Prevalence of at-risk MASH, MetALD and alcohol-associated steatotic liver disease in the general population.

BACKGROUND: The prevalence of at-risk metabolic dysfunction-associated steatohepatitis (at-risk MASH) has not been systematically assessed. AIM: To delineate the prevalence of at-risk MASH in a large population-based cohort. METHODS: We conducted a cross-sectional analysis of 40,189 patients in the UK Biobank who underwent liver MRI. Hepatic steatosis was determined by proton density fat fraction (PDFF) ≥5%. Based on AASLD criteria, participants were classified as alcohol-associated steatotic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), combined metabolic alcoholic liver disease (MetALD) and at-risk MASH. RESULTS: Among 40,189 patients, 10,886 (27.0%) had a PDFF ≥5%, indicating SLD. Among patients with SLD, 1% had ALD, 89.0% had MASLD, 7.9% had MetALD and 2.2% had at-risk MASH. The at-risk MASH group, which included 0.6% of the general population, had the highest mean liver fat on MRI and the highest BMI. Serum biomarkers highlighted increased inflammation and metabolic changes in at-risk MASH. The prevalence of MASLD was significantly higher among men with a BMI ≥30 kg/m2. Non-obese women showed only a 12% risk of MASLD. Conversely, MetALD had similar prevalence in obese men and women and was absent in non-obese women. CONCLUSIONS: MASLD is prevalent among patients with elevated PDFF on MRI. There are different sex- and BMI-specific prevalence of different steatotic liver disorders. At-risk MASH demonstrates the most severe metabolic and inflammatory profiles. This study provides novel estimates for the at-risk MASH population that will be eligible for treatment with pharmacologic therapy when approved by regulatory authorities.

Non-alcoholic fatty liver disease associated with greater herpes zoster risk than alcoholic fatty liver disease.

BACKGROUND: Disease-related stress can trigger the occurrence of herpes zoster (HZ). Fatty liver disease (FLD) can have adverse effects on the human body and may induce stress in affected individuals. In this study, we investigated whether FLD is associated with an elevated risk of HZ. METHODS: For this study, we utilized data from the National Health Insurance Research Database, patients with FLD from 2000 to 2017 were observed (follow-up until 2018). Patients were considered to have FLD if they had at least two outpatient visits or at least one admission record with a diagnostic code of FLD. Patients with FLD were matched 1:1 by age, sex, comorbidities, and index year with control patients. Additionally, the FLD was further categorized into non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) groups. Multivariable Cox proportional hazards model was used to calculate the incidence rate and adjusted hazard ratio (aHR) of HZ for FLD and AFLD and for various age groups, sex and comorbidities. Cumulative incidence curve for HZ was plotted through the Kaplan-Meier method, and p-value was calculated using the log-rank test. RESULTS: After 1:1 propensity-score matching, each cohort comprised 62,418 patients. The FLD cohort was further divided into NAFLD and AFLD groups, which respectively comprised 55,709 and 6709 patients. The FLD cohort had a risk of HZ significantly higher than that of the control cohort (aHR = 1.06; p < 0.001). Additionally, the NAFLD group exhibited a significantly higher risk of HZ than did the AFLD group (aHR = 1.22; p < 0.001). Among patients without any comorbidities, those with FLD had a higher risk of HZ than did those without FLD (aHR = 1.14; p < 0.001). CONCLUSION: Patients with FLD are at an increased risk of HZ development. Additionally, NAFLD is associated with a higher risk of HZ than AFLD. Therefore, patients with NAFLD should be informed of their increased risk of HZ.

Prevalence of alcohol-associated liver disease: a systematic review and meta-analysis.

BACKGROUND: Alcohol-associated liver disease (ALD) is a common cause of morbidity and premature mortality. To date, there has been no systematic synthesis of the prevalence of ALD. This systematic review was done with the aim of reporting the prevalence of ALD across different health care settings. METHODS: PubMed and EMBASE were searched for studies reporting the prevalence of ALD in populations subjected to a universal testing process. Single-proportion meta-analysis was performed to estimate the prevalence of all ALD, alcohol-associated fatty liver, and alcohol-associated cirrhosis, in unselected populations, primary care, and among patients with alcohol-use disorder (AUD). RESULTS: Thirty-five studies were included reporting on 513,278 persons, including 5968 cases of ALD, 18,844 cases of alcohol-associated fatty liver, and 502 cases of alcohol-associated cirrhosis. In unselected populations, the prevalence of ALD was 3.5% (95% CI, 2.0%-6.0%), the prevalence in primary care was 2.6% (0.5%-11.7%), and the prevalence in groups with AUD was 51.0% (11.1%-89.3%). The prevalence of alcohol-associated cirrhosis was 0.3% (0.2%-0.4%) in general populations, 1.7% (0.3%-10.2%) in primary care, and 12.9% (4.3%-33.2%) in groups with AUD. CONCLUSIONS: Liver disease or cirrhosis due to alcohol is not common in general populations and primary care but very common among patients with coexisting AUD. Targeted interventions for liver disease such as case finding will be more effective in at-risk populations.

Metabolic Dysfunction-associated Fatty Liver Disease and Mortality Among Chinese Adults: a Prospective Cohort Study.

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) was renamed metabolic dysfunction associated with fatty liver disease (MAFLD) recently. OBJECTIVE: We aimed to explore the risk of all-cause deaths in MAFLD participants and compare it with NAFLD in Chinese adults. METHODS: We enrolled 152 139 participants with abdominal ultrasonography in the Kailuan Cohort from 2006 to 2012. We categorized the participants into MAFLD and non-MAFLD, NAFLD and non-NAFLD, and 4 groups of Neither FLD, MAFLD only, NAFLD only, and MAFLD-NAFLD, respectively. We used Cox regression models to estimate the hazard ratios (HRs) and 95% CI of death. RESULTS: The prevalence of MAFLD and NAFLD was 31.5% and 27.3%, respectively. After a median follow-up of 12.7 years, MAFLD and NAFLD both were associated with increased mortality, especially in men younger than 40 years, with HR (95% CI) of 1.51 (1.19-1.93) and 1.37 (1.06-1.78), respectively. The MAFLD-only group had higher mortality than the NAFLD-only in males 60 years or older (adjusted HR = 1.43; 95% CI, 1.00-2.03) and lower risk in males aged 40 to 59 years (adjusted HR = 0.65; 95% CI, 0.48-0.90). MAFLD with overweight/obesity-only decreased, but those with diabetes and/or metabolic dysregulation increased the risk of death. MAFLD with positive hepatitis B surface antigen and/or excessive alcohol consumption further increased the risk of death, especially in men younger than 40 years (HR = 9.86; 95% CI, 2.44-39.98). CONCLUSION: MAFLD was associated with increased all-cause mortality among the Chinese population, which was different according to the status of overweight/obesity, diabetes, other metabolic indicators, and second causes. MAFLD patients should be managed by metabolic indicators and second causes to fulfill precise treatment and management.

Obesity and metabolic abnormalities as risks of alcoholic fatty liver in men: NAGALA study.

BACKGROUND: Hepatic steatosis has a pivotal role in the development of chronic liver diseases, even in alcohol-related liver disease. Alcoholic fatty liver disease is an important phenotype among alcohol-related liver diseases. While metabolic syndrome is a dominant risk factor of incident nonalcoholic fatty liver disease, the role of metabolic syndrome in alcoholic fatty liver disease has not been clarified yet. METHODS: A retrospective cohort study was performed at a health check-up center in Japan. Subjects consisted of male participants without fatty liver who consumed ethanol of 420 g/week or higher. Adjusted hazard ratios and 95% confidence intervals at the baseline examinations for incident alcoholic fatty liver disease were estimated using Cox model. RESULTS: A total of 640 participants were included in this study. During 3.91 years (IQR 1.63-7.09) of follow-up, 168 new cases of alcoholic fatty liver disease developed (49.1 cases per 1000 persons per year). After adjustment for age, smoking status, alcohol consumption, the hazard ratio for a 1 kg/m2 increase in body mass index was 1.2 (1.12-1.28). The hazard ratio of subjects with high triglyceride and low high-density lipoprotein-cholesterol levels were 1.56 (1.12-2.18) and 1.52 (1.03-2.25), respectively. CONCLUSIONS: Obesity, high triglyceridemia, and low high-density lipoprotein-cholesterolemia are independent risk factors of alcoholic fatty liver disease in Japanese men who consumed alcohol habitually. In people with these risks, triglyceride lowering and high-density lipoprotein-cholesterol raising by improving insulin resistance and weight maintenance in addition to abstinence from alcohol would be effective in preventing the development of alcoholic fatty liver disease.

Alcohol consumption in the general population is associated with structural changes in multiple organ systems.

Background: Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample. Methods: We assessed global effect sizes of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta, and liver of UK Biobank participants who reported drinking alcohol. Results: We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (-1.7 × 10-3 ± 0.76 × 10-3 per doubling of alcohol consumption, p=3.0 × 10-14). Alcohol consumption was also associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption. Conclusions: Our results imply that there is not a 'safe threshold' below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited. Funding: See acknowledgements.

Association of Cardiovascular Risk Factors and Metabolic Syndrome with non-alcoholic and alcoholic fatty liver disease: a retrospective analysis.

BACKGROUND: Although many studies on non-alcoholic fatty liver disease (NAFLD) are underway worldwide, and several existing studies have investigated the association between NAFLD and cardiovascular risk factors, studies comparing NAFLD and alcoholic fatty liver disease (AFLD) are scarce. This study aimed to evaluate differences between the incidence of cardiovascular risk factors and metabolic syndrome in NAFLD and AFLD. METHODS: A retrospective analysis of 913 patients who underwent abdominal computed tomography (CT) was performed to compare the incidence of cardiovascular risk factors and metabolic syndrome between NAFLD and AFLD. Subjects were divided into three groups based on criteria: healthy (n = 572), NAFLD (n = 295), and AFLD (n = 46). The healthy group had no liver disease. NAFLD was defined as fatty liver diagnosed on CT and drinking less than 140 g/week for men or 70 g/week for women. AFLD was defined as fatty liver diagnosed on CT and drinking more than 140 g/week for men or 70 g/week for women. We compared the incidence of cardiovascular risk factors and metabolic syndrome between the three groups. The relationship between each group and the metabolic syndrome risk was analyzed through multivariate logistic regression analysis. RESULTS: No significant differences in several cardiovascular risk factors were observed between the NAFLD and AFLD groups. Upon analyzing the metabolic syndrome status in each group after making appropriate adjustments, the odds ratios (ORs) in the NAFLD (OR = 2.397, P = 0.002) and AFLD groups (OR = 4.445, P = 0.001) were found to be significantly higher than that in the healthy group; the incidence rate of metabolic syndrome was similar in the NAFLD and AFLD groups. CONCLUSIONS: Both the NAFLD and AFLD groups had more cardiovascular risk factors and higher metabolic syndrome risk than the healthy group. Thus, the prevention of fatty liver disease, regardless of the specific type, should involve the identification of cardiovascular and metabolic syndrome risk factors. If abdominal CT reveals a fatty liver, whether NAFLD or AFLD, the risk of cardiovascular disease and metabolic syndrome should be assessed.

Estudio descriptivo de la esteatosis hepática y la morbilidad asociada en atención primaria. (Estudio ESTEATOAP) / Descriptive study of hepatic steatosis and associated morbidity in Primary Care. (ESTEATOAP Study)

OBJETIVO: Estudiar la prevalencia registrada de esteatosis hepática en atención primaria, así como la proporción de pacientes con diagnóstico de EHGNA que incluye el hígado graso simple no alcohólico (HGNA) y de esteatohepatitis no alcohólica frente a la esteatosis por otras causas. Además, se estudió la proporción de las morbilidades cardiometabólicas asociadas al HGNA. MATERIAL Y MÉTODOS: Estudio observacional descriptivo. La población de estudio es la de todos los pacientes con diagnóstico registrado de esteatosis hepática en un Centro de Salud urbano que atiende a una población de 25.747 mayores de 14 años. Se calculó un tamaño muestral de 229 pacientes. Se describen las características demográficas y clínicas asociadas. RESULTADOS: La prevalencia de esteatosis fue del 2,17%. Y de EHGNA del 1,51%. La media de edad de 62,42. Mujeres 114 mujeres (50,2%) y 113 varones (49,8%). Ciento cuarenta y siete (64,8%) fueron EHGNA y 64 (28,2%) fueron esteatosis por otras causas. La proporción de pacientes con EHGNA y transaminasas elevadas fue del 24,13% y la proporción de pacientes con EHGNA y elevación de GGT fue el 18,6%. Se ha encontrado una proporción elevada de EHGNA con factores de riesgo cardiometabólico: 93,9% de sobrepeso y obesidad, 55,1% de diabetes, 54,4% de hipertensión, 32,9% de síndrome metabólico, 35,2% hipertrigliceridemia y HDL de riesgo 19,6%. Entre los factores de riesgo cardiometabólicos y la EHGNA se encontró relación significativa en la diabetes, la obesidad y el síndrome metabólico. DISCUSIÓN: La prevalencia fue de solo el 1,51%, quizás por la escasa importancia que se da a esta enfermedad. Hay una proporción alta de EHGNA con factores de riesgo cardiometabólicos y más en la población general. Si se consideran todas las causas de esteatosis hay una asociación significativa entre obesidad, diabetes mellitus y síndrome metabólico con la EHGNA. CONCLUSIONES: La prevalencia registrada de EHGNA es muy inferior a la de los estudios poblacionales, además se ha encontrado una alta presencia de los factores cardiometabólicos en estos pacientes

OBJECTIVE: To study the recorded prevalence of hepatic steatosis in Primary Care, as well as the proportion of patients diagnosed with fatty liver diseases (FLD) including simple non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) versus steatosis by other causes. In addition, the proportion of cardiometabolic morbidities associated with NAFLD liver was studied. MATERIAL AND METHODS: A descriptive observational study was carried out on a population that included all patients with a recorded diagnosis of hepatic steatosis in an urban health centre that serves a population of 25,747 over the age of 14. A sample size of 229 patients was calculated. The demographic and clinical characteristics associated with hepatic steatosis are described. RESULTS: The prevalence of steatosis was 2.17% and 1.51% for NAFLD. The mean age was 62.42 years. The study included 114 (50.2%) women and 113 (49.8%) males. NAFLD was found in 147 (64.8%), and 64 (28.2%) were steatosis due to other causes. The proportion of patients with NAFLD and high transaminases was 24.13%, and the proportion of patients with NAFLD and GGT elevation was 18.6%. A high proportion of NAFLD had been found with cardiometabolic risk factors: 93.9% overweight and obesity, 55.1% diabetes, 54.4% hypertension, 32.9% metabolic syndrome, 35.2% hypertriglyceridaemia, and HDL risk 19.6%. A significant association was found between cardiometabolic risk factors and NAFLD in diabetes, obesity, and metabolic syndrome. DISCUSSION: Prevalence was only 1.51%, perhaps because of the low importance given to this disease. There is a high proportion of NAFLD with cardiometabolic risk factors and more in the general population. If all the causes of steatosis are considered there is a significant association between obesity, diabetes mellitus, and metabolic syndrome with NAFLD. CONCLUSIONS: The recorded prevalence of NAFLD is much lower than that of population studies, and a high presence of cardiometabolic factors has been found in these patients

Changes in metabolic complications in patients with alcoholic fatty liver disease monitored over two decades: NAGALA study.

Objective: The social conditions are changing in the world, which may contribute to the change in lifestyle, including alcohol consumption and dietary intake; however, changes in metabolic complications in patients with alcoholic fatty liver disease (AFLD) have never been reported. Therefore, here we compare the metabolic complications in current AFLD with those of two decades ago. Methods: We performed this cross-sectional study in a Japanese health check-up centre. Consecutive participants who visited the facilities between June 1994 and December 1997 or between January 2014 and December 2017 were enrolled. A total of 7499 participants (4804 men, 2695 women) in the past cohort and 20 029 participants (11 676 men, 8353 women) in the current cohort were entered to this study. Results: The prevalence of drinkers in the current cohort was significantly lower (4.7%) than that in the past cohort in men (5.9%, p<0.001) but significantly higher in women (1.9% in the current vs 1.1% in the past, p<0.001). The prevalence of fatty liver in drinkers has increased in men (22.3% in the past cohort, 36.6% in the current cohort; p<0.001) but not in women (13.3% in the past cohort, 14.7% in the current cohort; p=1.0), while the prevalence of all fatty liver has increased in men and women (men: 24.0% in the past cohort, 36.2% in the current cohort, p<0.001; women: 9.3% in the past cohort, 12.8% in the current cohort, p<0.001). Regarding metabolic abnormalities, the prevalence of hyperglycaemia increased from 25.4% to 43.0% in men with AFLD (p<0.001) and from 25.1% to 39.1% in women with AFLD (p=1.0). Conclusions: AFLD currently tends to be accompanied by hyperglycaemia. The prevalence of fatty liver in drinkers increased in men, although alcoholic consumptions did not increase. We should pay attention to fatty liver combined with hyperglycaemia for individuals who consume alcohol today.

Increased Prevalence of Obesity and Metabolic Syndrome in Patients with Alcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: Obesity and diabetes are risk factors for advanced alcoholic liver disease, and both are components of the metabolic syndrome. We aimed to assess the prevalence of metabolic syndrome and its components in a contemporary US cohort of adults with alcoholic liver disease and compare it to a historic cohort to assess changes over time. METHOD: Individuals 18 years or older who participated in the National Health and Nutrition Examination Survey during 2009-2014 and 1999-2001 were used as the contemporary and historic cohort, respectively. Alcoholic liver disease was defined as excessive alcohol consumption (men: ≥ 3 drinks/day; women: ≥ 2 drinks/day) and elevated alanine aminotransferase. Metabolic syndrome definition was based on the updated International Diabetes Federation criteria. Data are presented as mean ± standard error or unweighted frequency. A logistic regression analysis was performed to assess differences in metabolic syndrome components between the two period cohorts while adjusting for central obesity. RESULTS: The mean age for our contemporary cohort was 41.9, 66.1% being male. Central obesity was present in 66.3%, type 2 diabetes in 18.7%, low high-density lipoprotein in 28.3%, hypertriglyceridemia in 44.8%, and hypertension in 54.7%. 36.9% met the criteria for metabolic syndrome. Compared to the historic cohort, patients in the contemporary cohort were more likely to have central obesity (50% vs. 66%, p = 0.002), metabolic syndrome (26% vs. 37%, p = 0.044), and type 2 diabetes (12% vs. 19%, p = 0.099). CONCLUSIONS: Prevalence of both obesity and metabolic syndrome is increasing in alcoholic liver disease patients. Further studies are required to investigate effective interventions to avoid disease progression in these high-risk patients.

Alcoholic and Nonalcoholic Fatty Liver Disease and Incident Hospitalization for Liver and Cardiovascular Diseases.

BACKGROUND & AIMS: We compared the associations of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (AFLD) with risk of incident hospitalization for liver and cardiovascular diseases. METHODS: We collected data from the Kangbuk Samsung Health Study on 218,030 men and women in Korea who underwent a health examination from 2011 through 2016. Fatty liver disease (FLD) was detected by ultrasound during the initial examination. The Fibrosis-4 index was used to identify individuals with liver fibrosis. Participants were followed up for as long as 5.9 years and data on hospitalizations for liver and cardiovascular diseases were collected. RESULTS: The prevalence of NAFLD was 22.0% and the prevalence of AFLD was 6.4%. Over a median follow-up period of 4.2 years, we observed 51 and 1097 incident cases of liver disease- or cardiovascular disease-related hospitalizations, respectively. After adjustment for potential confounders, the multivariable-adjusted hazard ratios for liver disease-related hospitalization, comparing NAFLD and AFLD with the reference category (no excessive alcohol intake and no FLD), were 1.73 (95% CI, 0.76-3.96) and 5.00 (95% CI, 2.12-11.83), respectively. The corresponding hazard ratios for cardiovascular disease hospitalization were 1.20 (95% CI, 1.02-1.40) and 1.08 (95% CI, 0.86-1.34), respectively. Among participants with FLD, the risk of liver disease-related hospitalization increased with high Fibrosis-4 index scores, whereas the risk of incident cardiovascular disease did not. CONCLUSIONS: In a large cohort study, we found an increased risk of liver disease-related hospitalizations for patients with NAFLD or AFLD, especially among those with Fibrosis-4 index scores. An increased risk of cardiovascular disease-associated hospitalization was observed in patients with NAFLD but not AFLD.

HIV and the liver.

Among individuals with HIV infection, liver disease remains an important cause of morbidity and mortality, even with the availability of agents that cure hepatitis C infection and suppress hepatitis B replication. The causes of liver disease are multifaceted and continue to evolve as the population ages and new etiologies arise. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis and hepatitis viruses such as A, D, and E have emerged even as hepatitis C has receded. Newer antiretroviral agents may increase risk of weight gain and subsequent fatty infiltration, and prior use of nucleotide-based therapies may continue to impact liver health. Several barriers including economics, social stigma, and psychiatric disease impact identification of liver disease, as well as management and treatment interventions. Hepatocellular carcinoma is emerging as a more common and late-diagnosed complication in those with HIV infection and liver disease.

Changing trends in the disease burden of primary liver cancer caused by specific etiologies in China.

BACKGROUND: Liver cancer is a commonly diagnosed malignancy in China. The etiologies of liver cancer are widely known, although studies on temporal trends in liver cancer caused by specific etiologies are rare. METHODS: Data on the incidence and mortality of liver cancer were retrieved from the Global Burden of Diseases Study 2017. The estimated annual percentage change (EAPC) was used to quantify temporal trends in the age-standardized incidence rate (ASIR) and the age-standardized mortality rate (ASMR) of liver cancer from 1990 to 2017. RESULTS: Nationwide, the number of incident cases of liver cancer increased from 258 000 in 1990 to 515 900 in 2017. The ASIR decreased from 27.16 per 100 000 to 26.04 per 100 000 during this period, with an EAPC of -0.64 (95% confidence interval [CI] -0.84, -0.44). The number of deaths increased from 245 300 in 1990 to 418 200 in 2017, and the ASMR decreased from 26.72 to 21.30 (EAPC = -1.16, 95% CI -1.35, -0.97). The most pronounced decreases in the ASIR and ASMR were observed in liver cancer due to hepatitis B and in people aged 15-49 years. CONCLUSIONS: Since the extensive efforts for prevention of hepatitis B virus infection, the incidence of liver cancer due to hepatitis B has significantly decreased. However, liver cancer due to hepatitis C, NASH, and other causes remains a major public health concern. Additional preventive strategies tailored to liver cancer are needed to further reduce its disease burden in China.

Natural history of histologically proven alcohol-related liver disease: A systematic review.

BACKGROUND & AIMS: To date, studies into the natural history of alcohol-related liver disease (ALD) have lacked long-term follow-up, large numbers of participants, or both. We performed a systematic review to summarise studies that describe the natural history of histologically proven ALD. METHODS: PubMed and Medline were searched for relevant studies according to pre-specified criteria. Data were extracted to describe the prevalence of ALD, histological progression of disease and mortality. Single-proportion meta-analysis was used to combine data from studies regarding rates of progression or mortality. RESULTS: Thirty-seven studies were included, reporting data from 7,528 participants. Amongst cohorts of hazardous drinkers, on average 15% had normal histological appearance, 27% had hepatic steatosis, 24% had steatohepatitis and 26% had cirrhosis. The annualised rates of progression of pre-cirrhotic disease to cirrhosis were 1% (0-8%) for patients with normal histology, 3% (2-4%) for hepatic steatosis, 10% (6-17%) for steatohepatitis and 8% (3-19%) for fibrosis. Annualised mortality was 6% (4-7%) in patients with steatosis and 8% (5-13%) in cirrhosis. In patients with steatohepatitis on biopsy a marked difference was seen between inpatient cohorts (annual mortality 15%, 8-26%) and mixed cohorts of inpatients and outpatients (annual mortality 5%, 2-10%). Only in steatosis did non-liver-related mortality exceed liver-specific causes of mortality (5% per year vs. 1% per year). CONCLUSIONS: These data confirm the observation that alcohol-related hepatic steatohepatitis requiring admission to hospital is the most dangerous subtype of ALD. Alcohol-related steatosis is not a benign condition as it is associated with significant risk of mortality. LAY SUMMARY: Knowledge of the natural history of a disease allows clinicians and patients to understand the risks that are associated with a medical condition. In this study we systematically gathered all the published data regarding the natural history of alcohol-related liver disease in people who had a liver biopsy. We used this data to define the prevalence of the disease, the annual risk of progression to cirrhosis and the annual risk of death at each stage of the disease.

Fatty liver disease in persons with HIV infection.

The leading cause of non-HIV-related mortality is liver disease. Fatty liver disease can be characterized as alcoholic or nonalcoholic in nature. Alcohol use is prevalent among individuals with HIV infection and can lead to medication nonadherence, lower CD4+ cell count, inadequate viral suppression, and disease progression. The pathogenesis of nonalcoholic fatty liver disease (NAFLD) in individuals with HIV infection includes metabolic syndrome, hyperuricemia, HIV-related lipodystrophy, genetic polymorphisms, medications, HIV itself, and the gut microbiome. The prevalence of NAFLD in persons with HIV infection ranges from 30% to 65% depending on the modality of diagnosis. Individuals with HIV infection and NAFLD are at higher risk of cardiovascular disease; however, there is a dearth of longitudinal outcomes studies on this topic. Current therapies for NAFLD, such as vitamin E and pioglitazone, have not been studied in persons with HIV infection. There are several drugs in phase II and III clinical trials that specifically target NAFLD in HIV, including CC chemokine receptor 5 inhibitors, growth hormone-releasing factor agonists, and stearoyl-CoA desaturase inhibitors. Persons with HIV should be screened for NAFLD while pursuing aggressive risk factor modification and lifestyle changes, given the increased risk of cardiovascular mortality.

Alcoholic and non-alcoholic steatohepatitis: global perspective and emerging science.

Alcohol and high-fat diet are two major risk factors responsible for metabolic diseases, which are manifested as steatohepatitis and liver cancer in the liver, and chronic pancreatitis and pancreatic adenocarcinoma (PDAC) in the pancreas. These metabolic diseases are becoming increasingly prevalent around the globe, and more importantly, their two major etiologies commonly coexist to precipitate the disease processes. To highlight the importance of these metabolic diseases, Japanese Society of Gastroenterology (JSGE) and National Institute on Alcoholism and Alcohol Abuse of National Institute of Health cosponsored the JSGE's 7th International Forum jointly held with the 12th International Symposium on ALPD and Cirrhosis. Toward the main theme of "Frontiers in ASH, NASH, NBNC-HCC and PDAC", this platform showcased presentations by 12 invited international and Japanese speakers on brain-gut-liver interactions, emerging mechanisms of ASH and NASH, metabolic reprogramming, and new therapeutic targets for cirrhosis, HCC, and PDAC. This editorial discusses the most recent data on global statistics on how alcohol and obesity impact health and longevity as a prelude to a brief summary of the symposium presentations and discussions, primarily focusing on the first two session themes.

Association of thirty-year alcohol consumption typologies and fatty liver: Findings from a large population cohort study.

OBJECTIVE: To evaluate the longitudinal relationship between repeated measures of alcohol consumption and risk of developing fatty liver. PATIENTS AND METHODS: This study includes 5407 men and women from a British population-based cohort, the Whitehall II study of civil servants, who self-reported alcohol consumption by questionnaire over approximately 30 years (1985-1989 through to 2012-2013). Drinking typologies during midlife were linked to measures of fatty liver (the fatty liver index, FLI) when participants were in older age (age range 60-84 years) and adjusted for age, socio-economic position, ethnicity, and smoking. RESULTS: Those who consistently drank heavily had two-fold higher odds of increased FLI compared to stable low-risk moderate drinkers after adjustment for covariates (men: OR = 2.04, 95%CI = 1.53-2.74; women: OR = 2.24, 95%CI = 1.08-4.55). Former drinkers also had an increased FLI compared to low-risk drinkers (men: OR = 2.09, 95%CI = 1.55-2.85; women: OR = 1.68, 95%CI = 1.08-2.67). There were non-significant differences in FLI between non-drinkers and stable low-risk drinkers. Among women, there was no increased risk for current heavy drinkers in cross sectional analyses. CONCLUSION: Drinking habits among adults during midlife affect the development of fatty liver, and sustained heavy drinking is associated with an increased FLI compared to stable low-risk drinkers. After the exclusion of former drinkers, there was no difference between non-drinkers and low-risk drinkers, which does not support a protective effect on fatty liver from low-risk drinking. Cross-sectional analyses among women did not find an increased risk of heavy drinking compared to low-risk drinkers, thus highlighting the need to take a longitudinal approach.

Alcoholic and non-alcoholic fatty liver disease and associations with coronary artery calcification: evidence from the Kangbuk Samsung Health Study.

OBJECTIVE: Recent evidence suggests that alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) may differentially affect risk of cardiovascular mortality. To investigate whether early liver disease due to AFLD or NAFLD have similar or dissimilar effects on risk of early coronary artery atherosclerosis, we have investigated the associations between AFLD and NAFLD and coronary artery calcium (CAC). DESIGN: A cross-sectional study was performed in 105 328 Korean adults who attended a health check-up programme. CAC score was assessed using CT, daily alcohol intake was recorded as grams/day and liver fat by ultrasound. Logistic regression model was used to calculate ORs with 95% CIs for prevalent CAC. RESULTS: Both NAFLD and AFLD were positively associated with CAC score. After adjusting for potential confounders, multivariable-adjusted OR (95% CIs) for CAC >0 comparing NAFLD and AFLD to the reference (absence of both excessive alcohol use and fatty liver disease) were 1.10 (95% CI 1.05 to 1.16) and 1.20 (95% CI 1.11 to 1.30), respectively. In post hoc analysis, OR (95% CI) for detectable CAC comparing AFLD to NAFLD was 1.09 (95% CI 1.01 to 1.17). Associations of NAFLD and AFLD with CAC scores were similar in both non-obese and obese individuals without significant interaction by obesity (p for interaction=0.088). After adjusting for homeostasis model assessment of insulin resistance and high-sensitivity C reactive protein, the associations between fatty liver disease and CAC scores remained statistically significant. CONCLUSION: In this large sample of young and middle-aged individuals, early liver disease due to NAFLD and AFLD were both significantly associated with the presence of coronary artery calcification.

Metabolic factors affecting hepatocellular carcinoma in steatohepatitis.

BACKGROUND & AIMS: With the rising prevalence of alcoholism, obesity and metabolic syndrome, steatohepatitis will become the leading cause of end-stage liver disease and hepatocellular carcinoma in the United States by 2025. Patients with non-alcoholic steatohepatitis and alcoholic liver disease have similar clinical and histopathological presentations, whether these similarities persist in non-alcoholic steatohepatitis and alcoholic liver disease patients with hepatocellular carcinoma remains unknown. METHODS: A retrospective analysis of the clinical features of adult patients from a large transplant center who underwent liver transplantation for steatohepatitis due to non-alcoholic steatohepatitis and alcoholic causes (alcoholic liver disease) between 1/1/02 and 1/1/12 was performed. Clinical features, explant histopathology, and clinical outcomes were compared. RESULTS: Hepatocellular carcinoma was present in 80 of 317 patients, who underwent liver transplantation for steatohepatitis with equivalent distribution in non-alcoholic steatohepatitis and alcoholic liver disease patients (24% vs 26%; P = 0.8). On multivariate analysis, significant predictors of hepatocellular carcinoma included age, ethnicity (Hispanic), and diabetes, but not BMI, hypertension or smoking. A lower risk of hepatocellular carcinoma was associated with a clinical history of hyperlipidemia. Clinical parameters were similar between patients with alcoholic liver disease - hepatocellular carcinoma and non-alcoholic steatohepatitis-hepatocellular carcinoma, except sex and presence of metabolic syndrome. non-alcoholic steatohepatitis-hepatocellular carcinoma livers retained histopathological features of non-alcoholic steatohepatitis such as ballooning and Mallory bodies, while alcoholic liver disease-hepatocellular carcinoma livers did not. There were no significant differences in hepatocellular carcinoma recurrence rates or post-transplant overall survival. CONCLUSIONS: We report the largest single-center study evaluating clinical, histopathological and outcome measures of patients undergoing liver transplantation for steatohepatitis. Older patients, diabetics, and Hispanics may warrant more frequent cancer screening due to increased risk of hepatocellular carcinoma.