Hepatic Morbidity Research Articles

What is your diagnosis?: Case for diagnosis. Sclerodermiform manifestations of porphyria cutanea tarda secondary to hepatitis C

AbstractA 63-year-old black female patient with blisters and exulcerations on the face, neck, upper limbs, and subsequent evolution with hypochromic sclerotic areas and alopecia, is reported. Chronic hepatitis C and presence of high levels of porphyrins in urine were demonstrated. There was complete remission with the use of hydroxychloroquine, photoprotection, and treatment of hepatitis. Significant sclerodermoid involvement of the skin as a manifestation of porphyria cutanea tarda secondary to hepatitis C emphasizes the importance of diagnostic suspicion regarding skin manifestation in order to indicate the appropriate therapy, and to minimize the hepatic morbidity.

The Role of Radiologic Modalities in Diagnosing Nonalcoholic Steatohepatitis (NASH) and Fibrosis

The dramatic increase in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) fostered the development and evaluation of non-invasive, imaging based methods for diagnosing NAFLD, NASH, and its complications. We herein review different radiologic modalities in diagnosing steatosis, fibrosis, and liver cirrhosis. While routine abdominal ultrasound with hyperechogenic liver structure only detects moderate to severe steatosis, controlled attenuation parameter (CAP), magnetic resonance spectroscopy (MRS), and, especially, MRI-proton density fat fraction (MRI-PDFF) are more sensitive to diagnose and quantify steatosis. MRI-PDFF appears suitable to monitor treatment-related changes in liver fat in clinical trials. Liver fibrosis is related to hepatic and extrahepatic morbidity and mortality in NAFLD. Fibrosis and cirrhosis can be suspected by ultrasound-based elastography techniques (vibration-controlled transient elastography, VCTE; acoustic resonance forced impulse imaging, ARFI; shear wave elastography, SWE), which may be used to screen for fibrosis in high-risk patients. MR elastography (MRE) appears advantageous to quantify and stage fibrosis, while angiographic hepatic venous pressure gradient (HVPG) measurement can confirm portal hypertension in cirrhosis. Screening for hepatocellular carcinoma (HCC) in cirrhotic livers is done by ultrasound; suspicious nodules are followed by multiphasic CT/MRI, contrast-enhanced ultrasound (CEUS), or contrast-enhanced MRI. Different radiologic modalities exist to screen, diagnose, stage, and monitor steatosis, steatohepatitis, fibrosis, and HCC, thereby complementing liver biopsy and blood biomarkers in the management of patients with NAFLD.

Rationale for treatment of hepatitis C virus infection in end-stage renal disease patients who are not kidney transplant candidates.

Hepatitis C virus (HCV) infection is a common problem in patients treated with maintenance hemodialysis (HD) and is associated with an increased morbidity and mortality and lower quality of life. The major causes of HCV-associated mortality are liver and cardiovascular-related death. HCV-infected HD patients have a higher prevalence of inflammation-related metabolic and vascular diseases, leading to high rates of cardiovascular mortality in patients with end-stage renal disease. In the current era of highly effective direct-acting antiviral regimens, HCV treatment may also confer hepatic, cardiovascular and other morbidity and mortality benefits even to dialysis-dependent patients who do not qualify for kidney transplantation. Currently, the most accepted regimens in this patient population include elbasvir/grazoprevir and glecaprevir/pibrentasvir.

Risk factors of hepatic graft failure, morbidity and mortality after living donor liver transplantation (LDLT): Review Article

Risk factors of hepatic graft failure, morbidity and mortality after living donor liver transplantation (LDLT): Review Article

Co-infection of Schistosoma mansoni/hepatitis C virus and their associated factors among adult individuals living in fishing villages, north-western Tanzania

BackgroundSchistosoma mansoni and Hepatitis C virus (HCV) are co-existence in sub-Saharan Africa and co-infection is common among humans population. The immunological responses characterized with Th2-immune responses for S. mansoni and Th1-immune responses for HCV are responsible for development hepatic morbidities in infected individuals. However, the co-occurrences of S. mansoni and HCV infection, their related ultrasound detectable morbidities and associated risk factors at community levels have not been examined in fishing communities, north-western Tanzania. In this context, the present study covers that gap.MethodsA cross-sectional study was conducted among 1924 asymptomatic individuals aged 15–55 years in four fishing villages (Igombe, Igalagala, Sangabuye and Kayenze) of Northwestern Tanzania. A single stool sample was collected from each study participants and examined for S. mansoni eggs using Kato Katz technique. Hepatitis C surface antigen (HCVsAg) was determined from a finger prick blood sample using a rapid test.ResultsOverall, 51.8% (997/1924; 95%CI: 49.6–54.1) of the study participants were infected with S. mansoni and had a mean intensity of 223.7epg (95%; 202.4–247.1). Of the study participants, 90 (4.7%) were infected with hepatitis C virus (HCV). Overall, 2. 4% (47/1924) of the study participants were co-infected with S. mansoni and hepatitis C virus. Among the co-infected individuals, 42.6%, 70.2% and 19.1% had splenomegaly, hepatomegaly and periportal fibrosis (PPF). Factors associated with S. mansoni/HCV co-infection were being aged 26–35 years (aRR = 2.67, 95%CI: 1.03–6.93, P < 0.04), 46–55 years (aRR = 2.89, 95%CI: 1.10–7.57, P < 0.03) and having marked hepatomegaly (aRR = 2.32, 95%CI: 1.09–4.9, P < 0.03).ConclusionIn this setting, S. mansoni and Hepatitis C are co-endemic and a proportion of individuals were co-infected. Hepatosplenic morbidities characterized with hepatomegaly, splenomegaly, hepatosplenomegaly and PPF were observed in co-infected individuals. These results highlight the need for integrated interventions measures against parasitic and viral diseases.

Short-Term Outcomes after Simultaneous Colorectal and Major Hepatic Resection for Synchronous Colorectal Liver Metastases

Background/Aims: Resection of the liver is the standard therapeutic approach for patients with hepatic metastasis and is the only therapy with curative potential. The optimal timing of surgical resection for synchronous metastases has remained controversial. Methods: From January 1993 to December 2008, our strategy has been to use simultaneous resection for resectable synchronous colorectal and liver metastases. During this period, 115 patients underwent simultaneous colorectal and hepatic resection. We evaluated the short-term outcomes of these patients by reviewing operative and perioperative clinical data. Results: In patients with simultaneous resection, there was no evidence of colorectal complications associated with major hepatectomy or no evidence of hepatic complications related to rectal resection. But increased hepatic complications were apparent with major hepatectomy compared with minor hepatectomy (44 vs. 7.2%, p < 0.001) and patients with rectal resection had increased colorectal complications (23% in the rectal resection vs. 5.3% in the colectomy group, p = 0.034). Conclusions: Simultaneous major hepatectomy and rectal resection can increase the hepatic or colorectal morbidity, respectively. These patients may be considered for staged resections.

Presence of atrial fibrillation is associated with liver stiffness in an elderly Finnish population.

BackgroundChronic liver injury from different etiologies drives liver fibrosis. However, little is known about the associated factors, systemic factors in particular. Recently, non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation have been shown to be associated with each other. Thereby, we aimed to study the association between atrial fibrillation and liver stiffness.StudyExtensive clinical measurements including echocardiography of the heart, transient elastography (TE) of the liver and the presence of atrial fibrillation were determined in elderly Finnish study subjects (n = 76, mean age 73 years) from OPERA (Oulu Project Elucidating the Risk of Atherosclerosis) study cohort. Half of the study subjects had non-alcoholic fatty liver disease, whereas others did not have any known hepatic morbidity. The present study was cross-sectional by nature.ResultsThe subjects with atrial fibrillation had higher TE values (with atrial fibrillation TE = 9.3kPa, without atrial fibrillation TE = 6.3kPa, p = 0.018). When the cohort was divided to four subgroups (those without NAFLD or atrial fibrillation, with NAFLD but without atrial fibrillation, with both conditions, and with atrial fibrillation but without NAFLD), the TE value was the highest in the subjects with both conditions (5.3kPa, 7.4kPa, 10.8kPa and 7.8kPa, respectively, p = 0.019). Moreover, the higher the TE value, the more prevalent atrial fibrillation was (the atrial fibrillation prevalence by tertiles of TE 27% / 36% / 77%, p = 0.001). Likewise, the greater the TE value, the greater the left atrial diameter, a collateral of atrial fibrillation (left atrial diameters by tertiles of TE 39mm / 45mm / 48mm, p<0.001) was. All these p-values for continuous variables remained statistically significant even after adjustment for common clinically relevant risk factors.ConclusionsThere is an association between atrial fibrillation and liver stiffness. This novel association may have multiple explanations and mechanistic links, which are discussed here and need further studies, prospective studies in particular.

Nonalcoholic steatohepatitis-related hepatocellular carcinoma: is there a role for the androgen receptor pathway?

The epidemic of insulin resistance, obesity, and metabolic syndrome has led to the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of liver disease in the US. Patients with NASH are at an increased risk for hepatic disease-related morbidity and death, and chronic inflammation in NASH patients can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in males than in females, and genetic studies have identified androgen and androgen receptors (ARs) as partially responsible for the gender disparity in the development of liver disease and HCC. Although many factors are known to play important roles in the progression of inflammation in NASH patients, the role of androgen and AR in the progression of NASH to HCC has been understudied. This review summarizes the evidence for a potential role of androgen and the AR pathway in the development of NASH-related HCC and in the treatment of HCC. It has been proposed that AR plays a role in the progression of HCC: inhibitory roles in early stages of hepatocarcinogenesis and tumor-promoting roles in advanced stages. AR can be activated by several pathways, even in the absence of androgen. While AR has been explored as a potential therapeutic target in HCC, several clinical trials have failed to demonstrate a clinical benefit of antiandrogen drugs in HCC. This review discusses the potential reason for these observations and discuss the potential future trials design in this important setting.

From current status to optimization of HCV treatment: Recommendations from an expert panel

Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens. For such reason interferon-free regimens are now the treatments of choice for all patients. Successful anti-HCV treatment can stop liver disease progression and can solve the HCV-related extra hepatic manifestations, eventually reducing both liver-related and overall mortality.Together with the rapidly accumulating data about the evolution of treatment landscape, different guidelines from national and international Liver Scientific Societies have been published until today. However, these recommendations may not be applied worldwide as, due to high treatment costs, most of them identify as priority groups only patients with advanced liver disease. Moreover some types of patients pose clinical management problems for which even the guidelines do not always provide useful answers.With the aim of treatment optimization by filling some of the gaps of the current guidelines and addressing the remaining unmet needs in practice, a group of Italian experts, experienced on treatment of HCV infection, met in Stresa in February 2016. The summary of all the considerations arising from this two-day meeting and the final statements are reported in this position paper.

A portal pressure cut-off of 15 versus a cut-off of 20 for prevention of small-for-size syndrome in liver transplantation: A comparative study.

Portal hypertension has recently been implicated in the pathogenesis of small-for-size syndrome (SFSS) in adult-to-adult living-donor liver transplantation (A-LDLT). The aim of our study is to compare the portal venous pressure (PVP) cut-off values of 15mmHg and 20mmHg in terms of prevention of SFSS in A-LDLT. Seventy-six patients underwent A-LDLT. A PVP <20mmHg at the end of the operation was targeted using graft inflow modulation. Patients were divided into two groups: group A, final PVP <15mmHg; and group B, final PVP 15-19mmHg. Peak serum bilirubin and peak international normalized ratio in the first month after A-LDLT, as well as hepatic encephalopathy, SFSS, 90-day morbidity, and mortality were observed in both groups. Final PVP was well controlled below 20mmHg in all patients (group A, n = 39; group B, n = 37). Six patients suffered SFSS in group B (16.2%) compared to one patient (2.6%) in group A (P = 0.04). Nine patients died in group B (24.3%), four of whom died of SFSS, compared to three patients in group A (7.7%) (P = 0.047). A PVP cut-off of 15mmHg seems to be a more appropriate target level than a cut-off of 20mmHg for prevention of postoperative SFSS in A-LDLT.

Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia.

Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia.

Low-density lipoprotein receptor on peripheral lymphocytes as a candidate receptor for hepatitis C virus

Objective The aim of this work was to assess the role of low-density lipoprotein receptor ( LDLR ) on peripheral lymphocytes as a candidate receptor for hepatitis C virus (HCV) in patients with chronic HCV both without interferon treatment and after interferon treatment in comparison with a control group. Background HCV is one of the most prevalent infectious diseases in Egypt. It is considered the main cause of hepatic morbidity in Egypt, with progression to chronic liver disease, cirrhosis, and hepatocellular carcinoma. Pioneering studies have reported the involvement of the LDLR in the cellular entry of HCV. LDLR was found to play a role in the pathogenesis of HCV infection. Materials and methods Peripheral blood lymphocytes were isolated from 40 patients with chronic HCV without interferon treatment and 20 patients with HCV after interferon treatment. Quantification of LDLR expression was performed by flow cytometry and the results were compared with those of 20 normal volunteers as a control group. Results There was a significant difference between the mean ± SD of LDLR % between HCV cases (89.08 ± 4.89), post-interferon treatment cases (57.45 ± 4.72), and the control group (54.69 ± 8.48). There was a significant positive correlation between LDLR %, LDLR mean fluorescence intensity, and viral load. Conclusion There was a significant positive correlation between the amount of LDLR expression on peripheral lymphocytes and viral load as quantified by PCR. This indicates the involvement of LDLR in the pathogenesis of HCV infections.

Paediatric non-alcoholic fatty liver disease: an overview.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non-hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research.

FXR agonists as therapeutic agents for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and a risk factor for both cardiovascular and hepatic related morbidity and mortality. The increasing prevalence of this disease requires novel therapeutic approaches to prevent disease progression. Farnesoid X receptors are bile acid receptors with roles in lipid, glucose, and energy homeostasis. Synthetic farnesoid X receptor (FXR) agonists have been developed to specifically target these receptors for therapeutic use in NAFLD patients. Here, we present a review of bile acid physiology and how agonism of FXR receptors has been examined in pre-clinical and clinical NAFLD. Early evidence suggests a potential role for synthetic FXR agonists in the management of NAFLD; however, additional studies are needed to clarify their effects on lipid and glucose parameters in humans.

Regulator of G protein signaling 6 is a critical mediator of both reward-related behavioral and pathological responses to alcohol

Alcohol is the most commonly abused drug worldwide, and chronic alcohol consumption is a major etiological factor in the development of multiple pathological sequelae, including alcoholic cardiomyopathy and hepatic cirrhosis. Here, we identify regulator of G protein signaling 6 (RGS6) as a critical regulator of both alcohol-seeking behaviors and the associated cardiac and hepatic morbidities through two mechanistically divergent signaling actions. RGS6(-/-) mice consume less alcohol when given free access and are less susceptible to alcohol-induced reward and withdrawal. Antagonism of GABA(B) receptors or dopamine D2 receptors partially reversed the reduction in alcohol consumption in RGS6(-/-) animals. Strikingly, dopamine transporter inhibition completely restored alcohol seeking in mice lacking RGS6. RGS6 deficiency was associated with alterations in the expression of genes controlling dopamine (DA) homeostasis and a reduction in DA levels in the striatum. Taken together, these data implicate RGS6 as an essential regulator of DA bioavailability. RGS6 deficiency also provided dramatic protection against cardiac hypertrophy and fibrosis, hepatic steatosis, and gastrointestinal barrier dysfunction and endotoxemia when mice were forced to consume alcohol. Although RGS proteins canonically function as G-protein regulators, RGS6-dependent, alcohol-mediated toxicity in the heart, liver, and gastrointestinal tract involves the ability of RGS6 to promote reactive oxygen species-dependent apoptosis, an action independent of its G-protein regulatory capacity. We propose that inhibition of RGS6 might represent a viable means to reduce alcohol cravings and withdrawal in human patients, while simultaneously protecting the heart and liver from further damage upon relapse.

Estimating the clinical and economic benefit associated with incremental improvements in sustained virologic response in chronic hepatitis C.

IntroductionHepatitis C virus (HCV) infection is one of the principle causes of chronic liver disease. Successful treatment significantly decreases the risk of hepatic morbidity and mortality. Current standard of care achieves sustained virologic response (SVR) rates of 40–80%; however, the HCV therapy landscape is rapidly evolving. The objective of this study was to quantify the clinical and economic benefit associated with increasing levels of SVR.MethodsA published Markov model (MONARCH) that simulates the natural history of hepatitis C over a lifetime horizon was used. Discounted and non-discounted life-years (LYs), quality-adjusted life-years (QALYs) and cost of complication management were estimated for various plausible SVR rates. To demonstrate the robustness of projections obtained, the model was validated to ten UK-specific HCV studies.ResultsQALY estimates ranged from 18.0 years for those treated successfully in fibrosis stage F0 to 7.5 years (discounted) for patients in fibrosis stage F4 who remain untreated. Predicted QALY gains per 10% improvement in SVR ranged from 0.23 (F0) to 0.64 (F4) and 0.58 (F0) to 1.35 (F4) in 40 year old patients (discounted and non-discounted results respectively). In those aged 40, projected discounted HCV-related costs are minimised with successful treatment in F0/F1 (at approximately £300), increasing to £49,300 in F4 patients who remain untreated. Validation of the model to published UK cost-effectiveness studies produce R2 goodness of fit statistics of 0.988, 0.978 and of 0.973 for total costs, QALYs and incremental cost effectiveness ratios, respectively.ConclusionProjecting the long-term clinical and economic consequences associated with chronic hepatitis C is a necessary requirement for the evaluation of new treatments. The principle analysis demonstrates the significant impact on expected costs, LYs and QALYs associated with increasing SVR. A validation analysis demonstrated the robustness of the results reported.

Pre-operative Hepatic Dysfunction Could Predict Postoperative Mortality and Morbidities in Patients Undergoing Open-heart Surgery; Utilization of the MELD Scoring System

Pre-operative Hepatic Dysfunction Could Predict Postoperative Mortality and Morbidities in Patients Undergoing Open-heart Surgery; Utilization of the MELD Scoring System

Peritoneal surface disease with synchronous hepatic involvement treated with Cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Patients with peritoneal surface disease (PSD) often present with synchronous hepatic involvement (HI). The impact of addressing the hepatic component during CRS/HIPEC on operative and survival outcomes is not clearly defined. A prospective database of 1,067 procedures was reviewed based on primary tumor, performance status, resection status, type of liver involvement (superficial or parenchymal) and hepatic resection, morbidity, mortality, and overall survival. There were 108 (10%) CRS/HIPEC procedures performed with synchronous liver debulking in 99 patients with PSD from 27 (33%) appendiceal and 32 (39%) colorectal primary lesions. Ninety percent of patients underwent subsegmental hepatic resection, whereas 22% had disease with hepatic parenchymal involvement. Median intensive care unit (ICU) and hospital stay were 3.5 and 13.6days, respectively. Clavien grade III/IV morbidity was similar for patients with or without resected HI (18.9 vs. 22.5%; p=0.39). The 30-day mortality rate was 6.5 and 2.8% (p=0.07) for patients with and without resected HI, respectively. The median survival for all patients with low-grade appendiceal cancer was 42.1months with resected HI and 95.5months without HI (p=0.03). Median survival for colorectal cancer patients after complete cytoreduction was 21.2months with HI versus 33.6months without HI (p=0.03). Synchronous resection of limited HI does not increase the morbidity or mortality of CRS/HIPEC procedures. The survival benefit, although still meaningful, was less for patients with HI. Resectable low volume HI in patients with PSD from colon and appendiceal primary lesions should not be considered a contraindication for CRS/HIPEC procedures.

The Risk of Long-term Morbidity and Mortality in Patients With Chronic Hepatitis C

The impact of viral load suppression, genotype, race, and other factors on the risk of late-stage liver-related events in patients with hepatitis C (HCV) has been assessed previously using data from small observational cohorts or clinical trials. Data from large real-world practice samples are needed to improve risk factor estimates for late-stage liver events and death in HCV. To describe the natural history of HCV in real-world clinical practice. Observational cohort study. Patients with a detectable viral load (>25 IU/mL) and a recorded baseline genotype were selected from the Veterans Affairs (VA) HCV clinical registry (CCR), which compiles electronic medical records data from 1999 to present. Risk factors included genotype, race, age, sex, and time to achieving an observed undetected viral load. The primary outcomes were time to death and time to a composite of liver-related clinical events. Secondary outcomes included the components of the composite clinical outcome. Outcomes were measured using a time-to-event format and were analyzed using Cox proportional hazards models. RESULTS A total of 28,769 of 360,857 unique HCV CCR patients met all study criteria. Only 24.3% of patients received treatment, and 16.4% of treated patients (4.0% of all patients) achieved an undetectable viral load. The unadjusted death rates were 6.8 (95% CI, 6.0-7.7) per 1000 person-years for patients who achieved viral load suppression vs 21.8 (95% CI, 21.5-22.2) deaths per 1000 person-years in patients who did not achieve this goal. Cox model results found that achieving viral suppression reduced risk of the composite clinical end point by 27% (hazard ratio [HR], 0.73 [95% CI, 0.66-0.82]) and the risk of death by 45% (HR, 0.55 [95% CI, 0.47-0.64]). Genotype 2 patients were at significantly lower risk, and genotype 3 patients were at higher risk for all study outcomes relative to genotype 1. Black patients were at lower risk for all liver events than white patients. Achieving an undetectable viral load was associated with decreased hepatic morbidity and mortality. It remains to be determined whether newer treatment regimens can offer higher response rates with fewer adverse effects in real-world settings.

Hepatitis B virus reactivation in patients with hepatocellular carcinoma undergoing anti-cancer therapy.

Patients with hepatocellular carcinoma (HCC) often experience hepatic morbidity. Hepatitis B virus (HBV) reactivation is well documented as a serious hepatic morbidity during anti-cancer therapy. Reported rates of HBV reactivation in chronic carriers with HCC undergoing chemotherapy range from 4%-67%. Apart from chemotherapy, HBV reactivation has been increasingly identified in settings of hepatectomy and local ablation therapies. The rates of HBV reactivation vary with different levels of immunosuppression and depend on treatment, viral factors, and patient characteristics. The principal concern relating to reactivation is that a substantial proportion of patients with reactivation suffer from liver dysfunction during therapy, which often leads to disruption of planned, potentially life-prolonging treatments, adversely affecting the patients' final outcome. The first step in the management of HBV reactivation is identification of patients at risk of reactivation by testing for HBV serology prior to commencing anti-cancer therapy. Although it is a serious complication, HBV reactivation is preventable with prophylactic anti-HBV drugs. Multiple publications have shown the benefit of prophylactic or preemptive antiviral therapy in this setting and justified such an approach before the start of therapy. Given the tumors and underlying cirrhosis, long-term use of antivirals with high potency and low risk of resistance is recommended in patients with HCC. This topic review will summarize the epidemiology, pathogenesis, and clinical issues related to HBV reactivation in HCC patients, and will discuss proper management against HBV reactivation during anti-cancer therapy for HCC.