Alcohol-attributable burden on global health is increasing, and the relationship between population alcohol consumption and liver-related deaths is strong. Longstanding scientific and clinical work has led to a relatively thorough, if not complete, understanding of the effects of alcohol consumption on the liver. Pathologic features of alcoholic liver disease (ALD) are recognized by pathologists and used to assist clinicians in diagnosing and determining severity of disease in patients suspected of ALD. In this review, we discuss the pathologic manifestations of ALD and provide salient points on their pathophysiology. In addition, the benefits and indications of liver biopsy and important differential diagnoses, including features distinguishing these entities, are reviewed.

Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection and seropositivity worldwide, and it has been proposed that this enhanced susceptibility to HCV is related to coinfection with schistosomiasis. Although currently, there are no studies regarding the actual prevalence of both human schistosomiasis and schistosomiasis/HCV coinfection evidences strongly support that eliminating human schistosomiasis from Egypt is necessary to reduce both HCV prevalence and liver pathology. The present review highlights the significant impact of the neglected tropical disease human schistosomiasis on both susceptibility of Egyptians to HCV coinfection, severity of the resulting liver pathology, and poor response to antiviral therapy. The immune evasion mechanisms exerted by the HCV-NS3/4A protease domain, and the possible impact of immune evasion mechanisms exerted by proteases of larval, worm and egg stages of the parasite Schistosoma on human susceptibility to HCV infection are discussed. In addition, schistosome immune evasion mechanisms may include immunosuppression that in turn prevents clearance of HCV viremia and leads to relapsing HCV infection and severe liver pathology. I propose the generation of a replicon system from the most prevailing genotype (HCV-4a) in Egypt and establishing its replication on hepatoplastoma or immune cells in presence of bilharzial antigens. Finally, the use of a humanized small animal model that can acquire both HCV and S. mansoni infections will be important to further understand in real time the impact of coinfection on both the immune system and liver pathology.

Traditional Chinese Medicine (TCM) is popular around the world and encompasses many different practices with particular emphasis on herbal TCM. Using the PubMed database, a literature search was undertaken to assess the extent herbal TCM products exert rare hepatotoxicity. Analysis of reported cases revealed numerous specified herbal TCM products with potential hepatotoxicity. Among these were An Shu Ling, Bai Fang, Bai Xian Pi, Ban Tu Wan, Bo He, Bo Ye Qing Niu Dan, Bofu Tsu Sho San, Boh Gol Zhee, Cang Er Zi, Chai Hu, Chaso, Chi R Yun, Chuan Lian Zi, Ci Wu Jia, Da Chai Hu Tang, Da Huang, Du Huo, Gan Cao, Ge Gen, Ho Shou Wu, Hu Bohe You, Hu Zhang, Huang Qin, Huang Yao Zi, Hwang Geun Cho, Ji Gu Cao, Ji Ji, Ji Xue Cao, Jiguja, Jin Bu Huan, Jue Ming Zi, Kamishoyosan, Kudzu, Lei Gong Teng, Long Dan Xie Gan Tang, Lu Cha, Ma Huang, Mao Guo Tian Jie Cai, Onshido, Polygonum multiflorum, Qian Li Guang, Ren Shen, Sairei To, Shan Chi, Shen Min, Shi Can, Shi Liu Pi, Shou Wu Pian, Tian Hua Fen, White flood, Wu Bei Zi, Xi Shu, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, Zhen Chu Cao, and various unclassified Chinese herbal mixtures. Causality was firmly established for a number of herbal TCM products by a positive reexposure test result, the liver specific scale of CIOMS (Council for International Organizations of Medical Sciences), or both. Otherwise, the quality of case data was mixed, especially regarding analysis of the herb ingredients because of adulteration with synthetic drugs, contamination with heavy metals, and misidentification. In addition, non-herbal TCM elements derived from Agaricus blazei, Agkistrodon, Antelope, Bombyx, Carp, Fish gallbladder, Phellinus, Scolopendra, Scorpio, and Zaocys are also known or potential hepatotoxins. For some patients, the clinical course was severe, with risks for acute liver failure, liver transplantation requirement, and lethality. In conclusion, the use of few herbal TCM products may rarely be associated with hepatotoxicity in some susceptible individuals, necessitating a stringent pretreatment evaluation of the risk/benefit ratio, based on results of multicenter, randomized, double-blind, placebo-controlled clinical trials.

Human hepatitis E virus (HHEV) is the proposed name for a diverse group of RNA viruses from the family Hepeviridae that cause acute hepatitis among humans. Waterborne strains are regularly imported into Europe by international travelers, and virus transmission of zoonotic strains via contaminated aliments is involved in autochthonous cases. Therefore, in Europe, hepatitis E displays a unique dual character, having features of both imported and autochthonous infections. Environmental involvement of waterborne and zoonotic diseases puts alimentary safety at risk. In addition, it may lead to serious health problems derived from persistent infection among patients with immune impairment due to organ transplant, cancer, or human immunodeficiency virus infection. Although the European health authorities know at present that HHEV represents a problem worthy of consideration, the actual incidence of the disease in Europe is unknown, and attempts to ascertain the prevalence of the infection is hampered by unresolved technical issues. In order to determine the burden of hepatitis E in Europe, the World Health Organization Regional Office and the European Centre for Disease Prevention and Control should pay specific attention to hepatitis E, and research efforts in the continent should be transnational and collaborative. Development of a specific European network for hepatitis E would help to achieve these goals.

Hepatocellular carcinoma is one of the leading causes of death by cancer worldwide. Prognosis of hepatocellular carcinoma is determined by characteristics of the tumor and the surrounding cirrhotic liver. Several molecular signatures reflecting tumor biology and derived from tumor analyses predict early tumor recurrence and survival. In contrast, molecular signatures from cirrhotic non-tumor samples are enriched in immunity/inflammation related genes and could predict late tumor recurrence. Moreover, combination of clinical, pathological, and molecular features may refine prognosis prediction in these patients. Finally, molecular signatures from both tumor and non-tumor tissues will be helpful in the future to guide treatments in different clinical settings.

The prevalence of hepatitis B is high in China. Based on the National Disease Supervision Information Management System of China, the mean reported incidence of hepatitis B was 84.3 per 100,000 in China between 2005 and 2010. There are differences in population distribution based on region and ethnic group. Here, risk factors, virological characteristics, and prophylaxis of hepatitis B in China are reviewed. Although the prevalence of HBV infection is gradually declining, there are many challenges in HBV infection control, including higher prevalence in floating population, poor compliance of antiviral therapy, and high disease burden.

Proteomics has evolved into a powerful and widely used bioanalytical technique in the study of cancer, especially hepatocellular carcinoma (HCC). In this review, we provide an up to date overview of feasible proteome-analytical techniques for clinical questions. In addition, we present a broad summary of proteomic studies of HCC utilizing various technical approaches for the analysis of samples derived from diverse sources like HCC cell lines, animal models, human tissue and body fluids.

Autoimmune connective tissue diseases are associated with liver abnormalities and often have overlapping pathological and clinical manifestations. As a result, they can present great clinical challenges and evoke questions about diagnostic criteria for liver diseases. Moreover, discriminating between liver involvement as a manifestation of connective tissue disease and primary liver disease can be challenging since they share a similar immunological mechanism. Most patients with connective tissue diseases exhibit liver test abnormalities that likely result from coexisting, primary liver diseases, such as fatty liver disease, viral hepatitis, primary biliary cirrhosis, autoimmune hepatitis, and drug-related liver toxicity. Liver damage can be progressive, leading to cirrhosis, complications of portal hypertension, and liver-related death, and, therefore, must be accurately identified. In this review, we highlight the challenges facing the diagnosis of liver damage associated with connective tissue disease and identify immune mechanisms involved in liver damage associated with connective tissue diseases.

Ascites is the pathologic accumulation of fluid within the peritoneal cavity. Because many diseases can cause ascites, in particular cirrhosis, samples of ascitic fluid are commonly analyzed in order to develop a differential diagnosis. The concept of transudate versus exudate, as determined by total protein measurements, is outdated and the use of serum-ascites albumin gradient as an indicator of portal hypertension is more accurate. Lactate dehydrogenase (LDH), vascular endothelial growth factor (VEGF), and other tumor markers can be helpful in distinguishing between malignant and benign conditions. Glucose and adenosine deaminase levels may support a diagnosis of tuberculous disease, and amylase level may indicate a diagnosis of pancreatitis. Given the specificity and sensitivity of laboratory results, accurate diagnosis should be based on both laboratory data and clinical judgment.

Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the US and Japan. Therefore, eradication of HCV may reduce the occurrence of HCC in HCV-infected individuals. In 2011, the use of first-generation HCV NS3/4A protease inhibitors such as telaprevir and boceprevir was initiated for clinical treatment of HCV. Administration of telaprevir and boceprevir plus peginterferon and ribavirin increased rates of sustained virological response (SVR) in HCV genotype 1-infected patients. However, this treatment regimen also led to severe adverse events. Second-generation direct-acting antiviral agents (DAAs) for HCV, such as simeprevir plus peg-interferon and ribavirin also resulted in higher SVR rates, with similar adverse events to other peg-interferon and ribavirin treatments. Higher SVR rates in HCV genotype 1- and 2-infected patients were achieved with 12-16 weeks of sofosbuvir plus other class DAAs with/without ribavirin and 12 weeks of sofosbuvir plus ribavirin, respectively. For “difficult-to-treat” HCV-infected patients, more therapeutic options are needed. Further studies examining the efficacy and adverse effects of such therapies will be required for the development of additional treatments.

Primary sclerosing cholangitis (PSC) is a chronic and progressive cholestatic liver disease that often leads to the development of cirrhosis. Complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, dominant biliary strictures, gallstones, and hepatobiliary malignancies, most commonly cholangiocarcinoma (CCA). Despite the presumed autoimmune etiology of PSC, a clear benefit from immunosuppressive agents has not yet been established, and their use is limited by their side effects. Endoscopy is required in evaluation of biliary strictures in PSC to rule out the possibility of CCA. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease. However, disease recurrence can be a source of morbidity and mortality as transplanted patients survive longer. Further studies are needed to develop an optimal therapeutic strategy for patients with PSC to decrease the incidence of complications of the disease, to decrease the need for transplantation, and to extend life expectancy.

Sarcoidosis is a multisystem disease characterized by the presence of non-caseating granulomas in affected organs. Pulmonary involvement is the most common site of disease activity. However, hepatic involvement is also common in sarcoidosis, occurring in up to 70% of patients. Most patients with liver involvement are asymptomatic. Therefore, the majority of cases are discovered incidentally, frequently by the finding of elevated liver enzymes. Pain in the right upper quadrant of the abdomen, fatigue, pruritus, and jaundice may be associated with liver involvement. Portal hypertension and cirrhosis are complications linked to long-standing hepatic sarcoidosis. Liver biopsy is usually required to confirm the diagnosis. It is important to differentiate hepatic sarcoidosis from other autoimmune and granulomatous liver diseases. Not all cases of hepatic sarcoidosis require treatment. For symptomatic patients, the first line treatment includes corticosteroids or ursodeoxycholic acid. Various immunosuppressant agents can be used as second line agents. Rarely, severe cases require liver transplantation.

Hepatocellular cancer (HCC) is the fifth most prevalent cancer worldwide and the third leading cause of cancer-related deaths. Non-alcoholic fatty liver disease (NAFLD), a spectrum of hepatic disorders associated with obesity and the metabolic syndrome, is a recognized risk factor for HCC. NAFLD that is advanced to cirrhosis carries the highest risk for HCC, but there is increasing concern that NAFLD-associated HCC may also occur in non-cirrhotic liver. As NAFLD is rapidly becoming the most common liver condition, it has been implicated in the worrisome trend of rising HCC incidence in a number of countries, which may offset successful measures in reducing the effect of virus-related liver cancer. Independently or in synergy with cirrhosis, NAFLD may provide a special oncogenic microenvironment through its pathogenic association with chronic nutrient excess and adipose tissue remodeling, characterized by pro-inflammatory adipokine profiles, lipotoxicity, altered hepatocellular bioenergetics, and insulin resistance. Better understanding of this complex process, and development of reliable biomarkers for HCC will be critical for early recognition and risk prediction. Moreover, correcting deranged lipid metabolism and restoring insulin sensitivity by lifestyle measures and targeted pharmacotherapy holds major promise for effective prevention of NAFLD-associated HCC.