Porto-sinusoidal Vascular Disease and Portal Hypertension.

Porto-sinusoidal vascular disease (PSVD) is the medical diagnosis for a patient who has portal hypertension in the absence of cirrhosis on liver biopsy. There are several specific histologic findings for PSVD, including obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. Epidemiologic reports vary widely among regions; PSVD comprises less than 10% of causes of portal hypertension in Western countries but incidence has been found to be as high as 48% in India. There is an expansive list of etiologies that have been reported to cause PSVD.

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.

Sofosbuvir and Simeprevir Combination Therapy for HCV Genotype 1 Infection: Results of a Single-Center VA Experience.

Treatment of chronic hepatitis C virus (HCV) infection remains a priority in the veterans affairs (VA) health care system nationwide, as there is a high burden of liver disease due to HCV infection among US veterans. The combination of sofosbuvir and simeprevir was the first all-oral antiviral regimen used in clinical practice to treat veterans with HCV infection. In this study, we report a single-center experience showing both the feasibility and effectiveness of this all-oral combination to treat HCV genotype 1 infection. One hundred patients with HCV genotype 1 infection were treated between December 2013 and June 2014. Eighty-six patients were treated with sofosbuvir and simeprevir, with or without ribavirin, for 12 weeks; 12 patients were treated with sofosbuvir, pegylated interferon, and ribavirin for 12 weeks; and 2 patients were treated with sofosbuvir and ribavirin for 24 weeks. Overall, treatment was well tolerated and feasible, with compliance rates over 95% in patients treated with all-oral therapy. The sustained virologic response (SVR) rate for sofosbuvir and simeprevir (88.4%) was superior to the rate for sofosbuvir, pegylated interferon, and ribavirin (50.0%). Subgroup analysis showed diminished SVR rates in cirrhotic patients vs noncirrhotic patients. There were no significant differences in SVR when comparing treatment with or without ribavirin or among genotype subtypes. In conclusion, this study demonstrated excellent completion rates for all-oral treatment of veterans with chronic HCV infection. Additionally, treatment was highly effective, nearing a 90% cure rate. Thus, we recommend that the VA health care system continue to incorporate new HCV medications into its formulary so as to expand HCV treatment for US veterans.

Quality of Care Provided by Hepatologists to Patients with Cirrhosis at Three Parallel Health Systems.

BACKGROUND: Evidence-based guidelines and quality indicators for cirrhosis care have been established. Whether there are variations in adherence to these cirrhosis standards at different specialty settings has not been investigated. AIMS: To evaluate the quality of cirrhosis care delivered at diverse hepatology care sites. METHODS: We conducted a retrospective study comparing the quality of care at three hepatology specialty clinics: a Faculty Practice, safety-net hospital, and Veterans Affairs (VA) Medical Center. Consecutive patients with cirrhosis (85 Faculty Practice, 81 safety-net, and 76 VA) between 2010 and 2011 were included. Median follow-up was 2.3 years. Outcome measures were the adherence to six cirrhosis-specific quality-of-care indicators. RESULTS: Adherence to hepatitis A and B vaccinations was highest at the safety-net hospital, 81 and 74 %, compared to 46 and 30 % at the Faculty Practice (P < .001). Adherence to yearly hepatocellular carcinoma surveillance was highest at the safety-net site (79 %) versus the VA (50 %) and Faculty Practice (42 %), P = .001. In contrast, screening rates for esophageal varices were 75 % at the Faculty Practice and only 58 and 43 % at the VA and safety-net sites, respectively (P < .001). Liver transplant discussions were documented most consistently at the Faculty Practice (82 %) compared to the safety-net site (53 %) and VA (54 %), P < .001. CONCLUSIONS: Disparities in cirrhosis quality measures existed by site. Strategies to overcome these disparities need to be developed to improve the delivery of quality cirrhosis care as we face a rise in cirrhosis-related complications over the next two decades.

Increased hepatic progenitor cell response and ductular reaction in patients with severe recurrent HCV post-liver transplantation.

OBJECTIVES: Post-liver transplant (LT) hepatitis C virus (HCV) patients may develop allograft cirrhosis and rarely fibrosing cholestatic hepatitis (FCH), while others have a stable course. Hepatic progenitor cells (HPC) may be implicated in liver injury and fibrogenesis through ductular reaction (DR). We studied HPC response and DR in three distinct post-LT patterns of HCV: stable recurrence, allograft cirrhosis, and FCH. METHODS: We identified 52 patients with untreated recurrent HCV and longitudinal liver biopsies (20 stable/23 cirrhosis/9 FCH) and eight healthy controls. Archived liver biopsy specimens for three time points (LT; initial recurrence; and clinical outcome) were stained for cytokeratin-7. Manual HPC counts and DR quantification using image analysis were performed. RESULTS: HCV counts and DR at LT did not differ across groups. At initial recurrence, HPC expansion occurred only in patients who developed cirrhosis, while prominent DR was present in those who developed FCH vs. stable and controls (p < 0.05). At outcome biopsies, HPC response and DR were increased in cirrhosis and FCH vs. stable and controls (p < 0.05). HPC response and DR did not differ in stable vs. CONCLUSIONS: These findings suggest that an altered HPC response assessed by cytokeratin-7 stain after LT may predict severity of HCV recurrence.

Current Concepts in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic, cholestatic diseases of the liver with common clinical manifestations. Early diagnosis and treatment of PBC slows progression and decreases the need for transplant. However, one-third of patients will progress regardless of treatment. Bilirubin <1.0 and alkaline phosphatase <2.0 x the upper limit of normal at 1 year after treatment appear to predict 10-year survival. Ursodeoxycholic acid (UDCA) is the recommended treatment for PBC, and recent studies with obeticholic acid showed promising results for UDCA non-responders. Unlike PBC, no therapy has been shown to alter the natural history of PSC. The recommended initial diagnostic test for PSC is magnetic resonance cholangiopancreatography, typically showing bile duct wall thickening, focal bile duct dilatation, and saccular dilatation of the intra- and/or extrahepatic bile ducts. Immunoglobulin 4-associated cholangitis must be excluded when considering the diagnosis of PSC, to allow for proper treatment, and monitoring of disease progression. In addition to the lack of therapy, PSC is a pre-malignant condition and close surveillance is indicated.

Supersonic Shear Imaging and Transient Elastography With the XL Probe Accurately Detect Fibrosis in Overweight or Obese Patients With Chronic Liver Disease.

BACKGROUND & AIMS: Assessment of the severity of liver fibrosis is an important step in evaluating patients with chronic liver disease and determining their prognosis. We compared liver stiffness measurements (LSMs) made by supersonic shear imaging (SSI) with those of transient elastography (TE)-XL for their ability to determine the degree of liver fibrosis in overweight or obese patients with chronic liver disease. METHODS: We performed a prospective study of 258 patients with chronic hepatitis of different etiologies and a body mass index greater than 25, evaluated at the University of Miami from October 2013 to December 2014. Liver stiffness was measured using the TE-XL probe and SSI of the right and left lobes during the same clinic visit, and comparisons were made for fibrosis stage in 124 biopsy-proven patients. In addition, further analysis was performed on a subgroup of 102 chronic hepatitis C virus (HCV)-positive patients for whom biopsy data were available. RESULTS: Reliable LSMs were obtained from 96.1%, 94.6%, and 72.1% of patients using the TE-XL probe, SSI of the right lobe, and SSI of the left lobe, respectively. TE-XL, SSI of the right lobe, and SSI of the left lobe detected severe fibrosis (fibrosis stages 3-4), with area under the receiver operating characteristic curve (AUROC) values of 0.955, 0.954, and 0.910, respectively, compared with results from histologic analysis for the 124 biopsy-proven patients included in the study; these values were 0.952, 0.949, and 0.917, respectively, for the 102 biopsy-proven patients with HCV infection. TE-XL, SSI of the right lobe, and SSI of the left lobe detected fibrosis stage 4 with AUROC values of 0.920, 0.930, and 0.910, respectively, compared with histologic analysis, in all 124-biopsy proven patients, and with AUROC values of 0.907, 0.914, and 0.887, respectively, in the 102 biopsy-proven patients with chronic HCV infection. CONCLUSIONS: SSI and the TE-XL probe each accurately quantify liver fibrosis in overweight or obese patients with chronic liver disease, including those with HCV infection, when compared with data obtained from histologic analysis. SSI data obtained from the right lobe and the TE-XL probe can be used to evaluate fibrosis with similar accuracy.

Total pancreatectomy and islet autotransplantation in chronic pancreatitis: recommendations from PancreasFest.

DESCRIPTION: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure used to treat severe complications of chronic pancreatitis or very high risk of pancreatic cancer while reducing the risk of severe diabetes mellitus. However, clear guidance on indications, contraindications, evaluation, timing, and follow-up are lacking. METHODS: A working group reviewed the medical, psychological, and surgical options and supporting literature related to TPIAT for a consensus meeting during PancreasFest. RESULTS: Five major areas requiring clinical evaluation and management were addressed: These included: 1) indications for TPIAT; 2) contraindications for TPIAT; 3) optimal timing of the procedure; 4) need for a multi-disciplinary team and the roles of the members; 5) life-long management issues following TPIAP including diabetes monitoring and nutrition evaluation. CONCLUSIONS: TPIAT is an effective method of managing the disabling complications of chronic pancreatitis and risk of pancreatic cancer in very high risk patients. Careful evaluation and long-term management of candidate patients by qualified multidisciplinary teams is required. Multiple recommendations for further research were also identified.

A small percentage of patients with hepatitis C receive triple therapy with boceprevir or telaprevir.

BACKGROUND & AIMS: Protease inhibitor triple therapy for hepatitis C virus (HCV) infection (boceprevir or telaprevir with pegylated interferon and ribavirin) has been shown to increase rates of sustained virologic response in phase 3 trials. We investigated the proportion of patients who began therapy with this regimen in the 12 months after the Food and Drug Administration approval of boceprevir and telaprevir in the United States. METHODS: We performed a retrospective cross-sectional study of 487 patients with HCV genotype 1 infection (396 did not receive triple therapy, and 91 had begun triple therapy with boceprevir or telaprevir), who were seen at hepatology practices in Dallas and Miami from June 2011 through February 2012. The subjects were predominantly middle-aged, non-Hispanic white, and privately insured; 50% were treatment-naive, and most had advanced fibrosis. We compared features of patients who initiated triple therapy with those who deferred it. Treated patients were followed to determine the discontinuation rate in the first 12 weeks of treatment. RESULTS: Of patients assessed, only 18.7% began triple therapy, the same percentage as those receiving dual therapy (pegylated interferon and ribavirin) before boceprevir or telaprevir was approved for treatment of HCV infection in the United States. Reasons for deferring treatment included relative contraindications (50.5%), patient choice (22.5%), and less advanced liver disease (17.4%). Among treated patients, 15% discontinued prematurely because of serious adverse events. On the basis of multivariate analysis, factors associated with initiation of triple therapy included prior treatment relapse (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.1-9.9) and liver fibrosis of stage 3 (OR, 9.1; 95% CI, 3.1-27) or stage 4 (OR, 9.0; 95% CI, 3.3-25) but not hepatic decompensation. CONCLUSIONS: Only 18.7% of patients with HCV genotype 1 infection received triple therapy in the 12 months after Food and Drug Administration approval of boceprevir and telaprevir. This low percentage might result from concerns of side effects and recognition that more effective medications could be available in the future.

An update on the hepatitis E virus.

There have been recent key advances in the understanding of hepatitis E virus infection. Since the early 1980s, when the virus was first discovered, hepatitis E has been described as a disease that is endemic only in the African and Asian subcontinents, a disease that is transmitted via the fecal-oral route, and a disease that causes an acute illness that typically resolves, with the exception of the third trimester of pregnancy, when infection can be deadly. We now know that genotype 3 is likely a porcine zoonotic disease that is quite prevalent in certain industrialized nations. Hepatitis E carries high morbidity and mortality in patients with underlying liver disease and can become a chronic infection that causes fibrosis in immunocompromised hosts. Lastly, two vaccines have been developed and studied in clinical trials, with excellent results.

Clinical characterization of patients developing histologically-proven fibrosing cholestatic hepatitis C post-liver transplantation.

AIM: Fibrosing cholestatic hepatitis C (FCH) post-liver transplantation (LT) is an uncommon disorder with extremely poor outcome. Using stringent histological criteria, we sought to identify cases of FCH to better characterize its incidence, clinical features and outcomes. METHODS: From January 1991 to December 2007, 973 LT for hepatitis C virus (HCV) were performed at our center. Using the pathology database, 51 cases with a provisional diagnosis of FCH were identified. FCH was diagnosed histologically by cholestasis accompanied by thin periportal fibrous septa, ductular reaction and mild inflammation. RESULTS: FCH was reconfirmed in 24 recipients; seven had concurrent biliary problems. Twenty-seven cases were excluded; biopsy was unavailable in nine cases, 15 did not meet the histological criteria of FCH and three had missing clinical information. All received deceased donors at a mean age of 64.4 years (15/17 aged >50 years). Mean time from LT to FCH was 7.6 months with 16 of 17 diagnosed within 1 year of LT. At diagnosis, mean viral load was 14.4 million IU/mL, bilirubin 16.2 mg/dL, aspartate aminotransferase 262 IU/mL, alanine aminotransferase 192 IU/mL and alkaline phosphatase 299 IU/mL. All 17 patients died or required re-LT a mean of 7.8 months after the FCH diagnosis. CONCLUSION: FCH occurs infrequently and is typified by hyperbilirubinemia, donor age of more than 50 years, extremely high HCV RNA and specific histological changes occurring within the first several months post-LT with extremely poor patient and graft survival. Histology alone is not reliable for the diagnosis of FCH, especially in the setting of recurrent HCV with concurrent biliary problems.