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Antiviral therapy is the most important treatment for chronic hepatitis C. This paper reviews the progress in antiviral treatment over recent years, including the combination therapy with polyethylene glycol-Interferon (PEG-IFN) and ribavirin (RBV), specific target therapy, and gene therapy. The paper believes that the anti-hepatitis C virus treatment needs more effective drug combination therapies, shorter courses, less side effect, higher drug resistance threshold, etc.

Early diagnosis and timely treatment of hepatic steatosis is very important for controlling the development and improving the prognosis of disease. This paper introduces the controlled attenuation parameter (CAP), a novel non-invasive method to quantitatively assess hepatic steatosis. This paper briefly describes the advantages of CAP compared with other methods for detecting hepatic steatosis: CAP is simple, fast, repeatable, and generally accepted by patients. CAP is of great value for early detection of fatty liver. Moreover, this paper reviews the optimal cut-off values of CAP for detection of fatty liver in different studies. CAP can be used to dynamically monitor the progression and regression of fatty liver as a guide to clinical treatment.

Acute kidney injury (AKI) is a common complication of liver cirrhosis and mainly manifests as a rapidly elevated serum creatinine level, a reduced glomerular filtration rate, and oliguria or anuria. Type 1 hepatorenal syndrome (HRS-1) is a special type of AKI, and patients with untreated HRS-1 have an extremely high risk of death. Early diagnosis and treatment are of great importance. This paper summarizes the latest diagnostic criteria for hepatorenal syndrome (HRS) type of AKI and research advances in the treatment of HRS-1.

Autoimmune hepatitis (AIH) is the first liver disease which has proved responsive to glucocorticoids, and the standard therapeutic method is hormone combined with azathioprine. Given that some patients fail to reach the standard of immunosuppressive therapy, and the long-term use of immunosuppressive therapy has many adverse effects, it is necessary to reasonably use anti-inflammatory and liver-protecting drugs to minimize the dose of immunosuppressants, control liver inflammation, reduce the damage of liver cells, and delay the progression of the disease. This paper reviews the advances in the application of anti-inflammatory and liver-protecting drugs in the treatment of AIH, in order to help clinicians make rational decisions.

Chronic hepatitis B (CHB) is one of the major causes of liver cirrhosis and hepatocellular carcinoma. Interferon and nucleos(t)ide analogues can control disease progression. However, they cause very low HBsAg clearance or seroconversion rates and relapse in most patients after treatment withdrawal. In recent years, the further understanding of the interaction between hepatitis B virus (HBV) and host gives birth to a large number of novel drugs that hold promise for successful cure of CHB. This paper reviews several novel drugs against HBV in phase Ⅰ, Ⅱ, or Ⅲ clinical trials, and points out that these novel drugs against HBV have preliminarily indicated a bright future.

Hepatocyte nuclear factor 4 alpha (HNF4α), a member of the nuclear receptor superfamily, has a high expression level in mature hepatocytes. HNF4α can regulate hepatocyte-specific gene expression at a transcriptional level, promote hepatocyte development and differentiation, participate in establishment and maintenance of hepatocyte polarity, and enhance the synthetic, metabolic, and detoxifying functions of the liver. Through inhibiting the activation of hepatic stellate cells, reversing epithelial-mesenchymal transition, and inhibiting the proliferation, invasion, and metastasis of hepatoma cells, HNF4α may be involved in the development and progression of various liver diseases including liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. This paper elaborates on the biological functions of HNF4α, and summarizes and analyzes the research advances in the mechanisms of action of HNF4α in the pathological process of liver diseases, in order to provide references for further investigation of the potential targeted therapies for liver diseases.

Hepatic encephalopathy is one of the most common complications of liver failure and has a high incidence in hospitalized patients. Most patients with hepatic encephalopathy have varying degrees of malnutrition. In recent years, more and more clinical trials have confirmed that the nutritional support therapy is beneficial to patients with hepatic encephalopathy, and more attention has been paid to nutritional therapy. This paper introduces the pathogenesis of malnutrition in hepatic encephalopathy, and reviews the methods for nutrition evaluation and nutritional therapy in patients with hepatic encephalopathy.

Erlotinib achieves antitumor activity by selective inhibition of the epidermal growth factor receptor. This paper summarizes the results of phase Ⅱ-Ⅲ clinical trials of erlotinib in the treatment of hepatocellular carcinoma (HCC). Two phase Ⅱ clinical trials demonstrated the modest antitumor activity of erlotinib alone in patients with HCC. Additionally, two phase Ⅱ clinical trials conducted in the USA showed the excellent efficacy of erlotinib combined with bevacizumab for HCC, but with an increased risk of variceal bleeding. By contrast, two phase Ⅱ clinical trials conducted in Asia showed the poor efficacy of erlotinib combined with bevacizumab for HCC. Recently, a randomized controlled phase Ⅲ trial failed to confirm any substantial improvement in overall survival time in HCC patients treated with sorafenib combined with erlotinib compared with sorafenib alone. Future studies should identify the candidates for erlotinib among patients with HCC based on the clinical and molecular prognostic biomarkers.

With the release of new oral direct-acting antiviral agents (DAAs), the interferon (IFN)-free treatment for hepatitis C comes out, and the clinical efficacy in phase II and III clinical trials is close to cure, which seems to announce the end of the era of hepatitis C. In China, an area of high incidence of hepatitis C, pegylated interferon (PEG-IFN) combined with ribavirin (RBV) (the standard of care) has been the dominant treatment regimen for hepatitis C, and it is uncertain whether it will be completely replaced by interferon-free treatment regimen. In this background, this paper analyzes the possible problems of DAAs and the main treatment direction of hepatitis C in China at the present stage based on the history and present situation of treatment of hepatitis C, especially the advantage of PEG-IFN combined with RBV in the treatment of hepatitis C in China, and the research advances in DAAs at home and abroad. It is found that PEG-IFN combined with RBV will remain the dominant treatment regimen for chronic hepatitis C at the present stage.

The infection/clearance and antiviral therapy of hepatitis B virus (HBV) are affected by various factors, such as the host, virus, and environment. Recent studies have proven that interleukin 28B (IL-28B) polymorphisms are highly associated with the clearance and antiviral therapy of hepatitis C virus. Since then, great attention has been paid to the role of IL-28B genetic variations in chronic hepatitis B (CHB), with a research focus on the loci rs12979860, rs12980275, and rs8099917. This paper reviews the role of IL-28B polymorphisms in the infection/clearance of HBV and interferon therapy of CHB. Despite the conflicting findings, IL-28B polymorphisms are considered to have a potential clinical value in the field of CHB.

There are 400 million individuals infected with chronic hepatitis B virus (HBV) all over the world. The management of chronic hepatitis B (CHB) has been improved markedly over the last decade, primarily due to the availability of oral nucleoside analogue (NA) therapy. Among the numerous NAs, tenofovir disoproxil fumarate (TDF) stands out for its high therapeutic efficacy, low drug resistance, and wide disease spectrum against several types of chronic CHB that can not be cured with NAs. Thus, TDF has been widely used for clinical treatment of chronic HBV infection. This paper describes the efficacy of TDF in nave and treated patients and analyzes its effect on cirrhosis. Furthermore, the safety of TDF therapy is assessed. It is considered that TDF has low resistance rate and high safety, which provides a first-line drug for CHB treatment.

Nonalcoholic fatty liver disease (NAFLD) is prevalent in patients with characteristics of metabolic syndrome. The main clinicopathological manifestations of NAFLD are fatty degeneration of liver parenchyma cells and fat storage, which can progress to liver cirrhosis and eventually lead to liver failure. Toll-like receptor 4 (TLR4) signaling pathway is involved in the development and progression of NAFLD. At present, the role of TLR4 in the onset of NAFLD is highly valued by clinical doctors. This paper reviews the structure of TLR4, the composition of TLR4 signaling pathway, the regulation of TLR4 expression, the function of TLR4, and the relationship between TLR4 and NAFLD, suggesting that TLR4 signaling pathway is going to be an important research field in the treatment of NAFLD in the future.

Epithelial cellular adhesion molecule (EpCAM) is a transmembrane glycoprotein expressed in epithelial tissues and most epithelial-derived malignant tumors. EpCAM is associated with cell adhesion, migration, proliferation, and differentiation, as well as tumor development and progression. In recent years, EpCAM has been identified as a stem cell marker of hepatocellular carcinoma (HCC). This paper elucidates the roles of EpCAM in the diagnosis, treatment, and prognosis of HCC, which shed light on the potential molecular targeted therapy in future.

Decompensated hepatitis B cirrhosis is one of the final outcomes of chronic hepatitis B and liver fibrosis. Extensive studies have demonstrated that antiviral therapy can slow disease progression, improve clinical outcomes, reduce complications, slow decompensated cirrhosis progression, and improve survival. At present, nucleoside and nucleotide analogues are the most common antiviral agents in the treatment of decompensated hepatitis B cirrhosis. This paper introduces effective antiviral agents against decompensated hepatitis B cirrhosis and discusses potential problems in antiviral treatment, suggesting that personalized medication should be achieved on the basis of standardized antiviral treatment in clinical practice.

Liver cirrhosis is a late-stage hepatic fibrosis, which results from various risk factors such as viruses, alcohol, fat, drugs and immunity, and genetic metabolism, leading to chronic liver damage. This paper reviews the etiological treatment and therapy for complications. It is pointed out that liver transplantation, which is currently the only effective approach to the treatment of liver cirrhosis, is limited by liver donor shortage and high cost. Stem cell therapy becomes a hot spot of research due to its huge potential for the treatment of liver cirrhosis. However, its mechanism remains unclear with many pending problems.

Hepatic stellate cells (HSCs) are the source of fibre in the liver which can produce a large number of extracellular matrix via proliferation and activation, and this is the central link of hepatic fibrosis. Following further research on hepatic fibrosis, signal transduction involved in the activation of HSCs have been researched as a popular topic. This paper generalizes the main signaling transduction pathways involved in activation of HSCs and Hedgehog/Gli pathway, and introduces recent advances in related research. It is promising to make new breakthroughs in the prevention and treatment of hepatic fibrosis through in-depth study of these signaling pathways.

Since the liver is the major iron storage organ in human body, iron metabolism disorder is closely related to chronic hepatitis. So far, the mechanisms underlying iron overload in chronic hepatitis C (CHC) have not been fully elucidated. Highly complex regulation of hepcidin relies on a number of variables, including hepatic inflammatory conditions of different stages, transferrin-bound iron circulation, and intracellular iron storage. All these factors are associated with variations in hepatic iron concentrations among patients with hepatitis C virus (HCV)-related chronic liver disease. This paper discusses the regulation of systemic iron homeostasis, the relationship between CHC and iron metabolism disorder, and the mechanism of inducing iron overload. In-depth understanding about iron homeostasis and the relationship between relevant signaling pathways will contribute to the control and therapy of HCV-related diseases.

Interventional therapy has become the first choice of non-surgical treatment for hepatocellular carcinoma (HCC) due to its advantages such as little trauma and marked local effect. However, the clinical efficiency is less than expected. One of the possibilities is the resistance of cancer cells to anti-cancer drugs. Increasing attention has been paid to the combination of traditional Chinese medicine (TCM) and interventional therapy in HCC treatment. This paper reviews the progress in TCM combined with interventional therapy for HCC at animal experiment and clinical study levels in recent ten years. It is pointed out that the combination therapy with TCM and intervention for HCC has a unique advantage.

Recent studies have demonstrated that coagulation function and liver microcirculation disturbance are important in the development and progression of liver diseases. ADAMTS13, also known as von Willebrand factor-cleaving protease, is a metalloproteinase produced by hepatic stellate cells, with major functions to cleave the von Willebrand factor multimers produced by vascular endothelial cells, regulate the adhesive capacity of platelets, and influence the body′s coagulation function and microcirculation. The important role of ADAMTS13 in the pathophysiological processes of various severe liver diseases such as liver cirrhosis, severe alcoholic hepatitis, hepatic veno-occlusive disease after stem cell transplantation, and liver graft dysfunction is reviewed in this paper, and its association with the severity of liver diseases is clarified. Plasma ADAMTS13 is involved in the development and progression of various liver diseases, and measurement of its level and activity can help the diagnosis and differential diagnosis of liver diseases.

To date, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system has been widely used to edit the genome in many species and cells. The system is the third generation of artificial endonuclease, which can edit DNA by recognizing short DNA sequences. This paper reviews the structural features of the system and its application in virus research, such as the functional studies of virus-related genes and the exploration of antiviral therapies (including HIV, HBV, and EB virus), looking forward to the future direction of virus research.

Portal vein tumor thrombus (PVTT) is one of the common manifestations in patients with advanced hepatocellular carcinoma (HCC). It is the decisive factor leading to severe complications and causes extremely poor prognosis. With the development of molecular biology and imaging techniques, both single and combined therapy modalities, including surgical resection, embolization and chemotherapy, radiation therapy, a variety of ablation therapies, and molecular targeted therapy, have achieved substantial progress. However, there are no guidelines for reasonable and effective treatments. In this paper, new progress in the treatment of HCC with PVTT in recent years is summarized to provide a standardized approach for future treatment options.

Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is involved in many important biological processes such as cell metabolism, growth, proliferation, and angiogenesis. And its high-level activation is closely related to the development and progression of many malignant tumors. In this paper, mTOR and PI3K/Akt/mTOR signaling pathway are introduced, and their action mechanisms in the development and progression of hepatocellular carcinoma, cholangiocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma are expounded, and then the role of mTOR inhibitors in the treatment of malignant hepatobiliary tumors is briefly described. It is thought that the PI3K/Akt/mTOR signaling pathway provides new therapeutic targets for malignant hepatobiliary tumors in advanced stage and the constant development of new mTOR inhibitors provides some new hope for the patients with malignant hepatobiliary tumors in advanced stage.

With the continuous improvement of endoscopic technology and equipment, minimally invasive treatment of bile duct stones becomes increasingly diversified. In this paper, the concept of minimally invasive treatment of bile duct stones, surgical indications and contraindications, surgical methods, and the advantages and disadvantages of surgical methods are introduced. It is shown that the application of laparoscope has laid the foundation for the minimally invasive treatment of bile duct stones, and the combined application of choledochoscope and endoscope has brought new ideas for minimally invasive treatment of bile duct stones. The combination of three endoscopes avoids the disadvantages of traditional open surgery: large trauma and long operation time, and reduces the patient′s pain and complications. In the near future, the combination of three endoscopes still has much room for growth. As long as the indications for several surgeries are mastered and the safety and efficacy are evaluated objectively, the combination of three endoscopes will play the biggest role.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, with a very complex mechanism of development and progression. Clusterin (CLU) has been confirmed to play an important role in the development and progression of HCC. This paper reviews the molecular structure and biological function of CLU and its value for early diagnosis of HCC and analyzes its association with multi-drug resistance in chemotherapy and the prospect of targeted therapy. CLU holds promise as a new molecular marker of HCC and the therapeutic target.

Pancreatic encephalopathy (PE) is one of the severe complications of severe acute pancreatitis (SAP). Early diagnosis mostly depends on the history of disease as well as clinical symptoms and signs. PE progresses rapidly and is often complicated by multiple organ dysfunction, and it may finally develop into multiple organ failure with a high fatality rate if not treated in time. It is currently known that demyelination is one of the important pathological features of this disease, with fat-soluble demyelination of cerebral gray matter and white matter, as well as inflammatory changes such as hemorrhage and edema. The target antigen of demyelinating lesions, however, is myelin basic protein (MBP). This paper reviews the changes in MBP levels in the demyelinating lesions of the central nervous system among PE patients, with the purpose of providing clues for the early diagnosis and prognostic study of demyelinating lesions in PE.

In recent years, gut microecology has attracted increasing attention because of its close relationship with the development and progression of various liver diseases and associated complications. The impairment of liver function can disturb gut microecology, whereas the imbalance in gut microecology in turn promotes the aggravation of liver diseases. This paper reviews the relationship between gut microecology and various liver diseases, and discusses the role of modulating gut microecology in the treatment of liver diseases. A new idea is provided for the prevention and treatment of liver diseases based on the modulation of gut microecology.

The metabolism of amino acids mainly takes place in the liver, and patients with liver cirrhosis may develop metabolic disorders of proteins, carbohydrates, fats, and amino acids, which in turn causes dysfunction of multiple organs and systems, as well as complications like hepatic encephalopathy, esophageal variceal bleeding, and ascites, resulting in high mortality. This paper summarizes the metabolic characteristics of amino acids and the application of branched-chain amino acids (BCAAs) in the treatment of liver cirrhosis, and it points out the significance of BCAAs in regulating serum aminogram, increasing the ratio of BCAAs to aromatic amino acids, preventing complications of liver cirrhosis, and improving the quality of life for patients with the disease.

The primary aim of preventing variceal bleeding in liver cirrhosis is to reduce portosystemic pressure gradient. Carvedilol is a non-selective beta blocker with selective inhibition of α-1 receptor and blockage of calcium channel. This paper reviews the role of carvedilol in reducing hepatic venous pressure gradient and preventing variceal bleeding. Analysis has shown that carvedilol is superior to propranolol in reducing portosystemic pressure gradient. Carvedilol may be similar to propranolol or endoscopic ligation for the primary and secondary prevention of variceal bleeding. Further randomized controlled trials with a larger sample size are warranted to confirm these findings.

Ascites is a common complication of liver cirrhosis. Liver ascites may occur repeatedly, which increases the therapeutic difficulty. This paper reviews the definition of intractable liver ascites, general treatment measures, and current treatment of common complications such as spontaneous bacterial peritonitis and hepatorenal syndrome, as well as the advances in conventional, unconventional, and surgical treatment of intractable liver ascites. It is pointed out that abdominocentesis for excessive drainage and active preparation for liver transplantation are the preferred approach to the treatment of intractable liver ascites.

Liver steatosis is a frequent histological feature in patients with chronic hepatitis C (CHC), and it is associated with the progression of CHC and antiviral efficacy. This paper reviews recent research advances in the viral and host factors involved in the pathogenesis of steatosis among CHC patients and the prognostic impact of steatosis. The pathogenesis of liver steatosis in CHC patients needs further studies.

Silymarin is a traditional hepatoprotective herb for the adjuvant therapy of liver diseases, which shows marked pharmacological activities such as antioxidant and anti-inflammatory properties. This paper introduces the action mechanism of silymarin in regulating liver function, ameliorating hepatic fibrosis, protecting pancreatic cells, suppressing the growth of tumor cells, and inhibiting the replication of hepatitis C virus. Silymarin is considered to be a natural medicine with little toxic or side effect at a high dose. It holds promise for anti-tumor, antioxidant, anti-inflammatory, and antiviral application.