TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.

SARS-CoV-2 vaccination and risk of severe COVID-19 outcomes in patients with autoimmune hepatitis.

BACKGROUND: Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. PATIENTS AND METHODS: We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. RESULTS: We included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10-0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11-0.35). CONCLUSIONS: SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.

Post COVID-19 irritable bowel syndrome.

OBJECTIVES: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. DESIGN: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. RESULTS: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. CONCLUSION: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. TRIAL REGISTRATION NUMBER: NCT04691895.

Determination of the upper limits of normal serum alanine aminotransferase (ALT) level in healthy Turkish population.

Background and Aim: Recent studies have reported that the widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN<40U/L) is high for the healthy population. We aimed to find the correct ULN level for men and women in a presumed healthy liver population group. Materials and Methods: The data of 7410 healthy subjects visiting the check-up clinics were retrospectively analysed in this study. Patients were divided in to "healthy liver group" (n=2694) and "high-risk liver group" (n=4716) based on fatty liver on ultrasound, existing of chronic liver disease, ongoing significant alcohol consumption, diabetes mellitus and dyslipidaemia. Receiver operating characteristic (ROC) curves were generated and the area under the curve (AUC) was calculated at the 95th percentiles for both men and women. Results: The AUC score of ALT for men was 0.92, and the ULN for the serum ALT in men was found as 32.10 U/L (sensitivity of 0.89, specificity 0.85). The AUC score of ALT for women was 0.90, and the ULN for serum ALT was found as 23.15 U/L (sensitivity of 0.90, the specificity of 0.88). Conclusion: ULN for serum ALT level should be lowered and different cut-off values should be used for men (32.10 U/L) and women (23.15 U/L).

Regular coffee intake improves liver enzyme levels and liver histology in patients with chronic alcohol consumption, non-alcoholic fatty liver and non-alcoholic steatohepatitis: Report of 259 cases.

Background and Aim: This study aims to investigate the effects of chronic coffee consumption (>5 years) and type of coffee in non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFLD) and patients who have regular alcohol consumption. Materials and Methods: In this study, 158 healthy individuals and 101 patients with histologically proven NASH were enrolled. The daily amount of coffee intake, amount of alcohol use and type of coffee were calculated for all patients. The degree of steatosis and fibrosis was analyzed by transient elastography and liver ultrasound in non-NASH and by liver biopsy in NASH patients. Results: Patients with a history of coffee consumption (n=132) had lower liver enzyme levels compared to the non-coffee group (n=127) (p=0.001). Serum ALT level was significantly lower [ALT: 21.2±11.7 U/L vs. 56.4±15.6 U/L (p=0.004)], and the liver histopathology was significantly better for patients with a coffee consumption of daily for >5years (p=0.045 for fibrosis score for NASH, p=0.036 for LSM and p=0.015 for CAP measurements for the non-NASH patient). Conclusion: Coffee seems to have a positive protective effect on liver histology and liver enzyme levels in healthy individuals, in patients with chronic alcohol consumption, NAFLD and NASH. These results are more prominent in patients who drink coffee on a regular daily base for more than five years.

Admissions for hepatitis B reactivation in patients receiving immunosuppressive therapy remain unchanged from 1999 to 2014.

BACKGROUND: Reactivation of hepatitis B virus (HBV) replication in patients with chronic or past HBV infection receiving immunosuppressive therapy (IST) can be prevented through HBV screening and prophylactic antiviral therapy. We aimed to determine the occurrence of severe HBV reactivation secondary to IST in the era of HBV nucleos/tide analogs, the implicated IST, and outcomes. METHODS: We conducted a retrospective chart review of adult patients who were HBsAg+ and HBV DNA+ and had received IST within 90 days of admission to our hospital. RESULTS: Of 1446 patients with HBV diagnosis code admitted from 1999 to 2014, 17 had HBV reactivation, 8 of whom were admitted after 2009. Nine patients had hematologic conditions, three solid organ transplants, one hepatocellular carcinoma, and four other nonmalignant diseases. Implicated IST included chemotherapy, prednisone, antirejection therapies, budesonide, and a JAK-2 inhibitor. Three patients were screened for HBV prior to IST, but none was given antiviral prophylaxis. Six patients were initially admitted to other facilities, only two were tested for HBV, and one was started on antiviral therapy prior to transfer. At admission to our hospital, all 17 were HBsAg+ and HBV DNA+. Despite antiviral therapy, five patients decompensated, three died, and two had a liver transplant. CONCLUSION: Severe HBV reactivation requiring hospital admission continues to occur because HBV screening was not performed and a prophylactic antiviral not given to those who tested positive. HBV reactivation can occur in a variety of clinical settings and in association with drugs not considered to be highly immunosuppressive.

Telbivudine in liver transplant recipients: Renal protection does not overcome the risk of polyneuropathy and myopathy.

The recently reported benefit of telbivudine for renal function has not been systematically studied in long-term liver transplantation (LT) recipients who are at high risk for renal impairment. We aimed to examine whether switching lamivudine therapy to telbivudine could improve renal function in LT recipients who have impaired renal function. This single-center, prospective cohort study enrolled LT recipients who were on lamivudine for hepatitis B virus (HBV) prophylaxis and who had renal impairment for at least 1 year. Lamivudine was switched to telbivudine. The primary outcome was to evaluate the change in renal function at weeks 12, 24, 36, and 48. The secondary outcomes were to assess the efficacy of telbivudine for HBV prophylaxis and the safety profile of telbivudine in the posttransplant setting. After 45 patients were enrolled, the study was terminated early because of increased rates of polyneuropathy/myopathy. During telbivudine treatment (median, 64 weeks), estimated glomerular filtration rate (eGFR) increased in 34 patients (76%). The improvement in renal function was prominent after 24 weeks of telbivudine treatment. Telbivudine was effective as prophylaxis against HBV recurrence. Twenty-six patients (58%) developed polyneuropathy and/or myopathy. The 1-year estimated incidence of polyneuropathy/myopathy was 28%. Diabetes was the strongest predictor of polyneuropathy/myopathy (hazard ratio, 4.13; 95% confidence interval, 1.49-11.50; P = 0.007). In conclusion, although it seems to have a favorable effect in the improvement of renal function and seems to be effective in the prevention of HBV recurrence, the high risk of polyneuropathy and myopathy hampers the use of telbivudine in LT recipients.

Outcomes of patients with chronic hepatitis B who do not meet criteria for antiviral treatment at presentation.

BACKGROUND & AIMS: The availability of potent, well-tolerated, oral antivirals with low rates of resistance has led many experts to recommend liberalizing indications for the treatment of chronic hepatitis B (CHB). This study sought to determine the rate of transitions to an active phase of infection, the frequency of treatment initiation, and the clinical outcomes of patients with CHB who did not meet treatment criteria at presentation. METHODS: We reviewed medical records of patients with CHB, seen in the liver clinics at the University of Michigan Health System from 1999 through 2010, who did not receive antiviral treatment within 6 months of presentation. We collected data on transitions between different phases of CHB, hepatitis B e antigen (HBeAg) seroconversion, loss of hepatitis B surface antigen (HBsAg), and the development of hepatocellular carcinoma (HCC). Data analyses were censored or truncated at the time of treatment initiation or development of an outcome. RESULTS: Of the 234 patients analyzed, 52.1% were men (median age, 35 y), 72.2% were Asian, and 81.2% were HBeAg-negative. During a median follow-up period of 51 months, 19.2% of patients transitioned to a more active disease phase and 18.8% started antiviral therapy. Of the 44 HBeAg-positive patients, 4 patients (9%) had spontaneous HBeAg seroconversion. Nine HBeAg-negative patients but none of the HBeAg-positive patients lost HBsAg. The cumulative probability of HBsAg loss among HBeAg-negative patients was 1% at year 5 and 21% by year 10. No patients had flares of icteric hepatitis or hepatic decompensation. None of the HBeAg-positive patients developed HCC, whereas 2 HBeAg-negative patients developed HCC. CONCLUSIONS: Careful monitoring of patients with CHB who did not meet treatment criteria at presentation permits timely initiation of treatment, with a low risk of adverse clinical outcomes, based on a retrospective study with a median follow-up period of 4.3 years. These findings indicate that current guidelines for initiating treatment are appropriate.

TLR2 and TLR4 gene expression levels and associated factors during acute attack and attack-free periods in familial Mediterranean fever.

The purpose of this clinical study was to determine if the expression of the TLR2 and/or TLR4 genes is involved in triggering the auto-inflammatory attacks in patients with familial Mediterranean fever (FMF). Thirty patients with FMF and 20 healthy control subjects were recruited. Comparisons were made in TLR2 and TLR4 gene expression levels during FMF attack episodes and attack-free periods, as well as with baseline levels in healthy control subjects. There was no significant difference in TLR2 and TLR4 gene expression between the attacks and attack-free periods in the entire group of FMF patients. However, among female patients, expression level of TLR4 gene was significantly higher during the attack than in the attack-free period (TLR2 Log 2.04 ± 0.14 vs. 2.52 ± 0.10, respectively, P = 0.02). There was not a significant difference between FMF patients and healthy subjects. The patients who had higher levels of TLR2 expression during the acute attack experienced their first attacks at an earlier age (r = -0.571; P = 0.001). The frequency of attacks, acute-phase response, MEFV mutations, and colchicine response were not associated with TLR2 and TLR4 levels. We conclude that changes in the expression of TLR2 and TLR4 genes do not appear to be involved in triggering FMF attacks. A higher level of TLR2 expression during acute attack may be related to the early onset of the disease. Further studies using specific cell populations such as neutrophils, monocytes, and dendritic cells may be useful to explore any changes in the sensitivity of toll-like receptors to their agonists, such as lipopolysaccharides, in the onset of attacks.

Sexual activity does not predispose to reflux episodes in patients with gastroesophageal reflux disease.

BACKGROUND: The role of sexual activity on gastroesophageal reflux disease (GERD) is an under-recognized concern of patients, and one rarely assessed by physicians. OBJECTIVE: The objective of this article is to determine the influence of sexual activity on the intraesophageal acid exposure and acid reflux events in GERD patients. METHODS: Twenty-one patients with the diagnosis of GERD were prospectively enrolled. Intraesophageal pH monitoring was recorded for 48 hours with a Bravo capsule. All patients were instructed to have sexual intercourse or abstain in a random order two hours after the same refluxogenic dinner within two consecutive nights. Patients were requested to have sex in the standard "missionary position" and women were warned to avoid abdominal compression. The patients completed a diary reporting the time of the sexual intercourse and GERD symptoms. The percentage of reflux time and acid reflux events were compared in two ways: within 30 and 60 minutes prior to and after sexual intercourse on the day of sexual intercourse and in the same time frame of the day without sexual intercourse. RESULTS: Fifteen of 21 GERD patients were analyzed. The percentage of reflux time and number of acid reflux events did not show a significant difference within the 30- and 60-minute periods prior to and after sexual intercourse on the day of sexual intercourse and on the day without sexual intercourse, as well. CONCLUSION: Sexual activity does not predispose to increased intraesophageal acid exposure and acid reflux events. Larger studies are needed to confirm our findings in patients who define reflux symptoms during sexual intercourse.

A severe case of esophageal ulcer causing a tight stricture despite long-term D-penicillamine treatment.

D-penicillamine has long been used in the management of rheumatic diseases due to the effects on inhibition of collagen synthesis. Herein, we report a severe case of esophageal ulcer causing a tight stricture extending through the distal esophagus despite the long-term D-penicillamine treatment in a patient with Wilson's disease. D-penicillamine would theoretically be expected to contribute to the healing of an esophageal ulcer. However, the drug failed to have a favorable outcome, which is notable and worth reporting.

Management of hepatitis B: our practice and how it relates to the guidelines.

Seven drugs have been approved for the treatment of chronic hepatitis B. Antiviral treatment has been shown to be effective in suppressing hepatitis B virus replication, decreasing inflammation and fibrosis in the liver, and preventing progression of liver disease. However, current medications do not eradicate hepatitis B virus; therefore, a key question is which patients need to start treatment and which patients can be monitored. Professional societies have developed guidelines to assist physicians in recognition, diagnosis, and optimal management of patients with chronic hepatitis B. These guidelines suggest preferred approaches, and physicians are expected to exercise clinical judgment to determine the most appropriate management based on the circumstances of the individual patient. This article reviews recommendations in hepatitis B guidelines and the basis for those recommendations, and we discuss what we do in our practice to illustrate factors that may influence decisions regarding hepatitis B management.