Progressive changes in platelet counts and Fib-4 scores precede the diagnosis of advanced fibrosis in NASH patients.

BACKGROUND: Cirrhosis and its complications develop in a subgroup of patients with non-alcoholic fatty liver disease (NASH). Early detection of liver fibrosis represents an important goal of clinical care. AIM: To test the hypothesis that the development of cirrhosis in nonalcoholic fatty liver disease patients is preceded by the long-term trends of platelet counts and Fib-4 scores. METHODS: We identified all patients in our healthcare system who had undergone fibrosis staging by liver biopsy or magnetic resonance elastography (MRE) for non-alcoholic fatty liver disease during the past decade (n = 310). Platelet counts, serum glutamic-pyruvic transaminase and serum glutamic oxalacetic transaminase values preceding the staging tests were extracted from the electronic medical record system, and Fib-4 scores were calculated. Potential predictors of advanced fibrosis were evaluated using multivariate regression analysis. RESULTS: Significant decreases in platelet counts and increases in Fib-4 scores were observed in all fibrosis stages, particularly in patients with cirrhosis. In the liver biopsy group, the presence of cirrhosis was best predicted by the combination of the Fib-4 score at the time closest to staging (P < 0.0001), the presence of diabetes (P = 0.0001), and the correlation coefficient of the preceding time-dependent drop in platelet count (P = 0.044). In the MRE group, Fib4 score (P = 0.0025) and platelet drop (P = 0.0373) were significant predictors. In comparison, the time-dependent rise of the Fib-4 score did not contribute in a statistically significant way. CONCLUSION: Time-dependent changes in platelet counts and Fib-4 scores contribute to the prediction of cirrhosis in NASH patients with biopsy- or MRE-staged fibrosis. Their incorporation into predictive algorithms may assist in the earlier identification of high-risk patients.

Successful Hepatitis C Birth Cohort Screening and Linkage to Care in a US Community Health System.

CONTEXT: Birth cohort ("baby boomer") screening represents a well-validated strategy for the identification of asymptomatic hepatitis C-infected patients. However, successful linkage of newly diagnosed patients to antiviral therapy has been more difficult to accomplish. OBJECTIVE: To analyze the results of a systemwide birth cohort screening program in a US community health care system. DESIGN: We analyzed the data from an ongoing hepatitis C virus (HCV) screening and treatment program that was established at NorthShore University Health System in 2015. Hepatitis C virus screening by primary care providers was prompted through automated Best Practice and Health Maintenance alerts. Patient visits and screening orders were tracked using a customized HCV dashboard. Virologic, demographic, and treatment data were assessed and compared with those of a cohort of patients with previously established HCV infection. RESULTS: Since program inception, 61 8161 (64.3%) of the entire NorthShore baby boomer population of 96 001 patients have completed HCV antibody testing, and 160 patients (0.26%) were antibody positive. Of 152 antibody-positive patients who underwent HCV RNA testing, 53 (34.2%) were viremic. A total of 39 of 53 patients (73.6%) underwent antiviral therapy and achieved a sustained virologic response. Compared with patients identified through screening, a comparison cohort of patients with previously established HCV had more advanced fibrosis and significantly lower dropout rates. The COVID-19 pandemic was associated with a decrease in the number of outpatient visits of screening-eligible patients and with a reduction in HCV screening rates. CONCLUSION: Our data demonstrate the electronic medical records-assisted systemwide implementation of HCV birth cohort screening and successful linkage to antiviral therapy in a community-based US multihospital system.

Esophageal Perforation Due to a Calcium Supplement Tablet.

Pill-induced esophagitis due to calcium supplements is extremely uncommon. We present a 60-year-old female patient with pill-induced esophageal perforation complicated by mediastinal abscess and esophago-pleural fistula following ingestion of a single over-the-counter "bone supplement" tablet containing mainly calcium.

Transjugular Liver Biopsy with Hemodynamic Evaluation: Correlation between Hepatic Venous Pressure Gradient and Histologic Diagnosis of Cirrhosis.

OBJECTIVES: Measurement of hepatic vein pressures is the accepted gold standard for the evaluation of portal hypertension. This study was conducted to evaluate the correlation between hepatic vein pressure measurements and histologic findings from transjugular liver biopsies. The hypothesis was that higher hepatic venous pressure gradients would correlate with a histologic diagnosis of cirrhosis. MATERIAL AND METHODS: We identified all patients who underwent transjugular liver biopsies at our institution between January 2015 and December 2019. Of these, 178 patients who had undergone hemodynamic evaluations during the biopsy procedure were included in the study. Demographic information and laboratory data were extracted from the patients' electronic medical records. The hepatic vein pressure gradient (HVPG) was determined by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure (WHVP), and the portosystemic gradient (PSG) was determined by subtracting the right atrial pressure from the WHVP. HVPG and PSG were compared by linear regression analysis and by calculating their receiver operating characteristics (ROC). RESULTS: HVPG and PSG measurements were significantly associated with cirrhosis, with area under the ROC curve of 0.79 and 0.78, respectively. At the optimal cutoff of 9 mmHg, sensitivity and specificity for HVPG were 71% and 83% for HVPG and 67 % and 81% for PSG, respectively. No statistical difference was observed between the two measurements. CONCLUSION: A transhepatic venous pressure gradient above a cutoff of 9 mmHg is predictive of histologic cirrhosis, regardless of whether it is expressed as HVPG or PSG, with acceptable to excellent performance characteristics.

Sustained and cumulative impact of an electronic medical record-based alert on a hepatitis C birth cohort screening programme.

The study aimed to assess the effect of an electronic medical record-embedded best practice alert (BPA) on HCV age cohort screening in primary care clinics. HCV testing by primary care physicians was monitored prior and subsequent to the implantation of the BPA. Four intervals of 9 months duration were analysed in detail, including a pre-BPA baseline analysis and three annual post-BPA assessments. Pre- and post-BPA orders consistently followed a power law distribution, characterized by small groups of physicians placing the majority of test orders. Significant correlations were present between the numbers of tests orders by each physician, suggesting that 'high' and 'low' screening performances tended to be physician-specific. Testing rates increased markedly in response to the BPA, resulting in completion of screening in 56.8% (50,468 of 88,914%) of the entire age cohort within less than 3 years. In conclusion, HCV age cohort testing by primary care physicians follows a power-law distribution, with high-performing physicians contributing disproportionately to the overall effort. A simple BPA resulted in a sufficient increase in testing to allow testing of the entire target population within a reasonable time frame.

Effect of a Best Practice Alert on Birth-Cohort Screening for Hepatitis C Virus.

INTRODUCTION: We assessed the influence of a best practice alert (BPA) embedded within the electronic medical record on improving hepatitis C virus (HCV) birth-cohort screening by primary care physicians (PCPs). METHODS: Screening by 155 PCPs was monitored during 2 consecutive 9-month periods before and after implementation of the BPA. All tests were reviewed to differentiate true screening from other testing indications. RESULTS: Of 155 PCPs, 131 placed screening orders before and after BPA. Twenty-two PCPs started testing after BPA (P = 0.02). The number of tests placed and screening rates per PCP increased from 16 to 84 and from 3.3% to 13.2%, respectively (P < 0.0001). Before BPA, most PCPs rarely ordered screening HCV tests, whereas a small group of physicians generated most tests, indicative of an underlying power-law distribution. After the BPA, a new group of high-performing PCPs emerged, whose screening patterns were again characterized by a power-law distribution. However, pre-BPA test rates of individual PCPs were not predictive of their post-BPA rates. Overall, the introduction of the BPA narrowed the gap between low- and high-performing testers, indicating that modest increases in testing by a large number of low-performing PCPs could drive substantial improvement in program implementation. DISCUSSION: HCV birth-cohort screening by PCPs was shaped by an underlying power-law distribution. This distribution was preserved after the implementation of a BPA, although pre-BPA test rates were not predictive of post-BPA rates. Increases in test rates by high- and low-performing PCPs both contributed to the overall success of the BPA.

Ketogenic, Hypocaloric Diet Improves Nonalcoholic Steatohepatitis.

BACKGROUND AND OBJECTIVES: Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity. A weight loss of ≥10% is necessary to improve NASH severity, but this goal has rarely been achieved in published studies using different diet protocols. The effect of a ketogenic, hypocaloric, commercial diet ("Ideal Protein," IP) on body weight, metabolic markers, and liver tests in a group of NASH patients is evaluated in this study. Daily calorie intake was tailored to achieve a weight loss of ≥10%. METHODS: We analyzed 38 patients with NASH who were placed on the IP diet between 2014 and 2018 and compared their outcomes with 6 control patients who declined the diet. All patients were evaluated by a trained health coach in weekly intervals throughout the study period. Clinical and laboratory data obtained before and at 6.5 months after intervention were compared using paired t-testing. RESULTS: The patients on the IP diet experienced a significant weight reduction (217 ± 8 lb vs. 194 ± 7 lb; mean ± S.E.M.), corresponding to an average weight loss of 9.7% ± 1.6%. Significant changes in systolic blood pressure (133 ± 3 mmHg vs. 123 ± 3 mmHg), triglycerides (200 ± 21 mmol/L vs. 132 ± 11 mmol/L), hemoglobin A1c (6.71% ± 0.29% vs. 5.74% ± 0.19%), SGPT (97.3 ± 11.1 IU/L vs. 44.2 ± 5.9 IU/L), SGOT (82.4 ± 10.5 IU/L vs. 32.8 ± 5.2 IU/L), and Fib-4 scores (2.25 ± 0.23 vs. 1.40 ± 0.13) were also observed (P<0.05 in all cases). In the IP group, 50.5% of patients lost ≥10% body weight. In contrast, no significant changes were observed in the control group. The IP diet was well tolerated, and no safety signals were noticed. CONCLUSIONS: A ketogenic, hypocaloric resulted in striking weight loss and significant improvements in metabolic parameters and liver tests, suggesting that this approach carries promise for the dietary management of patients with NASH.

Rapid Development of Bleeding Esophageal Varices after Placement of Continuous Flow Left Ventricular Assist Device.

We describe a patient with compensated cirrhosis and portal hypertension who underwent continuous flow LVAD implantation. Shortly after LVAD implantation, the patient developed new onset bleeding esophageal varices and ultimately had a fatal outcome. Our experience suggests that even well-compensated cirrhotic patients with significant portal hypertension are at risk of variceal bleeding after LVAD placement.

A Case of Severe, Nilotinib-Induced Liver Injury.

Idiosyncratic hepatotoxicity is a leading reason for the discontinuation or dose modification of Food and Drug Administration (FDA)-approved medications in the United States. We report the case of a 53-year-old woman with chronic myeloid leukemia who developed acute cholestatic hepatitis in response to the tyrosine kinase inhibitor nilotinib. Nilotinib was discontinued, and the patient's liver function tests normalized over the next 3 months. We conclude that nilotinib may cause life-threatening hepatotoxicity and recommend that patients on the medication undergo regular monitoring of their liver tests.

Hepatitis C Screening in Commercially Insured U.S. Birth-cohort Patients: Factors Associated with Testing and Effect of an EMR-based Screening Alert.

BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) testing rates among U.S. birth-cohort patients have been studied extensively, limited data exists to differentiate birth-cohort screening from risk- or liver disease-based testing. This study aims to identify factors associated with HCV antibody (HCV-Ab) testing in a group of insured birth cohort patients, to determine true birth cohort testing rates, and to determine whether an electronic medical record (EMR)-driven Best Practice Alert (BPA) would improve birth cohort testing rates. METHODS: All birth-cohort outpatients between 2010 and 2015 were identified. HCV-Ab test results, clinical, and demographic variables were extracted from the EMR, and factors associated with testing were analyzed by logistic regression. True birth-cohort HCV screening rates were determined by detailed chart review for all outpatient visits during one calendar month. An automated Best Practice Alert was used to identify unscreened patients at the point of care, and to prompt HCV testing. Screening rates before and after system-wide implementation of the BPA were compared. RESULTS: The historic HCV-Ab testing rate was 11.2% (11,976/106,753). Younger age, female gender, and African American, Asian, or Hispanic ethnicity, and medical comorbidities such as chronic hemodialysis, HIV infection, and rheumatologic and psychiatric comorbidities were associated with higher testing rates. However, during the one-month sampling period, true age cohort-based testing was performed in only 69/10,089 patients (0.68%). Following the system-wide implementation of the HCV BPA, testing rates increased from 0.68% to 10.76% (P<0.0001). CONCLUSIONS: We documented low HCV-Ab testing rates in our baby boomers population. HCV testing was typically performed in the presence of known risk factors or established liver disease. The implementation of an EMR-based HCV BPA resulted in a marked increase in testing rates. Our study highlights current HCV screening gaps, and the utility of the EMR to improve screening rates and population health.

Management of Incidental Liver Lesions on CT: A White Paper of the ACR Incidental Findings Committee.

The ACR Committee on Incidental Findings presents recommendations for managing liver lesions that are incidentally detected on CT. These recommendations represent an update from the liver component of the ACR 2010 white paper on managing incidental findings in the pancreas, adrenal glands, kidneys, and liver. The Liver Subcommittee-which included five abdominal radiologists, one hepatologist, and one hepatobiliary surgeon-developed this algorithm. The recommendations draw from published evidence and expert opinion and were finalized by informal iterative consensus. Algorithm branches categorize liver lesions on the basis of patient characteristics and imaging features. They terminate with an assessment of benignity or a specific follow-up recommendation. The algorithm addresses most, but not all, pathologies and clinical scenarios. The goal is to improve the quality of care by providing guidance on how to manage incidentally detected liver lesions.

Utility of Electronic Medical record-based Fibrosis Scores in Predicting Advanced Cirrhosis in Patients with Hepatitic C Virus Infection.

OBJECTIVE: To determine whether advanced cirrhosis - defined by the detection of nodular liver contours or portal venous collaterals on imaging studies - could be predicted by fibrosis algorithms, calculated using laboratory and demographic features extracted from patients' electronic medical records. To this end, we compared seven EMR-based fibrosis scores with liver imaging studies in a cohort of HCV patients. METHODS: A search of our health system's patient data warehouse identified 867 patients with chronic HCV infection. A total of 565 patients had undergone at least one liver imaging study and had no confounding medical condition affecting the imaging features or fibrosis scores. Demographic and laboratory data were used to calculate APRI, Fib4, Fibrosis Index, Forns, GUCI, Lok Index and Vira-HepC scores for all viremic patients who had undergone liver imaging. Data points selected for the calculation of these scores were based on laboratory results obtained within the shortest possible time from the imaging study. Areas under the receiver operating curves (AUROC), optimum cut-offs, sensitivities, specificities and positive and negative predictive values were calculated for each score. RESULTS: Seven algorithms were performed similarly in predicting cirrhosis. Sensitivities ranged from 0.65 to 1.00, specificities from 0.67 to 0.90, positive predictive values from 0.33 to 0.38, and negative predictive values from 0.93 to 1.00. No individual test was superior, as the confidence intervals of all AUROCs overlapped. CONCLUSIONS: EMR-based scoring systems performed relatively well in ruling out advanced, radiologically-defined cirrhosis. However, their moderate sensitivity and positive predictive values limit their reliability for EMR-based diagnosis.

Relapse of HCV Genotype 1b Infection After Sofosbuvir/Ledipasvir Treatment Presenting as De Novo Cryoglobulinemic Vasculitis.

Relapse of hepatitis C virus (HCV) genotype 1 infection after combination therapy with sofosbuvir and ledipasvir is unusual. We report a treatment-naïve, non-cirrhotic patient in whom the relapse of genotype 1b HCV infection was accompanied by de novo cryoglobulinemic vasculitis and glomerulonephritis, requiring hemodialysis for acute renal failure. Sequence analysis revealed several resistance-associated variants in the HCV NS5a gene but not in NS3/4A. The patient's vasculitis was successfully treated with immunosuppression and plasmapheresis, followed by retreatment of HCV with a combination of sofosbuvir, simeprevir, and ribavirin. The patient achieved sustained virological response, recovered his renal function, and remains in remission from cryoglobulinemia.

Identification and Fibrosis Staging of Hepatitis C Patients Using the Electronic Medical Record System.

BACKGROUND AND AIMS: The aim of this study was to noninvasively assess the severity of chronic hepatitis C virus (HCV) in large patient populations. It would be helpful if fibrosis scores could be calculated solely on the basis of data contained in the patients' electronic medical records (EMR). We performed a pilot study to identify all HCV-infected patients in a large health care system, and predict their fibrosis stage on the basis of demographic and laboratory data using common data from their EMR. MATERIALS AND METHODS: HCV-infected patients were identified using the EMR. The liver biopsies of 191 HCV patients were graded using the Ishak and Metavir scoring systems. Demographic and laboratory data were extracted from the EMR and used to calculate the aminotransferase to platelet ratio index, Fib-4, Fibrosis Index, Forns, Göteborg University Cirrhosis Index, Lok Index, and Vira-HepC. RESULTS: In total, 869 HCV-infected patients were identified from a population of over 1 million. In the subgroup of patients with liver biopsies, all 7 algorithms were significantly correlated with the fibrosis stage. The degree of correlation was moderate, with correlation coefficients ranging from 0.22 to 0.60. For the detection of advanced fibrosis (Metavir 3 or 4), the areas under the receiver operating characteristic curve ranged from 0.71 to 0.84, with no significant differences between the individual scores. Sensitivities, specificities, and positive and negative predictive values were within the previously reported range. All scores tended to perform better for higher fibrosis stages. CONCLUSIONS: Our study demonstrates that HCV-infected patients can be identified and their fibrosis staged using commonly available EMR-based algorithms.

Post-Transjugular Intrahepatic Portosystemic Shunt Follow-Up and Management in the VIATORR Era.

The transjugular intrahepatic portosystemic shunt (TIPS) is a non-selective portosystemic shunt created using endovascular techniques. The first TIPS was performed in Germany in 1988. The VIATORR self-expandable PTFE covered stent-graft (WL Gore, Flagstaff AZ) was approved by the FDA for a TIPS application in December of 2004. This stent-graft offers excellent shunt patency rates and it is possible that it has a beneficial effect on patient survival. Patient surveillance and post-procedural management have changed after the introduction of this stent-graft. This article presents the current management strategies that are followed at our Institution for patients who have undergone a TIPS procedure with a VIATORR stent graft including imaging follow-up, management of encephalopathy, medical management and nutritional aspects.

Granulomatous hepatitis due to Bartonella henselae infection in an immunocompetent patient.

BACKGROUND: Bartonella henselae (B. henselae) is considered a rare cause of granulomatous hepatitis. Due to the fastidious growth characteristics of the bacteria, the limited sensitivity of histopathological stains, and the non-specific histological findings on liver biopsy, the diagnosis of hepatic bartonellosis can be difficult to establish. Furthermore, the optimal treatment of established hepatic bartonellosis remains controversial. CASE PRESENTATION: We present a case of hepatic bartonellosis in an immunocompetent woman who presented with right upper quadrant pain and a five cm right hepatic lobe mass on CT scan. The patient underwent a right hepatic lobectomy. Surgical pathology revealed florid necrotizing granulomatous hepatitis, favoring an infectious etiology. Despite extensive histological and serological evaluation a definitive diagnosis was not established initially. Thirteen months after initial presentation, hepatic bartonellosis was diagnosed by PCR studies from surgically excised liver tissue. Interestingly, the hepatic granulomas persisted and Bartonella henselae was isolated from the patient's enriched blood culture after several courses of antibiotic therapy. CONCLUSION: The diagnosis of hepatic bartonellosis is exceedingly difficult to establish and requires a high degree of clinical suspicion. Recently developed, PCR-based approaches may be required in select patients to make the diagnosis. The optimal antimicrobial therapy for hepatic bartonellosis has not been established, and close follow-up is needed to ensure successful eradication of the infection.

Granulomatous hepatitis, choroiditis and aortoduodenal fistula complicating intravesical Bacillus Calmette-Guérin therapy: Case report.

BACKGROUND: Intravesical instillation of Bacillus Calmette-Guérin (BCG) is the treatment of choice for superficial bladder carcinoma. Complications of BCG therapy include local infections and disseminated BCG infection with multiple endorgan complications. CASE PRESENTATION: We report a case of disseminated, post-treatment BCG infection that initially presented with granulomatous hepatitis and choroiditis. After successful anti-mycobacterial therapy and resolution of the hepatic and ocular abnormalities, the patient developed an acute upper gastrointestinal hemorrhage from an aortoduodenal fistula that required emergency surgery. The resection specimen revealed multifocal, non-caseating granulomas, indicating mycobacterial involvement. CONCLUSIONS: This case highlights the varied end organ complications of disseminated BCG infection, and the need for vigilance even in immuno-competent patients with a history of intravesical BCG treatment.

Hepatocyte GP73 expression in Wilson disease.

BACKGROUND/AIMS: Wilson disease (WD) is a disorder of copper transport caused by mutations within the ATP7B gene. WD is phenotypically variable and can present with predominantly hepatic or neurologic manifestations. The mechanisms responsible for this variability are unknown. GP73, a Golgi membrane protein, is expressed in hepatocytes in response to acute and chronic liver disease. METHODS: Hepatocyte GP73 expression was examined in the livers of WD patients by semiquantitative immunohistochemistry. GP73 mRNA levels were measured in mice with a deletion of the WD gene (Atp7b(-/-)) by real-time PCR, and these values were compared to the concomitant histological abnormalities and previously reported copper levels. RESULTS: Hepatocyte GP73 expression was more frequently observed in patients with hepatic versus neurologic presentation (79% vs. 30%, p<0.05). Furthermore, GP73 expression was significantly higher (44.7+/-14.0 vs. 2.0+/-0.81, p<0.05) in patients with hepatic phenotype. In Atp7b(-/-) mice, GP73 mRNA was significantly elevated at 20-46 weeks of age, coincident with extensive hepatic inflammation and fibrosis, but not at 6 weeks, when hepatic histology was normal despite significant copper overload. GP73 mRNA levels normalized concomitantly with the resolution of hepatic injury at 60-weeks. However, in tumor-like nodules GP73 was strikingly elevated. CONCLUSION: Increased hepatocyte GP73 expression is more commonly a feature of hepatic than neurologic WD, and is triggered in response to inflammation, fibrosis, and dysplasia, rather than copper overload.