Incidence and management patterns of alcohol-related liver disease in Korea: a nationwide standard cohort study.

The recent incidence and management patterns of alcohol-related liver disease (ARLD) are not well defined in Korea. We sought to evaluate the epidemiology of ARLD with regard to disease severity and alcohol cessation management after diagnosis. We performed an observational cohort study of standardized Common Data Model data from the Health Insurance Review and Assessment-National Patient Samples database between 2012 and 2016. The incidence and demographic properties of ARLD were extracted and divided into non-cirrhotic alcoholic liver disease (ALD) and alcoholic liver cirrhosis (ALC). ALC was compared with non-alcoholic cirrhosis by severity at diagnosis. The management patterns were captured by the initiation of pharmaco- and behavioral therapy for alcohol cessation. We analyzed data from 72,556 ALD to 7295 ALC patients. The ALD incidence was stable from 990 to 1025 per 100,000 people. In ALD, the proportion of patients who were ≥ 65 years old, the proportion of female patients, and the comorbidity index increased significantly during the study period (all P values < 0.001). ALC accounted for > 20% of all cirrhosis, with decompensation occurring twice as often as in non-alcoholic cirrhosis. The initiation of alcoholism management was stationary in ARLD, remaining at < 10% for both pharmacotherapy and behavioral therapy, regardless of severity or the site of diagnosis. The incidence of ARLD did not decrease during the study period. Moreover, an increasing trend in the proportion of people vulnerable to drinking was observed. Unfortunately, management for the cessation of alcohol use remains very low. The best way to manage ARLD should be evaluated in further study.

Alcohol-attributable healthcare attendances up to 10 years prior to diagnosis of alcoholic cirrhosis: a population based case-control study.

BACKGROUND & AIMS: Cirrhosis because of alcohol could be avoided if drinking behaviour could be altered earlier in the disease course. Our aim was to quantify the burden of morbidities in patients prior to alcoholic cirrhosis diagnosis, as this may inform the earlier identification of people at high risk for targeted interventions. METHODS: We carried out a case-control study using 2479 incident cases of alcoholic cirrhosis and 24 790 controls identified from 357 primary and secondary care centres in England. We assessed the prevalence of morbidities that are partly attributable to alcohol (namely malignant neoplasms, diabetes, epilepsy, injuries, cardiovascular and digestive diseases) prior to alcoholic cirrhosis diagnosis. We compared prevalence in cases to the control population and used logistic regression to derive odds ratios (95% CI). RESULTS: Fifty-eight per cent of cases compared to 29% of controls had had at least one alcohol-attributable condition before cirrhosis diagnosis. The most frequent conditions (proportion in cases vs. controls) were intentional injuries (35.9% vs. 11.9%) and cardiovascular diseases (23.2% vs. 15.6%), followed by diabetes (12.8% vs. 5.3%), digestive diseases (6.1% vs. 1.2%) and epilepsy (5.0% vs. 1.1%). The strongest association with alcoholic cirrhosis was found for digestive diseases [OR 5.4 (4.4-6.7)], epilepsy [OR: 4.4 (3.5-5.5)] and injuries [OR: 4.0 (3.7-4.4)] particularly among those aged 18-44 years. CONCLUSION: These data highlight the high burden of other alcohol-attributable conditions in patients prior to alcoholic cirrhosis diagnosis. Reviewing those consistently presenting with any of these conditions more closely could help practitioners reduce/avoid the long-term consequences of development of alcoholic liver disease.

Subjective parameters markedly limit the referral of transplantation candidates to liver transplant centres.

BACKGROUND & AIMS: Equality of access to organ transplantation is a mandatory public health requirement. Referral from a local to a university hospital and then registration on the national waiting list are the two key steps enabling access to liver transplantation (LT). Although the latter procedure is well defined using the Model for End-stage Liver Disease score that improves equality of access, the former is mostly reliant on the practices of referring physicians. The aim of this study was to clarify the factors determining this initial step. METHODS: This observational study included consecutive inpatients with cirrhosis of whatever origin in a cohort constituted between 2003 and 2008, using medical records and structured questionnaires concerning patient characteristics and the opinions of hospital clinicians. Candidates for LT were defined in line with these opinions. RESULTS: Four hundred and thirty-three patients, mostly affected by alcoholic cirrhosis, were included, 21.0% of whom were considered to be candidates for LT. Factors independently associated with their candidature were: physician empathy [odds ratio (OR) = 10.8; 95% CI: 4.0-29.5], adherence to treatment (OR = 16.6; 95% CI: 3.7-75.2), geographical area (OR = 6.8; 95% CI: 2.2-21.3) and the patient's physiological age (OR = 2.3; 95% CI: 1.1-4.7). CONCLUSIONS: Several subjective markers restrict the referral of patients from local hospitals to liver transplant centres. Their advancement to this second step is thus markedly weakened by initial subjectivity. The development of objective guidelines for local hospital physicians to assist them with their initial decision-making on LT is now necessary.

Transient and 2-Dimensional Shear-Wave Elastography Provide Comparable Assessment of Alcoholic Liver Fibrosis and Cirrhosis.

BACKGROUND & AIMS: Alcohol abuse causes half of all deaths from cirrhosis in the West, but few tools are available for noninvasive diagnosis of alcoholic liver disease. We evaluated 2 elastography techniques for diagnosis of alcoholic fibrosis and cirrhosis; liver biopsy with Ishak score and collagen-proportionate area were used as reference. METHODS: We performed a prospective study of 199 consecutive patients with ongoing or prior alcohol abuse, but without known liver disease. One group of patients had a high pretest probability of cirrhosis because they were identified at hospital liver clinics (in Southern Denmark). The second, lower-risk group, was recruited from municipal alcohol rehabilitation centers and the Danish national public health portal. All subjects underwent same-day transient elastography (FibroScan), 2-dimensional shear wave elastography (Supersonic Aixplorer), and liver biopsy after an overnight fast. RESULTS: Transient elastography and 2-dimensional shear wave elastography identified subjects in each group with significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) with high accuracy (area under the curve ≥0.92). There was no difference in diagnostic accuracy between techniques. The cutoff values for optimal identification of significant fibrosis by transient elastography and 2-dimensional shear wave elastography were 9.6 kPa and 10.2 kPa, and for cirrhosis 19.7 kPa and 16.4 kPa. Negative predictive values were high for both groups, but the positive predictive value for cirrhosis was >66% in the high-risk group vs approximately 50% in the low-risk group. Evidence of alcohol-induced damage to cholangiocytes, but not ongoing alcohol abuse, affected liver stiffness. The collagen-proportionate area correlated with Ishak grades and accurately identified individuals with significant fibrosis and cirrhosis. CONCLUSIONS: In a prospective study of individuals at risk for liver fibrosis due to alcohol consumption, we found elastography to be an excellent tool for diagnosing liver fibrosis and for excluding (ruling out rather than ruling in) cirrhosis.

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

Non-invasive diagnostic assessment tools for the detection of liver fibrosis in patients with suspected alcohol-related liver disease: a systematic review and economic evaluation.

BACKGROUND: Excessive alcohol consumption may lead to the development of alcohol-related liver disease (ALD). Liver biopsy may be used in patients with suspected ALD to confirm the diagnosis, exclude other or additional liver pathologies, and provide accurate staging of the degree of liver injury in order to enable the prediction of prognosis and inform treatment decisions. However, as it is an invasive procedure that carries the risk of morbidity and mortality, current UK guidance recommends that biopsy is not required to confirm the diagnosis in patients with a high clinical suspicion of ALD in whom blood tests have excluded other causes of liver disease, unless it is necessary to confirm a diagnosis of acute alcoholic hepatitis in order to inform specific treatment decisions. OBJECTIVES: To evaluate the diagnostic accuracy, cost-effectiveness, and effect on patient outcomes of four non-invasive tests for liver fibrosis [the Enhanced Liver Fibrosis (ELF™) test (Siemens Healthcare Diagnostic Inc., Tarrytown, NY, USA), FibroTest (BioPredictive, Paris, France), FibroMAX (BioPredictive, Paris, France) and transient elastography (FibroScan(®); produced by EchoSens, Paris, France and distributed in the UK by Artemis Medical Ltd, Kent, UK)] in patients suspected of having ALD. DATA SOURCES: A systematic review was undertaken to identify studies reporting the diagnostic and prognostic accuracy of the ELF test, FibroTest, FibroMAX, and FibroScan for the identification of liver fibrosis and associated conditions in patients with suspected ALD. The following databases were searched in January 2010: MEDLINE (from 1950 to January 2010), MEDLINE In-Process & Other Non-Indexed Citations (from 1950 to January 2010), EMBASE (from 1980 to January 2010), Cochrane Database of Systematic Reviews (from 1996 to January 2010), Cochrane Central Register of Controlled Trials (from 1898 to January 2010), Cochrane Methodology Register (from 1904 to January 2010), Database of Abstracts of Reviews of Effects (from 1995 to January 2010), HTA Database (from 1995 to January 2010), NHS Economic Evaluation Database (from 1995 to January 2010), Cumulative Index to Nursing and Allied Health Literature (from 1982 to January 2010), Web of Knowledge and Science Citation Index (from 1969 to January 2010). REVIEW METHODS: Study quality was assessed using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) checklist. Owing to the heterogeneity of the studies, no formal meta-analysis was undertaken. A de novo mathematical model was constructed to estimate the incremental costs and incremental quality-adjusted life-years (QALYs) associated with alternative strategies compared with a biopsy-all strategy. The tests are assessed first as a replacement for liver biopsy, and secondly as an additional test prior to liver biopsy. Thirty-six scenarios were assessed for each non-invasive test strategy, which varied the sensitivity of biopsy, the anxiety associated with biopsy, sensitivity and specificity values and whether or not the biopsy was percutaneous or transjugular. For each scenario, threshold levels were reported where biopsying all patients was more cost-effective than the strategy for two parameters (the decreased level of abstinence associated with the strategy compared with biopsying all and the level of incidental QALY gain associated with biopsy). RESULTS: No studies were identified that specifically assessed the ELF test, although a study was identified that evaluated the diagnostic accuracy of the European Liver Fibrosis Test (essentially, the ELF test with the addition of age to the algorithm) compared with biopsy. Three studies of FibroTest, no relevant studies of FibroMax, and six studies of FibroScan assessing accuracy compared with biopsy in patients with known or suspected alcohol-related liver disease were identified. In all studies, the number of patients with suspected ALD was small, meaning that the estimated sensitivities and specificities were not robust. No conclusive estimate of the cost per QALY of each non-invasive test could be provided. Scenarios exist in which each of the strategies analysed is more cost-effective than biopsying all patients and, in contrast, scenarios exist in which each strategy is less cost-effective than biopsying all patients. LIMITATIONS: Study selection and data analysis were undertaken by one reviewer. CONCLUSIONS: No conclusive result can be provided on the most cost-effective strategy until further data are available. A large number of parameters require data; however, the following are selected as being of most importance: (1) the sensitivity and specificity of each non-invasive liver test (NILT) against biopsy at validated and pre-selected cut-off thresholds; (2) the influence of potential confounding variables such as current drinking behaviour and the degree of hepatic inflammation on the performance of NILTs; and (3) the likelihood, and magnitude, of decreases in abstinence rates associated with a diagnosis of significant ALD by diagnostic modality and the incidental gains in QALYs that may be associated with biopsy. FUNDING: The National Institute for Health Research Technology Assessment programme.

[Nutritional assessment of alcoholic liver cirrhotic patients treated in the liver Clinic of the Mexico's General Hospital]. / Evaluación del estado nutricional de pacientes con cirrosis hepática alcohólica atendidos en la Clínica de Hígado del Hospital General de México.

Malnutrition in the cirrhotic patient is associated to a higher morbidity and mortality rate; however, the diagnosis is complex, so the study objective was to assess the nutritional status using different methods. Adult patients with alcoholic liver cirrhosis treated in the Liver Clinic of the Mexico's General Hospital were evaluated. Anthropometric measurements and a 24 hours recall were made; screening tools (Malnutrition Universal Screening Tool, Nutritional Risk Screening-2002) and a method for assessing nutritional status specifically in cirrhotic patients (Royal Free Hospital Global Assessment) were used. We included 62 patients, 51.6% of them were men. Malnutrition by arm muscle area was 31.3% in men and 10% in women, and by arm fat area was 23.3% in women and 3.1% in men (p < 0.05). With the screening tools the percentages of malnutrition risk were 43.5% and 54.8% respectively, vs. 1.6% identified as "low weight" with the Body Mass Index. With the Royal Free Hospital Global Assessment tool the percentage of malnutrition was 45.2%. Patients with malnutrition had an energy and protein intake significantly lower than the well-nourished: 19.7 kcal/kg and 0.89 g/kg vs 30 kcal/kg and 1.25 g/kg (p < 0.005). Malnutrition is a common complication in patients with liver cirrhosis. Men have higher depletion of muscle mass and women a higher loss of body fat. The Body Mass Index is not a reliable tool for assessing malnutrition. It's advisable to use tools with indicators of body composition such as the Royal Free Hospital Global Assessment.

Utility of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in patients with end-stage liver disease awaiting liver transplant.

UNLABELLED: Cognitive impairment is common among patients with end-stage liver disease (ESLD). This study examined cognitive dysfunction in patients with ESLD using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). METHOD: 66 patients with ESLD awaiting liver transplant were recruited. Patients were evaluated with the RBANS, Peabody Picture Vocabulary Test-Revised, and Beck Depression Inventory-II. RESULTS: Patients with ESLD uniformly performed below expectations on all RBANS index scores compared to the healthy normative sample (all p's<.0001) and they also displayed a "subcortical" pattern of cognitive performance (p<.0001). Performances on RBANS attention, language, immediate memory, and total index scores were correlated with education and ethnicity (r's range=|.32-.57|; p's<.01). There was no association between performance on any of the RBANS index scores or subtests and ESLD patient characteristics. In summary, the RBANS appears to adequately characterize known patterns of cognitive dysfunction in ESLD patients.

Umbilical varix presenting as an incarcerated umbilical hernia--a costly mistake if not recognised.

Incarcerated umbilical hernias commonly present as emergencies. Often they are diagnosed clinically and repaired surgically. In the case reported here, surgery could have been complicated by a major haemorrhage. An accurate history, high index of suspicion and attention to detail are paramount.

Non-invasive assessment of diffuse liver disease by in vivo measurement of proton nuclear magnetic resonance relaxation times at 0.08 T.

44 patients with a range of parenchymal liver diseases diagnosed by biopsy or laboratory investigations underwent proton nuclear magnetic resonance (NMR) relaxometry of the liver at 0.08 T. T1 maps were produced using an interleaved saturation recovery and inversion recovery sequence and T2 maps using a four echo Carr-Purcell-Meiboom-Gill sequence. Significantly raised relaxation times compared with a previously studied group of 42 normal volunteers were found in groups of patients with alcoholic cirrhosis (p < 0.001 for T1 and T2), chronic active hepatitis (CAH) (p < 0.01 for T1 and T2) and minor liver abnormalities (p < 0.01, T2 only). T1 was significantly higher in cirrhotics than in patients with CAH (p < 0.002) and minor abnormalities (p < 0.001). This suggests a role for relaxometry in the confirmation of the presence of cirrhosis (sensitivity = 75%, specificity approximately 97%, taking T1 > 266 ms as a positivity criterion). Reduced T2 values were found in patients with liver iron overload prior to venesection (p < 0.001 versus normals, p < 0.02 versus venesected patients). Although this latter test has relatively low sensitivity and specificity, it may have a role in the monitoring of treatment for iron overload.

Diagnostic utility of laboratory tests in alcoholic liver disease.

Alcoholic liver disease is an important health problem in the US. A public health approach is proposed, using laboratory tests to identify patients with early fibrosis of the liver. A variety of serological markers of liver fibrosis based on collagen-related products (e.g., amino-terminal propeptides of type III procollagen) have been investigated. Further studies are needed to determine the optimal combination of tests for discriminating between steatosis and early fibrosis. Laboratory tests are also useful in excluding nonalcoholic liver diseases such as viral hepatitis, hemochromatosis, and Wilson disease. The monitoring of sobriety in patients with alcoholic liver disease by currently available tests is far from ideal. A new marker of excessive alcohol consumption, carbohydrate-deficient transferrin, is not usually affected by liver disease and thus shows promise as a marker of relapse in alcoholic patients. The development of reliable screening markers of fibrosis and sobriety could potentially reduce the health costs and suffering associated with the complications of alcoholic cirrhosis.

O vírus da hepatite B na doença hepática alcoólica: avaliaçäo clínica e bioquímica / The hepatitis B virus in alcoholic liver disease: its clinical and biochemical assessment

Foram estudados prospectiva e sequencialmente 107 pacientes com doença hepática alcoólica (DHA) crônica, sendo 83 casos de cirrose e 24 de hepatite alcoólica. Além do etilismo, ingestäo mínima de 70 gramas de etanol puro ao dia por período superior a sete anos, todos apresentaram disfunçäo hepatocelular. De acordo com o perfil sorológico para o VHB os pacientes foram alocados em quatro grupos a saber: grupo I infectados: AgHBs e anti-HBc positivos; grupo II imunes: anti-HBs e anti-HBc positivos; grupo III sem marcadores do VHB: AgHBs, anti-HBc e anti-HBs negativos; grupo IV IV anti-HBc positivo isoladamente. A prevalência de infecçäo pelo VHB na DHA foi alta: 42,06 por cento apesar dos índices elevados de imunidade: 26,17 por cento sugerindo que na DHA ocorre maior exposiçäo ao VHB com resposta imunológica deficiente. A análise dos parâmetros clínico-bioquímico, quando considerados isoladamente, näo mostrou diferenças estatisticamente significantes entre os grupos I, II, e III, entretanto a clasificaçäo de Child/Campbell, discriminou o grupo infectado, onde houve predomínio da classe C, de pior prognóstico

[The hepatitis B virus in alcoholic liver disease: its clinical and biochemical assessment]. / O vírus da hepatite B na doença hepática alcoólica: avaliação clínica e bioquímica.

The aim of our work was to study the prevalence of HBV markers in Alcoholic Liver Disease (ALD) by evaluating clinical and biochemical parameters that could further characterize the association. A prospective and sequential study of 107 patients with ALD was performed, including 83 cases of cirrhosis and 24 cases of alcoholic hepatitis. Daily ingestion of pure ethanol was of at least 70 gm for seven years or more and always associated with hepatocellular disfunction. According to the serological profile for HBV markers the patients were allocated to one of four groups: group I infected (positivity of HBsAg and anti-HBc); group II immunized (positivity of anti-HBs and anti-HBc); group III without HBV markers (negativity of HBsAg, anti-HBc and anti-HBs); group IV isolated anti-HBc. The prevalence of HBsAg positivity in ALD was high: 15.89% whereas immunity was low: 26.17% suggesting a great exposure to the virus and a deficient immunological response. No significant statistical differences were found among the three groups when clinical and biochemical parameters were individually considered. Nevertheless, when a Child/Campbell classification was applied, patients with ALD associated with HBV (group I) showed a significant difference, presenting a predominance of child C, with a bad prognosis.

[Diagnostic and prognostic value of the assessment of selected indicators of humoral immunity in alcoholism-related pathology of the liver]. / Diagnostyczne i prognostyczne znaczenie oceny wybranych wskazników humoralnej odczynowosci immunologicznej w poalkoholowej patologii watroby.

The purpose of the study was evaluation of the usefulness of selected indices of humoral immune responsiveness in the differential diagnosis of post-alcoholic hepatocellular damage. The study was carried out in 105 patients: 10 patients with a history of alcohol abuse without clinical and biochemical evidence of hepatocellular damage, 2) patients with alcoholic cirrhosis, 3) patients with post-inflammatory cirrhosis. The prognostic usefulness of the determinations of serum IgM, C3 and C4 complement components and circulating immune complexes in early diagnostic of alcoholic liver disease was demonstrated. It was noted also that increased serum IgA level may be a useful index differentiating of cirrhosis after hepatitis from alcoholic cirrhosis.

[Sonographic assessment of the portal system in portal hypertension]. / Sonographische Beurteilung des portalen Gefässsystems bei der portalen Hypertension.

Three hundred and thirty-seven patients with portal hypertension and recurrent bleeding from oesophageal varices were examined by sonography. The situation was correctly elucidated in 17 out of 21 patients (81%) with pre-hepatic blocks, in 275 out of 313 cases (88%) with intra-hepatic blocks and in two out of three cases with post-hepatic blocks. The relevant findings consisted of stenoses and occlusions of the portal venous system and collaterals in pre-hepatic blocks, dilatation of the portal venous system and hepato-fugal collaterals in intra-hepatic blocks and occlusion of the hepatic veins in post-hepatic blocks. Sonography is recommended in cases of portal hypertension because of its non-invasive nature and high accuracy as the primary form of investigation. Spleno-portography should be used only if surgery is indicated.