Increasing Prevalence and Racial Disparity of Alcohol-Related Gastrointestinal and Liver Disease During the COVID-19 Pandemic: A Population-Based National Study.

OBJECTIVES: One consequence of social distancing during the coronavirus disease 2019 (COVID-19) pandemic was an increase in alcohol use disorders. We postulated that this would be associated with a rise in alcohol-related gastrointestinal and liver disease. METHODS: Using Explorys Inc., an aggregate of electronic health records from US health care systems from 1999 to June 2021, we identified patients with "alcoholic hepatitis," "inflammation of pancreas caused by alcohol," and "alcoholic gastritis," based on Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). We compared patients utilizing health care during the pandemic to those before it. RESULTS: We identified 8,445,720 patients treated from June 21, 2020 to June 20, 2021 ("COVID cohort") and 65,587,860 patients treated before this ("pre-COVID cohort"). African American patients were more likely to be treated for all causes during COVID-19 [odds ratio (OR): 1.65; P <0.0001]. Alcoholic hepatitis (OR: 2.77), alcoholic pancreatitis (OR: 3.67), and alcoholic gastritis (OR: 1.70) (for each, P <0.0001) were more likely in all patients in the COVID cohort. African Americans in the COVID cohort were more likely to be diagnosed with alcoholic hepatitis (OR: 2.63), alcoholic pancreatitis (OR: 2.17), and alcoholic gastritis (OR: 3.09) [for each, P <0.0001]. CONCLUSIONS: The prevalence of alcohol-related liver and gastrointestinal disease increased during COVID-19. We suspect these increases are associated with increased alcohol use disorder resulting from the stress of social isolation. These data suggest COVID-19 disproportionately affected African Americans in overall health care utilization and increased burden of alcoholic gastrointestinal and liver disease.

Continuing Medical Education Questions: May 2021.

Article Title: ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury.

Epidemiology of Autoimmune Hepatitis (AIH) in the United States Between 2014 and 2019: A Population-based National Study.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a chronic, inflammatory disease of the liver with increasing prevalence. However, limited epidemiological data exist for the prevalence of AIH in the United States. We used a large database to describe the prevalence of AIH in the United States and the autoimmune diseases associated with it. APPROACH AND RESULTS: Data was collected from a commercial database (Explorys Inc., Cleveland, OH), an aggregate of Electronic Health Record data from 26 major integrated health care systems in the United States. We identified a cohort of patients with a diagnosis of AIH from April 2014 to April 2019 based on a Systemized Nomenclature of Medicine-Clinical Terms and calculated the prevalence of AIH. Of the 37,161,280 individuals active in the database from April 2014 to 2019, we identified 11,600 individuals with a diagnosis of AIH with an overall prevalence rate of 31.2/100,000. The prevalence of AIH was increased in females compared with males [odds ratio (OR)=3.21, P<0.0001], elderly (aged above 65 y) compared with adults (aged 18 to 65 y) and children (aged below 18 y) (OR=2.51, P<0.0001) and whites compared with African Americans, Asians, and Hispanics (OR=1.12, P<0.0001). Moreover, patients with AIH were more likely to have Sjögren syndrome, systemic lupus erythematosus, ulcerative colitis, celiac disease, rheumatoid arthritis, Crohn's disease, and autoimmune thyroiditis as compared with patients without AIH. CONCLUSIONS: We found that the estimated prevalence of AIH in the United States is 31.2/100,000, which is comparable to the reported prevalence of AIH in Europe. We confirmed that AIH has a strong association with other autoimmune diseases studied in the literature.

ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries.

Clinicians are required to assess abnormal liver chemistries on a daily basis. The most common liver chemistries ordered are serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin. These tests should be termed liver chemistries or liver tests. Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels. Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels. The majority of bilirubin circulates as unconjugated bilirubin and an elevated conjugated bilirubin implies hepatocellular disease or cholestasis. Multiple studies have demonstrated that the presence of an elevated ALT has been associated with increased liver-related mortality. A true healthy normal ALT level ranges from 29 to 33 IU/l for males, 19 to 25 IU/l for females and levels above this should be assessed. The degree of elevation of ALT and or AST in the clinical setting helps guide the evaluation. The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency. In addition, a history of prescribed and over-the-counter medicines should be sought. For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken. Total bilirubin elevation can occur in either cholestatic or hepatocellular diseases. Elevated total serum bilirubin levels should be fractionated to direct and indirect bilirubin fractions and an elevated serum conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings. A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible.

A case of complete resolution of gastric varices.

BACKGROUND: A 49-year-old woman with hepatitis C and peptic ulcer disease presented to the emergency department after an onset of sudden massive hematemesis. She had a history of alcohol abuse, but denied any recent excessive drinking. INVESTIGATIONS: Physical examination, laboratory investigations including complete blood cell counts and liver function tests, esophagogastroduodenoscopy, abdominal angiography and venography, CT scans of the abdomen and pelvis. DIAGNOSIS: Gastric variceal hemorrhage, severe portal hypertensive gastropathy, splenic vein thrombosis. MANAGEMENT: Blood transfusion, splenic artery embolization and balloon-occluded retrograde transvenous obliteration of gastric varices. Immediate postprocedural CT scans of the abdomen, with repeat imaging 30 months later.

Transmission of human immunodeficiency virus and hepatitis C virus through liver transplantation.

In November 2007, a liver transplant recipient was confirmed to have human immunodeficiency virus (HIV) and hepatitis C (HCV) infection after the organ procurement agency notified our institution that the donor has been HIV and HCV positive. We reviewed medical records and the collected blood sample results for HIV and HCV testing. A 66 year old female with nonalcoholic steatohepatitis cirrhosis underwent liver transplantation. The donor was a male who had sex with men who received multiple blood transfusions during resuscitation. Preoperative testing for HIV and HCV antibodies were negative for both donor and recipient. Ten months later, HIV and HCV were identified with nucleic acid testing in the recipient and in the stored donor sera. This is the first reported case of HIV transmission from solid organ transplantation in 20 years, and the first ever reported case of simultaneously transmitted HIV and HCV. The current case represents a high risk donor with newly-acquired HIV and HCV who transmitted the diseases during the window period of the infections. In this era of organ shortages one option would be avoidance of any high-risk donor organs. Another option would be to continue the use of such organs with appropriate informed consent, acknowledging the limitations of current screening tests for HIV and HCV. This report should serve as a wake-up call to the transplant community to consider revamping organ donor screening for HIV and HCV using nucleic acid testing as well as reconsidering the ongoing use of high-risk donors.

Acute sinusoidal obstruction syndrome after 6-thioguanine therapy for Crohn's disease.

6-Thioguanine (6-TG), the active metabolite of 6-mercaptopurine and its prodrug azathioprine, are thought to be responsible for clinical efficacy in the treatment of active Crohn's disease. Its use as a therapeutic agent for inflammatory bowel disease (IBD) has been limited to patients who are resistant to or intolerant of other antimetabolites. Short-term experience with this agent has not demonstrated an increased incidence of hematologic or hepatic toxicity; however long-term safety data are scarce. We herein report a patient who developed acute sinusoidal obstruction syndrome after 14 months of successful thioguanine treatment. This is the first report of such a complication in an adult treated with 6-TG for active Crohn's disease.

Autoimmune hepatitis associated with the use of black cohosh: a case study.

Herbal remedies generate more than 1.8 billion dollars in annual sales in the United States. Herbal products have been associated with a wide spectrum of hepatic toxicities. With the recent Women's Health Initiative Study demonstrating increased risk of breast cancer and cardiovascular events associated with hormone therapy, many women may resort to herbal remedies for persistent menopause symptoms. We report a case of autoimmune hepatitis likely triggered by the use of black cohosh (Actaea racemosa), an agent marketed to treat menopause symptoms. Given this case report, we recommend close monitoring of women using this herbal preparation.

The effect of immunosuppressive regimens on the recurrence of primary biliary cirrhosis after liver transplantation.

Recurrence of primary biliary cirrhosis (PBC) has been described in liver transplant recipients. Type of immunosuppression has been reported to influence the frequency of recurrence. The aim of this study is to evaluate the occurrence and pattern of recurrent PBC in our liver transplant recipients and determine any association of immunosuppressive agents with its recurrence. Patients who underwent orthotopic liver transplantation (OLT) for PBC were identified from the University of Chicago Liver Transplant Database. Recurrent PBC was diagnosed based on specific pathological criteria. Of 46 patients who underwent OLT for PBC between 1984 and 2000, a total of 7 patients (15%) were diagnosed with recurrent PBC at a median of 78 months (range, 27 to 120 months) after OLT. Forty-three percent of patients were administered cyclosporine, whereas 57% were administered tacrolimus before disease recurrence. Rates of recurrence were not different between patients maintained on cyclosporine therapy (16%) compared with those maintained on tacrolimus therapy (18%; P = 1.0). There also was no difference in frequency of rejection episodes or duration of corticosteroid therapy between those who did and did not have recurrent PBC. In conclusion, recurrent PBC developed in a small number of patients 2 years or longer after OLT. In our population, there was no difference in recurrence rates between those administered cyclosporine or tacrolimus for immunosuppression.

The safety and outcome of joint replacement surgery in liver transplant recipients.

A small group of patients may require total hip arthroplasty, total knee arthroplasty, or other joint replacement surgery after OLT for osteoporotic fractures, osteonecrosis, and osteoarthritis. Although arthroplasty is safe in the general population, its safety in liver transplant recipients is unclear. The aim of the study was to determine the safety and outcome of joint replacement surgery in our liver transplant recipients. A retrospective analysis was performed on all liver transplant recipients who had total joint arthroplasty at a single teaching institution between 1986 and 2002. Data regarding major intraoperative and postoperative complications was obtained from the medical charts and a hospital-based computer system. Of over 1,200 liver transplant recipients, we identified 7 patients who underwent 12 total arthroplasties (8 knee, 3 hip, 1 ankle). Joint replacements were performed electively for osteonecrosis (5 of 12) and osteoarthritis (5 of 12), whereas two hip arthroplasties were performed emergently for fractures. All patients with osteonecrosis or hip fracture had been treated with prolonged corticosteroids. There were no deaths or major complications in the intraoperative and postoperative periods. On long-term follow-up, no patients have had pain, dislocation, or infection in the postsurgical joint. No joint revision surgery has been required. In conclusion, a small number of stable liver transplant recipients at our institution underwent joint replacement surgery without major short-term or long-term complications. Our study suggests that joint replacement surgery may be safely and successfully performed in this population, although larger, randomized, prospective trials are needed to confirm our findings.

Varicella infection following varicella vaccination in a liver transplant recipient.

Varicella infection may result in significant morbidity and mortality in patients who have received an orthotopic liver transplant (OLT). It is unclear if vaccinating these patients against varicella-zoster virus (VZV) infection is safe or effective. We report on a liver transplant recipient with no prior history of VZV infection who was given the varicella vaccine after an indirect VZV exposure. The patient was subsequently hospitalized twice for treatment of cutaneous varicella infection. We will discuss VZV infection, particularly in relation to liver transplantation, and review the prophylaxis and management of VZV infection after OLT.

Duplex Doppler ultrasound of the hepatic artery in patients with acute alcoholic hepatitis.

BACKGROUND: Acute alcoholic hepatitis (AAH) is a clinical diagnosis associated with increased hepatic artery diameter and flow. Duplex Doppler ultrasound (DDU) has been shown to accurately measure arterial flow in both liver and kidney transplant patients. The authors conducted a blinded, controlled study to evaluate the accuracy of measuring hepatic artery parameters with DDU in diagnosing AAH. STUDY: Duplex Doppler ultrasound was performed by an investigator, blinded to group makeup, on 22 consecutive hospital inpatients with the clinical diagnosis of AAH. The diagnosis of AAH was based on specific criteria, including the following: recent alcohol abuse, hyperbilirubinemia, prolonged prothrombin time, leukocytosis, hepatomegaly, hepatic bruit, and marked redistribution of isotope on 99mTc-sulfur colloid liver-spleen scan. Controls were 12 cirrhotic patients without AAH and 17 healthy volunteers. Duplex Doppler ultrasound measurements were obtained most consistently from the proximal right hepatic artery. Measured parameters included the following: peak systolic velocity (PSV); resistive index = (PSV - end diastolic velocity [EDV])/PSV; pulsatility index = (PSV - EDV)/mean velocity; and hepatic artery diameter. RESULTS: The mean hepatic artery diameter was significantly larger in patients with AAH (3.55 +/- 0.72 mm) than in patients with cirrhosis (2.75 +/- 0.69 mm; p = 0.003) and healthy controls (2.68 +/- 0.69 mm; p = 0.001). The mean PSV was significantly higher in patients with AAH (187 +/- 52 cm/s) compared with cirrhotic (67 +/- 51 cm/s) and healthy (66 +/- 51 cm/s) controls (p = 0.0001). The mean resistive index was lower in AAH patients (0.60 +/- 0.11) compared with cirrhotic (0.69 +/- 0.10; p value was not significant) and healthy controls (0.72 +/- 0.11; p = 0.004). The mean pulsatility index was lower in AAH patients (1.04 +/- 0.47) compared with cirrhotic (1.36 +/- 0.45; p value was not significant) and healthy controls (1.53 +/- 0.45; p = 0.01). CONCLUSIONS: In the appropriate clinical setting, an elevated hepatic artery diameter or PSV measurement is suggestive of AAH. Duplex Doppler ultrasound offers a noninvasive test to assist in the diagnosis of AAH.