Liver Cancers Research Papers - Academia.edu (original) (raw)

With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D) nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1) Lung; (2) Bone marrow; (3) Brain; (4) Breast; (5) Urinary system (kidney, bladder and prostate); (6) Intestine; and (7) Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart-liver-intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET) of anticancer drugs and more realistically recapitulate tumor in vivo-like microenvironment.

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- Computer Science, Brain cancer, Medicine, Lung Cancer

- by hajar moghadas
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- Brain cancer, Lung Cancer, Tumor microenvironment, Kidney

Liver disease accounts for approximately 2 million deaths per year worldwide with cirrhosis, viral hepatitis, and malignancy being the most common causes. Consequently, the regenerative capacity of the liver is a topic of extreme interest in the search for curative therapies to end-stage liver disease. Mesenchymal stem cells (MSCs) have emerged as a promising new therapy for hepatic regeneration. MSCs have multiple properties that make them an appropriate treatment option for liver disease including easy accessibility, targeted migration, immunomodulatory potential and antifibrotic/antioxidant effects. Additionally, MSCs have potential clinical applications in acellular therapy and tissue engineering. Liver regeneration with concurrent attenuation of liver injury makes MSCs a compelling therapeutic target in the setting of severe liver disease. This review outlines the mechanisms of MSC-driven liver regeneration and suggests potential clinical applications.

- by Hepatoma Research and +3
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- Liver diseases, Mesenchymal stem cells, Liver Cancers, Liver regeneration

Primary sclerosing cholangitis (PSC) is a rare disease that may well be notified as a premalignant condition due to the increased cancer risk. The risk is highest for hepatobiliary cancer and increased by 28-398 times compared to the general population. When comorbidity with inflammatory bowel disease exists, the risk for colorectal cancer is increased 5-12 times and may even be higher after liver transplantation. The cancer risk estimates have decreased with time but vary according to study design. More recent population-based studies have approximated lower cancer risk than previous studies. Higher awareness and earlier detection of PSC together with increased surveillance over time may have influenced risk estimates. Surveillance for PSC patients is recommended for early tumor detection in both the liver and colon to enable curative treatment. The evidence for the efficacy of surveillance for early detection of hepatobiliary cancer is weak and an accepted common strategy worldwide is lacking. The high risk of hepatobiliary cancers has been confirmed repeatedly and future studies in PSC should focus on individualizing follow-up strategies and treatment.

- by Hepatoma Research and +1
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- Epidemiology, Pancreatic Cancer, Colorectal cancer, Liver diseases

Surgical resection and chemotherapy are the mainstay of the treatment for undifferentiated embryonal sarcoma of the liver. Whether neoadjuvant chemotherapy should be systematically performed is a matter of debate; perioperative morbidity and mortality should be carefully weighed against chemotherapy-associated complications. In order to manage undifferentiated embryonal sarcoma of the liver and to allow for accurate outcome analysis, there is a clear need for standardization of disease extent as well as for a risk stratification system, including the PRETEXT grouping system, patient age, and tumor size.

- by Hepatoma Research and +1
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- Pediatrics, Liver diseases, Gastroentrology & Hepatology, Liver Cancers

Fibrolamellar hepatocellular carcinoma (FHCC) is a rare primary malignancy of the liver for which data remain limited. This tumor is more often diagnosed in younger patient populations in the absence of underlying cirrhosis and hepatitis. These lesions can be diagnosed on computed tomography scan or magnetic resonance imaging with common findings including central calcifications, a central stellate scar, and radiating fibrotic bands. Laboratory markers have not proved useful for diagnosis; however, pathologic analysis can be implemented to aid in diagnosis with findings including ample granular eosinophilic cytoplasm, nuclei with open chromatin and prominent macronuclei, hyaline and pale bodies, and dense lamellar fibrosis that divides the cells into cords or trabeculae. FHCC demonstrates aggressive malignant potential with nodal spread. Treatment patterns have remained mainly surgical; however, systemic therapies have been implemented and are under further investigation with clinical trials. Locoregional therapies and radiation therapies have been trialed sparingly. In this focused review, we discuss the most up-to-date perspective on epidemiology, clinical presentation, diagnostic approach, differential diagnosis, treatment regimens, prognosis, and future directions of FHCC.

- by Hepatoma Research
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- Surgery, Hepatocellular Carcinoma, Liver Cancers

Liver cancer accounts for 4.7% of all newly diagnosed cancers and 8.2% of cancer deaths annually. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. There are 2 curative strategies in HCC: resection and transplant. Unfortunately, 50% of patients who undergo resection will relapse in 2 years and many patients on transplant lists become ineligible for transplant due to disease progression. The majority of patients still require systemic therapies. Tyrosine kinase inhibitors have successfully extended the overall survival in patients with hepa-tocellular carcinoma. However, these treatments have been noted to cause severe side effects including liver toxicity, hypertension, gastrointestinal toxicity and cutaneous adverse effects. This article will focus on the adverse skin reactions seen during the treatment of hepatocellular carci-noma by various tyrosine kinase inhibitors. The focus will be symptomatology, management, and whether the development of cutaneous toxicities can be prognostic.

- by Hepatoma Research and +1
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- Dermatology, Hepatology, Gastroentrology & Hepatology, Toxicity

Progressively, as chemotherapy has become more effective, more children with liver malignancies are amenable to liver transplantation, and indications have expanded from a limited range of cases (mostly hepatoblastoma) to a range of other unresectable malignant liver tumors; as a result, more children with hepatocellular carcinoma are also now proposed to transplantation, even and often outside the Milan criteria, for a cure. Recent series have highlighted that patient and graft survivals after transplantation for hepatoblastoma and hepatocellular carcinoma have improved in the last decade. Although consensus has not yet been reached about transplantation as a possible cure for other tumor types than hepatoblastoma and hepatocellular carcinoma, liver transplantation, generally speaking, has become an important pillar in the management of pediatric liver malignancies. Remaining limitations and inquiries relate to patient selection (in term of selection criteria considering the risk of recurrence), the role and usefulness of chemotherapy after transplantation, or the best immunosuppression strategy to both protect renal function and improve outcome. Although some prospective studies are on the way regarding these aspects, more studies are needed to explore this rapidly changing aspect of care.

- by Hepatoma Research and +2
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- Liver diseases, Hepatocellular Carcinoma, Liver Transplantation, Liver Cancers

Global prevalence of non-alcoholic fatty liver disease (NAFLD) and of NAFLD-hepatocellular carcinoma (HCC) is estimated to grow in the next years. The burden of NAFLD and the evidence that NAFLD-HCC arises also in non-cirrhotic patients, explain the urgent need of a better characterization of the molecular mechanisms involved in NAFLD progression. Obesity and diabetes cause a chronic inflammatory state which favors changes in serum cytokines and adipokines, an increase in oxidative stress, DNA damage, and the activation of multiple signaling pathways involved in cell proliferation. Moreover, a role in promoting NAFLD-HCC has been highlighted in the innate and adaptive immune system, dysbiosis, and alterations in bile acids metabolism. Several dietary, genetic, or combined mouse models have been used to study nonalcoholic steatohepatitis (NASH) development and its progression to HCC, but models that fully recapitulate the biological and prognostic features of human NASH are still lacking. In humans, four single nucleotide polymorphisms (PNPLA3, TM6SF2, GCKR, and MBOAT7) have been linked to the development of both NASH and HCC in cirrhotic and non-cirrhotic patients, whereas HSD17B13 polymorphism has a protective effect. In addition, higher rates of somatic ACVR2A mutations and a novel mutational signature have been recently discovered in NASH-HCC patients. The knowledge of the molecular pathogenesis of NAFLD-HCC will be helpful to personalized screening programs and allow for primary and secondary chemopreventive treatments for NAFLD patients who are more likely to progress to HCC.

- by Hepatoma Research and +1
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- Liver Cirrhosis, Liver, Hepatocellular Carcinoma, non alcoholic fatty liver disease (NAFLD)

Background: Discordance in hepatocellular carcinoma (HCC) staging between pre-transplant imaging and explant pathology is associated with an increased risk of recurrence and death. Our aim was to evaluate variables that predicted concordance/discordance in the era of new generation locoregional therapies (LRT) and improved radiologic technology in diagnosis. Methods: A single-center retrospective study was performed on patients who received a liver transplant for HCC between 2008-2019. Pre-and post-LT variables, including type of LRT, downstaging (DS), transplant time period, and radiologic response to LRT, were analyzed for concordance/discordance. Kaplan-Meier analysis was used to assess post-LT survival. Discordance was associated with ≥ 3 HCC lesions at diagnosis but not newer generation LRT (transarterial radioembolization/ stereotactic body radiation therapy), traditional LRT or combination. No differences in discordance were seen between transplant periods (2008-2013 vs. 2014-2019), but those within MC in the earlier period had higher concordance rates. A trend was observed between DS and discordance. Conclusion: HCC stage discordance remains common and poorly predictable. Discordance was associated with three or more HCC lesions at the time of diagnosis. Patients within MC transplanted between 2008-2013 was associated with concordance, while a trend was noted between DS and discordance. No other pre-or post-LT variables predicted discordance/ concordance. Discordance was associated with decreased survival.

- by Hepatoma Research and +1
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- Liver Transplantation, Liver Cancers

When do you need to take biopsies of the liver, and what information will you get is the topic of this review on hepatocellular carcinoma (HCC). If, clinically, the differential diagnosis of HCC after imaging is suggested, a biopsy has become obligatory as a diagnostic confirmation of HCC in the non-cirrhotic liver prior to definitive therapeutic interventions, as well as in a palliative therapy concept. In the case of hepatic lesions with an uncharacteristic contrast uptake, a biopsy should be performed immediately to confirm the diagnosis of HCC. After diagnosing HCC, a treatment strategy is evaluated. Further, the biopsy, or in case of surgical treatment, the resected tissue, shows us the different subtypes of HCC, with the steatohepatitic subtype being the most common and the lymphocyte-rich subtype being the least common. Further, the histological grade of HCC is determined according to the grading system of the WHO or the Edmonson and Steiner System. Through biopsies, HCC can be differentiated from intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma or metastases of other malignant tumors, especially metastases of the gastrointestinal tract. In summary, biopsies are fundamental in the diagnosis of HCC.

- by Hepatoma Research and +1
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- Histology, Liver diseases, Liver, Hepatocellular Carcinoma

- by Hepatoma Research and +1
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- Histology, Liver diseases, Hepatocellular Carcinoma, Liver Cancers

The resectability of hepatocellular carcinoma (HCC) has been assessed based on the liver functional test, the liver volume of the future liver remnant (FLR), and, more recently, the functional liver volume of FLR. Liver volume is estimated via multi-detector computed tomography and three-dimensional image visualization technologies, and functional liver volume is investigated via 99mTc-galactosyl human serum albumin scintigraphy, 99mTc-mebrofenin hepatobiliary scintigraphy, and gadoxetic acid-enhanced magnetic resonance imaging. Several special techniques have been developed to promote FLR hypertrophy, thus allowing for safe hepatectomy. As an interventional technique, portal vein embolization (PVE) is essential, and, along with transarterial chemoembolization or hepatic vein embolization, this is beneficial in promoting a much larger FLR. Dual embolization is recommended for patients with very small FLR or with PVE failure. Radioembolization by Yttrium-90 microspheres (i.e., radiation lobectomy) can help in achieving FLR hypertrophy and has an anticancer effect on HCC. Transarterial chemoembolization on PVE has a similar anticancer effect. Surgical procedures, such as two-stage hepatectomy as well as associated liver partition and portal vein ligation for staged hepatectomy, are somewhat invasive. Therefore, they should be applied as a salvage procedure for patients with HCC who had inadequate response to the interventional approach. However, the best approach should be selected mainly based on the functional volume of FLR and the patients’ condition; in addition, the resources of each facility should be considered.

FTIR microspectroscopy was applied for studying macro- molecular changes in human serum samples from pa- tients with healthy livers, and those diagnosed with liver cirrhosis or hepatocellular carcinoma (HCC). Our study demonstrated that the serum samples from HCC and cir- rhotic patients could readily be discriminated from those from healthy controls based on macromolecular differ- ences related to their lipid and protein structure. Spectral changes appeared to indicate that the secondary struc- ture of protein from HCC sample groups contained a more distinctive b-sheet structure and a lower lipid con- tent compared to samples from the healthy and cirrhosis group. This was correlated with measurements of large decreases in albumin levels in serum from diseased pa- tients. We argue that this technique shows potential as a simple, rapid, inexpensive, and non-subjective methodol- ogy for the screening patients suspected of liver disease.

- by Siwatt Pongpiachan
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- FTIR spectroscopy, Synchrotron Radiation, Liver Cancers

Subtypes of hepatocellular carcinoma are important for 2 primary reasons: they help improve diagnostic accuracy, as different subtypes have their own diagnostic pitfalls; they are an important building block to the personalization of patient care, as subtypes are enriched for shared genetic changes and biological associations. The most common subtype of hepatocellular carcinoma is steatohepatitic hepatocellular carcinoma (SH-HCC), a subtype that is strongly linked to tumorigenesis in the setting of the metabolic syndrome and metabolic-associated liver disease (MAFLD) and/or alcoholic hepatitis. SH-HCC shows macrovesicular steatosis, balloon cells, Mallory hyaline, intratumoral inflammation, and intratumoral fibrosis. This review examines the historical development of this subtype and explores in detail the histological features that are used to define SH-HCC. The strongest molecular correlates to-date include a low frequency of CTNNB1 mutations and possible activation of the IL6/JAK/STAT pathway. In addition, critical unresolved questions are discussed in detail to refine the histological definition of SH-HCC, including the minimal histological thresholds needed to make the diagnosis, as well as whether or not SH-HCC currently is a mixed category of tumors, containing some tumors where the distinctive morphology is driven by tumor-specific genetic changes, and other tumors where the findings are an epiphenomenon, a reflection of metabolic or alcohol-associated fatty liver disease, and not necessarily of genetic/epigenetic changes.

- by Hepatoma Research and +1
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- Medical Sciences, Hepatology, Gastroentrology & Hepatology, Liver

Hepatocellular carcinoma (HCC) is a significant global health problem with high morbidity and mortality. Its incidence is increasing exponentially worldwide with a close overlap between annual incidence and death rates. Even though significant advances have been made in HCC treatment, fewer than 20% of patients with HCC are suitable for potentially curative treatment. Hereditary hemochromatosis (HH) is an important genetic risk factor for HCC. HH is an autosomal recessive disorder of iron metabolism, characterised by elevated iron deposition in most organs including the liver, leading to progressive organ dysfunction. HCC is a complication of HH, nearly always occurring in patients with cirrhosis and contributes to increased mortality rates. Identifying the susceptibility of development of HCC in HH patients has gained much traction. This review summarises the current knowledge with regard to the association of HH and HCC in order to encourage further research. In this review, we focus particularly on HFE gene-related HH. Herein, we highlight and discuss emerging clinical research which addresses the prevalence of HCC in HH patients and the coincidence of HH with other risk factors for HCC development. We also focus on the therapeutic tools in the management of HCC associated with HH.

- by Hepatoma Research
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- Hepatology, Gastroentrology & Hepatology, Liver Cirrhosis, Liver

Manual Merck - Perturbações do fígado e da vesícula biliar

- by Tania Reis
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- Liver diseases, Liver Cirrhosis, Liver, Liver Fibrosis

Non-alcoholic fatty liver disease (NAFLD) and its advanced complication, non-alcoholic steatohepatitis (NASH), have become leading causes of hepatocellular carcinoma (HCC) worldwide. In this review, we discuss the role of metabolic, gut microbial, immune and endocrine mediators which promote the progression of NAFLD to HCC. In particular, this progression involves multiple hits resulting from lipotoxicity, oxidative stress, inhibition of hepatic autophagy and inflammation. Furthermore, dysbiosis in the gut associated with obesity also promotes HCC via induction of proinflammatory cytokines and Toll like receptor signalling as well as altered bile metabolism. Additionally, compromised T-cell function and impaired hepatic hormonal action promote the development of NASH-associated HCC. Lastly, we discuss the current challenges involved in the diagnosis and treatment of NAFLD/NASH-associated HCC.

- by Hepatoma Research and +1
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- Hepatology, Liver diseases, Gastroentrology & Hepatology, Liver

Liver cancer stem cells (LCSCs), a small subpopulation that constitutes liver cancer heterogeneity, play a vital role in cancer initiation, invasion, recurrence, metastasis, and resistance to chemo-radiotherapy. It is believed that therapies targeting LCSCs can improve the efficacy of conventional chemotherapy and radiotherapy by completely eliminating tumors while preventing recurrence. Therefore, during last decades, numerous surface markers for LCSCs have been identified and characterized in many subtypes of liver cancer, especially in hepatocellular carcinoma (HCC). These well-recognized surface markers significantly promote the therapeutic efficacy that identifies, targets and destroys LCSCs. Meanwhile, there have been intensive studies that aim to investigate the molecular mechanism of how stemness contributes to liver cancer relapse, recurrence and resistance. However, liver cancer stemness seems to be regulated by a hierarchical organization and crosstalk of a wide variety of signaling pathways. Using individual or few LCSC surface markers may not be able to completely reveal the intrinsic stemness hierarchy. From an integrated perspective, understanding of recent advances in LCSC surface markers remains important and urgent. In this review, we concentrate on demonstrating the indispensable roles of LCSC surface markers in identification and characterization of multiple cancer stages including initiation, invasion, metastasis, resistance and highlighting the cutting-edge therapeutic strategies against cancer stem cells in HCC.

- by Hepatoma Research
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- Cancer stem cells, Hepatology, Stem Cell Research, Gastroentrology & Hepatology

The multiplicity and phenotype of intratumoral immune infiltrate have been shown to influence the clinical outcome of hepatocellular carcinoma (HCC), thus providing a strong rationale to therapeutic interventions aimed at restoring the dysfunctional immune response against the tumor. Improving the knowledge of the complex interactions between transformed hepatocytes, nonparenchymal resident cells, and infiltrating immune cells (characterizing the HCC microenvironment) will be instrumental to increase the success rate of existing immunotherapeutic strategies and to identify new potential targets for intervention or biomarkers to optimize the selection of candidate patients.

- by Hepatoma Research
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- Immune response, Cytokines, Macrophages, Hepatology

With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D) nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1) Lung; (2) Bone marrow; (3) Brain; (4) Breast; (5) Urinary system (kidney, bladder and prostate); (6) Intestine; and (7) Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart–liver–intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET) of anticancer drugs and more realistically recapitulate tumor in vivo-like microenvironment.

- by Navid Kashaninejad and +5
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- Brain cancer, Lung Cancer, Tumor microenvironment, Kidney

Patients with hepatocellular carcinoma (HCC) often present with underlying liver disease and significant comorbidities, limiting treatment tolerance. With the development of improved toxicity models and highly conformal radiation delivery systems, external beam radiotherapy has become a valuable treatment option for liver cancer. Using cutting edge technology, stereotactic ablative radiotherapy (SABR) allows for the delivery of ablative doses in few fractions while sparing uninvolved liver tissue. This approach permits dose escalation and precise tumor targeting with minimal risk of radiation induced liver disease. This review clarifies SABR's role alongside liver-directed treatments such as radiofrequency ablation, transarterial radioembolization, and transarterial chemoembolization in the management of HCC. It also examines the promising potential of SABR combined with immunotherapy to treat advanced HCC.

- by Hepatoma Research
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- Radiotherapy, Hepatology, Gastroentrology & Hepatology, Liver

Hepatocellular carcinoma (HCC) is the most lethal and common type of liver cancer with limited treatment options at the advanced stage. The use of immune checkpoint inhibitor (ICI) based immunotherapy is exponentially increasing in the treatment of patients with advanced solid tumors. The expression of immune checkpoints on tumor cells leading to lower activity of T-cells is one of the major mechanisms of immune escape. Checkpoint blockade immunotherapies with antibodies against PD-1, PD-L1 or CTLA-4 are being investigated in clinical trials in HCC patients. ICIs have improved survival in patients with inoperable advanced stage HCC where other curative treatments are not applicable. However, the response rates remain low with only a small subset of patients responding to this therapy. There is an unmet need to identify predictive markers to select those HCC patients who would benefit from ICI therapies. Importantly, epithelial-to-mesenchymal transition (EMT), a major process driving HCC invasion and metastasis by regulating the phenotypic cellular switching from epithelial to mesenchymal state, has been implicated as a resistance mechanism associated with ICI therapies. The role of EMT as a regulator of immune checkpoint molecule in HCC is just emerging. However, the consequence of EMT as a resistance mechanism in HCC patients undergoing ICI treatments remains unexplored. In this review, we summarize the recent clinical studies with ICIs in HCC and highlight the trials underway featuring novel monotherapies and combinatorial approaches based on immune and non-immune therapies. We will discuss the ongoing efforts to discover new immune checkpoint molecules in HCC as potential drug targets. We also highlight the role of EMT in facilitating therapy resistance in HCC treated with ICIs and discuss potential strategies to circumvent resistance in ICI treated HCC patients.

- by Hepatoma Research
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- Cancer Immunotherapy, Hepatology, Liver diseases, Gastroentrology & Hepatology

Most patients diagnosed with hepatocellular carcinoma (HCC) present with advanced or metastatic disease. The lack of therapeutic options in the treatment of advanced HCC accounts for its high mortality and recurrence rate. HCC is known as an immunogenic tumor, which develops in chronically inflamed livers. Anti-PD-1/PD-L1 antibodies (immune checkpoint inhibitors, ICB) were approved by the FDA to treat advanced HCC in patients previously treated with sorafenib as a second line. This has opened up a new era of anticancer treatment, although the response rate of HCC to anti-PD-1/PD-L1 antibodies is only around 20%. Other than ICB treatment, adoptive cell transfer, dendritic cell-based vaccines and oncolytic therapy are currently under clinical trials. In this review, different immunotherapy approaches for HCC is presented. Current knowledge on the mechanisms of action for each approach is discussed and relevant, ongoing clinical trials are presented. We also discuss the future of immunotherapy and combination treatment for HCC patients.

- by Hepatoma Research
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- Immune response, Cytokines, Cancer Immunotherapy, Dendritic Cells

Primary liver cancer is one of the leading causes of cancer-related deaths worldwide. China has more than 55% liver cancer cases globally. The development of hepatocellular carcinoma (HCC) was caused by a variety of risks factors, including chronic inflammation by virus, alcohol consumption and non-alcoholic steatohepatitis. Emerging evidence has notarized inflammation as a critical component of HCC progression. The development of HCC is a multistep process which may originate from liver chronic injury and inflammation to subsequent fibrosis and/or cirrhosis and finally HCC. A large number of studies indicate that chemokines and cytokines are candidates linking molecules between inflammation and liver cancer. Here, we will describe a few of the key cytokines and chemokines and signal pathways which are involved in the inflammation of HCC. Inhibitors of inflammation for the prevention and overcoming antitumor immunity for treatment of liver cancer are promising candidates for the future management of patients with HCC.

- by Hepatoma Research
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- Cytokines, Inflammation, Hepatology, Gastroentrology & Hepatology

Immuno-oncology, particularly with the development of immune checkpoint inhibitors (ICIs), has become a frontline category of cancer-directed therapy, including in the treatment of hepatocellular carcinoma (HCC). While liver transplant (LT) offers a potential cure for HCC, the use of ICIs is a topic of safety concern both pre-and posttransplant due to the risk of donor graft rejection. Nonetheless, some scenarios for which the therapeutic effects of ICI may be highly beneficial include the downstaging of unresectable HCC pre-transplant, or the treatment of recurrent HCC and secondary malignancies post-transplant. In this review, we explored the evidence surrounding the use of ICI in the peri-transplant setting, including safety and efficacy. In a comprehensive review of 28 cases of ICI use post-transplant, we found graft rejection in 9 of 28 cases (32%). Some factors that may increase the risk of rejection include younger age, less time between LT and ICI therapy, and PD-1/PD-L1 expression in the donor graft (particularly when using anti-PD-1/anti-PD-L1 ICIs). Despite these concerns, we relay a case of successful HCC downstaging with nivolumab and subsequent LT. We also describe several cases of response to ICIs post-LT (7 of 28 cases) among a group that is often heavily pre-treated. We conclude that ICIs are valuable options in the peritransplant setting that have demonstrated promising efficacy based on case reports. Controlled clinical trials are needed to further investigate the conditions that may allow safe delivery of these therapies.

- by Hepatoma Research
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- Hepatocellular Carcinoma, Immunotherapy, Liver Transplantation, Liver Cancers

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of liver disease worldwide, and represents an increasingly important cause of hepatocellular carcinoma (HCC). As the prevalence of NAFLD has increased, the burden of NAFLD-related HCC has been rising in parallel. This is particularly evident in Western countries, where NAFLD is estimated to account for 10%-59% of all HCC. NAFLD-related HCC can occur in the presence or absence of cirrhosis, and, while those with cirrhosis remain at the greatest risk, factors such as steatohepatitis, age, genetic polymorphisms, type 2 diabetes mellitus and obesity also appear have an impact on the risk of developing HCC in NAFLD. In this review, we present the epidemiology of NAFLD-related HCC from a Western perspective, highlighting gaps in current knowledge and future directions for research in this field.

- by Hepatoma Research
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- Epidemiology, Hepatology, Liver diseases, Gastroentrology & Hepatology

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It is now the third leading cause of cancer deaths worldwide. The incidence of HCC is highest in Asia and Africa, where the endemic high prevalence of hepatitis B and hepatitis C strongly predisposes to the development of chronic liver disease and subsequent development of HCC. The present study was conducted to investigate the protective effect of cynara scolymus leaves extract against N-nitrosodiethylamine (NDEA) at a dose of 100 mg/kg b.wt and carbon tetrachloride (CCl4) at a dose of 3ml/kg b.wt -induced hepatocarcinogenesis in male Wistar albino rats. Main methods: rats were pretreated with Cynara scolymus extract, silymarin or both for six weeks prior to the injection of
NDEA. Then rats administered with a single intraperitoneal injection of NDEA followed by subcutaneous injections of CCl4 once a week for 6 weeks and the pretreatment was continued for another six weeks. At the end of the experiment, blood samples were taken for biochemical analysis and liver tissues were histopathologically examined. Results of the current study showed significant increase in serum levels of AST, ALT, ALP, total and direct bilirubin and alpha fetoprotein (AFP) as well as significant decrease in albumin was observed in NDEA-intoxicated group, compared to normal control group. Pretreatment with Cynara scolymus extract, silymarin and their
combination limited the increase in serum levels of AST, ALT, ALP, total and direct bilirubin and alpha fetoprotein (AFP) and produced significant increase in albumin, compared to NDEA- intoxicated group. Histopathological examination of liver of NDEA and Ccl4 treated group revealed obvious cellular damage and hepatocellular carcinoma with frequent mitotic activity and nuclear pleomorphism, meanwhile other groups pretreated with either silymarin, Cynara scolymus extract or a combination of silymarin and Cynara scolymus extract revealed improvement in the liver architecture . The current results indicated that Cynara scolymus extract possess hepatoprotective effect.

- by Hany M O A W A D Fayed
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- Herbal Medicine, Liver Cancers

Hepatocellular carcinoma (HCC) is often associated with pre-existing chronic liver pathologies of different origin infections of hepatitis B virus (HBV) and hepatitis C virus. Clinically, the diagnosis and therapy for HCC are very important for the prognosis of patients. However, current methods for HCC diagnosis and therapy have no an optimal accuracy due to the tumor heterogeneity and the frequent late diagnosis. This review summarizes the new advances in molecular diagnosis and therapy of HCC, based on the recent novel biomarkers and new therapeutic strategies for HCC, including alpha-fetoprotein-L3, glypican-3, heat shock protein 90, dickkopf WNT signaling pathway inhibitor 1, paraoxonase 1, highly up-regulated in liver cancer. Moreover, epigenetic regulation, signal pathway, cellular and molecular targets for the immunotherapy, tumor microenviroment and genome sequencing analysis may serve as the molecular expression signatures in clinical practice. For promising new treatment strategy of HCC, targeting molecular therapy based on the restoration of tumor suppressor genes lost and inhibition of oncogenic genes is attractive. The new clinical trials for other molecular-targeted agents, including pembrolizumab, nivolumab, tivantinib, lenvatinib, cabozantinib, and ramucirumab, are ongoing in clinic. Interestingly, anti-HBV drugs display an amazing therapy for HBV-related HCC. In future, the global determination of more biomarkers may provide new insights into the diagnosis of HCC. More importantly, the diagnostic markers should be used to trace patient's follow-up disease progression, guiding doctors to judge and prescribe drugs for status of an illness, prognosis and other processes.

- by Hepatoma Research
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- Molecular Biology, Hepatitis C, Hepatology, Gastroentrology & Hepatology

Hepatocellular carcinoma (HCC) is the most recurrent hepatic malignancy and the third in the cancer-related casualties in the west. The frequently-documented causes of HCC are chronic liver infections by hepatitis B virus or hepatitis C virus, nonalcoholic fatty liver disease, cirrhosis, exposure to aflatoxins and tobacco smocking, etc. Clinical presentation of this fatal disease ranges from asymptomatic to upper abdominal pain or common health conditions like weight loss or lethargy. Among current surveillance strategy for suspected patients, liver imaging and serum alpha fetoprotein estimation has been regularly recommended. However, sensitivity of this diagnostic methodology especially in early detections, often suffers from compromised sensitivity and selectivity. Various image based and serological biomarkers for HCC has been introduced in recent decades with varied sensitivity as stand-alone or combined diagnostic protocol. The current article will review the status of HCC diagnosis with respect to common diagnostic protocol, and upcoming novel biomarkers.

- by Hepatoma Research
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- Magnetic Resonance Imaging, Biomarkers, Hepatology, Liver diseases

Hepatocellular carcinoma (HCC) is the most common cancer associated with chronic liver disease and cirrhosis. The most common cause of HCC is chronic hepatitis C virus infection and many studies in Europe, Asia and North America have focused on its etiology, epidemiology, diagnostic tools, and therapeutic options. However, little is known about these issues in Latin America. The aim of this review is to address these aspects of HCC in Latin America. The main risk factors associated with developing HCC in this region are: age, concomitant cirrhosis, hepatitis C infection, obesity and hereditary disease such as hemochromatosis. On the other hand, screening tests and diagnostic methods of HCC are mostly serum alpha fetoprotein quantification, liver ultrasound, computed tomography, magnetic resonance, and histopathology. Novel diagnostic methods include gut microbiota analysis and the use of nanotechnology and they continue to be tested. Finally, according to the Barcelona Clinic Liver Cancer, curative treatments used in HCC patients are mainly liver resection, liver transplantation, and local ablation, each with advantages and disadvantages. In conclusion, clear strategies are urgently needed to understand the extent of HCC and related problems in this part of the world. This review provides greater knowledge of HCC for the proper design of preventive programs by taking into consideration specific characteristics of our population. Also, this review allows for an understanding of individualizing treatments according to the patient's needs.

- by Hepatoma Research and +3
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- Epidemiology, Hepatitis C, Hepatology, Gastroentrology & Hepatology

Hepatocellular carcinoma (HCC) is a major and increasing cause of clinical and economic burden worldwide. Now that there are effective therapies to control or eradicate viral aetiologies, the landscape of HCC is changing with alcoholic and metabolic liver diseases becoming major catalysts. The pathogenesis of HCC is complex and incompletely understood, hampering improvements in therapy. Animal models are essential tools for advancing study on the cellular and molecular processes in HCC and for screening potential novel therapies. Many models of hepatocarcinogenesis have been established using various methods including genetic engineering, chemotoxic agents and dietary manipulation to direct implantation of tumour cells. However, none of these can accurately replicate all features found in human diseases. In this review, we provide an overview of different mouse models of HCC with a particular focus on cancer arising from alcoholic liver disease, non-alcoholic fatty liver disease and hereditary haemochromatosis. We also highlight their strengths and limitations and provide perspectives for future study.

- by Hepatoma Research
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- Hepatology, Liver diseases, Gastroentrology & Hepatology, Liver

A B S T R A C T Purpose: To compare five liver metastasis stereotactic ablative radiotherapy (SABR) plans optimised in fourteen centres with 3D-Conformal-RT, IMRT, VMAT, CyberKnife and Tomotherapy and identify possible dosimetric differences. Methods: Dose prescription was 75 Gy in 3 fractions, normalised at 67%–95% isodose. Results: Excluding few cases, all institutions achieved the planning objectives. Differences up to 40% and 25% in mean dose to liver and PTV were found. No significant correlations between technological factors and DVH for target and OARs were observed; the optimisation strategies selected by the planners played a key role in the planning procedure. Conclusions: The human factor and the constraints imposed to the target volume have a greater dosi-metric impact than treatment planning and radiation delivery technology in stereotactic treatment of liver metastases. Significant differences found both in terms of dosimetric target coverage and OAR sparing should be taken into consideration before starting a multi-institutional SARB clinical trial. Introduction Stereotactic Body Radiation Therapy (SBRT), or Stereotactic Ab-lative Radiotherapy (SABR) as it is commonly known nowadays, is a radiation therapy technique for treating small excranial tumours with high doses of radiation with a rapid dose fall off. The main features of SABR are the reduced number of fractions and large dosage per fraction. The efficacy of SABR was tested in several patient populations with primary and metastatic limited tumours [1]. In particular, SABR may be appropriate for patients suffering from oligo-metastatic disease, defined as fewer than five lesions [2] or with organ-confined limited volume primary tumours. The liver is a frequent metastasis location for most common solid tumours. In particular, in the event of an oligo-metastatic scenario , local therapy could increase overall survival. A non-invasive local approach using SABR was reported for both primary and secondary liver tumours, with local control rates higher than 90% and with limited toxicity in the setting of limited tumour burden [1,3–11]. However, the ideal dose to the target and the adequate dose constraints to liver and other organs at risk have not yet been standardised. Moreover, SABR efficacy has seldom been assessed in

- by Marco Esposito and +3
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- Liver Cancers, SBRT

Purpose: To investigate the modulatory effect of the natural phytochemical, carvacrol, on Topotecan (TOPO) cytotoxicity and cellular uptake in different cancer cell lines. Methods: The cytotoxicity of the carvacrol/TOPO combination therapy was determined in vitro using crystal violet assay. Coomassie blue and DAPI fluorescent stains were used for cellular morphology and molecular cell death assessments, respectively. Additionally, TOPO cellular uptake after carvacrol/TOPO combination therapy was determined. Results: Treatment of HeLa and HCT116 with carvacrol/TOPO resulted in 7.70-and 5.71-fold reduction in TOPO half maximal inhibitory concentration (IC 50), respectively, relative to TOPO single treatment. On the other hand, treatment of MCF-7, HepG2, SKOV3, and A549 cancer cells with carvacrol/TOPO resulted in increasing the IC 50 of TOPO by 1.49-, 1.33-, 1.50-and 1.26-fold, respectively, relative to TOPO single treatment. Conclusion: Carvacrol had enhanced TOPO cytotoxicity and cellular uptake in HeLa and HCT116 cancer cells but might cause TOPO resistance in MCF-7, HepG2, SKOV3 and A549 cells.

- by Mayson H . Alkhatib
- •
- Pharmacy, Chemotherapy, Ovarian Cancer, Colorectal cancer

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the liver, with poor prognosis and high mortality. Traditional treatments for patients with HCC have shown poor efficacy especially for advanced liver cancer. Compared with other organs, the liver has more natural immune cells such as Kupffer cells, natural killer cells and natural killer T cells. Immunotherapy for liver cancer has become the focus in current research. The theoretical basis of immunotherapy rests on immune tolerance and suppression in the tumor microenvironment. Common immunotherapy methods include vaccines, cytokines, adoptive cell therapies, immune checkpoint inhibitors, and oncolytic viruses. Compared with traditional treatment, immunotherapy can enhance the body's immune function, delay tumor progression, and prolong survival. This article reviews the HCC microenvironment and immunotherapy both in the clinical and basic research aspects.

- by Hepatoma Research and +1
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- Immune response, Cancer Immunotherapy, Hepatology, Gastroentrology & Hepatology

Hepatocellular carcinoma (HCC) is the main tumor of the liver and is the sixth most frequently diagnosed tumor in the world. It is the evolution of chronic hepatic injury secondary to different etiologies. Chronic hepatitis B virus and hepatitis C virus infection, chronic alcoholic hepatitis, as well as non-alcoholic fatty liver disease are the most common causes behind the development of HCC. The introduction of effective prophylaxis and treatment against hepatitis B, the recent use of highly effective hepatitis C treatments, as well as lifestyle changes observed in recent decades in the general population causing an increase in obesity and metabolic syndrome have led to significant epidemiological change in HCC in relation to the changed etiologic prevalence of liver injury. Increasing evidence was emerging, emphasizing how the development of HCC is a complex and multifactorial process. The knowledge of the molecular mechanisms involved is important for the understanding of the basic factors of the development of hepatocarcinogenesis and of possible therapeutic approaches. Several pathogenic mechanisms and clinical expression of HCC occur in relation to the different etiologies of the underlying liver disease. The different clinical behavior of HCC often makes diagnosis difficult at an early stage, that is necessary for an effective therapeutic approach. This review analyzes the possible different pathogenic mechanisms involved in the development of HCC and emphasizes the different epidemiological and clinical aspects of HCC observed in the most common forms of liver diseases of viral and non-viral origin.

- by Hepatoma Research
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- Hepatitis C, Hepatology, Liver diseases, Gastroentrology & Hepatology

Hepatocellular carcinoma (HCC) is a major health problem with a high incidence and mortality all over the world. Natural history of HCC is severe and extremely variable, and prognostic factors influencing outcomes are incompletely defined. Over time, many staging and scoring systems have been proposed for the classification and prognosis of patients with HCC. Currently, the non-ideal predictive performance of existing prognostic systems is secondary to their inherent limitations, as well as to a non-universal reproducibility and transportability of the results in different populations. New serological and histological markers are still under evaluation with promising results, but they require further evaluation and external validation. The aim of this review is to highlight the main tools for assessing the prognosis of HCC and the main concerns, pitfalls and warnings regarding its staging systems currently in use.

- by Marcello Maida
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- Cancer, Cancer Epidemiology, Cancer Research, Staging Systems

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide. It comprises simple steatosis and non-alcoholic steatohepatitis (NASH), which can further progress to cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD involves genetic, environmental, and endocrine factors, and several molecular mechanisms have been identified. In this review, we discuss the recent findings on the role of autophagy, in particular lipophagy and mitophagy, in hepatic lipid oxidation. We discuss the pre-clinical and clinical evidence suggesting that impairment of autophagy exacerbates NAFLD progression and restoration of autophagy exerts beneficial effects on NAFLD. We discuss how thyroid hormone (TH) simultaneously regulates lipophagy, mitophagy, and mitochondrial biogenesis to increase β-oxidation of fatty acids and reduce steatosis in the liver. Lastly, we discuss the recent clinical progress in using TH or thyromimetics in treating NAFLD/NASH.

- by Hepatoma Research
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- Autophagy, Liver diseases, Hepatocellular Carcinoma, Thyroid Hormones

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. In recent years, the metabolic syndrome epidemic is changing the etiological landscape of HCC, with metabolic liver disease comprising an exponentially increasing proportion of HCC cases. In this review, we discuss HCC in the context of metabolic syndrome, including its epidemiology, its unique clinical and pathological characteristics, and its multifactorial pathogenesis. We also discuss HCC prevention and management as relates to these patients.

As the first step in this direction; biosynthesis and characterization of zinc oxide nanoparticles (ZnO-NPs) and their use to ameliorate the toxic effects of aflatoxicosis in rabbit in comparison with curcumin were studied. Thirty-five healthy New Zealand rabbits were divided into 5 groups, each including 7 rabbits. Group 1 was kept as negative control without any treatment. Rabbits in the groups 2, 3, 4 and 5 were given AFB 1 orally at a dose of 50 ug dissolved in 0.5 ml of olive oil/ animal daily, for 4 weeks. On day one following the administration of AFB 1 , curcumin was orally administered at a dose of 15 mg/kg b.w. for group 3. While, animals of Group 4, were orally administered AFB1 + ZnO-NPs (25 ug / kg of B.W. of animal /0.2 mL of buffer/day)(low dose). Animals of Group 5, were orally administered aflatoxins + ZnO-NPs (50 ug / kg of B.W. of animal /0.2 mL of buffer/day) (high dose). The biochemical evaluation of rabbit sera after experimental study showed that AFB 1 increased the concentration of NO and MDA, while decreased the level of GSH and activities of SOD, CAT and GSH-P X. Significant decreased values in plasma total protein, albumin, alpha globulin, beta globulin, and gamma globulin. Decrease in serum globulin in toxin fed group might be due to the adverse effect of aflatoxin B 1 on synthesis of total proteins and globulin. The AFB 1 had a drastic effect on liver and kidneys with marked genotoxic effect and inhibition of DNA, RNA and protein synthesis. These changes were improved by administration of ZnO-NPs or curcumin to aflatoxicated animal through the immune strengthening effect and protection of lipid and protein from oxidative damage. It is concluded that the addition of ZnO-NPs and curcumin to animal feed possesses hepato-protective effect through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify the free radicals. These factors protect hepatic cells from the damaging effect by AFB 1 that could be progress to hepatocarcinmoa. K e y w o r d s

- by atef A hassan
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- Nanotechnology, Animal Health Economics, Liver Cirrhosis, Mycotoxins

A deeper understanding of the genetic and molecular basis of hepatoblastoma (HB) has fueled the hope to help in identifying genes and signaling pathways that are amenable to therapeutic intervention. However, it has become clear that HB is a genetically very simple cancer and that rather alterations of the transcriptome or epigenome will facilitate a more stratified and rationalized approach to current therapeutics. In this review, we discuss recent findings on genomic, transcriptomic, and epigenomic data and their potential to serve as biomarkers and predictors of patient's outcome. We also describe the state of the art in HB experimental biology, the in vitro and in vivo HB models that are currently available, and their use to improve our understanding of this disease and identify new treatment options.

- by Hepatoma Research
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- Liver diseases, Epigenomics, Liver, Liver Cancers

Aim: Long-term survival after hepatocellular cancer (HCC) is difficult to achieve likely related to recurrence. This study aimed to identify factors that were predictive of 10-year survival after the diagnosis of HCC.
Methods: In a prospectively collected database of 1374 HCC cases (1993-2019), we identified 70 patients who survived over 10 years regardless of treatment. We then identified 164 patients in the entire cohort who either had liver resection or transplant, and died before 10 years. Demographics, tumor characteristics, treatment, recurrence and treatment of recurrence were compared.
Results: Of the 10-year survivors, 36 underwent transplant, 27 had liver resection and 7 patients had only locoregional therapy. Compared to the non-survivors, the 10-year survivors were younger and had fewer comorbidities or recurrence, smaller tumor size, lower AST, ALT, AFP, platelets, neutrophil-to-lymphocyte ratio. Multivariate analysis showed only age and diabetes to be negative predictors. Recurrence occurred in 24 survivors (34.3%) with mean time to recurrence with standard deviation 57.1 ± 42.6 months compared to 80 non-survivors (48.7%) with mean time to recurrence of 15.3 ± 14.8 months. For hepatic resection, 10-year survivors had longer time to recurrence compared to non-survivors (median: 31.3 months).
Conclusion: Long-term survivors mostly occur after resection or transplant, but 10% of our cohort survived 10 years with only locoregional therapy. Underlying health status maybe an important predictor of 10-year survival for patients receiving liver resections. Recurrence of HCC occurs in both 10-year survivors and non-survivors, but later recurrence with aggressive treatment of the recurrence may allow for 10-year survival.

- by Hepatoma Research and +1
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- Hepatology, Liver diseases, Gastroentrology & Hepatology, Liver

In multistep hepatocarcinogenesis, sizable lesions can precede the development of hepatocellular carcinoma (HCC). These lesions are currently classified as low grade (LG)-and high grade (HG)-dysplastic nodules. Following international guidelines recommending the surveillance of cirrhotic patients, a growing number of 1-2 cm hepatocellular nodules are recognized including early hepatocellular carcinoma (eHCC) and DN the latter accounting for as many as 70% of nodules < 1 cm. HG-DN are currently considered the most advanced HCC precursors. The histological diagnosis of low-grade dysplastic nodule (LG-DN), high-grade dysplastic nodule (HG-DN) and eHCC in small liver biopsies requires a comprehensive stepwise morphological and immunocytochemical approach. By imaging the differential diagnosis among these lesions is a challenge. According to vascular enhancement at dynamic computed tomography (CT) or magnetic resonance imaging (MRI) these precursors are classified as hypo-vascular/ indeterminate nodules even though distinction between LG-DN and HG-DN is almost impossible. The introduction of gadoexetic acid-enhanced MRI has represented an extremely important advance in this field allowing a better differentiation of dysplastic lesions from eHCC and progressed HCC. Additional MRI features as diffusion-weighted imaging further improved diagnostic accuracy of imaging. According to Liver Imaging Reporting and Data System (LI-RADS), either CT/MRI or Contrast-Enhanced Ultrasound LI-RADS, the dysplastic lesions should be categorized as LR-3 or LR-4. Natural history of these lesions confirmed that HCC can develop from HG-DN but which nodule and when it will undergo malignant transformation is not predictable. The search and validation of radiological and tissue markers able to select lesions more prone to HCC development, is currently underway. Whether and how HG-DN should be ablated or closely followed up is currently debated.

- by Hepatoma Research
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- Medical Imaging, Ultrasound Imaging, Hepatology, Gastroentrology & Hepatology

Present study reports an update on the molecular interaction of antiviral drugs with viral and host cell components during hepatitis C virus (HCV) infection. In addition to the traditional therapeutic drug regimen, termed as standard of care, some recent drugs have been added in the existing regimen used for HCV infection. These drugs were categorized as direct-acting antivirals (DAAs) agents and "other agents", with their efficacious impact in the control of HCV infection. They target both viral proteases and host cell receptor proteins/enzymes involved in HCV entry into the cell, replication, and assembly to check their propagation both in situ as well as in cell to cell transmission. Recent studies have reported a significant rise in sustained virological response after the use of these drugs both alone and in combination with pegylated interferon-α (PegIFN-α) plus ribavirin. Recently, DAAs have been reported to be highly effective in eradication of HCV infection, especially liver cirrhosis, reducing but not avoiding the occurrence of liver cancer. Some studies have demonstrated that the presence of resistant HCV variants, arising during viral replication, may be controlled by the new drug regimen. It is important to note here that all these drugs are influenced by viral as well as host factors including basic viral load, HCV genotypes, IFN action, interleukin 28B polymorphism and some liver and metabolic diseases, etc. This is an area with ongoing investigations to explore more antiviral agents that may address new challenges in HCV therapy.

- by Hepatoma Research
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- Hepatitis C, Hepatology, Liver diseases, Gastroentrology & Hepatology

Patel and colleagues' study substantiates
our observation of an association between
infection with Helicobacter pylon and coronary
heart disease.' The first report from the group2
prompted our retrospective serological study
among patients presenting to the emergency care
unit of our hospital.3 Currently we are recruiting all
patients admitted to the coronary unit of our
hospital with acute myocardial infarction during
the time that one of us (MTLR) is on duty there.
Patients recruited from 1 July to 30 September
1995 are analysed here. In addition to being tested
for antibodies, all patients were assessed for the
presence of H pylon infection with the carbon- 13
urea breath test, which was performed according
to the European standard protocol.4 Volunteer
blood donors attending the blood bank of our
hospital served as controls.
Twenty four (89%) of the 27 patients with
myocardial infarction and 291 (47%/6) of the 619
blood donors were found to be infected with
Hpyloni. As only two women had been admitted to
the coronary unit (both of whom were positive for
H pyloin infection) we assessed only the male
patients and compared them with blood donors
of similar age. Table 1 gives the results; the
Mantel-Haenszel weighted odds ratio was 4-4 (95%
confidence interval 1-2 to 20 6).
The preliminary findings from this population
case-control study confirm previous reports of an
increased risk of acute myocardial infarction in
men infected with H pylon. In our final analysis
several potentially confounding variables will be
taken into account. We believe, however, that a
randomised study is needed to determine more
Table 1-Prevalence of H pylori infection among
men with myocardial infarction and controls aged
40 and over. Figures are numbers (percentages)
Age Patients with myocardial
(years) infarction Controls
40-49 6/6 (100) 80/142 (56)
50-59 5/7 (71) 85/135 (63)
60-69 8/9 (89) 18/33 (55)
¢70 3/3 (100) -
¢40 22/25 (88) 183/310 (59)
clearly the effect of eradicating Hpyloni infection in
patients at high risk of myocardial infarction.
ANTONIO PONZETTO
Scientific coordinator,
department of experimental gastroenterology
MARIA TERESA LA ROVERE
Assistant professor, division of cardiology
PATRIZIA SANSEVERINO
Biologist, department of microbiology
Ospedale Molinette,
Turin,
Italy
FRANCO BAZZOLI
Professor ofgastroenterology
University of Bologna,
Bologna,
Italy
1 Patel P, Kendall MA, Carrington D, Strachan DP, Leatham E,
Molineaux N, et al. Association of Helicobacter pylori and
Chlamydia pneumoniae infections with coronary heart disease.
BMJ 1995;311:711-4. (16 September.)
2 Mendall MA, Goggin PM, Levy J, Molineaux N, Strachan DP,
Camm A, et al. Relation of Helicobacter pylori infection and
coronary heart disease. BrHearty 1994;71:437-9.
3 Morgando A, Sanseverino P, Perotto C, Molino F, Gai V,
Ponzetto A. Helicobacter pylori seropositivity in myocardial
infarction. Lancet 1995;345:1380.
4 Bazzoli F, Zagari RM, Fossi S, Pozzato P, Alampi G, Simoni P,
et al. Short-term, low-dose triple therapy for the eradication
of Helicobacter pylori infection. European Journal of Gastroenterology and Hepatology 1994;6:773-7.

- by Antonio Ponzetto
- •
- Cancer, Cancer Biology, Hepatitis B, Infection Control

Potential risk factors for hepatocellular carcinoma were investigated in a case-control study among inhabitants of north east Thailand. Sixty-five cases from 3 hospitals, with matched controls, were included. Infection with hepatitis-B virus was the major risk factor—chronic carriers of HB surface antigen had an estimated relative risk of 15.2. Infection with hepatltis-C virus appeared to be rare. No increase In risk was found with recent aflatoxin intake, as estimated by consumption of possibly contaminated foods, or by measuring aflatoxin-albumln adducts in serum. Regular use of alcohol (2 or more glasses of spirits per week) was associated with a nonsignificant elevation in risk (o.r. = 3.4, 95% c.i. 0.8–14.6), but the number of regular drinkers in the population was small. The meaning of an apparent protection conferred by certain food items is uncertain, but a possible role of betel nut in the aetiology deserves further investigation.

- by Pornarong Chotiwan
- •
- Liver Cancers

Despite the fact that non-alcoholic fatty liver disease (NAFLD) and its severe clinical forms [non-alcoholic steatohepatitis (NASH) and NASH-cirrhosis] are highly prevalent in the general population, there are no licensed drugs for NAFLD, and lifestyle intervention remains the only treatment accepted by international guidelines. This is despite massive investments in research by pharmaceutical companies. In the presence of type 2 diabetes, novel anti-diabetic drugs offer an opportunity to reduce the burden of NAFLD, by adequate control of glucose and lipid metabolism, also reducing the risk of NASH progression, advanced fibrosis, and finally hepatocellular carcinoma. We extensively reviewed the literature, based either on registration studies, ad hoc randomized studies or real-world data, to define the effectiveness of anti-diabetic drugs in the treatment of NAFLD and prevention of hepatocellular carcinoma (HCC). Metformin provides the best evidence for decreased risk of HCC, piogli...

- by Francesca Alessandra Barbanti
- •
- Diabetes, Medicine, Liver diseases, Liver Cirrhosis