Knut Stokkeland

Improved prognosis for patients hospitalized with esophageal varices in Sweden 1969–2002

Liver cirrhosis may be complicated by the development of esophageal varices. The treatment of esophageal varices has changed radically during the last 30 years. Our aim was to study whether the prognosis for patients with esophageal varices had improved in Sweden between 1969 and 2002. We linked register data from the Hospital Discharge Register and from the Causes of Death Register at The National Board of Health in Sweden between 1969 and 2002 to identify and follow‐up all patients with esophageal varices according to International Classification of Diseases—8, —9, and —10. There were 12,281 patients hospitalized with esophageal varices, and for all patients there was an increase in the 5‐year survival in the years between 1969 and 1979 as opposed to the years between 1990 and 2002. Better survival occurred for women compared with men, for younger patients compared with older, and for patients hospitalized in the latest decade compared with the earlier decades. We found a significant decrease in the mortality caused by esophageal varices during the years studied but no decrease attributable to other causes. In conclusion, mortality for patients hospitalized with esophageal varices in Sweden decreased between 1969 and 2002. The decrease is seen for both 1‐ and 5‐year mortality, and this suggests that the use of new treatment strategies both for acute variceal hemorrhage and secondary prophylaxis has had an impact on prognosis. (HEPATOLOGY 2006;43:500–505.).

Morbidity and mortality in liver diseases in Sweden 1969–2001 in relation to alcohol consumption

Objective. In Sweden, there is stable or slightly increased total alcohol consumption but a decrease in mortality in liver disease. The aim of the study was to determine the temporal relation between alcohol-related liver disease morbidity and mortality and type of alcohol beverage consumption. Material and methods. Data on patients with liver disease from the Swedish Hospital Discharge Register and from the Causes of Death Register between 1969 and 2001were analysed. Data on the registered sales of the different beverages were taken from the Swedish State Monopoly. Results. Liver disease mortality increased from 1969 to 1976, coinciding with the increase in sales of spirits. Both mortality and spirits sales decreased thereafter, whereas there was no decrease in beer or wine sales. Hospitalization rates were reduced after 1987. Depending on age and gender, there was a 30–80% 5-year mortality rate following discharge. Among men, but not among women, differences in the alcohol and non-alcohol-related liver diagnoses in the Hospital Discharge Register and in the Cause of Death Register were sometimes recorded in the same patient. Conclusions. There was a reduction in hospitalization rates and mortality in liver diseases, and the reduction in mortality in liver diseases in Sweden from 1969 to 2001 seems to be associated with sales of spirits. Patients hospitalized for liver disease have a poor prognosis. There were difficulties in differentiating between alcohol and non-alcohol liver diseases.

Adverse outcomes of pregnancy in women with non‐alcoholic fatty liver disease

Non‐alcoholic fatty liver disease (NAFLD) is considered the most common liver disease in the world, but little is known about its potential association with pregnancy outcomes. We aimed to investigate pregnancy outcomes in NAFLD.

Alcohol consumption in patients with primary sclerosing cholangitis

AIM To assess the alcohol drinking patterns in a cohort of primary sclerosing cholangitis (PSC) patients and the possible influence on the development of fibrosis. METHODS Ninety-six patients with PSC were evaluated with a validated questionnaire about a patients 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. RESULTS 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 μmol/L vs 0.33 μmol/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). CONCLUSION 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.

Increased Risk of Esophageal Varices, Liver Cancer, and Death in Patients With Alcoholic Liver Disease

BACKGROUND AND AIMS During the last decades, a multitude of different treatments for chronic liver disease have been introduced. New surveillance programs have been established to detect esophageal varices and liver cancer. The aims of our study were to assess whether the prognosis for patients hospitalized with liver diseases between 1969 and 2006 had improved and to study the differences in mortality and complications between patients with alcoholic liver disease and nonalcoholic liver diseases. METHODS We used the Swedish Hospital Discharge Register and Cause of Death Register at the National Board of Health and Welfare in Sweden between 1969 and 2006 to identify and follow-up a cohort of patients with liver disease according to the International Classification of Diseases-8, -9, and -10. RESULTS There were 36,462 patients hospitalized with alcoholic and 95,842 with nonalcoholic liver diseases. The main finding was that patients hospitalized with alcoholic liver disease had an increased mortality risk, compared to patient with nonalcoholic liver disease, 1.89 (1.85 to 1.92). In addition, the patients with alcoholic liver disease had an increased risk for esophageal varices and liver cancer. There was a reduced risk for hospitalization with esophageal varices for patients with nonalcoholic liver disease up to 1998. CONCLUSIONS We found that the prognosis for patients hospitalized with chronic liver diseases had not improved. Patients with alcoholic liver disease have an increased risk of complications, which suggest that the disease is more aggressive and are in need of closer follow-up than other chronic liver diseases.

The underreporting of hepatocellular carcinoma to the Cancer Register and a log-linear model to estimate a more correct incidence

The Cancer Register (CR) in Sweden has reported that the incidence of primary liver cancer (PLC) has slowly declined over the last decades. Even though all cancers, irrespective of diagnostic method, should be reported to the CR, the PLC incidence may not reflect the true rate. Improved diagnostic tools have enabled diagnosis of hepatocellular carcinoma based on noninvasive methods without histological verification, possibly associated with missed cancer reports or misclassification in the CR. Our objective was to study the completeness and assess the underreporting of PLC to the CR and to produce a more accurate estimate based on three registers. The CR, the Cause of Death Register, and the Patient Register were investigated. Differences and overlap were examined, the incidence was estimated by merging data from the registers, and the number reported to none of the registers was estimated using a log‐linear capture‐recapture model. The results show that 98% of the PLCs reported to the CR were histologically verified; 80% were hepatocellular carcinoma and 20% were intrahepatic cholangiocarcinoma. Unspecified liver cancer decreased over time and constituted <10% of all reported liver cancers. The CR may underestimate the liver cancer incidence by 37%‐45%, primarily due to missed cancer reports. The estimated annual number of liver cancers increased over time, but the standardized incidence was stable around 11 per 100,000. Hepatitis C‐associated liver cancer increased and constituted 20% in 2010. Conclusion: There was an underreporting of PLC diagnosed by noninvasive methods; the incidence was considerably higher than estimated by the CR, with a stable incidence over time; reporting needs to improve and combining registers is recommended when studying incidence. (Hepatology 2017;65:885‐892).

Increased risk of preterm birth in women with autoimmune hepatitis – a nationwide cohort study

The aim of our study was to investigate the risks of pregnancy and childbirth complications in women with autoimmune hepatitis compared to the population controls.

Alcohol intake measured by phosphatidylethanol in blood and the lifetime drinking history interview are correlated with the extent of psoriasis.

Background: Psoriasis has been reported to be associated with alcohol consumption. Objective: To investigate the level of alcohol intake in individuals with psoriasis and correlate intake with the extent of disease and pruritus. Methods: Twenty-nine outpatients (15 females and 14 males) with stable chronic plaque psoriasis of moderate severity were recruited. The Psoriasis Area and Severity Index (PASI) and the degree of pruritus (visual analogue scale) were compared with measures of drinking habits as determined by the Lifetime Drinking History (LDH), the Alcohol Use Disorders Identification Test and whole-blood phosphatidylethanol (PEth), an alcohol-specific biomarker. Results: The majority of patients were social drinkers with moderate alcohol consumption as determined by PEth and LDH. Alcohol consumption correlated significantly with the PASI score. There was no correlation between alcohol use and pruritus. Conclusion: The level of alcohol consumption is correlated with the extent of psoriasis.

Increased risks of epilepsy and neuropsychiatric diseases in children of mothers with alcoholic liver disease.

Pregnancy in women with liver disease may increase the risk of fetal complication. Data on disease frequencies in children born to mothers with alcoholic liver disease do not exist, although we do know that prenatal alcohol exposure may affect the fetus negatively.

Mothers with Alcoholic Liver Disease and the Risk for Preterm and Small-for-gestational-age Birth

AIMS To study pregnancy outcome in women with alcoholic liver disease (ALD). METHODS Using the Swedish nation-wide Patient and Medical Birth Registers, we investigated risk of adverse pregnancy outcome in 720 women diagnosed with ALD before and 1720 diagnosed after birth and compared them with 24 460 population-based control births. RESULTS Women with ALD diagnosed before or after birth were generally of higher age and body mass index, more likely to smoke cigarettes during pregnancy and to have a low socio-economic status compared with controls. Women diagnosed with ALD before birth had an increased risk of moderately and very preterm birth, adjusted odd ratio (OR) = 1.53 (95% confidence interval (CI): 1.37-1.72 and 1.15-2.06 95%), respectively. Infants of mothers with ALD before birth were more often small-for-gestational age, adjusted OR = 1.22 (95% CI: 1.05-1.43), and were at increased risk for low Apgar scores (<7) at 5 min, adjusted OR = 1.49 (95% CI: 1.15-1.92) compared with controls. Similar associations with slightly lower-risk estimates were found among women diagnosed with ALD after birth. CONCLUSIONS ALD is associated with adverse-birth outcomes, highlighting the importance of screening women for alcohol dependence in antenatal care.