Occult Liver Disease Research Articles

Occult liver disease: A multinational perspective

Occult liver disease refers to the presence of unrecognized chronic liver disease and cirrhosis. Liver disease is currently the eleventh cause of death globally, representing 4% of all deaths in the world. Alcohol consumption is the leading cause of cirrhosis globally, accounting for approximately 60% of cases. The estimated global prevalence of non-alcoholic fatty liver disease (NAFLD) is 32.4% and has been steadily increasing over the last years. Viral hepatitis B and C accounted for 1.3 million deaths in 2020.Several studies in populations at high risk of chronic liver disease (elevated liver enzymes, type 2 diabetes, excessive alcohol consumption) have found an elevated prevalence of occult liver disease. Attempts should be made to assess the prevalence of occult liver disease in Latin America, a region with one of the highest rates of metabolic diseases and excessive alcohol consumption.Screening for NAFLD in high-risk subjects and screening for excessive drinking and alcohol use disorders at every level of medical care is relevant. Efforts should also focus on the early treatment of occult liver disease to try to reduce liver disease burden and, in the case of occult viral hepatitis infection, prevent further spreading.

P1178 Detection of occult liver disease in patients with Inflammatory Bowel Disease

Abstract Background Investigation of liver disease is recommended in the ECCO Guidelines for Extraintestinal Manifestations in Inflammatory Bowel Disease (IBD). The aim of this study was to analyse the prevalence of liver disease in IBD patients, to examine the frequency of different aetiologies, and to investigate a possible correlation between the severity of liver disease and IBD. Methods Cross-sectional descriptive study including all patients with inflammatory bowel disease (IBD) of nine hospitals in Spain. The study of liver disease was carried out in two phases: patients with FIB-4 greater than 1.3 (greater than 2 in those aged 65 years or more), as well as those with APRI greater than 0.5 and/or elevated transaminases were selected as those at risk of liver disease. In the second phase, these patients underwent a medical history, comprehensive blood tests, abdominal ultrasound with SWE elastography and Fibroscan® (including transitional elastography (TE) and Controlled Attenuation Parameter (CAP)). Results In total, 5302 patients were enrolled and 1640 (31%) were identified as at risk for liver disease. The University Hospital of Burgos has completed the second phase of the study in patients diagnosed with IBD between 2010 and 2021 (n=151). Of these patients, 72.2% were male and the median age was 61 years. Ulcerative colitis (57%) was the most common type of IBD and 62% of the patients were overweight or obese, while 12% of the patients had high-risk alcohol consumption. Metabolic hepatic steatosis was the most frequent cause of liver disease (35%). Moderate/severe steatosis was detected in 44.3% of patients by CAP and 24% by ultrasound. The prevalence of advanced fibrosis was 10.6% and 12% when assessed by ET and SWE, respectively. Notably, 12.6% displayed ultrasound signs of chronic liver disease. A positive correlation was found between the ET and the SWE for liver fibrosis, with a correlation coefficient of ĸ = 0.663. On univariate analysis, an increased risk of significant fibrosis (p=0.011) and moderate/severe steatosis (p=0.00) was found only in those who were overweight or obese. However, no association with severity of liver disease was found for perianal disease, use of immunosuppressants or history of previous surgery. Conclusion The incidence of unrecognised liver disease in IBD patients is substantial, with metabolic hepatic steatosis being the most common cause. The severity of liver disease in these patients cannot be ignored, with one in ten patients having advanced fibrosis. In the univariate study, only obesity was found to correlate with the severity of steatosis and fibrosis, while IBD severity showed no significant association with liver disease severity.

NASH-RELATED CIRRHOSIS: AN OCCULT LIVER DISEASE BURDEN.

NASH-RELATED CIRRHOSIS: AN OCCULT LIVER DISEASE BURDEN.

Coffee and Tea Consumption Are Associated With a Lower Incidence of Chronic Liver Disease in the United States

Coffee drinking has been suggested to protect against liver injury, but it is uncertain whether this is of clinical significance. We examined the relationship of coffee and tea consumption with the incidence of hospitalization or death from chronic liver disease (CLD). Participants in the population-based, first National Health and Nutrition Examination Survey, 1971-1975, were asked about coffee and tea consumption, which was categorized as <1 cup (mean, 0.2 cups), 1 to 2 cups, and >2 cups per day (mean, 4.0 cups). A second analysis included persons who, in 1982-1984, were asked more detailed questions on coffee and tea drinking. Participants were followed through 1992-1993 for a hospital or death certificate diagnosis of CLD or cirrhosis (ICD-9-CM 571). Hazard rate ratios for CLD according to coffee and tea intake were calculated using Cox proportional hazards analysis. Among 9849 persons followed for a median of 19.0 years (range, 0.02-22.1), the cumulative incidence of CLD was 1.4%. In multivariate analysis, participants who drank >2 cups per day had less than half the rate of CLD as those who drank <1 cup per day (hazard ratio, 0.43, 95% confidence interval: 0.24-0.78). Protection by coffee and tea was limited to persons at higher risk for liver diseases from heavier alcohol intake, overweight, diabetes, or high iron saturation. Among 9650 participants who provided detailed drink information in 1982-1984, intake of regular ground coffee and of caffeine was associated with lower incidence of CLD. Coffee and tea drinking decreases the risk of clinically significant CLD.

Sensitivity and Specificity of Tests of Liver Injury

Editor - In the recent “Outpatient Practice Management Tips: Tests of Liver Injury”, Musana et al.1 make a broad statement that “All tests of liver injury are neither highly sensitive nor specific.” This statement, by itself, is probably not accurate, nor helpful in the practical sense. The following quotes from Harrison's Principles of Internal Medicine textbook illustrate the problems with your statement regarding liver disease and tests of liver function: “Diagnosis of liver disease is greatly aided by the availability of reliable and sensitive tests of liver injury and function.”2 “To increase both the sensitivity and the specificity of laboratory tests in the detection of liver disease, it is best to use them as a battery.”3 Thus, I would rather the statement read “No single test of liver injury is neither highly sensitive nor specific.” Harrison's Principles of Internal Medicine is clear in the basic wisdom of diagnosing liver injury that these tests are highly sensitive when used in a battery and goes on to add: “When more than one of these tests provide abnormal findings, or the findings are persistently abnormal on serial determinations, the probability of liver disease is high. When all test results are normal, the probability of missing occult liver disease is low.”3

One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation.

Living donor liver transplantation allows an increasing number of patients with end-stage liver disease the opportunity for effective treatment in the face of a critical shortage of cadaveric organs. Hepatic steatosis decreases functional graft mass and may contribute to graft dysfunction. Screening liver biopsy allows accurate quantitation of hepatic fat, but is an invasive procedure that is not universally employed in the evaluation of living donors. We studied 100 consecutive prospective right lobe living donors, all evaluated with liver biopsy, imaging studies, and various clinical parameters. The accuracy and predictive value of body mass index (BMI) and imaging were compared with biopsy in determining the amount of hepatic fat. There were no complications to biopsy, with 33% showing some degree of steatosis. BMI correlated only weakly with biopsy, with 73% of overweight (BMI > 25) donors having little or no hepatic fat. Imaging was only 12% sensitive to small amounts (5% to 10%) of fat, with increasing sensitivity to more severe steatosis. Imaging diagnosed steatosis in 2 donors without hepatic fat and failed to identify a candidate denied with biopsy-proven 30% steatosis. Conversely, 9% of candidates with BMIs of 25 or less had 10% or greater steatosis. Moreover, three candidates were denied surgery because biopsy detected occult liver disease. Accurate quantification of hepatic fat is not afforded by BMI and imaging studies alone. Screening liver biopsy has a low complication rate and may serve to increase donor safety. Biopsy is essential in identifying donor grafts at risk for poor recipient outcome while maximizing the donor pool.

Pancreatic Cancer: Adjuvant radiotherapy and chemotherapy for biliary and pancreatic cancer

Due to the limited efficacy of surgery in pancreatico-biliary cancer, perioperative treatment modalities are of high clinical interest. Adjuvant chemoradiation with protracted infusion 5-FU for these tumors is an attractive direction for continued clinical research and may increase local control. Improved local control may influence survival as has been demonstrated by the results of adjuvant chemoradiation for operable rectal cancer. Newer combinations of chemotherapy and external beam radiotherapy (ExBRT) will need to be tested. The results of combined modality therapy indicate that increased normal tissue reactions occur and caution must be exercised during treatment especially in the areas of nutrition and fluid balance. New treatment strategies with electron beam IORT are also investigating higher doses of radiotherapy than those achieved with ExBRT alone in order to achieve better permanent tumor eradication. Data from our institution have demonstrated the safety of aggressive preoperative chemoradiation, surgical resection and IORT. Prophylactic hepatic and whole abdominal chemoradiation for occult liver disease needs further testing in clinical trials, since the liver is the single most frequent site of failure outside the primary site.

Periportal halo: a CT sign of liver disease.

Periportal halos are defined as circumferential zones of decreased attenuation identified around the peripheral or subsegmental portal venous branches on contrast-enhanced computed tomography (CT). These halos probably represent fluid or dilated lymphatics in the loose areolar zone around the portal triad structures. While this CT finding is nonspecific, it is abnormal and should prompt close scrutiny of the liver in search of an underlying etiology. Periportal halos which may be due to blood are commonly seen in patients with liver trauma. Periportal edema may cause this sign in patients with congestive heart failure and secondary liver congesion, hepatitis, or enlarged lymph nodes and tumors in the porta hepatis which obstruct lymphatic drainage. This CT sign has also been observed in liver transplants (probably secondary to disruption and engorgement of lymphatic channels) and in recipients of bone marrow transplants who might develop liver edema from microvenous occlusive disease. While the precise pathophysiologic basis of periportal tracking has not been proven, it represents a potentially important CT sign of occult liver disease.

Plasma bile salt levels in patients presenting with generalised pruritus: an improved indicator of occult liver disease.

Fasting plasma bile salt concentrations were measured in 26 patients presenting to a Skin Department who had generalised pruritus without primary skin disease, as part of a screening investigation for systemic causes of pruritus. The results were compared with conventional tests of hepatic function. Plasma-conjugated cholate measurements identified all patients with hepatobiliary disease. Conventional liver function tests were abnormal in these patients but also in five patients with no other evidence of hepatic dysfunction. Fasting conjugated-cholate measurements offer a useful screening test for identifying hepatobiliary disease in patients presenting with generalised pruritus.

Assessment of liver function using fasting bile salt concentrations in psoriasis prior to and during methotrexate therapy

To determine if fasting bile salt concentrations are an accurate indicator of pre-existing and methotrexate-induced liver disease in patients with psoriasis, the plasma concentrations of conjugated cholate, chenodeoxycholate and sulpholithocholate were measured in 18 patients being assessed for methotrexate therapy and 21 receiving long-term therapy. The results were compared with other liver function tests and liver histology. The liver function tests were a poor indicator of occult liver disease and, whilst fasting bile salts appeared more sensitive, they were still unreliable and inadequate for the clinical assessment of the hepatopathy associated with psoriasis. The reasons for these discrepancies are discussed.

Admission screening for hepatitis B surface antigen in a university hospital.

Upon admission to the hospital, 7,984 patients were tested for hepatitis B surface antigen (HBsAg) by radioimmunoassay. Seventy-one patients had sera positive for HBsAg. Twenty-four (34%) were possible asymptomatic carriers in whom liver function was not further evaluated and occult liver disease could not be excluded: 16 (23%) had either a previous history or admitting diagnosis of hepatic dysfunction; eight(11%) had occult liver disease, revealed after HBsAg antigenemia was discovered; and 25 (34%) were unsuspected asymptomatic carriers whose liver function was normal. We concluded that screening for HBsAg was an effective preventive tool in identifying HBsAg-positive patients. Screening solely for the detection of occult liver disease is not an effective method because of the high cost. Perhaps because of the unsolicited nature of this data collection, screening for HBsAg was not clinically effective for the majority of patients, as evidenced by the high incidence of inadequate clinical evaluations and lack of serologic follow-up. Proposals to alleviate ineffectiveness are discussed.

Chronic active hepatitis in hepatitis B surface antigen (HBsAg) carriers. The need for liver biopsy

Four cases of chronic active hepatitis were found in hepatitis B surface antigen (HB_sAg) positive blood donors. Despite minimal symptoms, the full histologic spectrum of chronic hepatitis was seen. Because clinically occult liver disease can be histologically severe, liver biopsy is indicated when liver enzyme levels are persistently abnormal in long-term HB_sAg carriers. (<i>JAMA</i>237:50-51, 1977)

Chronic Active Hepatitis in Hepatitis B Surface Antigen (HBsAg) Carriers

Four cases of chronic active hepatitis were found in hepatitis B surface antigen (HBsAg) positive blood donors. Despite minimal symptoms, the full histologic spectrum of chronic hepatitis was seen. Because clinically occult liver disease can be histologically severe, liver biopsy is indicated when liver enzyme levels are persistently abnormal in long-term HBsAg carriers.

Direct Serum Bilirubin and the Sulfobromophthalein Test in Occult Liver Disease

When a sensitive method for measuring direct serum bilirubin (DB) was used, a third of the patients with liver or biliary tract disease had elevated DB levels, but normal levels of total serum bilirubin (TB). The correlation of DB and sulfobromophthalein (BSP) retention was studied because DB and BSP are cleared through the same hepatic pathway. Our findings support the clinical and chemical validity of DB measurements as an index of occult liver disease.