Risk of hepatic and extrahepatic cancer in NAFLD: A population-based cohort study.

BACKGROUND AND AIMS: Individuals with non-alcoholic fatty liver disease (NAFLD) may be at greater risk of cancer. This study aimed to investigate the risk of hepatic and extrahepatic cancer compared to the general population in a population-based cohort of patients with NAFLD. METHODS: We used the Swedish National Patient Registry from 1987 to 2016 to identify patients with a NAFLD diagnosis and no prior cancer. All patients with NAFLD were compared to up to 10 controls matched for age, sex and living location. The primary outcome was the first occurrence of any cancer as ascertained from national registries. As secondary outcomes, we analysed the risk of pre-specified cancer subtypes. Cox regression models, adjusted for baseline diabetes, hypertension, hyperlipidaemia and chronic obstructive pulmonary disease were applied. RESULTS: We identified 8415 patients with NAFLD. Over a median follow-up of 6.0 years (IQR 2.5-11.2 years), an increased risk for any cancer was found in patients with NAFLD compared to controls (9.7 vs. 8.6 cases per 1000 person-years): hazard ratio (HR) = 1.22 (95% confidence interval, CI = 1.12-1.33). The risk for hepatocellular carcinoma (HCC) was particularly high (adjusted HR, aHR = 12.18, 95% CI = 7.15-20.79). The risk for some other cancer subtypes increased (colorectal [aHR 1.38], kidney [aHR 2.12], bladder [aHR 2.51] and uterine [aHR 1.78]), but was low in absolute terms. CONCLUSION: In this population-based cohort, NAFLD was associated with an increased risk of developing cancer (especially HCC). The absolute risk for other forms of cancer was generally comparable to the control population.

Etiologies and outcomes of cirrhosis in a large contemporary cohort.

BACKGROUND AND AIMS: Patients with liver cirrhosis have high mortality, often estimated by the Child-Pugh or MELD scores. Etiologies of cirrhosis are rapidly shifting, and it is unclear if these scores perform similarly across subgroups of patients. Here, we describe the characteristics and outcomes of a large contemporary cohort of patients with cirrhosis. METHODS: This was a cohort study with retrospectively collected data. All patients with a verified diagnosis of cirrhosis during 2004-2017 at the Karolinska University Hospital, Sweden, were identified. Data at baseline to calculate Child-Pugh, MELD and confounders for mortality was collected. Competing risk regression was used to estimate risk for outcomes, adjusted for age, sex, baseline Child-Pugh score, etiology of cirrhosis and type 2 diabetes. RESULTS: We identified 2609 patients, with a median age of 61 years, and 68% men. Etiologies of cirrhosis shifted during the study period, with a -29% relative decrease in hepatitis C-cirrhosis and a + 154% increase in cirrhosis due to non-alcoholic fatty liver disease. The highest overall mortality was seen in patients with alcohol-related cirrhosis. MELD and Child-Pugh scores predicted 3-month and 1 to 2-year mortality reasonably well, but with a lower predictive performance in alcohol-related cirrhosis. Men were more likely than women to receive a liver transplant (sHR = 1.39, 95%CI = 1.08-1.78). CONCLUSIONS: We confirm previous findings of a rapid shift in the etiologies of cirrhosis. Differences in sex in regard to access to liver transplantation deserve further attention.

A personalized treatment program in persons with type 2 diabetes is associated with a reduction in liver steatosis.

BACKGROUND AND AIMS: It is unclear if improving glycemic control in persons with type 2 diabetes (T2D) also has liver-related effects. We aimed to evaluate if a personalized treatment program associates with improvement of liver-related parameters in persons with advanced T2D in a real-life setting. METHODS: Persons with advanced T2D underwent a 4-day personalized treatment program, with the aim of improving glycemic control by dietary advice, instructions on how to achieve optimal glucose control and individualized dosage of medications. Transient elastography was used to estimate liver steatosis and fibrosis. Persons with liver diseases other than non-alcoholic fatty liver disease (NAFLD) were excluded. After 3 months, study participants were offered re-examination. RESULTS: Ninety-one persons were included. Of these, 75 persons (82%) had controlled attenuation parameter (CAP) measurements of acceptable quality at baseline. Of these, 57 (76%) had NAFLD (defined as >268 dB/m). Twenty-two persons (24%) had elevated liver stiffness (>7.9 kPa), and eight (9%) had liver stiffness above 13.9 kPa, indicating advanced fibrosis. Over a median follow-up of 101 days, mean CAP in persons with NAFLD was reduced by 18.33 dB/m (P = 0.035). In persons with elevated liver stiffness, mean stiffness was reduced by 2.6 kPa (P = 0.047). In linear regression, one-unit improvement in fasting glucose (mg/dl) was associated with a decrease in hepatic steatosis with 0.48 dB/m (adjusted R2 = 0.35, P < 0.01). CONCLUSION: The prevalence of NAFLD with advanced fibrosis is high in persons with advanced T2D. Improving glycemic control through a personalized treatment program is associated with a reduction in liver steatosis and stiffness in this cohort.

Risk Factors for Severe Liver Disease in Patients With Type 2 Diabetes.

BACKGROUND & AIMS: Type 2 diabetes is a risk factor for development of cirrhosis and hepatocellular carcinoma. However, risk factors that identify persons with the highest risk for these outcomes are missing from unselected, population-based cohorts. METHODS: The National Diabetes Register contains data on about 90% of persons in Sweden with type 2 diabetes. In this cohort study, persons with type 2 diabetes listed in the National Diabetes Register were compared with 5 individuals from the general population (controls), matched for age, sex, and county. In total, 406 770 persons with type 2 diabetes and 2 033 850 controls were included and followed for 21 596 934 person-years. We used population-based registers to determine the incidence of severe liver disease, defined as a diagnosis of hepatocellular carcinoma, cirrhosis, decompensation, liver failure and/or death due to liver disease during follow up. Cox regression was performed to estimate the risk of severe liver disease and to examine risk factors in persons with type 2 diabetes. RESULTS: Risk for severe liver disease was increased in patients with type 2 diabetes compared to controls (hazard ratio, 2.28; 95% CI, 2.21-2.36). Risk factors associated with severe liver disease in persons with type 2 diabetes were higher age, male sex, hypertension, higher body mass index, lower glomerular filtration rate, microalbuminuria, and smoking. Statins were associated with a decreased risk of severe liver disease. CONCLUSIONS: Persons with type 2 diabetes have an increased risk for severe liver disease. Knowledge of risk factors can be helpful in identifying persons with type 2 diabetes who have a high risk for severe liver disease.

Histologic Scores for Fat and Fibrosis Associate With Development of Type 2 Diabetes in Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a strong risk factor for development of type 2 diabetes, but little is known about how long-term NAFLD or its histologic features affect risk. We aimed to investigate the cumulative incidence of type 2 diabetes in patients with NAFLD and to identify histologic factors that affect risk of diabetes. METHODS: We performed a retrospective study of 396 patients in Sweden diagnosed with NAFLD by biopsy analysis from 1971 through 2009 who did not have type 2 diabetes at baseline. Data on development of type 2 diabetes were collected from patient charts and national registers. Patients were categorized into groups with fibrosis stages 0-2 (n = 357) or stages 3-4 (n = 39). Hazard ratios of histologic parameters for type 2 diabetes development were calculated separately in a multivariate Cox regression model adjusted for sex, age, body mass index, and serum levels of triglycerides greater than 150 mg/dL. RESULTS: During a mean follow-up period of 18.4 years (range, 0-41 years), 132 individuals (33%) developed type 2 diabetes. A significantly higher proportion of patients with fibrosis stages 3-4 (51.2%) developed type 2 diabetes than patients with fibrosis stages 0-2 (31.3%) (P = .02). For patients with fibrosis stages 0-2, fat score associated independently with development of type 2 diabetes (adjusted hazard ratio, 1.34; 95% confidence interval, 1.03-1.74; P = .03). No histologic factors associated with development of diabetes in patients with fibrosis stages 3-4. Presence of nonalcoholic steatohepatitis was not associated with development of type 2 diabetes. CONCLUSIONS: In a retrospective study we found a higher proportion of patients with fibrosis stages 3-4 to develop type 2 diabetes than patients with fibrosis stages 0-2. In patients with fibrosis stages 0-2, fat score associates with risk of type 2 diabetes.