Brain-penetrating neurotrophic factor mimetics: HER-096 as a disease-modifying therapy for Parkinson’s disease

Neurotrophic factors as a therapeutic approach in neurodegenerative diseases:A major unmet need in the field of central nervous system diseases is disease-modifying treatments.While for decades there have been various symptomatic treatments available to alleviate the symptoms of the disease,disease-modification,i.e.treatments that stop,significantly delay,or reverse the progression of the disease,has been turned out to a difficult goal to achieve.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

The dopaminergic system and Alzheimer's disease

Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.

Interleukins in liver disease treatment

Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B:A meta-analysis

BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Effect of continuous nursing on treatment compliance and side effect management of coronary heart disease

BACKGROUND There are relatively few studies on continuing care of coronary heart disease(CHD),and its research value needs to be further clarified.AIM To investigate the effect of continuous nursing on treatment compliance and side effect management in patients with CHD.METHODS This is a retrospective study with patients from January 2021 to 2023.The study was divided into two groups with 30 participants in each group.Self-rating anxiety scale(SAS)and Self-rating depression scale(SDS)were used to assess patients'anxiety and depression,and medical coping questionnaire was used to assess patients'coping styles.The pelvic floor dysfunction questionnaire(PFDI-20)was used to assess the status of pelvic floor function,including bladder symptoms,intestinal symptoms,and pelvic symptoms.RESULTS SAS score decreased from 57.33±3.01before treatment to 41.33±3.42 after treatment,SDS score decreased from 50.40±1.45 to 39.47±1.57.The decrease of these two indexes was statistically significant(P<0.05).PFDI-20 scores decreased from the mean 16.83±1.72 before treatment to 10.47±1.3the mean after treatment,which was statistically significant(P<0.05).CONCLUSION The results of this study indicate that pioneering research in continuous care of CHD has a positive impact on improving patients'treatment compliance,reducing anxiety and depression levels,and improving coping styles and pelvic floor functional status.

Dual-targeted treatment for inflammatory bowel disease:Whether fecal microbiota transplantation can be an important part of it

Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.

Advances in understanding and managing celiac disease:Pathophysiology and treatment strategies

In this editorial,we comment on an article published in the recent issue of the World Journal of Gastroenterology.Celiac disease(CeD)is a disease occurring in genetically susceptible individuals,which is mainly characterized by gluten intolerance in the small intestine and clinical symptoms such as abdominal pain,diarrhea,and malnutrition.Therefore,patients often need a lifelong gluten-free diet,which greatly affects the quality of life and expenses of patients.The gold standard for diagnosis is intestinal mucosal biopsy,combined with serological and genetic tests.At present,the lack of safe,effective,and satisfactory drugs for CeD is mainly due to the complexity of its pathogenesis,and it is difficult to find a perfect target to solve the multi-level needs of patients.In this editorial,we mainly review the pathological mechanism of CeD and describe the current experimental and improved drugs for various pathological aspects.

Surgical treatment of inflammatory bowel disease:From the gastroenterologist’s stand-point

Treatment of ulcerative colitis(UC)and Crohn’s disease(CD)represents,in the majority of cases,a real challenge to the gastroenterologist’s abilities and skills as well as a clinical test concerning his/her levels of medical knowledge and experience.During the last two decades,our pharmaceutical arsenal was significantly strengthened,especially after the introduction of the so-called biological agents,drugs which to a large extent not only improved the results of conservative treatment but also changed the natural history of the disease.However,colectomy is still necessary for some patients with severe UC although smaller compared to the past,precisely because of the improvements achieved in the available conservative treatment.Nevertheless,surgeries to treat colon dysplasia and cancer are increasing to some extent.At the same time,satisfactory improvements in surgical techniques,the pre-and post-operative care of patients,as well as the selection of the appropriate time for performing the surgery have been noticed.Regarding patients with CD,the improvement of conservative treatment did not significantly change the need for surgical treatment since two-thirds of patients need to undergo surgery at some point in the course of their disease.On the other hand,the outcome of the operation has improved through good preoperative care as well as the wide application of more conservative surgical techniques aimed at keeping as much of the bowel in situ as possible.This article discusses the indications for surgical management of UC patients from the gastroenterologist’s point of view,the results of the emerging new techniques such as transanal surgery and robotics,as well as alternative operations to the classic ileo-anal-pouch anastomosis.The author also discusses the basic principles of surgical management of patients with CD based on the results of the relevant literature.The self-evident is emphasized,that is,to achieve an excellent therapeutic result in patients with severe inflammatory bowel disease in today’s era;the close cooperation of gastroenterologists with surgeons,pathologists,imaging,and nutritionists is of paramount importance.

Intestinal Behçet's disease: A review of clinical diagnosis and treatment

Behçet's disease(BD)is a chronic inflammatory disorder prone to frequent re-currences,with a high predilection for intestinal involvement.However,the ef-ficacy and long-term effects of surgical treatment for intestinal BD are unknown.In the current issue of World J Gastrointest Surg,Park et al conducted a retrospec-tive analysis of 31 patients with intestinal BD who received surgical treatment.They found that elevated C-reactive protein levels and emergency surgery were poor prognostic factors for postoperative recurrence,emphasizing the adverse impact of severe inflammation on the prognosis of patients with intestinal BD.This work has clinical significance for evaluating the postoperative condition of intestinal BD.The editorial attempts to summarize the clinical diagnosis and treatment of intestinal BD,focusing on the impact of adverse factors on surgical outcomes.We hope this review will facilitate more precise postoperative management of patients with intestinal BD by clinicians.

Effectiveness of anti-psychiatric treatment on visual and haptic perceptual disorder for a patient with Alzheimer’s disease: A case report

BACKGROUND Perception is frequently impaired in patients with Alzheimer’s disease(AD).Several patients exhibit visual or haptic hallucinations.CASE SUMMARY A 71-year-old Chinese man presented with visual and haptic hallucinations he had been experiencing for 2 weeks.The clinical manifestations were the feeling of insects crawling and biting the limbs and geison.He looked for the insects while itching and scratching,which led to skin breakage on the limbs.He was treated with topical and anti-allergic drugs in several dermatology departments without any significant improvement.After admission,the patient was administered risperidone(0.5 mg)and duloxetine(2 mg/day).One week later,the dose of risperidone was increased to 2 mg/day,and that of duloxetine was increased to 60 mg/day.After 2 weeks of treatment,the patient’s sensation of insects crawling and biting disappeared,and his mood stabilized.CONCLUSION This patient manifested psychiatric behavioral symptoms caused by AD brain atrophy.It was important to re-evaluate the patient’s cognitive-psychological status when the patient repeatedly went to the hospital for treatment.Follow-up attention to cognitive function and the consideration of perceptual deficits as early manifestations of AD should be considered.

Application of traditional Chinese herbal medicine in the prevention and treatment of swine viral infectious diseases

This study aims to explore the current application status and development prospects of Chinese herbal medicine in preventing and treating swine viral infectious diseases over the past five years.By adopting the method of literature review,we collect,organize,and analyze relevant research literature,with the goal of summarizing and summarizing the research progress in this field.Through research,we found that swine infectious diseases have caused serious economic losses in the breeding industry and that some diseases cannot be fully protected by using vaccines.Therefore,we need new means to prevent diseases.The use of Chinese herbal medicine for the prevention and treatment of related diseases has become a reliable means.This study first briefly introduces the common infectious diseases of pigs and the risks and challenges faced by prevention and treatment,then reads the literature comparing the treatment with Western medicine and traditional Chinese medicine,proving the reliability of traditional Chinese medicine treatment and the unique advantages of Chinese herbal medicine.Afterwards,we summarized the literature on the prevention and treatment of related swine diseases with Chinese herbal medicine in the past five years,and finally made a summary and outlook,hoping to provide ideas for relevant researchers and workers.

Effect of Health Management in Raising Awareness Rate of Disease Prevention and Treatment in Patients with Prehypertension

Objective: To analyze the effect of health management on improving the awareness rate of disease prevention and treatment in patients with prehypertension, so as to provide guidance for clinical management of patients with prehypertension. Methods: 108 patients diagnosed with prehypertension in our hospital were divided into a control group and an experimental group. The control group was not given management measures, while the experimental group was given health management. The incidence of hypertension and cognition level of hypertension knowledge were compared between the two groups after management. Results: The incidence of hypertension in the experimental group was 7.41% lower than that in the control group 29.63%. The cognitive level of hypertension in the patients (66.54 ± 1.25) was significantly higher than that in the patients without health management (41.45 ± 2.45), and P < 0.05;Conclusion: For patients with prehypertension, the implementation of health management is helpful to improve their cognition of hypertension, master related prevention knowledge, and reduce the incidence of hypertension.

A Study of the Treatment of Disfiguring Diseases in the “Qian Jin Fang”

Traditional Chinese medicine(TCM)has been passed down for more than 2,000 years.TCM beauty products driven by the principles of identification and treatment with various dosage forms and exhibit mild and safe efficacy are bound to become a main component of the beauty industry in the future.Xu once commented that“Qian Jin Fang”is different from the traditional prescription system,which emphasizes the use of medicines.In this paper,we mainly selected the prescriptions for the treatment of disfigurement diseases such as acne,scarring,black dryness,face hyperpigmentation,black mole,and rosacea from the article titled,“Upper Seven Orifices Disease-Facial Medicine IX”in the Bei Ji Qian Jin Yao Fang[1].By studying and analyzing the original composition of the formula,understanding the etiology and pathogenesis of the disease,and exploring the characteristics of the formula concerning the efficacy of TCM,their properties,flavors,and meridians,we summarized the characteristics of the Qian Jin Fang.It is based on the external treatment of disfigurement diseases,with a wide variety of drugs,flexibility,and accuracy.This method draws upon analogies while utilizing excipients and harmonizers to focus on the combined healing approach of treatment and nourishment.

Treatment of Coronary Heart Disease from the Perspective of Liver Controlling Dispersion

The liver is in charge of distributing and regulating the movement of qi throughout the whole body,coordinating the transportation and transformation of the internal organs in the middle part of the body,promoting the biochemical circulation of qi,blood,and body fluids,and regulating emotions.Liver dysfunction can disrupt the transportation and transformation of qi,blood,and body fluids,causing phlegm turbidity,blood stasis,and other unwanted symptoms.Poor regulation of emotion further aggravates the accumulation of pathological substances,resulting in the obstruction of heart vessels,and ultimately coronary heart disease(CHD).Through regulating lipid metabolism,inflammatory reaction,vasoactive substances,platelet function,neuroendocrine,and other factors,liver controlling dispersing qi plays a comprehensive role in the prognosis of atherosclerosis,the primary cause of CHD.Therefore,it is recommended to treat CHD from the perspective of liver-controlling dispersion.

Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Treat to target in Crohn’s disease:A practical guide for clinicians

A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.

Update in lean metabolic dysfunction-associated steatotic liver disease

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.

Treatment options for alcoholic and non-alcoholic fatty liver disease: A review

Alcoholic liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma.Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver(simple steatosis),a small percentage develops progressive liver disease.Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available.The treatment for ALD remains as it was 50 years ago:abstinence,nutritional support and corticosteroids(or pentoxifylline as an alternative if steroids are contraindicated).As for NAFLD,the treatment modality is mainly directed toward weight loss and co-morbidity management.Therefore,new pathophysiology directed therapies are urgently needed.However,the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy.Hence,a combination therapy towards multiple targets would eventually be required.In this review,we delineate the treatment options in ALD and NAFLD,including various new targeted therapies that are currently under investigation.We hope that soon we will be having an effective multi-therapeutic regimen for each disease.