Autoimmune diseases as comorbidities for liver,gallbladder, and biliary duct cancers in Sweden

Background

Autoimmune diseases are associated with many cancers but there is a lack of population-based studies with different autoimmune diseases that have a long follow-up. This is also true of hepatobiliary cancers, which include hepatocellular cancer (HCC) and rarer entities of gallbladder cancer (GBC), intra- and extrahepatic cholangiocarcinoma (iCCA and eCCA), and ampullary cancer.

Methods

Diagnostic data on 43 autoimmune diseases were collected from the Swedish Inpatient Register from 1987 to 2018, and cancer data were derived from the national cancer registry from 1997 onward. Relative risks were expressed as standardized incidence ratios (SIRs).

Results

In a population of 13.6 million, 1.1 million autoimmune diseases were diagnosed and subsequent hepatobiliary cancer was diagnosed in 3191 patients (17.2% of cancers). SIRs for HCC were 2.73 (men) and 2.86 (women), 3.74/1.96 for iCCA, 2.65/1.37 for GBC, 2.38/1.64 for eCCA, and 1.80/1.85 for ampullary cancer. Significant associations between autoimmune disease and HCC were observed for 13 autoimmune diseases, with the highest risks being for autoimmune hepatitis (48.92/73.53, men/women) and primary biliary cirrhosis (38.03/54.48). GBC was increased after six autoimmune diseases, with high SIRs for ulcerative colitis (12.22/3.24) and men with Crohn disease (9.16). These autoimmune diseases were also associated with a high risk of iCCA, which had seven other associations, and eCCA, which had five other associations. Ampullary cancer occurrence was increased after four autoimmune diseases.

Conclusion

An autoimmune disease is a common precursor condition for hepatobiliary cancers. This calls for careful control of autoimmune disease symptoms in each patient and encouragement to practice a healthy lifestyle.     

Interleukin-6 and its receptor, key players in hepatobiliary inflammation and cancer

In recent years, the relationship between interleukin-6 (IL-6), hepatobiliary inflammation, and cancer has been studied. It is becoming clear that this cytokine plays an important role in the pathogenesis of both cholangiocarcinoma (CCA, cancer of the bile ducts) and hepatocellular carcinoma (HCC, cancer arising from the liver parenchyma). Inflammation due to various chronic hepatobiliary diseases including hepatitis B, hepatitis C, alcoholic liver injury, and primary sclerosing cholangitis (PSC) has been associated with increased levels of IL-6 and with increased rates of malignancy. In this review, we will summarize the current knowledge linking inflammation to hepatobiliary cancer, and discuss the key role of IL-6 and its signaling pathways in mediating this link. We will first review the major signaling pathways that are triggered when IL-6 engages its receptor. These include PI3 kinase, JAK/STAT, p38 MAP kinase and others that ultimately lead to cell proliferation, protection from apoptosis and increased metastatic potential. We will then discuss data linking IL-6 and hepatobiliary cancer, namely HCC and CCA.     

Autoimmune disease and subsequent digestive tract cancer by histology

BackgroundDysregulation of the immune function in autoimmune diseases could potentially lead to cancer development and there is definite evidence linking some autoimmune mechanisms with cancer. We analyzed systematically the occurrence of histology-specific digestive tract cancers in patients diagnosed with 33 different autoimmune diseases in order to address the question of shared susceptibility.Patients and methodsStandardized incidence ratios (SIRs) were calculated for subsequent digestive tract cancers up to the year 2008 and in patients hospitalized for autoimmune disease after the year 1964.ResultsMyasthenia gravis associated with five different cancers with SIRs ranging from 1.35 to 2.78. Pernicious anemia, Crohn disease, ulcerative colitis, systemic lupus erythematosis and psoriasis were also associated with cancers at multiple sites. Rheumatoid arthritis associated with no cancer and the standardized incidence ratio was decreased for colon adenocarcinoma, also in ankylosing spondylitis patients.ConclusionsIncreased risks of cancer were observed in patients with several autoimmune diseases. Myasthenia gravis and pernicious anemia were associated with many cancers; this is possibly related to immunosuppressant medication in myasthenia gravis. The decreased risks in colon and rectal adenocarcinomas in rheumatoid arthritis and ankylosing spondylitis suggest underlying inflammatory mechanisms as the risks may have been suppressed by the use of anti-inflammatory medication.     

Current standards and future perspectives in adjuvant treatment for biliary tract cancers

Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only ~20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60–70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, which included a variety of additional tumours (e.g. pancreatic and ampullary tumours); most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies.Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community.This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored.     

Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma

BACKGROUND: The goal of the current study was to evaluate the efficacy and toxicity of capecitabine in patients with nonresectable hepatobiliary carcinoma. METHODS: The authors performed a retrospective analysis of all patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), or gallbladder carcinoma (GBC) who were ever treated with oral capecitabine. The medical records of 116 patients with hepatobiliary carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between July 1998 and March 1999 were reviewed. RESULTS: A total of 63 patients were treated with capecitabine (37 with HCC, 18 with CCA, 8 with GBC). Capecitabine 1000 mg/m(2) was administered twice daily for 14 days. Treatment was repeated every 21 days. Each patient received 1-15 treatment cycles. Nine patients (14%)-11% of patients with HCC, 6% of patients with CCA, and 50% of patients with GBC-had either a complete response (CR) or a partial response. A CR was radiologically confirmed in one patient with HCC and in two patients with GBC. The median survival times were 10.1 months (95% confidence interval [CI], 4.5-15.7 months) for patients with HCC, 8.1 months (95% CI, 7.4-8.9 months) for patients with CCA, and 9.9 months (95% CI, 4.4-15.4 months) for patients with GBC. The most common toxicity was hand-foot syndrome (37%). Grade 3 thrombocytopenia occurred in 8% of patients with HCC. No other significant toxicities were observed. For all patients, response to treatment was positively correlated with survival and decline in tumor markers. CONCLUSIONS: Capecitabine was found to be safe for patients with hepatobiliary carcinoma, including those with cirrhosis. The antitumor activity of single-agent capecitabine was most pronounced in patients with GBC, was modest in patients with HCC, and was poor in patients with CCA.     

Hepatocellular Carcinoma: Prevention and Therapy

Hepatocellular carcinoma (HCC) is an aggressive malignancy of the liver and occurs most often in the setting of chronic liver disease. The most common acquired causes for this are chronic viral hepatitis infections (mostly HBV and HCV), and alcohol. Other causes include nonalcoholic fatty liver disease–related nonalcoholic steatohepatitis, autoimmune liver disease, and biliary diseases. In addition, certain heritable diseases like hemochromatosis and α-1-antitrypsin deficiency can also lead to HCC. Therefore, prevention of HCC can be achieved by preventing and controlling these problems. For treatment, curative modalities are surgical resection and liver transplantation. However, most patients are not candidates for these surgical maneuvers, and outcomes are poor. New therapeutic developments have brought some improvement with both local and systemic disease control.     

Cholangiocarcinoma: Expanding the Spectrum of Risk Factors

Introduction

Cholangiocarcinoma (CCA) is an epithelial cancer originating from the bile ducts with features of cholangiocyte differentiation. The global incidence of this rare disease is on the rise, and it is the second most common primary hepatobiliary malignancy. We reviewed risk factors for cholangiocarcinoma development and also described potential screening strategies for this malignancy. We also report two cases in which CCA developed in patients without previously determined risk factors known for CCA.

Discussion

The first case is a patient with longstanding secondary sclerosing cholangitis (SSC), and the second is a patient with autoimmune hepatitis (AIH). These two cases may indicate a possible association between SSC and AIH with CCA, thus, expanding the spectrum of risk factors of CCA.     

Cancer risks in ulcerative colitis patients

Patients diagnosed with ulcerative colitis (UC) are known to be at an increased risk of colorectal and liver cancers and leukemia. UC is an autoimmune disease, which may present a wider spectrum of cancers. We wanted to examine the risk of cancer in a large population of UC patients in order to reach high statistical power. A UC research database was constructed by identifying UC patients from the Swedish Hospital Discharge Register and cancer patients from the Cancer Registry. Follow-up of 27,606 UC patients hospitalized for the first time during the years 1964-2004 identified 2,058 patients with cancer. Standardized incidence ratios were calculated for cancer in UC patients by comparing to subjects without hospitalization for UC. The novel tumor sites in UC patients included small intestinal (carcinoid), pancreatic, breast and prostate cancers, nonthyroid endocrine gland tumors, non-Hodgkin lymphoma and multiple myeloma. A total of 11 sites showed an increased risk, which remained at 6 sites when tumors diagnosed in the year of UC hospitalization were excluded; even chronic myeloid leukemia was in excess. Cancer risks depended on the age at first hospitalization for UC. The SIRs for colon, rectal, liver and pancreatic cancers declined by age at hospitalization for UC, while for endocrine tumors the older patients were at higher risk. Our large study identified novel subsequent cancers in UC patients. However, some of these, including small intestinal carcinoids, prostate cancers and nonthyroid endocrine tumors, may be in excess because of intensified medical surveillance of the patients.     

Familial association of histology specific breast cancers with cancers at other sites

Breast cancer histologies show important differences in their incidence pattern, method of detection and management. Aggregation of breast cancer occurs also in families diagnosed for cancer at sites different from the breast. Therefore, the familial association of histology specific breast cancers with cancers at other sites is of great interest. The nationwide Swedish Family-Cancer Database was used to calculate standardised incidence ratios (SIRs) for breast cancer when parents or sibling were diagnosed with cancer at the most common sites. Significant SIRs were found when parents had breast, ovarian, laryngeal, endometrial, prostate, lung and colon cancers. If women were diagnosed before the age of 50 years, the SIRs were significant when parents were diagnosed with breast, ovarian, and prostate cancers, and leukaemia, and when siblings were diagnosed with squamous cell skin, pancreatic, breast and endometrial cancers. If mothers were diagnosed with breast cancer, histology-specific SIRs were ranked as comedo > tubular > ductal > lobular; SIR for medullary carcinoma was not significant but it was high when mothers presented with ovarian cancer. Other associations were between the upper aerodigestive tract and lobular, colon and comedo, larynx and ductal cancer. Moreover, cervical cancer was associated with comedo and endometrial cancer with the medullary histology. In conclusion, histology-specific breast cancers were associated with specific cancer sites and the strength of the association varied among histologies.     

Cancer risks in Crohn disease patients

Background: Patients diagnosed with Crohn disease (CD) are knownto be at an increased risk of bowel cancers and lymphoma. CDis an autoimmune disease and we hypothesize that the patientsare predisposed to a wider spectrum of cancers. Patients and methods: A CD research database was constructedby identifying hospitalized CD patients from the Hospital DischargeRegister and cancer patients from the Swedish Cancer Registry.Follow-up of 21 788 CD patients first hospitalized during theyears 1964–2004 identified 1424 cancer cases. Standardizedincidence ratios (SIRs) were calculated by comparing cancersin CD patients with subjects without CD. Results: In addition to the known sites, many additional siteswere in excess in CD patients. These included liver, pancreatic,lung, prostate, testicular, kidney and skin (squamous cell)cancers; nonthyroid endocrine tumors and leukemia. The previouslyestablished sites showed the highest SIRs; however, SIRs >2.0were noted for the novel sites of the liver, testis and kidney.For testicular cancer, the SIR of seminoma was 2.74. Cancerrisks were influences by age at first hospitalization for CDbut whether the age effects were increasing or decreasing dependingon the cancer type. Conclusions: This large study identified many novel subsequentcancers in CD patients. Key words: age at onset, autoimmunity, cancer risk, inflammatory bowel disease, subsequent cancer Received for publication February 22, 2008. Revision received July 29, 2008. Accepted for publication July 30, 2008.     

Cancer risk in patients with type 2 diabetes mellitus and their relatives

Epidemiological studies indicate that risks of certain cancers are increased in individuals hospitalized for type 2 diabetes mellitus (T2DM), which may not be representative of the entire population of T2DM patients as most of them are treated in primary health cares. To examine the subsequent cancer risk in individuals with T2DM from hospitals and primary health cares, and in their siblings and spouses, standardized incidence ratios (SIRs) were used to assess systematically risks of 35 cancer sites/types in individuals with T2DM using a nationwide Swedish database covering the period 1964 through 2010. Increased SIRs were recorded for 24 cancer sites/types in individuals with T2DM. The highest SIRs were for pancreatic cancer and liver cancer (2.98 and 2.43, respectively). A decreased SIR was noted for prostate cancer. Five cancers showed increased SIRs during the whole follow‐up period: colon, liver, pancreatic, endometrial and kidney cancers. T2DM patients in inpatient, outpatient and primary health care showed similar risk patterns. The overall SIRs for cancer in the siblings and spouses of individuals with T2DM were 0.97 and 1.01, respectively. The insulin users showed an overall increased risk of cancer. This study showed increased risks of 24 cancers in individuals with T2DM, but not in their siblings or spouses, suggesting that the profound metabolic disturbances of the underlying disease may explain the observed increases. Further studies examining the endogenous and exogenous factors underlying these associations are needed.     

Hepatocellular Carcinoma and its Early Detection by AFP Testing in Mongolia

Liver cancer is one of the leading causes of cancer death in Mongolia. Since 1982-1986 , when HCC became themost frequent cancer among the Mongolian population, the rate has been increasing continuously. In the period2000-2005 years 35.3%of all newly registered cancer cases were liver cancers, with an incidence rate of 51.3 per100,000 population. Compared to the previous 5 year period, the rate increased by 11%. The objective here was toanalyze hepatitis B (HBV) and C virus (HCV)-related HCC cases and to evaluate the possibility of tumor marker(AFP) testing for early detection in Mongolia. Sera from a total of 513 patients with chronic liver diseases, livercirrhosis and HCC were analyzed for liver function (ALAT, ASAT) and hepatitis virus markers (HBsAg, anti-HCV).Sera from 316 patients were also examined for alpha-fetoprotein (AFP) levels. The overall incidence of HBsAg oranti-HCV were very high ( 95.3%) among all patients. Some 33.5% (66/197) of patients with HCC were positive forHBsAg and 45.2% (89/197) for anti-HCV. Moreover, 17.3% ( 34/197) of HCC patients demonstrated co-infectionwith HBV and HCV. AFP levels were elevated in 4.6% (11/238) and 29.5% (23/78) of chronic hepatitis and cirrhosispatients, respectively. In HCC cases, 84.3% (166) of patients had increased level of AFP ranging from 32ng/ml tomore than 400 ng/ml. We conclude that HBV/HCV infection is the main factor related to development of HCC inMongolia and that testing for AFP serum levels is a useful tool for early detection and diagnosis.     

Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity

Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. It evolves from several chronic liver diseases, most of which culminate in cirrhosis. As the most common causes, other than alcoholic cirrhosis, are chronic hepatitis B and C infections, its prevalence worldwide is linked to the prevalence of these two viruses. Thus, the highest rates are in southeast Asia and sub-Saharan Africa, the world's most populous nations, where hepatitis B virus infection is endemic. In most western countries, hepatitis C virus infection is the predominant cause, and hepatitis B-related liver cancer occurs largely among immigrants from countries of high hepatitis B endemicity. In most western countries, the incidence and mortality from HCC is increasing as a consequence of the chronic sequelae of the 'epidemic' of hepatitis C of the 1960-1980s. In the US, modeling of this infection predicts a continued rise in liver cancer over the next decade. Surveillance by the National Cancer Institute and the Centers for Disease Control confirms the increasing incidence of and mortality from HCC to the year 2000, although subsequent analyses suggest a slowing or possibly decline in the rate of increase. Whether this trend will continue requires further evaluation.     

Cellular and molecular mechanisms involved in hepatocellular carcinoma gender disparity

Hepatocellular carcinoma (HCC) represents the most common primary liver cancer and one of the most fatal human cancers. Besides alcoholic liver disease as well as genetic and environmental factors, hepatitis B and C viral infections also represent the most important risk factors for onset and development of the disease. In fact, HCC worldwide prevalence varies widely and mirrors the geographical distribution of chronic viral hepatitis. Interestingly, a gender difference was described for this disease: in almost all populations, a male/female ratio averaging between 2:1 and 4:1 was reported. Here, we analyze the implication of cytokines and sex hormones in this issue. Exploiting the emerging knowledge on the possible differential role of hepatitis viruses B and C, we discuss the role of reactive oxygen species and apoptosis dysregulation in the characterization of the molecular mechanisms of gender disparity in the development of HCC.     

Risk of cancer in patients with medically diagnosed hay fever or allergic rhinitis

Data on allergic conditions as risk or protective factors for cancer are controversial probably because most studies have used self‐reported data on mixed groups of allergies in a case–control setting. We define cancer risks in medically diagnosed hay fever/allergic rhinitis patients in a nationwide cohort study. A total of 138,723 hay fever/allergic rhinitis patients were identified from three Swedish health care databases and standardized incidence ratios (SIRs) were calculated for subsequent cancers identified from the Swedish Cancer Registry. Overall cancer risk was not changed (SIR 1.03). For individual cancers, the highest SIR was observed for nasal cancer (SIR 2.63), followed by testicular (1.46) and endocrine tumors (1.42), and kidney (1.31), prostate (1.18) and breast (1.11) cancers. The results were consistent in the three sources of data and all SIRs were above unity, albeit mainly not statistically significant. The SIRs for nervous system tumors were above unity and of borderline significance. SIRs were decreased for esophageal (0.50), liver (0.62) and lung (0.78) cancers, and the three sources of data agreed in the direction of the effect. The increased risks for testicular, renal, prostate and endocrine cancers may be explained by immunological mechanisms. Excess risk for these cancer accounts for a significant population attributable fraction. Nervous system cancers showed a borderline increase and none of the histological types were significantly decreased, providing strong evidence against the published case–control studies, which have reported protective effects. The reasons for the reduced risks for esophageal, liver and lung cancer remain to be explained.     

Significant increase in the antibody to Gal alpha 1-3Gal structure in sera of patients with hepatocellular carcinoma after transcatheter arterial embolization

Sera from the patients with chronic liver diseases and hepatocellular carcinoma (HCC) were tested for reactivity with neutral glycosphingolipids extracted from rabbit liver plasma membrane by enzyme-linked immunosorbent assay and thin-layer chromatography immunostaining. IgG class antibody to neutral glycosphingolipids was detected in 29.6% (8 of 27), 6.3% (1 of 16), 0% (0 of 8), 0% (0 of 25), and 6.9% (2 of 29) in the sera of patients with HCC, liver cirrhosis, autoimmune chronic active hepatitis, chronic hepatitis, and normal individuals, respectively. Using the serum positive for the antibody to neutral glycosphingolipids, the target antigen glycolipid was isolated. Negative ion fast atom bombardment mass spectrometry, exoglycosidases treatment, and permethylation analysis revealed that the main target antigen was IV3 alpha Gal-nLc4Cer. In enzyme-linked immunosorbent assay, IgG class antibody to IV3 alpha Gal-nLc4Cer was detected in 33.3% (9 of 27), 18.8% (3 of 16), 25% (2 of 8), 4% (1 of 25), and 6% (3 of 50) in the sera of patients with HCC, liver cirrhosis, autoimmune chronic active hepatitis, chronic hepatitis, and normal individuals, respectively. Of 9 HCC patients positive for the antibody, 6 had received transcatheter arterial embolization (TAE) therapy. Six of 10 patients who received TAE therapy had the antibody, whereas only 3 of 17 patients without TAE therapy had the antibody. This antibody may be a heterophile antibody, which recognizes Gal alpha 1-3Gal structure at the nonreducing terminal of the antigen. Since the occurrence of this antibody was closely related with TAE therapy, the necrosis of HCC induced by TAE therapy may stimulate the production of the antibody.     

Tissue distribution of 2-3 and 2-6 sialyl Lewis A antigens and significance of the ratio of two antigens for the differential diagnosis of malignant and benign disorders of the digestive tract

The authors investigated the tissue distribution of two kinds of sialylated derivatives of Lewis A (Le(a)) antigen in patients with cancers of the digestive system using specific monoclonal antibodies, and evaluated the significance of determining the 2-3 and 2-6 sialylated Le(a) antigen levels for the diagnosis of cancer. In most specimens from patients with cancers of the pancreas, biliary tract, stomach, and colon, the 2-3 sialylated Le(a) antigen was strongly expressed in cancer cells. However, 2-6 sialylated Le(a) antigen was less frequently expressed in cancer cells. The former is therefore more specific to cancer than the latter. Also, the serum level of the 2-3 sialylated Le(a) antigen was significantly higher than that of the 2-6 counterpart in patients with cancers of pancreas, biliary tract, stomach, and colon. The resulting ratio of serum 2-3/2-6 sialylated Le(a) antigens was frequently high in patients with malignancy and was low in patients with benign disorders of these digestive organs. Therefore, the 2-3/2-6 sialylated Le(a) antigen ratio is a useful for the differential diagnosis of malignant disorders in these organs. However, liver disorders were found to be exceptional in that both antigens were mostly absent in hepatocellular carcinoma (HCC) cells in immunohistologic examination, as well as in nonmalignant parenchymal liver cells. Only the epithelial cells of the intrahepatic bile ducts expressed the 2-6 sialylated Le(a) antigen strongly, and expressed the 2-3 sialylated Le(a) antigen moderately. The levels of both antigens were sometimes high in patients with liver disorders, but the ratio always remained low in patients with HCC as well as benign liver disorders such as cirrhosis or chronic hepatitis. The sialylated Le(a) antigens, which sometimes accumulate in the sera of patients with HCC, were concluded to originate from the epithelial cells of the proliferating small bile ducts, and those serum antigens cannot be considered as evidence for the presence of liver cancer cells.     

Human hepatocellular carcinoma: Expression profiles-based molecular interpretations and clinical applications

Primary liver cancer is the fifth most common cancer worldwide and hepatocellular carcinoma (HCC) accounts for over 85% of all primary liver cancers. The clinical management of advanced and metastatic HCC is challenging on many counts. Besides largely occurs within a background of underlying chronic liver disease and cirrhosis, HCC is a phenotypically and genetically heterogeneous polyclonal disease and resistant to most conventional chemotherapy. Early manifestation of HCC is characteristically slow growing with few symptoms, and HCC is therefore often diagnosed at an advanced stage when potentially curative surgical or local ablative therapy is not feasible. In this review, I have summarized my presentation at the recent HCC workshop at IARC, Lyon, on our knowledge generated from comprehensive molecular studies of primary liver cancer tissues and attempt to translate these results to gain molecular insights, especially on identification of biomarkers that could confer pathological and functional changes associated with the pathogenesis and progression of HCC, hoping to provide important molecular basis for the development of novel diagnosis and treatments to alter clinical outcomes of this disease.     

Hepatocellular carcinoma in patients with chronic renal disease: Challenges of interventional treatment

Hepatocellular carcinoma (HCC) is a common malignancy worldwide, recognized as the fourth most common cause of cancer related death. Many risk factors, leading to liver cirrhosis and associated HCC, have been recognized, among them viral hepatitis infections play an important role worldwide. Patients suffering from chronic kidney disease (CKD), especially those on maintenance dialysis, show a higher prevalence of viral hepatitis than the general population what increases the risk of HCC onset. In addition, renal dysfunction may have a negative prognostic impact on both immediate and long-term outcomes after malignancy treatment. Several interventional procedures for the treatment of HCC are currently available: thermal ablation, transcatheter arterial chemoembolization, liver surgery or even liver transplantation. The Barcelona Clinic Liver Cancer system provides an evidence-based treatment algorithm to address different categories of patients to the most-effective treatment in consideration of the extension of disease, liver function and performance status. Liver resection and transplantation are usually reserved to patients with early stage HCC and acceptable performance status, while the other treatments are more indicated in case of impaired liver function or locally advanced or unresectable tumors. However, there is no validated treatment algorithm for HCC in CKD patients, mainly due to the rarity of reports in this cohort of patients. Hereby we discuss the available evidences on interventional HCC treatments in CKD patients, and briefly report up-to-date pharmacological therapy for HCC patients affected by viral hepatitis.