Comparison of 2D Shear Wave Elastography, Transient Elastography, and MR Elastography for the Diagnosis of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.

OBJECTIVE. The aim of the present study was to compare the diagnostic accuracy of liver stiffness measurements (LSMs) obtained using MR elastography (MRE), transient elastography (TE), and 2D shear wave elastography (SWE) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS. We prospectively enrolled 62 adult subjects (mean age [± SD], 50 ± 13 years; 58% women; body mass index [weight in kilograms divided by the square of height in meters], 35 ± 7). Two-dimensional SWE, MRE, and TE were performed at a mean of 105 ± 86 days after liver biopsy. The area under the ROC curve (AUROC) values and 95% CIs for the corresponding LSMs (expressed in kilopascals) were calculated, with significant fibrosis (Metavir liver fibrosis score, F2-F4) and advanced fibrosis (F3-F4) used as outcome measures. Pairwise comparisons of AUROC values were conducted using the DeLong test. Statistical significance was set at p < 0.05. RESULTS. For the 62 subjects, valid LSMs were obtained for 57 subjects with the use of 2D SWE, for 59 subjects with TE, for 59 subjects with MRE, and for 54 subjects with all three modalities combined. The AUROC values (95% CIs) of 2D SWE, TE, and MRE for the diagnosis of significant fibrosis were 0.80 (0.67-0.92), 0.77 (0.64-0.89), and 0.85 (0.74-0.95), respectively. The AUROC values (95% CIs) of 2D SWE, TE, and MRE for the diagnosis of advanced fibrosis were 0.89 (0.80-0.98), 0.86 (0.77-0.95), and 0.95 (0.89-1.00), respectively. Pairwise comparisons revealed similar diagnostic accuracy for significant fibrosis (2D SWE vs MRE, p = 0.431; 2D SWE vs TE, p = 0.317; and MRE vs TE, p = 0.052) and advanced fibrosis (2D SWE vs MRE, p = 0.348; 2D SWE vs TE, p = 0.293; and MRE vs TE, p = 0.059). CONCLUSION. For patients with biopsy-proven NAFLD, 2D SWE, MRE and TE exhibited comparable and very good to excellent diagnostic accuracy for advanced fibrosis and comparable but lower accuracy for significant fibrosis.

Is severe progressive liver disease caused by alpha-1-antitrypsin deficiency more common in children or adults?

The classical form of alpha-1-antitrypsin deficiency (A1ATD) is known to cause liver disease in children and adults, but there is relatively little information about the risk of severe, progressive liver disease and the need for liver transplantation. To better understand how newly evolving pharmacological, genetic, and cellular therapies may be targeted according to risk for progressive liver disease, we sought to determine the age distribution of A1ATD as a cause of severe liver disease, as defined by the need for liver transplantation. Using 3 US liver transplantation databases for the period 1991-2012, we found 77.2% of 1677 liver transplants with a reported diagnosis of A1ATD were adults. The peak age range was 50-64 years. Using 2 of the databases which included specific A1AT phenotypes, we found that many of these adults who undergo liver transplantation with A1ATD as the diagnosis are heterozygotes and have other potential causes of liver disease, most notably obesity and ethanol abuse. However, even when these cases are excluded and only ZZ and SZ phenotypes are considered, severe liver disease requiring transplantation is more than 2.5 times as likely in adults. The analysis also showed a markedly increased risk for males. In the pediatric group, almost all of the transplants are done in children less than 5 years of age. In conclusion, A1ATD causes progressive liver disease most commonly in adults with males in the highest risk category. In the pediatric group, children less than 5 years of age are highest in risk. These results suggest that A1ATD most commonly causes liver disease by mechanisms similar to age-dependent degenerative diseases and more rarely in children by powerful modifiers. Liver Transplantation 22 886-894 2016 AASLD.

Plasma from chronic liver disease subjects exhibit differential ability to generate thrombin.

Liver fibrosis in chronic liver disease (CLD) results in complex alterations in procoagulant and anticoagulant proteins. Although an elevated international normalized ratio (INR) is a prominent feature of progressive fibrosis, the utility of the INR to accurately reflect the net effect of these changes on the coagulation system is uncertain. In subjects with CLD, elevated INRs have been observed in both bleeding and thrombotic complications, suggesting limitations of the INR in characterizing the coagulation status. Unlike the INR, which is preferentially sensitive to the extrinsic pathway, the direct measurement of thrombin generation better captures the global coagulation cascade. We conducted a pilot study measuring the INR, chromogenic factor X and thrombin generation in CLD subjects and compared them with control subjects and subjects on warfarin anticoagulation. We observed a large interquartile range in thrombin generation among compensated CLD subjects across a narrow INR range, suggesting that the INR is a suboptimal surrogate measure of thrombin generation in CLD subjects.

Incidence and Management of Rash in Telaprevir-Treated Patients.

BACKGROUND: Telaprevir-induced rash is a common, therapy-limiting adverse drug event (ADE) for patients with hepatitis c virus (HCV) infection. Given the similarity between telaprevir and simeprevir, real-world management of rash during treatment with an NS3/4A protease inhibitor and its implications are important. OBJECTIVE: The objectives of this study were to determine the incidence of rash in telaprevir-treated patients, its management, and the impact on sustained virological response and to identify any risk factors for rash development. METHOD: This was a retrospective study of adult patients who were treated with telaprevir in a hepatology clinic from July 1, 2011, to August 31, 2012. Pertinent information on demographics, past medical history, medications, laboratory data, outcomes of rash, other ADEs related to treatment, and physician grading of rash were collected. RESULT: Of 159 patients included, 44% (70/159) developed rash, and 4% (7/159) discontinued therapy because of rash. Median number of days until rash did not differ between patients who continued and discontinued therapy (25 vs 45, respectively; P = 0.88). Patients who developed rash were more likely to have lower actual body weight (ABW) or body mass index (BMI; P ≤ 0.01). No significant difference in rash development when drug-allergy history was considered was found. Most patients who continued telaprevir were prescribed topical corticosteroids (93.7%) and cetirizine (41.3%). Patients who discontinued therapy were more likely to be evaluated by dermatology (P = 0.002), prescribed oral corticosteroids (P = 0.02), hydroxyzine (P = 0.001), and topical triamcinolone (P = 0.01). CONCLUSION: ABW and BMI appear to be related to rash development. This finding may have implications in the treatment of HCV with simeprevir, given its similarity to telaprevir.

Underlying steatohepatitis, but not simple hepatic steatosis, increases morbidity after liver resection: a case-control study.

UNLABELLED: Despite the high prevalence of fatty liver disease, the safety of liver resection in settings of steatohepatitis (SH) or hepatic steatosis is poorly understood. The aim of this study was to determine whether underlying SH or simple hepatic steatosis increases morbidity after liver resection. We compared patients undergoing liver resection with underlying SH or greater than 33% simple hepatic steatosis to controls selected for similar demographics, diagnoses, comorbidities, preoperative chemotherapy treatments, and extent of partial hepatectomy. Primary endpoints included postoperative overall and hepatic-related morbidity. One hundred and two patients with SH and 72 with greater than 33% simple hepatic steatosis who underwent liver resection from 2000 to 2011 were compared to corresponding controls. There were no differences in extent or approach of liver resection, malignant indications, preoperative chemotherapy treatment, elements of metabolic syndrome, alcohol use history, American Society of Anesthesiologists score, age, or gender between patients with SH or simple steatosis and corresponding controls. Ninety-day postoperative overall morbidity (56.9% versus 37.3%; P = 0.008), any hepatic-related morbidity (28.4% versus 15.7%; P = 0.043), surgical hepatic complications (19.6% versus 8.8%; P = 0.046), and hepatic decompensation (16.7% versus 6.9%; P = 0.049) were greater among SH patients, compared to corresponding controls. In contrast, there were no differences in postoperative overall morbidity (34.7% versus 44.4%; P = 0.310), any hepatic-related morbidity (19.4% versus 19.4%; P = 1.000), surgical hepatic complications (13.9% versus 9.7%; P = 0.606), or hepatic decompensation (8.3% versus 9.7%; P = 0.778) between simple hepatic steatosis patients and corresponding controls. Using multivariable logistic regression, SH was independently associated with postoperative overall (odds ratio [OR], 2.316; 95% confidence interval [95% CI]: 1.267-4.241; P = 0.007) and any hepatic-related (OR, 2.722; 95% CI: 1.201-6.168; P = 0.016) morbidity. CONCLUSION: Underlying SH, but not simple hepatic steatosis, increases overall and hepatic-related morbidity after liver resection.

Portal hypertension and variceal hemorrhage.

Portal hypertension is a progressively debilitating complication of cirrhosis and a principal cause of mortality in patients who have hepatic decompensation. This article describes the classification system and pathophysiology of portal hypertension. It also discusses a practical approach to prevention of first variceal hemorrhage, general management of the acute bleeding episode, and secondary prophylaxis to prevent rebleeding. Pharmacologic, endoscopic, radiologic, and surgical modalities are all described in detail.

Streptococcus salivarius bacteremia and spontaneous bacterial peritonitis in liver transplantation candidates.

Bacterial infections are a serious complication of end-stage liver disease (ESLD) that occurs in 20% to 60% of patients. We retrospectively reviewed medical records of patients with ESLD who were identified by our microbiology laboratory as having Streptococcus salivarius bacteremia. Of 592 patients listed for transplantation between January 1998 and January 2006, 9 (1.5%) had 10 episodes of S salivarius bacteremia. Of 2 patients already receiving quinolone prophylaxis for spontaneous bacterial peritonitis (SBP), 1 later presented with a second episode. The male-to-female ratio was 1:1.2. Medians for age, Model for End-Stage Liver Disease score, and Child-Turcotte-Pugh score were 50 years, 17, and 10, respectively. Presenting symptoms and signs in 10 episodes of infection were ascites (in 8 episodes), elevated temperature (6), abdominal pain (5), and encephalopathy (4). Median laboratory values included: white blood cell count, 15.1 x 10(9)/L; creatinine, 0.9 mg/dL; albumin, 3.1 gm/dL; aspartate aminotransferase, 64 U/L; alanine aminotransferase, 52.5 U/L; ammonia, 67 mug/dL; and prothrombin time, 17.3 seconds. Ascitic fluid in patients with peritonitis showed a median white blood cell count of 466 cells/mm(3) (range, 250-12,822 cells/mm(3)), with 66% polymorphs, protein of 0.9 gm/dL, and albumin of 0.4 gm/dL. S salivarius may cause primary bacteremia and SBP in liver transplantation candidates despite quinolone prophylaxis.

Nonalcoholic fatty liver disease: a clinical review.

Nonalcoholic fatty liver disease may be the most common liver disease in the United States, with a high prevalence in the obese, type 2 diabetic population, and it is probably underestimated as a cause for cirrhosis. Clinicopathologically, it represents a wide spectrum of histologic abnormalities and clinical outcomes, ranging from benign hepatic steatosis to cirrhosis. Pathophysiologically, insulin resistance is thought to be pivotal in the development of steatosis, after which a second oxidative stressor produces lipid peroxidation and nonalcoholic steatohepatitis (NASH). Liver biopsy is the gold standard for diagnosis and prognosis. The need for an effective treatment is both clear and urgent, yet in the absence of proven therapies, treatment is directed toward weight loss and comorbidity management. For patients with NAFLD at risk of disease progression, there is a lack of large, randomized, placebo-controlled trials of adequate treatment duration, with baseline stratification according to histologic severity.

Jejunal gastrointestinal stromal tumor: a cause of obscure gastrointestinal bleeding.

In cases of obscure gastrointestinal bleeding, when a source for blood loss is not apparent from examination of the colon and upper gastrointestinal tract, the small bowel usually becomes the focus of investigation. A tumor with interesting pathologic features was found in a patient who presented with recurrent episodes of massive obscure gastrointestinal hemorrhage. This case highlights the importance of considering small intestinal tumors as the likely cause of obscure gastrointestinal hemorrhage in young patients and how a noninvasive test, eg, abdominal computed tomography scan, might obviate the need for more invasive testing.

Progression of liver fibrosis in patients with chronic hepatitis C after orthotopic liver transplantation.

BACKGROUND: Hepatitis C virus (HCV)-related cirrhosis is the leading indication for orthotopic liver transplantation (OLTx). HCV recurrence is universal after OLTx, with a highly variable course. This study aimed to find factors that affect progression of fibrosis in recurrent HCV. METHODS: Fifty-eight HCV patients underwent OLTx at our center who were selected on the basis of available preOLTx serum or explanted liver sample and liver biopsy obtained at least 6 months postOLTx. All liver biopsies were performed when clinically indicated and were scored using the modified Hepatitis Activity Index (HAI). Primary immunosuppression consisted of tacrolimus and prednisone. RESULTS: The group included 41 males (mean age 49.6 years). HCV genotype distribution was 1a, 31 (53%); 1b, 16 (28%), and others 11 (19%). The mean follow-up was 53.1 months. Patients with genotype 1a (n=31; mean 46.3 months) had significantly lower fibrosis-free survival analyzed by the presence of fibrosis stages 5 and 6 when compared with other genotypes (n=27; mean 60.1 months; P=0.0088, log rank test). Mean HAI scores were significantly higher in HCV genotype 1a, although there were no differences in survival between genotypes. Similarly, patients with cytomegalovirus (CMV) infection postOLTx (n=4) had a higher fibrosis progression rate compared with those without CMV (n=54) (mean fibrosis-free survival 29.0 vs. 53.0 months P=0.0004, log-rank test). Human leukocyte antigen matching and rate of acute rejection did not influence progression of fibrosis. CONCLUSION: Patients with HCV genotype 1a and those developing CMV postOLTx have a higher rate of hepatic fibrosis progression after OLTx for HCV-related chronic liver disease.