Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. It encompasses a spectrum of disease, including fatty liver disease, alcoholic hepatitis (AH), and alcoholic cirrhosis. AH can range from mild to severe disease, with severe disease being defined as: Discriminant Function (DF) ≥ 32, or Model for End-stage Liver Disease (MELD) ≥ 21, or presence of hepatic encephalopathy. Management of the mild disease consists mainly of abstinence and supportive care. Severe AH is associated with significant mortality. Currently, there is no ideal medical treatment for this condition. Besides alcohol cessation, corticosteroids have been used with conflicting results and are associated with an inherent risk of infection. Overall steroids have shown short term benefit when compared to placebo, but they have no obvious long term benefits. Pentoxifylline does not improve survival in patients with severe AH and is no longer recommended based on the results of the STOPAH (Steroid Or Pentoxifylline for Alcoholic Hepatitis) trial. Anti-tumor necrosis factor (TNF) agents are associated with increased risk of life threatening infections and death. Currently, early stage trials are underway, mainly targeting novel pathways based on disease pathogenesis, including modulation of innate immune system, inhibition of gut-liver axis and cell death pathways, and activation of transcription factor farnesyl X receptor (FXR). Future treatment may lie in human induced pluripotent stem cell (iPSC) technology, which is currently under investigation for the study of pathogenesis, drug discovery, and stem cell transplantation. Liver transplantation has been reported with good results in highly selected patients but is controversial due to limited organ supply.

Background: Hepatitis C (HCV) direct acting antiviral agents (DAAs) are safe, effective, and tolerable. Most contraindications to interferon-based treatment are no long applicable. The aims of this study were to understand the predictors of approval to drug accessibility.

Methods: We studied all consecutive patients with HCV prescribed DAAs between October 2014 and July 2015. Data on demographic, socio-economic status, comorbidities, baseline laboratory values, and assessment of liver disease severity, insurance, and specialty pharmacy type were collected. Multivariate analyses were performed to identify predictors of prescription approval.

Results: In total, 410 patients were prescribed DAAs between October 2014 and July 2015. Of those, 332 (81%) patients were insurance approved for therapy. Of the 332 patients accepted, 251 were accepted after the first prescription attempt, and 38 were accepted after the second and third attempts. The number of attempts for the other 43 approved patients was unknown. Older age (p = 0.001), employment (p = 0.001), lack of comorbidities (p = 0.02), liver transplantation (p = 0.018), and advanced liver disease (p = 0.001) were more likely associated with obtaining approval. Household income was not associated with insurance approval. In the multivariate analysis, Medicare insurance (odds ratio [OR]) 2.67, 95% confidence interval [CI] 0.96–7.20), lack of nonliver comorbidities (OR 2.72, 95% CI 1.35–5.43), and the presence of advanced liver disease (OR 1.82, 95% CI 1.04–3.24) independently predicted drug approval.

Conclusion: Despite the availability of DAAs for HCV, barriers from insurance carriers continue to impair widespread use. Patients with advanced liver disease, Medicare, and without comorbidities are most likely to be insurance approved for DAAs.

Hepatic abscess (HA) remains a serious and often difficult to diagnose problem. HAs can be divided into three main categories based on the underlying conditions: infectious, malignant, and iatrogenic. Infectious abscesses include those secondary to direct extension from local infection, systemic bacteremia, and intra-abdominal infections that seed the portal system. However, over the years, the etiologies and risks factors for HA have continued to evolve. Prompt recognition is important for instituting effective management and obtaining good outcomes.

Background and Aims: Previous studies have shown increased hepatic decompensation in patients with cirrhosis undergoing surgery. However, there are little data available in cirrhotics undergoing orthopedic surgery compared to cirrhotics who did not undergo surgery. The aim of this study was to examine the demographics, comorbid conditions, and clinical factors associated with hepatic decompensation within 90 days in cirrhotics who underwent orthopedic surgery. Methods: This is a retrospective matched cohort study. Inclusion criteria were cirrhosis diagnosis, age > 18 years, ≥ 6 months continuous health plan membership, and a procedure code for orthopedic surgery. Up to five cirrhotic controls without orthopedic surgery were matched on age, gender, and cirrhosis diagnosis date. Data abstraction was performed for demographics, socioeconomics, clinical, and decompensation data. Chart review was performed for validation. Multivariable analysis estimated relative risk of decompensation. Results: Eight hundred fifty-three orthopedic surgery cases in cirrhotics were matched with 4,263 cirrhotic controls. Among the cases and matched controls, the mean age was 60.5 years, and 52.2% were female. Within 90 days after surgery, cases had more decompensation compared to matched controls (12.8% vs 4.9%). Using multivariable analysis, orthopedic surgery, a 0.5 g/dL decrease in serum albumin, and a 1-unit increase in Charlson Comorbidity Index were associated with a significant increase in decompensation within 90 days of surgery. Diabetes, chronic obstructive pulmonary disease, and chronic kidney disease were seen with increased frequency in cases vs. matched controls. Conclusions: Cirrhotics who underwent orthopedic surgery had a significant increase in hepatic decompensation within 90 days of surgery compared to matched controls. An incremental decrease in serum albumin and an incremental increase in the Charlson Comorbidity Index were significantly associated with hepatic decompensation after surgery.

Viral infection in the liver, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, is a major health problem worldwide, especially in developing countries. The infection triggers a pro-inflammatory response in patients that is crucial for host defense. Recent studies have identified multiple transmembrane and cytosolic receptors that recognize pathogen-derived nucleic acids, and these receptors are essential for driving immune activation in the liver. In addition to sensing DNA/RNA from pathogens, these intracellular receptors can be activated by nucleic acids of host origin in response to sterile injuries. In this review, we discuss the expanding roles of these receptors in both immune and nonimmune cells in the liver.

Background and Aims: It remains controversial whether granulocyte colony-stimulating factor (G-CSF) prolongs survival in liver failure (LF) patients. This meta-analysis was performed to evaluate the effect of G-CSF on patients with LF.

Methods: PubMed, EMBASE, and Web of Science databases were searched to identify English language randomized controlled trials comparing G-CSF with control therapy published before14 February 2015. A meta-analysis was performed to examine changes in liver function and patient survival. The association was tested using odds ratio (OR) or risk ratio (RR) with 95% confidence intervals (CI).

Results: Five randomized controlled trials were eligible for the meta-analysis. Significant amelioration of prothrombin time and total bilirubin in LF patients was attributed to G-CSF therapy (OR, −0.064; 95% CI,−0.481 to 0.353; p< 0.001; and OR, −0.803; 95% CI, −1.177 to −0.430; p = 0.000, respectively). Treatment with G-CSF resulted in improved Model for End-Stage Liver Disease and Child-Turcotte-Pugh scores (OR, −1.741; 95% CI, −2.234 to −1.250; p = 0.000; and OR, −0.830, 95% CI, −1.194 to −0.465; p = 0.000, respectively). A lower incidence of sepsis was found in patients treated with G-CSF (RR, 0.367; 95% CI, 0.158 to 0.854; p = 0.020). G-CSF therapy significantly increased survival rate in LF patients (RR, 2.25; 95% CI, 1.517 to 3.338; p = 0.000).

Conclusions: The results of this meta-analysis indicate that G-CSF treatment in patients with LF significantly improved liver function, reduced the incidence of sepsis, and prolonged short-term survival.

Hepatitis C virus (HCV) infection affects as many as 185 million people globally, many of whom are chronically infected and progress over time to cirrhosis, decompensated liver disease, hepatocellular carcinoma, and eventually death without a liver transplant. In the United States, HCV genotype 1 constitutes about 75% of all infections. While interferon and ribavirin therapy was the cornerstone of treatment for many years, interferon-free treatments have become the standard of care with the emergence of new direct-acting agents, resulting in more effective treatment, shorter duration of therapy, better tolerability, lower pill burden, and ultimately better adherence. This review will summarize the evidence for the currently available combination therapies as well as emerging therapies in phase 3 trials for treatment of HCV genotype 1.

Hepatitis B virus (HBV) infection remains an endemic disease in most parts of the world despite available prophylactic vaccines. Non-Hodgkin’s lymphoma is the most common hematological malignancy, and certain patients undergoing therapy are at increased risk of HBV reactivation. Rituximab, a monoclonal antibody, is well studied in HBV reactivation, but newer agents have been implicated as well. Here, we review novel agents suspected in HBV reactivation and effective strategies to prevent HBV reactivation. Fifteen years of literature were reviewed in order to better understand the reactivation rates of hepatitis B in patients with non-Hodgkin’s lymphoma. Anti-CD20 antibodies continue to be the main medications that can lead to HBV reactivation, and HBV reactivation rates have decreased with increased awareness. HBV reactivation is uncommon when using other novel agents. Entecavir and lamivudine remain the agents of choice to prevent HBV reactivation in high risk patients. In conclusion, the immunosuppressive effect of NHL and its therapy provide a pathway for HBV reactivation, especially in patients treated with anti-CD20 antibody. Since many HBV positive patients are often excluded from clinical trials of novel agents in NHL, more aggressive post-market surveillance of new agents, well-designed best practice advisories, and timely case reports are needed to reduce the incidence of HBV reactivation. Lastly, large prospective investigations coupled with well-utilized best practice advisories need to be conducted to understand the impact of more potent novel NHL therapy on HBV reactivation.

Worldwide incidence of hepatocellular carcinoma (HCC) is steadily increasing, highlighting its status as a public health concern, particularly due to its significant association with other comorbidities, such as diabetes. However, nonalcoholic fatty liver disease (NAFLD) has emerged as a primary risk factor, with its own prevalence increasing in recent years, and it has gradually caught up with the historical primary etiological factors of infection with hepatitis B virus and hepatitis C virus, exposure to aflatoxin, or alcohol liver disease. The deeply worrisome aspects of all of these high risk factors, however, are their remarkable presence within populations. Systemic and genetic mechanisms involved in the malignant transformation of liver cells, as well as useful biomarkers of early stage HCC are being investigated. However, the exact mechanisms underlying the interrelation of NAFLD and HCC remain largely unknown. In this review, some of the recent advances in our understanding of liver lipid accumulation are summarized and discussed to provide insights into the relationship between NAFLD and hepatocyte malignant transformation.

Cancer is a condition characterized by uncontrolled growth of cells that leads to formation of lumps or masses of tissues called tumors. There are different types of cancer, each of which are basically linked to the type of cell that it affects. Cancer may be caused by hereditary factors, environmental factors, carcinogenic agents and exposure to radiation, among other sources. Often referred to as the “Silent Killer,” cancer is one of the deadliest diseases affecting human populations worldwide. In India, approximately 1 million cases of cancer are detected annually and added to the total pool of patients suffering from this disease. Cancer cases are rising at an alarming rate over the last decade in India, with increases being particularly high in the North Eastern part of the country. Head and neck cancer leads the list in northeast India, as per reports from the National Cancer Registries and ICMR. Researchers all over the globe, however, have adopted numerous ways to study the molecular mechanisms associated with cancer biology and all their approaches can be broadly summarized under genomic and proteomic studies. Many pathways have been proposed to reflect the mechanisms involved in cancer. However, the one mediated by P53 and the myeloid differentiation factor 88 (MyD88) has gained significant attention. P53 is a tumor suppressor protein, encoded by the gene TP53 in humans. It acts by regulating the cell cycle via integration of various signals linked to cell life and death, and as such plays a crucial role in preventing cancer. It also activates the programmed cell death pathway, or apoptosis, thereby arresting cell growth. While a substantial amount of data has been published on p53, the MyD88 pathway remains much less studied and largely unknown; research efforts are ongoing with the aim of elucidating the signaling mechanism of MyD88 in cancer. In this article, emphasis is laid on discussing the signaling pathways associated with MyD88.

Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur. Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients. Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level, with focus on the underlying molecular signaling pathways.

Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide. Liver steatosis is a common finding in many hepatic and extrahepatic disorders, the most common being metabolic syndrome (MS). Over time, it has been shown that the frequent coexistence of these two conditions is not coincidental, since many epidemiological, clinical, and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic derangements. Here, we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this association. It has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple mechanisms. Substantial research has suggested that HCV interferes with insulin signaling both directly and indirectly, inducing the production of several proinflammatory cytokines. HCV replication, assembly, and release from hepatocytes require close interactions with lipid droplets and host lipoproteins. This modulation of lipid metabolism in host cells can induce hepatic steatosis, which is more pronounced in patients with HCV genotype 3. The risk of steatosis depends on several viral factors (including genotype, viral load, and gene mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic predisposition, medication use, and alcohol consumption). HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life, due to their association with resistance to antiviral therapy, progression of hepatic fibrosis, and development of hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes in lipid and iron metabolism lead to glucose intolerance, arterial hypertension, hyperuricemia, and atherosclerosis, resulting in increased cardiovascular mortality.

Background: Evaluation of advanced fibrosis in patients with hepatitis C virus (HCV) infection is used to facilitate decisions on treatment strategy and to initiate additional screening measures. Unfortunately, most studies have predominately Caucasian (Cau) patients and may not be as relevant for African Americans (AA). Aims: This study specifically addresses the issue of defining minimal vs. significant fibrosis in African Americans (AA) with chronic hepatitis C (CHC) using noninvasive assays. Methods: All patients (n = 319) seen between 1 January 2008 and 30 June 2013 for whom a FibroSpect II® (FSII) assay was performed and had data for calculation of aspartate aminotransferase (AST) platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were identified using the medical records. Results: When liver biopsy score and FSII assay results for the AA patients with CHC were compared, 31% of AA had advanced FSII fibrosis scores (F2-F4) despite a biopsy score of F0-F1. In contrast, 10% of Cau over-scored. The AA false positive rate was 14% for APRI and 34% for FIB-4. Combining FSII with either APRI (7% false positive) or FIB-4 (10% false positive) improved the false positive rate in AA to 7% (FSII + APRI) and 10% (FSII + FIB-4) but reduced the sensitivity for significant fibrosis. Conclusions: The FSII assay overestimates fibrosis in AA and should be used with caution since these patients may not have significant fibrosis. If the APRI or FIB-4 assay is combined with the FSII assay, minimal fibrosis in AA can be defined without subjecting the patients to a subsequent biopsy.

Cystic echinococcosis (CE) is a widely endemic helminthic disease caused by infection with metacestodes (larval stage) of the Echinococcus granulosus tapeworm. E. granulosus are common parasites in certain parts of the world, and are present on every continent with the exception of Antarctica. As a result, a large number of people are affected by CE. The increased emigration of populations from endemic areas where prevalence rates are as high as 5–10% and the relatively quiescent clinical course of CE pose challenges for accurate and timely diagnoses. Upon infection with CE, cyst formation mainly occurs in the liver (70%). Diagnosis involves serum serologic testing for antibodies against hydatid antigens, but preferably with imaging by ultrasound or CT/MRI. Treatment methods include chemotherapy with benzimidazole carbamates and/or surgical approaches, including percutaneous aspiration injection and reaspiration. The success of these methods is influenced by the stage and location of hepatic cysts. However, CE can be clinically silent, and has a high risk for recurrence. It is important to consider the echinococcal parasite in the differential diagnosis of liver cystic lesions, especially in patients of foreign origin, and to perform appropriate long-term follow-ups. The aim of this review is to highlight the epidemiology, natural history, diagnostic methods, and treatment of liver disease caused by E. granulosus.