 5 Danish regions, with at least two hospital/outpatient clinic visits during the study period.Results: We identified 990 CHB patients who remained untreated throughout the study period, and 265 who initiated treatment. At their last visit 952/990 (96%, 95% CI 95-97) untreated patients did not meet current national criteria for treatment initiation while 198/265 (75%, 95% CI 69-80) who initiated treatment met the national criteria. Overall, 198/236 (84%, 95% CI 79-88) who met national treatment criteria, initiated treatment.Conclusion: The majority of CHB patients received care in line with national guideline recommendations for treatment initiation. We found that only few patients eligible for treatment remained untreated. However, a fourth of patients who received treatment were not eligible according to national guidelines.

[Elimination of hepatitis C virus in Denmark].

In Denmark, about 50% of patients with chronic hepatitis C virus (HCV) infection are undiagnosed. Since 2014, therapy containing direct-acting antivirals (DAA) has proven efficient and is available to all patients, who have a chronic HCV infection and a Danish personal identification number. The World Health Organization has a goal of elimination of viral hepatitis in 2030. Elimination of HCV in Denmark should focus on reducing HCV transmission, incidence and prevalence, combined with treatment with DAA of all infected patients. Micro-elimination strategies may play a major role, but a national strategy is lacking.

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.

Importance of post-treatment follow-up to secure sufficient eradication therapy for Helicobacter pylori.

INTRODUCTION: To optimize the care for Helicobacter pylori-associated diseases, we wanted to evaluate the completeness of follow-up after H. pylori eradication therapy in a single Danish endoscopy unit. Furthermore, the eradication rates and possible clinical characteristics associated with failure of eradication therapy were considered. MATERIAL AND METHODS: Patients who tested positive for H. pylori infection using a rapid urease test (RUT) during a three-year period were evaluated retrospectively according to demographics, eradication rate, type of eradication therapy, endoscopic findings and number of former attempts of eradication therapy. RUT-positive patients without a post-treatment evaluation were invited for a urea breath test. RESULTS: The overall H. pylori infection rate was 15% (117/796). Only 48/105 (46%) patients had a post-treatment examination to test the effect of H. pylori eradication therapy. The eradication rate by first-line therapy was 75% (58/77). The second-line eradication rate was 87%. 94% (72/77) had the recommended standard triple therapy for first-line eradication therapy. The number of former eradication attempts was the only clinical characteristic that significantly predicted failure of eradication therapy. Among patients with H. pylori-positive peptic ulcer, 21/28 (75%) achieved successful eradication after first-line treatment. CONCLUSION: Organised follow-up regimes are recommended, especially in patients with absolute treatment indications with a view to optimizing the care for patients infected with H. pylori.

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.

Symptomatic response to blocked and unblocked pentagastrin stimulation in functional dyspepsia. Comparison of responders and non-responders to omeprazole identified in a single-subject trial model.

BACKGROUND: The role of acid in functional dyspepsia is controversial and drug treatment trials indicate that only a subset of patients has acid-related symptoms. A novel single-subject trial design, the Random Starting Day trial (RSD trial), was developed to identify acid-related symptoms. We hypothesized that RSD trial responders and non-responders would react differently to gastric acid stimulation. Development of epigastric pain was expected in RSD trial responders after pentagastrin stimulation during placebo treatment, but not during omeprazole treatment. In non-responders, epigastric pain was expected not to be influenced by gastric acid stimulation or type of treatment. METHODS: Nineteen patients were evaluated. Symptomatic response to pentagastrin (6 microg/kg) was assessed twice in each patient following placebo and omeprazole (40 mg bid) treatment in a randomized, double-blind, cross-over design. Epigastric pain was assessed every 15 for 90 min after stimulation using a 5-graded Likert scale and a VAS scale. A positive acid provocation test was defined as an increase of the Likert score of epigastric pain by at least one grade after pentagastrin stimulation during placebo treatment but not during omeprazole treatment. RESULTS: The acid provocation test was positive in 43% (3/7) of responders compared to only 17% (2/12) non-responders. VAS-score changes showed trends towards a more pronounced symptom reduction during omeprazole treatment in responders compared to non-responders. CONCLUSION: Patients identified as having acid-related dyspepsia more often developed epigastric pain following acid stimulation during placebo and not during omeprazole treatment. Due to the low sample size the difference was not considered significant.

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

PURPOSE: To describe a Doppler waveform index representing the hepatic vein flow velocity pattern and to examine its relationship to the degree of hepatic fibrosis. METHODS: Doppler waveforms were obtained in 66 patients scheduled for percutaneous liver needle biopsy and categorized as normal (with a retrograde flow phase) or abnormal (without retrograde flow). Waveforms were also characterized using a hepatic vein waveform index (HVWI): (maximum - minimum velocity)/(maximum velocity). Biopsy specimens were graded for fibrosis. RESULTS: There was a highly significant decrease in HVWI with increasing fibrosis score in the biopsy (p < 0.001, Jonckheere trend test). The biopsy showed cirrhosis in 14 of 29 patients (48%) with absent retrograde flow and 5 of 37 patients (14%) with a normal flow pattern. Using HVWI as the criterion, cirrhosis was present in 13 of 21 (62%) patients with HVWI < 0.75, in 6 of 31 (19%) patients with 0.75 < HVWI < 1.50, and in none of 14 (0%) patients with HVWI > 1.50. CONCLUSIONS: HVWI is inversely correlated to the degree of liver fibrosis and may be more efficient than the presence or absence of retrograde flow in diagnosing and grading hepatic fibrosis.