To assess the alcohol drinking patterns in a cohort of primary sclerosing cholangitis (PSC) patients and the possible influence on the development of fibrosis.
Ninety-six patients with PSC were evaluated with a validated questionnaire about a patient's lifetime drinking habits: the lifetime drinking history (LDH) questionnaire. In addition, clinical status, transient elastography and biochemistry values were analysed and registered. Patients were defined as having either significant or non-significant fibrosis. Significant fibrosis was defined as either an elastography value of = 17.3 kPa or the presence of clinical signs of cirrhosis. Patients were divided into two groups depending on their alcohol consumption patterns; no/low alcohol consumption (one drink or unit/d) and moderate/high alcohol consumption (= 1 drink or unit/d). LDH data were calculated to estimate lifetime alcohol intake (LAI), current alcohol intake, drinks per year before and after diagnosis of PSC. We also calculated the number of episodes of binge-drinking (defined as consuming = 5 drinks per occasion) in total, before and after the diagnosis of PSC.
The mean LAI was 3882 units of alcohol, giving a mean intake after onset of alcohol consumption of 2.6 units per week. Only 9% of patients consumed alcohol equal to or more than one unit per day. Current alcohol intake in patients with significant fibrosis (n = 26) was less than in patients without significant fibrosis (n = 70), as shown by lower values of phosphatidylethanol (B-PEth) (0.1 ?mol/L vs 0.33 ?mol/L, respectively, P = 0.002) and carbohydrate-deficient transferrin (CDT) (0.88% vs 1.06%, respectively, P = 0.02). Self-reported LAI was similar between the two groups. Patients with significant fibrosis reduced their alcohol intake after diagnosis from 103 to 88 units per year whereas patients without fibrosis increased their alcohol intake after PSC diagnosis from 111 to 151 units/year. There were no correlations between elastography values and intake of alcohol (units/year) (r = -0.036).
PSC patients have low alcohol consumption. The lack of correlation between fibrosis and alcohol intake indicates that a low alcohol intake is safe in these patients.
Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended in clinical guidelines. In real-life management, surveillance rates below 20% have been reported from the United States. We aimed to determine the use of HCC-surveillance in patients diagnosed with HCC in a European setting, and to identify the reasons for surveillance failures.
Age, gender, tumour characteristics, BCLC classification, Child-Pugh stage, pre-existing liver disease, treatment, survival, frequency of HCC surveillance and reasons for surveillance failures were retrospectively determined in 616 patients diagnosed with HCC at Karolinska University Hospital 2005-2012.
Hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease (NAFLD) were the most common diagnoses. The proportion of HCC patients diagnosed through surveillance was 22%. In 35% of cases, surveillance was missed due to doctor's failure to order surveillance or to diagnose the underlying liver disease. Diagnosis of NAFLD or alcoholic liver disease increased the risk of not receiving surveillance more than two-fold. Undiagnosed liver disease was most common in NAFLD patients. Patients who underwent surveillance had smaller tumours, more frequently received curative treatment, and had better survival compared to those in whom surveillance was indicated but missed.
In a European setting, only 22% of HCCs were diagnosed by surveillance, and in more than one-third of cases, surveillance was indicated but missed. NAFLD and alcoholic liver disease were associated with deficient surveillance. Survival was significantly better in patients who underwent surveillance compared with those in whom surveillance was missed although indicated.
High levels of ferritin in patients with non-alcoholic fatty liver disease (NAFLD) are associated with significant fibrosis and higher NAFLD activity score (NAS). It is unclear if this association has an impact on mortality. We investigated if high levels of ferritin, with or without iron overload, were associated with an increased mortality in NAFLD.
We included 222 patients between 1979 and 2009 with biopsy-proven NAFLD and available serum ferritin concentrations. The cohort was divided into 'high' (n = 89) and 'normal' (n = 133) ferritin values, using a cut-point of 350 µg/L in males, and 150 µg/L in females, and stratified upon iron overload status. Data on mortality were obtained from a national, population-based register. Poisson regression was used to estimate hazard ratios for mortality. The estimates were adjusted for age at biopsy, sex, smoking, BMI, diabetes, hypertension, cardiovascular disease and fibrosis stage at the time of biopsy.
The median follow-up time was 15.6 years (range: 0.5-34.2). Patients with high ferritin had more advanced fibrosis and higher NAS than patients with normal ferritin (P
The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected.
373 patients with hemochromatosis detected through routine health check-ups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.9 ± 5.8 years. The degree of liver fibrosis and survival were analyzed.
Overall survival among these patients was not significantly different from that of a matched normal population. The patients diagnosed through health check-ups and family screening were detected at an earlier age and had the highest rate of survival. Liver biopsy at the time of diagnosis revealed cirrhosis in 9% of those detected through the health check-ups and 5% in the case of family screening, compared with 13% for the group with arthralgia, 17% for other diseases/symptoms and 42% for liver disease.
Health check-ups and family screening allow detection of hereditary hemochromatosis at an earlier age and with less advanced liver fibrosis, although a few of these patients have already developed cirrhosis. Our study indicates that iron indices should be included in health check-ups, and if abnormal, should lead to further investigation.
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.
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.
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.
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.
Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD.
We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled.
An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76-0.97; p?=?.017). The lowest risk for fibrosis was found with the lowes`t odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08-0.66; p?=?.006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth =0.3?µmol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01-7.59; p?=?.047).
Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.
Centre for Digestive Diseases, Division of Hepatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. Electronic address: email@example.com.
The increased prevalence of overweight has been suggested to contribute to the worldwide increase in liver diseases. We investigated if body mass index (BMI) in late adolescence predicts development of severe liver disease later in life.
We performed a cohort study using data from 44,248 men (18-20years) conscribed to military service in Sweden between 1969 and 1970. Outcome data were collected from national registers to identify any diagnosis of severe liver disease (i.e., diagnosis of decompensated liver disease, cirrhosis or death in liver disease) until the end of 2009. A Cox regression model was applied using BMI as independent variable. The model was adjusted for use of alcohol, use of narcotics, smoking, high blood pressure and cognitive ability at time of conscription.
During a follow-up period of a mean of 37.8years, 393 men were diagnosed with severe liver disease (mean time to diagnosis 24.7years). BMI (Hazard ratio [HR]=1.05 for each unit increase in BMI, 95% confidence interval [CI]: 1.01-1.09, p=0.008) and overweight (HR=1.64 for BMI 25-30 compared to BMI 18.5-22.5, 95% CI: 1.16-2.32, p=0.006) were associated with an increased risk of development of severe liver disease.
Being overweight in late adolescence is a significant predictor of severe liver disease later in life in men.
We investigated close to 45,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40years of follow-up, we found that being overweight was a risk factor for developing severe liver disease, independent of established risk factors such as alcohol consumption.
Prognostication in hepatocellular carcinoma (HCC) is demanding. Not only tumour extent and performance status are to be considered, but also liver function, which is often limiting for both survival itself and for treatment possibilities. This study was conducted to assess whether patient-reported questionnaires containing general and liver-specific questions could improve prognostication of survival.
185 patients with hepatocellular carcinoma in Norway and Sweden were prospectively included. Patients completed the quality-of-life questionnaires EORTC QLQ C30 and HCC18, and clinical, radiological and laboratory parameters were registered. Multivariate Cox regression and Harrell's C-statistics were used to identify the model that best predicted mortality.
Quality-of-life data were prognostic for overall survival. Fatigue and nutrition scales were prognostic in the multivariable analyses alone and in combination with clinical parameters. The prognostic value of established scoring systems was increased by the addition of QoL data. The best prognostic power was achieved by combining HCC18 nutrition scale with selected background parameters.
Quality-of-life questionnaires can prognosticate mortality in HCC patients. When combined with established scoring systems, both the general cancer questionnaire EORTC QLQ C30, and the additional liver cancer-specific HCC18 increased the prognostic accuracy slightly.
A new score for the histological severity of nonalcoholic fatty liver disease (NAFLD), called SAF (Steatosis, Activity and Fibrosis) has been developed. We aimed to evaluate the impact of this score on overall mortality.
We used data from 139 patients with biopsy-proven NAFLD. All biopsies were graded according to the SAF scoring system and disease severity was classified as mild, moderate or severe. Causes of death were extracted from a national, population-based register. A Cox regression model, adjusted for sex, body mass index (BMI) and diabetes mellitus type 2, was applied.
At baseline 35 patients presented with mild or moderate disease respectively, and 69 patients with severe disease. During follow-up (median 25.3 years, range 1.7-40.8) 74 patients died, 11 in the mild group (31%), 18 in the moderate group (51%) and 45 in the severe group (65%), p?=?.002. Compared to patients with mild disease, patients with moderate disease did not have a significant increase in overall mortality (HR 1.83, 95%CI 0.89-3.77, p?=?.10). Patients with severe disease had a significant increase in mortality (HR 2.65, 95%CI 1.19-5.93, p?=?.017). However, when adjusting for fibrosis stage, significance was lost (HR 1.85, 95%CI 0.76-4.54, p?=?.18). NASH, defined as per the FLIP algorithm, was not associated with mortality compared to not having NASH (HR 1.46, 95%CI 0.74-2.90, p?=?.28).
After adjustment for fibrosis, the SAF score was not associated with increased mortality in NAFLD. This finding should be corroborated in larger cohorts with similar follow-up time.