Chronic hepatitis B infection and diabetes mellitus: a double liver trouble?

BACKGROUND: Concomitant Diabetes mellitus (DM) is commonly recognized in patients with chronic hepatitis B (CHB) infection, although its impact on liver-related outcomes remains controversial. We aimed to evaluate the effect of DM on the course, management and outcome of patients with CHB. METHODS: We performed a large retrospective cohort study utilizing the Leumit-Health-Service (LHS) database. We reviewed electronic reports of 692106 LHS members from different ethnicities and districts in Israel from 2000-2019 and included patients with CHB diagnosis based on ICD-9-CM codes and supportive serology results. These were divided into two cohorts of patients with CHB and DM (CHD-DM) (N.=252) and those with CHB without DM (N.=964). Clinical parameters, treatment figures and patients' outcomes were compared and multiple regression models and Cox regression analysis were performed to investigate the association between DM and cirrhosis/HCC risk in CHB patients. RESULTS: CHD-DM patients were significantly older (49.2±10.9 vs. 37.9±14, P<0.001), and had higher rates of obesity (BMI>30) and NAFLD (47.2% vs. 23.1%, and 27% vs. 12.6%, P<0.001, respectively). Both groups had a predominance of inactive carrier (HBeAg negative infection) state, but the HBeAg seroconversion rate was significantly lower in the CHB-DM group (25% vs. 45.7%; P<0.01). Multivariable Cox regression analysis showed that DM was independently associated with increased cirrhosis risk (HR 2.63; P=0.002). Older age, advanced fibrosis and DM were associated with HCC, but DM did not reach significance (HR 1.4; P=0.12) possibly due to the small number of HCC cases. CONCLUSIONS: Concomitant DM in CHB patients was significantly and independently associated with cirrhosis and possibly with increased risk of HCC.

Human Neutrophil α-Defensins 1-3 Are Upregulated in the Microenvironment of Fibrotic Liver.

Background and Objectives: Neutrophil infiltration is an established signature of Non-Alcoholic Fatty Liver Disease (NAFLD) and Steatohepatitis (NASH). The most abundant neutrophilic peptide, alpha-defensin, is considered a new evolving risk factor in the inflammatory milieu, intimately involved in lipid mobilization. Our objective is to assess for potential association between alpha-defensin immunostains and NAFLD severity. Materials and Methods: We retrospectively investigated the liver biopsies of NAFLD/NASH patients, obtained at Hillel Yaffe Medical center between the years 2012 and 2016. Patients' characteristics were recorded, including relevant blood tests at the time of biopsy. Each biopsy was semi-quantitatively scored using NAFLD Activity Score (NAS) and NASH fibrosis stage. The biopsies were immunostained for alpha-defensin. The precipitation of alpha-defensin was correlated to NAS and fibrosis. Results: A total of 80 biopsies were evaluated: male ratio 53.2%, mean age 44.9 ± 13.2 years, 54 had fibrosis grades 0-2, and 26 were grade 3-4. Conventional metabolic risk factors were more frequent in the high-grade fibrosis group. Immunostaining for alpha-defensin disclosed higher intensity (a.u.) in grade 3-4 fibrosis relative to grades 0-2, 25% vs. 6.5%, p < 0.05, respectively. Moreover, alpha-defensin staining was nicely co-localized with fibrosis. Conclusions: In our group of NASH/NAFLD patients, higher metabolic risk profile was associated with higher fibrosis grade. Immunostaining for alpha-defensin showed patchy intense staining concordant with high fibrosis, nicely co-localized with histological fibrosis. Whether alpha-defensin is a profibrotic risk factor or merely risk marker for fibrosis must be clarified in future studies.

The impact of ethnicity on chronic hepatitis B infection course and outcome: big data analysis from Israel.

OBJECTIVES: The effect of ethnicity on chronic hepatitis B virus (CHB) infection's course and outcome has attracted little research. We aimed to compare different aspects of ethnic disparities in CHB patients, including prevalence, phenotypes, management, and outcome between two major ethnic groups in Israel. DESIGN: We conducted a large retrospective cohort study utilizing the Leumit-Health-Service database. Electronic reports of almost 700,000 members from different ethnicities and districts throughout Israel from 2000 to 2019 were reviewed. Patients' ethnicity was categorized based on the classification of the Israeli Central Bureau of Statistics into two main groups, Arabs and Jews. CHB diagnosis was based on ICD-9-CM codes and supportive serology results. Prevalence, clinical backgrounds, disease course, and patients' outcomes were compared between both groups. RESULTS: The prevalence of CHB in the Arab minority group was almost twice and a half-higher when compared to their Jewish counterparts (4.3% vs. 1.8%), but they had a lower rate of referral for HBsAg testing (7% vs. 7.9%). The Arab CHB patients were significantly younger at the time of diagnosis (37.6± 13.5 vs. 45.3± 15; P < 0.001). Male predominance was noted in both groups. The Arab patients had a higher rate of active hepatitis (HBeAg-positive and/or negative hepatitis) phase (36.4% vs. 29.8%; P = 0.01), as well as a significantly higher rate of HBeAg seroconversion (45.2% vs. 35.4%; P = 0.033). Nucleos/tide analogue treatment figures were similar, with most patients in both groups receiving a high barrier to resistance treatment. Patients' outcome was similar in both groups as the rate of hepatocellular carcinoma, cirrhosis, and advanced fibrosis (after stratification analysis) were comparable between both groups. CONCLUSION: Marked by a prominently higher prevalence of HBV infection, patients in the Arab ethnic group had a lower rate of referral for HBsAg testing but received comparable management and had a similar outcome compared to their Jewish counterparts.

Pulmonary embolism risk in hospitalized patients with nonalcoholic fatty liver disease: A case-control study.

Abundant research has associated nonalcoholic fatty liver disease (NAFLD) with atherosclerosis, but very few reports have evaluated the association between NAFLD and venous thromboembolism. We aimed to investigate the association between NAFLD and pulmonary embolism (PE) in hospitalized patients. In this retrospective case-control study, we included consecutive patients from 2 university-affiliated hospitals who were referred for CT pulmonary angiograms for a suspected PE. Patients with a history of excessive alcohol consumption, chronic liver diseases or cirrhosis were excluded. The imaging studies of the entire cohort were reviewed by 2 expert radiologists who confirmed the diagnosis of PE and examined the liver to detect and grade hepatic steatosis. Accordingly, patients were categorized into NAFLD patients and non-NAFLD controls. Patient demographics, medical history, hospitalization details as well as patients' outcomes were documented. Multivariate analysis was performed to identify predictors for developing PE and hazard ratios with corresponding 95% confidence intervals were estimated. A total of 377 patients (101 with NAFLD and 276 controls) were included. NAFLD patients had significantly higher BMI values (33.16 ±â€…6.78 vs 26.81 ±â€…5.6; P < .001) and prevalence of diabetes (41 (40%) vs 85 (30.8%); P = .03). The prevalence of PE was significantly higher in the NAFLD group (80 (79.2%) vs 147 (53.3%), P < .001). In a multivariate analysis, older age, recent surgery or trauma, active malignancy, smoking, and NAFLD (HR ratio = 4.339, P < .0001 and 95% CI = 2.196-8.572) were independently associated with PE development. Patients with NAFLD were associated with an increased risk of developing PE independent of other classical risk factors for PE.

The role of endoscopy in the evaluation of iron deficiency anemia in premenopausal women.

BACKGROUND: Men and postmenopausal women with iron deficiency anemia are routinely evaluated to exclude a gastrointestinal source of suspected internal bleeding. Iron deficiency anemia in premenopausal women is often treated with simple iron replacement under the assumption that the condition is due to excessive menstrual blood loss. OBJECTIVES: To determine the yield of endoscopy evaluations in premenopausal women with iron deficiency anemia. METHODS: Upper and lower gastrointestinal endoscopic examinations were conducted in 45 premenopausal women with iron deficiency anemia not related to gynecologic or nutritional causes. RESULTS: Forty-three of the 45 women fulfilled the entry criteria and were enrolled. Their mean age was 35 +/- 15 years and their mean hemoglobin level 9.3 +/- 2.3 g/dl. Twenty-eight upper gastrointestinal lesions were demonstrated in 24 of the 43 patients (55.8%): erosive gastritis in 12 (27.9%), erosive duodenitis in 4 (9.3%), erosive esophagitis in 3 (7.0%), hiatus hernia (with Cameron lesions) in 3 (7.0%), active duodenal ulcer in 1 (2.3%) and hyperplastic polyp (10 mm) in 1 (2.3%). Five lower gastrointestinal lesions were detected in 5 patients (16.3%): 2 (4.6%) had adenocarcinoma of the right colon, 2 (4.6%) had pedunculate adenomatous polyp > 10 mm, and 1 (2.3%) had segmental colitis (Crohn's disease). One patient (2.3%) had pathologic findings in both the upper and lower gastrointestinal tracts. CONCLUSIONS: Our findings of a gastrointestinal source of chronic blood loss in 28 of 43 premenopausal women with iron deficiency anemia (65.1%) suggest that this population will benefit from bi-directional endoscopic evaluation of the gastrointestinal tract.

Trends in incidence of colorectal cancer in Jewish and Arab populations in central Israel.

BACKGROUND/AIMS: To compare the current differences with our earlier findings on the incidence and locations of colorectal cancer (CRC) among Israeli-born Jews and Arabs living within the same central coastal region in Israel. METHODS: Data on demographics and the incidence and locations of malignancies were retrieved from hospital files of pathology-diagnosed patients with CRC throughout 1997-2003 and compared with equivalent data from 1988 to 1996. RESULTS: Of the 624 patients recently diagnosed as having CRC, 562 (90.1%) were Jews and 62 (9.9%) were Arabs (p < 0.001). The average age of the entire cohort was significantly lower since our earlier study (72.9 +/- 12.5 compared to 67.9 +/- 12.7 years, p < 0.0001). The Jewish patients were significantly younger (p < 0.0001) but the Arab patients were not. The percentage of the adenocarcinoma being located in the right colon was significantly lower (p < 0.0006) and significantly higher in the rectum (p < 0.008). The reverse was true among the Jewish patients, but not significantly. CONCLUSIONS: Both study groups were younger than those in our earlier study. The lower incidence of CRC among the Arab patients persisted over time, but the location of their adenocarcinoma changed significantly. The increased incidence of CRC in 'westernized' countries is reflected in the Jewish but not the Arab community.