The link between chronic hepatitis C virus (HCV) infection and a subset of B-cell non-Hodgkin lymphomas (B-NHL) is strongly supported by epidemiological studies. Evidence demonstrating complete regression of lymphoma after antiviral treatments suggests possible chronic antigenic stimulation for the origin of B-NHL and provides evidence for a virus-mediated lymphomagenesis. B-NHL is a heterogeneous group of lymphomas with varied clinical presentation and may be indolent or aggressive. The optimal management of HCV related B-NHL is not clear. Antiviral treatment may be sufficient for low-grade lymphomas, but chemotherapy is necessary in patients with high grade lymphomas. Interferon (IFN)-based antiviral treatment regimens for HCV infection are limited by poor tolerance and suboptimal antiviral response. Recently approved novel direct acting antiviral (DAA) drugs are highly effective and safe. This has opened a new era for the treatment of HCV related B-NHL alone or in conjunction with chemotherapy. Treatment of HCV associated B-NHL should be performed in an interdisciplinary approach in close consultation with hematologist and hepatologist. In this review, we summarize data regarding clinical features and epidemiology of B-NHL and discuss novel therapeutic approaches, including DAAs, that may prove to be effective in the treatment of HCV associated lymphomas.

Viral hepatitis C is responsible for a large burden of disease worldwide. Treatment of hepatitis C infection is currently undergoing a revolution with the development of new direct acting antivirals that offer higher cure rates and fewer side effects than other medications currently available. Treatment options for children, although well-defined and evidence-based, are limited relative to adults as there are few trials regarding the use of these newly developed agents in children. With so much optimism in the development of novel therapeutic options for hepatitis C, it is timely to review and summarize the current standard of care treatment and indications for treatment of chronic hepatitis C in children. We provide here an overview of recent drug developments and their potential for use in children.

Liver fibrosis is part of the wound-healing response to liver damage of various origins and represents a major health problem. Although our understanding of the pathogenesis of liver fibrosis has grown considerably over the last 20 years, effective antifibrotic therapies are still lacking. The use of animal models is crucial for determining mechanisms underlying initiation, progression, and resolution of fibrosis and for developing novel therapies. To date, no animal model can recapitulate all the hepatic and extra-hepatic features of liver disease. In this review, we will discuss the current rodent models of liver injuries. We will then focus on the available ways to target specifically particular compounds of fibrogenesis and on the new models of liver diseases like the humanized liver mouse model.

Endoscopic stent placement is a common primary management therapy for benign and malignant biliary strictures. However, continuous use of stents is limited by occlusion and migration. Stent technology has evolved significantly over the past two decades to reduce these problems. The purpose of this article is to review current guidelines in managing malignant and benign biliary obstructions, current endoscopic techniques for stent placement, and emerging stent technology. What began as a simple plastic stent technology has evolved significantly to include uncovered, partially covered, and fully covered self-expanding metal stents (SEMS) as well as magnetic, bioabsorbable, drug-eluting, and antireflux stents.1

Nucleotide compounds like sofosbuvir, acyclovir, and tenofovir have proven to be amongst the most potent orally available antiviral treatments. These drugs exhibit high efficacy and a wide therapeutic index, with demonstrated utility in a number of chronic viral infections. The approval of Sovaldi™, brand name for sofosbuvir, by the U.S. Food and Drug Administration heralded improvements in chronic hepatitis C virus (HCV) treatment. Sofosbuvir was originally discovered by Pharmasset Corporation and named PSI-7977. It was subsequently acquired and advanced through phase 3 development by Gilead Sciences, Inc. In Sofosbuvir both a unique pharmacology and a high specificity for the HCV ribonucleic acid polymerase are present in a molecule that is well tolerated and highly efficacious. Phase 2 and 3 clinical trials have consistently demonstrated durable and high rates of sustained virologic response (SVR), curing patients in excess of 80% in all genotypes and >90% in treatment-naïve subjects being administered combination therapy with other agents. Harvoni® is the combination of sofosbuvir and the NS5A inhibitor ledipasvir in a fixed-dose oral tablet, and it has demonstrated high SVR rates in patients infected with HCV genotype 1, without the need for exogenous interferon and/or ribavirin. Here, we discuss the discovery, development, pharmacologic characterization, and results from the phase 3 trials of sofosbuvir. Hepatitis C is a chronic disease, for which most patients have been undiagnosed, are unwilling to start treatment, or are ineligible for treatment because of the high toxicity and low efficacy of interferon and ribavirin-based therapy. Clinical studies with sofosbuvir have demonstrated significant improvement over the prior standard of care, thus ushering in a new paradigm of HCV treatment and an update of treatment guidelines.

The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting.

Autoimmune hepatitis (AIH), a liver disorder affecting both children and adults, is characterized by inflammatory liver histology, elevated transaminase levels, circulating nonorganspecific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of AIH are recognized according to seropositivity: smooth muscle antibody and/or antinuclear antibody define AIH type 1 and antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 define AIH type 2. AIH type 1 affects both adults and children, while AIH type 2 is mainly a paediatric disease, though it does occasionally affects young adults. AIH should be considered during the diagnostic workup of any patient with increased liver enzyme levels. AIH is exquisitely responsive to immunosuppressive treatment with prednisolone with or without azathioprine, with symptom free long-term survival for the majority of patients. For those who do not respond to standard treatment, or who are difficult-to-treat, mycophenolate mofetil and, in the absence of a response, calcineurin inhibitors should be tried in addition to steroids. The pathogenesis of AIH is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4 T-cells, although recent studies support the involvement of diverse populations, including Th17 cells. A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigenspecific regulatory T-cells, which ultimately aim at restoring tolerance to liver-derived antigens.

Studies have shown that nonalcoholic fatty liver disease (NAFLD) is strongly associated with several metabolic disorders and diseases, such as obesity, type 2 diabetes mellitus, and dyslipidemia. In NAFLD, dyslipidemia is manifested as increased serum triglyceride and low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels, all of which are key risk factors for cardiovascular disease (CVD). CVD is a leading cause of mortality in NAFLD patients. Thus, implementation of an aggressive therapeutic strategy for dyslipidemia with hypolipidemic agents may mitigate the risk for CVD among NAFLD patients. Here, we provide a current review of literature regarding NAFLD, with particular emphasis on dyslipidemia and available treatment options.

Background and Aims: Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease. Diabetes mellitus (DM) is a common comorbidity among NAFLD patients. We performed this study with the specific aim to examine the impact of DM on progression of alcoholic liver disease (ALD) and NAFLD.

Methods: Medical charts of 480 patients with ALD or NAFLD (2004–2011) managed at a tertiary center were retrospectively reviewed. NAFLD was diagnosed based on exclusion of other causes of liver disease and alcohol use of <10 g/d. ALD was diagnosed based on alcohol use of >40 g/d in women or >60 g/d in men for >5 years.

Results: Of 480 patients (307 NAFLD), 200 diabetics differed from nondiabetics for: age (52±11 vs. 49±11 years; p=0.004); male gender (48% vs. 57%; p=0.03); metabolic syndrome (49% vs. 30%; p=0.0002); NAFLD (80% vs. 56%; p<0.0001); cirrhosis (70% vs. 59%; p=0.005); and hepatocellular carcinoma (HCC; 8% vs. 3%; p=0.009). Over a 3 year median follow-up period, diabetics relative to nondiabetics had a higher probability to develop cirrhosis (60% vs. 41%; p=0.022) and HCC (27% vs. 10%; p=0.045). There was a trend for increased development of hepatic encephalopathy in diabetics compared to nondiabetics (55% vs. 39%; p=0.053), and there was no difference between the two groups in survival or other liver disease complications.

Conclusion: DM increased risk for cirrhosis and HCC among patients with ALD and NAFLD. Prospective studies with longer follow-up periods are needed to examine the impact of DM on survival and the role of aggressive HCC screening in diabetic cirrhosis.

Hepatitis B virus (HBV) causes an endemic infection that affects nearly 2 billion patients worldwide. It is one of the leading causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). Recurrence of HBV infection after LT is due to specific HBV-host genome interactions. Although hepatitis B immunoglobulin treatment constituted the backbone of HBV recurrence, use of the nucleoside and nucleotide analogs (especially the ones with a higher genetic barrier to resistance), either alone or in combination, offer us new and powerful options in overcoming this serious issue.

The treatment of hepatitis c virus (HCV) infection in children is difficult as few options are available. The standard therapy is combination pegylated interferon (PEG–IFN) α-2a or 2b and ribavirin, and the duration of therapy depends on HCV genotype. New oral drug therapies available for adults have still not been approved for treatment in children. Here, we review the causes of HCV infection in children, the therapeutic options for children, and the side effects of these treatments. The problems faced by physicians managing HCV infection in children less than 12 years of age in a developing country are also discussed.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are two major types of chronic cholestatic liver disease. Each disorder has distinguishing features and variable progression, but both may ultimately result in cirrhosis and hepatic failure. The following offers a review of PBC and PSC, beginning with a general overview of disease etiology, pathogenesis, diagnosis, clinical features, natural course, and treatment. In addition to commonly associated manifestations of fatigue, pruritus, and fat-soluble vitamin deficiency, select disease-related topics pertaining to women's health are discussed including metabolic bone disease, hyperlipidemia and cardiovascular risk, and pregnancy-related issues influencing maternal disease course and birth outcomes. This comprehensive review of PBC and PSC highlights some unique clinical considerations in the care of female patients with cholestatic liver disease.

Alcohol consumption is often associated with viral hepatitis. Although alcohol is known to worsen viral liver disease, the interactions between alcohol and viral hepatitis are not fully understood. Molecular alterations in the liver due to alcohol and viral hepatitis include effects on viral replication, increased oxidative stress, cytotoxicity, and a weakened immune response. Clinically, alcohol enhances disease progression and favors induction of primitive liver neoplasm. The use of new antivirals for hepatitis C and well-established drugs for hepatitis B will determine how viral hepatitis can be controlled in a large percentage of these patients. However, alcohol-related liver disease continues to represent a barrier for access to antivirals, and it remains an unresolved health issue.