Andres F. Carrion

Sofosbuvir and simeprevir for treatment of hepatitis C virus infection in liver transplant recipients

Recurrent hepatitis C virus (HCV) infection occurs universally in the allograft in the absence of effective antiviral therapy before liver transplantation (LT). Antiviral therapy with sofosbuvir and simeprevir has proven to be highly effective and well tolerated in the nontransplant setting for treatment of HCV genotype 1 infection; therefore, we sought to evaluate the efficacy and safety of this regimen in LT recipients with recurrent HCV infection. This was a retrospective analysis of a single‐center treatment protocol of patients with HCV genotype 1 infection who received a 12‐week combination regimen of sofosbuvir and simeprevir. Sixty‐one patients (35 with genotype 1a and 26 with genotype 1b) completed treatment with simeprevir and sofosbuvir. Three patients received additional ribavirin. Laboratory data and clinical assessments performed at the baseline, on treatment, at the end of treatment, and 12 weeks after the completion of antiviral therapy [sustained virological response at 12 weeks (SVR12)] were analyzed. The median time after LT was 5.4 years [interquartile range (IQR), 1.9‐8.4 years], and tacrolimus was the most commonly used immunosuppressive agent (80.3%). Overall, SVR12 was achieved in 93.4% [95% confidence interval (CI), 84%‐97%] of LT recipients treated with 12 weeks of sofosbuvir and simeprevir. When they were analyzed according to the HCV subtype, LT recipients with genotype 1b had a 100% SVR12 rate (95% CI, 87%‐100%), whereas SVR12 was 89% (95% CI, 74%‐95%) for those with genotype 1a. Advanced fibrosis (METAVIR F3‐F4) was associated with diminished antiviral efficacy in LT recipients with genotype 1a [SVR12, 67% (95% CI, 39%‐86%); P = 0.01]. Overall, the incidence of adverse events (AEs) was low, and no severe AEs occurred during treatment. In conclusion, treatment with a 12‐week regimen of sofosbuvir and simeprevir was well tolerated and resulted in a high SVR12 rate for LT recipients with recurrent HCV genotype 1 infection. Genotype 1a patients with advanced fibrosis of the allograft were more likely to relapse. Liver Transpl 21:823‐830, 2015.

Chronic Liver Disease in the Hispanic Population of the United States

Chronic liver disease is a major cause of morbidity and mortality among Hispanic people living in the United States. Environmental, genetic, and behavioral factors, as well as socioeconomic and health care disparities among this ethnic group have emerged as important public health concerns. We review the epidemiology, natural history, and response to therapy of chronic liver disease in Hispanic patients. The review covers nonalcoholic fatty liver disease, viral hepatitis B and C, coinfection of viral hepatitis with human immunodeficiency virus, alcoholic cirrhosis, hepatocellular carcinoma, autoimmune hepatitis, and primary biliary cirrhosis. For most of these disorders, the Hispanic population has a higher incidence and more aggressive pattern of disease and overall worse treatment outcomes than in the non-Hispanic white population. Clinicians should be aware of these differences in caring for Hispanic patients with chronic liver disease.

Viral Hepatitis in the Elderly

As life expectancy continues to rise, elderly adults represent a rapidly growing proportion of the population. The likelihood of complications of acute and chronic liver disease and overall mortality are higher in elderly populations. Several physiological changes associated with aging, greater prevalence of co-morbid conditions, and cumulative exposure to hepatotropic viruses and environmental hepatotoxins may contribute to worse outcomes of viral hepatitis in the elderly. Although pharmacotherapy for hepatitis B and C continues to evolve, the efficacy, tolerability, and side effects of these agents have not been studied extensively in elderly adults. Immunization against hepatitis A and B in naïve elderly adults is an important public health intervention that needs to be revised and broadened.

New antiviral agents for the treatment of hepatitis C: ABT-450

Introduction: Hepatitis C virus (HCV) therapy continues to evolve rapidly. ABT-450 is a novel potent inhibitor of the non-structural 3/4A protease that has been studied in combination with several agents, allowing shorter duration of therapy and interferon-free/ribavirin-free all-oral regimens. Preliminary data from studies evaluating these new regimens are impressive with sustained virological response (SVR) rates of 88 – 100% after 12 weeks of therapy in patients with previously untreated HCV genotype 1 infection. SVR rates in treatment-experienced patients are also encouraging. Areas covered: Efficacy and tolerability of antiviral regimens containing ABT-450 boosted with ritonavir (ABT-450/r). Results from published studies and abstracts from recent meetings are presented. Expert opinion: Newer direct-acting antiviral agents such as ABT-450 promise effective and durable suppression of HCV with interferon/ribavirin-free all-oral regimens. This agent also allows for shorter duration of treatment and has tolerable side effects. Results of clinical trials including a broader spectrum of individuals with HCV infection are eagerly awaited.

Severe colitis associated with docetaxel use: A report of four cases

Diarrhea is a common side effect of chemotherapy. Pseudomembranous colitis is a well known complication of antibiotic treatment that can also be observed, albeit rarely, with certain chemotherapeutic agents. We present four cases of severe colitis in patients undergoing treatment with taxane-based chemotherapy for pancreatic, lung and breast cancer. None of them had recently received antibiotics. One patient presented with a bowel perforation and three had endoscopic findings of pseudomembranous colitis. Two of these three patients had negative stool toxin assays for Clostridium difficile. In the patient presenting with perforation, an emergency left hemicolectomy was performed and the pathological findings in the colon were acute inflammation and ischemic necrosis; the other three patients were treated with oral vancomycin and/or oral or intravenous metronidazole leading to complete resolution of the symptoms. Apart from pseudomembranous colitis, we describe patients presenting with neutropenic enterocolitis as well as ischemic colitis after docetaxel use. These cases provide some insight into the spectrum and varied clinical presentations of severe colitis associated with taxane-based chemotherapy.

Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.

Liver Transplant for Cholestatic Liver Diseases

Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT.

Should Ribavirin Be Used to Treat Hepatitis C in Dialysis Patients

Hepatitis C virus infection adversely affects outcomes in patients with chronic kidney disease undergoing maintenance dialysis. Pegylated interferon and ribavirin, the standard‐of‐care treatment in patients with intact renal function, is associated with severe side effects, toxicity, and high dropout rates in this population. Ribavirin has an important role in maintaining antiviral response following completion of therapy and increases sustained viral response (SVR) rates. However, the use of ribavirin in dialysis patients has been limited by the high frequency of severe hemolytic anemia and is currently reserved for study protocols and highly selected candidates treated at experienced centers. Encouraging data from small trials have shown a significant increase in SVR rates with the use of different dosing regimens of ribavirin in addition to interferon‐based therapy and aggressive erythroid‐stimulating agent support in dialysis patients. Use of ribavirin in selected dialysis patients, particularly renal transplant candidates, by experienced clinicians is appropriate.

What are the management issues for hepatitis C in dialysis patients?: natural history of hepatitis C in dialysis populations.

Hepatitis C virus (HCV) infection persists as a frequent cause of chronic liver disease in individuals with chronic kidney disease (CKD) on long-term renal replacement therapy (RRT). The seroprevalence of anti-HCV antibodies is approximately fivefold higher in individuals undergoing maintenance hemodialysis in the United States compared to the general US population (7.8% versus 1.6%, respectively) (1). The prevalence of HCV infection in hemodialysis populations is as high as 80% in countries such as Morocco, Moldavia, and Egypt (2). Nosocomial transmission within hemodialysis units is now the most important risk factor for HCV infection in individuals undergoing long-term RRT. The risk of HCV infection varies depending on the modality of RRT; long-term hemodialysis carries the highest risk of incident cases of HCV infection, whereas peritoneal dialysis is associated with the lowest risk, reflected in the higher anti-HCV seroprevalence in individuals undergoing hemodialysis compared to peritoneal dialysis (7.9% 5.5% versus 3.0% 2.0%, respectively) in the Asia-Pacific region (3). The risk of nosocomial transmission of HCV is proportional to time on hemodialysis and prevalence of HCV within individual hemodialysis units (4). Strict enforcement of universal precautions and standard infection control measures such as not sharing supplies, instruments, medication vials, or any ancillary equipment among patients has proven to be an effective and reproducible intervention to eliminate HCV transmission in hemodialysis units (5). In contrast to hepatitis B virus (HBV) infection, routine precautions do not include isolation of individuals with HCV infection by rooms, dialysis machines, or staff due to significantly lower infectivity of HCV compared to HBV, absence of viability of HCV at room temperature, and compelling data showing complete elimination of nosocomial transmission of HCV in dialysis centers where strict enforcement of infection control procedures was implemented (4). Highly trained staff and an appropriate personnelto-patient ratio also reduce the rates of HCV transmission in hemodialysis units (5). Universal screening of blood products using newer enzyme-linked immunosorbent assays (EIA) has significantly decreased the transmission of HCV among individuals with CKD (6). In addition, development and widespread use of recombinant erythroid-stimulating agents (ESA) has decreased the need for transfusion of blood products in this population.

Ileal lines: a marker of the ileocecal valve on wireless capsule endoscopy

Wireless capsule endoscopy (WCE) is a noninvasive, ambulatory imaging modality used for evaluation of the small bowel. The wireless capsule reaches the cecum in approximately 80% of patients, and documentation of complete evaluation of the small bowel is important. Nevertheless, WCE photographs of the cecum often lack distinctive characteristics of this segment of the colon seen at colonoscopy, and the presence of fecal effluent is frequently used as surrogate evidence of complete examination of the small bowel. We have identified a new endoscopic landmark, ileal lines (Barkin lines), which are readily identified with WCE and represent a group of longitudinal mucosal folds parallel to each other seen at the ileocecal valve. The characteristic appearance of ileal lines is likely due to flattening of the mucosa with less-obvious plicae circulares and less-pronounced mucosal crests and to the increased vascularity of the distal ileum. Ileal lines have a characteristic red color that distinguishes them from the surrounding mucosa and merge together, forming a rosette pattern in the terminal ileum (Fig. 1) of healthy individuals. Therefore, it may be expected, although unproven, that disease processes affecting the distal ileal mucosa (ie, Crohn disease) result in effacement and possibly complete disappearance of this enodoluminal landmark. Ileal lines are similar in appearance to the longitudinal lines seen at the gastroesophageal junction, which are markers of the gastroesophageal junction.