Hepatitis: Los Angeles

Shaye OS, Levine AM. · Division of Hematology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. · J Natl Compr Canc Netw. · Pubmed #16507274 No free full text.

Abstract: Marginal zone lymphomas (MZLs) comprise 3 distinct entities: extranodal MZL of mucosa-associated lymphoid tissue (MALT), splenic MZL, and nodal MZL. Gastric MALT lymphoma is the most common extranodal MZL and often develops as a result of chronic Helicobacter pylori gastritis. Such cases frequently respond to antibiotics directed against H. pylori. Antigen-driven lymphomatous disease can also be seen in the association of Borrelia burgdorferi with MALT lymphoma of the skin, Chlamydia psittaci with MALT lymphoma of the ocular adnexa, Campylobacter jejuni with immunoproliferative disease of the small intestine, and hepatitis C with splenic MZL. This article discusses the pathogenesis and clinical features of MZL and the treatment options available to patients.

Khalsa AM. · University of Southern California, Keck School of Medicine, Los Angeles, USA. · Am Fam Physician. · Pubmed #16445273 links to  free full text

Abstract: The epidemic of human immunodeficiency virus (HIV) continues, and the infection is converting into a treatable chronic disease; therefore, it is increasingly important for family physicians to be current with and comfortable in providing basic care to patients infected with HIV. Important aspects of counseling and patient education include stabilization of psychosocial issues and prevention of HIV transmission through behavior change counseling. Reporting HIV and acquired immunodeficiency syndrome (AIDS) is mandatory in most states, whereas partner notification laws vary from state to state. Baseline evaluation includes screening for comorbid conditions such as viral hepatitis, syphilis, and tuberculosis, as well as common HIV-related manifestations such as recurrent candidal infections and thrombocytopenia. Baseline testing includes CD4+ T-lymphocyte cell counts and HIV viral RNA levels to assess HIV disease stage, and numerous studies to screen for opportunistic infections. Initial preventive interventions include patient education to reduce exposure to infections, treatment of comorbid conditions such as human papillomavirus-related dysplasia, and vaccinations such as for pneumococcus and hepatitis B. Prophylaxis against opportunistic pathogens is recommended when CD4+ cell counts fall below 200 cells per mm3. Lastly, the indications for antiretroviral therapy include symptomatic patients or those with AIDS, and pre-AIDS patients with CD4+ cell counts of 200 to 350 cells per mm3 or HIV RNA above 55,000 to 100,000 copies per mL.

Nyamathi AM, Christiani A, Windokun F, Jones T, Strehlow A, Shoptaw S. · UCLA School of Nursing, UCLA, Los Angeles, CA 90095-1702, USA. · AIDS. · Pubmed #16251826 No free full text.

Abstract: OBJECTIVES: Homeless youth are at a high risk of substance abuse, mental illness and blood-borne infections, such as hepatitis C. In this paper, we review the implications of these conditions, discuss the unique challenges faced by homeless youth, and explore potential strategies for harm reduction and intervention in this vulnerable population. RESULTS: Interventions that combine youth-centered, service-based care, street outreach, case management, and motivational interviewing with integrated health services such as hepatitis A/B vaccination, and mental health and substance abuse programmes, are presented as innovative approaches to address the healthcare needs of homeless youth. CONCLUSION: Recommendations for age-appropriate interventions and further research are made.

Tangkijvanich P, Yee HF. · Department of Medicine (Digestive Diseases), UCLA School of Medicine, Los Angeles, California 90095, USA. · Eur J Surg Suppl. · Pubmed #16144208 No free full text.

Abstract: Cirrhosis, a pathological condition defined by deranged hepatic architecture resulting from progressive fibrosis, is the final common pathway through which nearly all chronic diseases of the liver produce morbidity and mortality. Historically, treatments for hepatic fibrosis have been directed against specific causes of chronic liver injury, and include corticosteroids for autoimmune hepatitis, interferon for hepatitis B and C, and iron depletion for haemochromatosis. However, there is no effective treatment for most causes of chronic liver disease. Fortunately, the past decade has witnessed great advances in our understanding of the fundamental pathophysiological mechanisms underlying fibrosis of the liver. It is now recognised that hepatic stellate cells (myofibroblast-like cells that encircle the sinusoids) are primarily responsible for hepatic fibrosis and subsequent progression to cirrhosis. In response to liver injury stellate cells undergo a phenotypic transformation that is termed activation, and characterised by chemotaxis, proliferation, contraction, fibrogenesis, and extracellular matrix degradation. Under conditions of persistent injury the behavioural responses of these stellate cells act in concert to bring about fibrosis of the liver. Recent investigations elucidating the signal transduction pathways that link hepatic injury to stellate cell function suggest novel targets at which treatment for fibrosis may be directed. For example, antagonism of TGF-beta receptor signaling has been shown to modulate fibrosis in animal models. This work, as well as other studies in both humans and animals, indicates that hepatic fibrosis may be slowed or reversed. These results suggest that a rational approach to treatment can be developed based on our detailed understanding of the molecular and cellular mechanisms underlying cirrhosis, which will have a major impact on the clinical management of patients with chronic liver disease.

Kim AI, Saab S. · Department of Medicine, West Los Angeles VA Medical Center, Los Angeles, California, USA. · Am J Med. · Pubmed #16084169 No free full text.

Abstract: Hepatitis C virus is a leading cause of chronic liver disease, with over 170 million people infected worldwide. It is also the leading indication for liver transplantation. Complications from chronic hepatitis C infection include cirrhosis, hepatic decompensation, and hepatocellular carcinoma. As a result, treatment strategies to prevent such complications have been widely researched, although many questions remain unanswered. To date, the standard therapy for chronic hepatitis C infection is the combination of peginterferon and ribavirin. Treatment strategies differ based on factors such as genotype and liver biopsy results. Other strategies must be considered for special groups, such as patients with acute hepatitis C infection, hepatitis C/human immunodeficiency virus (HIV) coinfection, and prior nonresponse to interferon or relapse after its use. The goal of therapy is to achieve a sustained virologic response (ie, no detectable hepatitis C ribonucleic acid 6 months after completion of therapy). The substantial adverse effects associated with both interferon alfa and ribavirin often make it difficult for patients to continue with their therapies.

Lai MM. · Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, 2011 Zonal Ave., HMR503C, Los Angeles, California 90033, USA. · J Virol. · Pubmed #15956541 links to  free full text

This publication has no abstract.

Yeh SH. · UCLA Center for Vaccine Research, Los Angeles Biomedical Research Institute at Harbor-UCLA, 1124 W. Carson St, Liu Research Building, Torrance, CA 90502, USA. · Expert Rev Vaccines. · Pubmed #15889985 No free full text.

Abstract: PEDIARIX is the first pentavalent combination vaccine licensed for use in infants in the USA. This vaccine is indicated for the prevention of diphtheria, tetanus, pertussis, hepatitis B and poliovirus. This article reviews the available data regarding the vaccine's immunogenicity and safety.

Han SH. · Pfleger Liver Institute, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Suite 214, Los Angeles, CA 90095, USA. · Expert Opin Investig Drugs. · Pubmed #15882124 No free full text.

Abstract: Telbivudine, beta-L-2'-deoxythymidine (LdT), is a new beta-L-nucleoside analogue with potent inhibitory activity against the hepatitis B virus. In in vitro studies and animal models, telbivudine has demonstrated potent and specific antiviral activity against hepatitis B. Additionally, in preclinical animal toxicology studies, telbivudine showed no adverse side effects or adverse effects on mitochondrial function. The promising results of the early in vitro and animal telbivudine studies prompted the development and initiation of Phase I and II human clinical trials. The Phase I clinical study demonstrated that end-of-treatment virological response rates were better for telbivudine recipients at multiple dosing levels as compared with placebo patients. The subsequent Phase IIb human clinical study demonstrated superior antiviral efficacy of telbivudine, significantly better ALT normalisation and better hepatitis B e-antigen loss as compared with lamivudine. Telbivudine was well tolerated with no identified safety issues. Virological breakthrough with telbivudine was significantly lower than with lamivudine.

Giboney PT. · Keck School of Medicine, University of Southern California, Los Angeles, California, USA. · Am Fam Physician. · Pubmed #15791889 links to  free full text

Abstract: Mild elevations in liver chemistry tests such as alanine transaminase and aspartate transaminase can reveal serious underlying conditions or have transient and benign etiologies. Potential causes of liver transaminase elevations include viral hepatitis, alcohol use, medication use, steatosis or steatohepatitis, and cirrhosis. The history should be thorough, with special attention given to the use of medications, vitamins, herbs, drugs, and alcohol; family history; and any history of blood-product transfusions. Other common health conditions, such as diabetes, heart disease, and thyroid disease, can cause or augment liver transaminase elevations. The recent American Gastroenterological Association guideline regarding the evaluation and management of abnormal liver chemistry tests proposes a practical, algorithmic approach when the history and physical examination do not reveal the cause. In addition to liver chemistries, an initial serologic evaluation includes a prothrombin time; albumin; complete blood count with platelets; hepatitis A, B, and C serologies; and iron studies. Depending on the etiology, management strategies may include cessation of alcohol use, attention to medications, control of diabetes, and modification of lifestyle factors such as obesity. If elevations persist after an appropriate period of observation, further testing may include ultrasonography and other serum studies. In some cases, biopsy may be indicated.

Spiegel BM, Younossi ZM, Hays RD, Revicki D, Robbins S, Kanwal F. · Division of Gastroenterology, VA Greater Los Angeles Healthcare System, USA. · Hepatology. · Pubmed #15791608 No free full text.

Abstract: Hepatitis C virus (HCV) diminishes health related quality of life (HRQOL), and it is now common to measure HRQOL in clinical trials. We sought to summarize the HRQOL data in HCV, and to establish the minimally clinically important difference (MCID) in HRQOL scores in HCV. We performed a systematic review to identify relevant studies, and converted HRQOL data from each study into clinically interpretable statistics. An expert panel used a modified Delphi technique to estimate the MCID in HCV. We found that patients with HCV scored lower than controls across all scales of the SF-36. Patients achieving sustained virological response (SVR) scored higher across all scales versus patients without SVR, especially in the physical health domains. HRQOL differences did not correspond with differences in liver histology or ALT levels. Based upon the published data, the expert panel concluded that the SF-36 vitality scale was most relevant in patients with HCV, and generated a mean MCID of 4.2 points on this scale. In conclusion, patients with HCV have a clinically significant decrement in HRQOL versus controls, and physical HRQOL improves in patients achieving SVR but not in those without SVR. The data further suggest that traditional outcomes fail to capture the full spectrum of illness related to chronic HCV. A difference of 4.2 points on the SF-36 vitality scale can be used as an estimate of the MCID in HCV, and this value may be used as the basis for power calculations in clinical trials evaluating HRQOL. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

Fabrizi F, Martin P, Dixit V, Bunnapradist S, Dulai G. · Center for Liver and Kidney Diseases and Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · Aliment Pharmacol Ther. · Pubmed #15606388 links to  free full text

Abstract: BACKGROUND: The natural history of hepatitis C virus infection among patients on long-term dialysis treatment remains incompletely understood. Efforts to elucidate the natural history of hepatitis C virus in this population are difficult because of the slowly progressive nature of hepatitis C virus with often an unrecognized onset in patients whose life-expectancy is substantially diminished by end-stage renal disease. AIM: To conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus infection on the survival of patients receiving chronic dialysis. The relative risk of mortality was regarded as the most reliable outcome end-point. METHODS: We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for mortality with hepatitis C virus across the published studies. RESULTS: We identified four clinical trials (2341 unique patients); three (75%) of them were prospective, cohort studies; the fourth was a case-control study. Pooling of study results demonstrated that presence of antihepatitis C virus antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for relative risk was 1.57 with a 95% confidence interval (CI) of 1.33-1.86. A test for homogeneity of the relative risks across the four studies gave a P-value of 0.77. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among antihepatitis C virus-positive than -negative dialysis patients. CONCLUSIONS: This meta-analysis demonstrates that antihepatitis C virus-positive patients on dialysis have an increased risk of mortality compared with hepatitis C virus-negative patients. The excess risk of death in hepatitis C virus-positive patients may be at least partially attributed to chronic liver disease with its attendant complications. Clinical trials with extended follow-up are currently under way to assess the effect of hepatitis C virus treatment on the excess risk of mortality in this population.

Poordad FF. · Cedars-Sinai Medical Center, Liver Transplant Dept, 8635 W Third Street, Suite 590W, Los Angeles, CA 90048, USA. · Curr Opin Investig Drugs. · Pubmed #15573871 No free full text.

Abstract: IDN-6556 is a lead compound from a class of small-molecule caspase protease inhibitors, and is currently under development by Idun as a potential treatment for acute alcoholic and infectious hepatitis. In October 2003, a phase II trial of IDN-6556 began in 100 patients undergoing liver transplantation.

Yu MC, Yuan JM. · Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. · Gastroenterology. · Pubmed #15508106 No free full text.

Abstract: Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most important risk factors for the development of hepatocellular carcinoma (HCC) in humans. HBV is the primary cause of HCC in high-risk areas including China and Africa, whereas in developed countries such as the United States, HCV plays a more prominent role and is at least partially responsible for the increase in HCC incidence in this country. Humans are exposed to hepatocarcinogenic aflatoxins through ingestion of moldy foods, a consequence of poor storage of susceptible grains. Highly exposed populations are primarily in sub-Sahara Africa and Asia, where dietary aflatoxins significantly enhance the carcinogenic effects of viral hepatitis. Heavy, long-term alcohol use is a risk factor for HCC, whereas moderate use (1-3 drinks/day) is not. Constituents of cigarette smoke are hepatic carcinogens in animals, and there is mounting evidence that the liver is an organ susceptible to tobacco carcinogenicity. Diabetic patients are at risk for HCC probably as a result of the hepatic injury, fibrosis, and eventual cirrhosis resulting from fatty liver disease. Given the current epidemic of obesity and diabetes in the United States, this risk factor will be increasingly important. Increased risk for HCC is evident in young noncirrhotic users of oral contraceptives in the United States and Europe. In summary, risk factors for HCC are identifiable in most patients and primarily are associated with chronic hepatic injury.

Poordad FF. · Hepatology & Liver Transplant Center, University of California, Los Angeles, Cedars-Sinai Medical Center 8635 W. 3rd Street, Suite 590W, Los Angeles, CA 90048, USA. · Clin Liver Dis. · Pubmed #15481350 No free full text.

Abstract: Current prophylactic measures have greatly reduced recurrence rates of hepatitis B after liver transplantation. HBIG remains a critically important compound and although there is variability in dosing regimens and target anti-HBs levels, it is the backbone of recurrence prevention. Adjuvant therapies with nucleoside/nucleotide analogs alone have been limited by drug-resistant strains of HBV, but the armamentarium of these molecules continues to grow and hence the management of the post-LT HBV patient will evolve further. Currently lamivudine with HBIG remains an excellent option provided the patient has not developed resistance, especially in the pre-LT period. Adefovir is the drug of choice in that setting and perhaps the preferred drug in the pre-LT setting to allow the use of lamivudine post-LT. Further testing with tenofovir and newer compounds in development will expand these options. The use of multiple nucleoside analogs is an intriguing option, based on the HIV experience of reducing drug resistance and optimizing viral suppression, and will likely be further studied.

Han SH. · Division of Digestive Diseases, Pfleger Liver Institute, David Geffen School of Medicine at UCLA, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095-7302, USA. · Clin Liver Dis. · Pubmed #15481347 No free full text.

Abstract: Several extrahepatic manifestations are associated with chronic HBV infection, many with significant morbidity and mortality. The cause of these extrahepatic manifestations is generally believed to be immune mediated. PAN is a rare, but serious, systemic complication of chronic HBV affecting the small- and medium-sized vessels. PAN is seen more frequently in North American and European patients and rarely in Asian patients. PAN ultimately involves multiple organ systems, some with devastating consequences, though the hepatic manifestations are often more mild. The optimal treatment of HBV-associated PAN is thought to include a combination of antiviral and immunosuppressive therapies. HBV-associated GN occurs mainly in children, predominantly males, in HBV endemic areas of the world, but is only occasionally reported in the United States. In children, GN is usually self-limited with only rare progression to renal failure. In adults, the natural disease course of GN may be more relentless, slowly progressing to renal failure. Immunosuppressive therapy in HBV-related GN is not recommended, but antiviral therapy with alpha-interferon has shown promise. The serum-sickness like "arthritis-dermatitis" prodrome is seen in approximately one third of patients acquiring HBV. The joint and skin manifestations are varied, but the syndrome spontaneously resolves at the onset of clinical hepatitis with few significant sequelae. Occasionally, arthritis following the acute prodromal infection may persist; however, joint destruction is rare. The association between HBV and mixed essential cryoglobulinemia remains controversial; but a triad of purpura, arthralgias, and weakness, which can progress to nephritis, pulmonary disease, and generalized vasculitis, has characterized the syndrome. Finally, skin manifestations of HBV infection typically present as palpable purpura. Though papular acrodermatitis of childhood has been reported to be caused by chronic HBV, this association remains controversial.

Tran TT, Martin P. · Cedars Sinai Medical Center, Geffen School of Medicine, UCLA, 8635 W. 3rd Street, Suite 590W, Los Angeles, CA 90049, USA. · Clin Liver Dis. · Pubmed #15481339 No free full text.

Abstract: Chronic infection with hepatitis B and its sequelae remains a major global health concern. Despite recommendations and implementation of vaccination programs, the health and economic burdens are still significant. People in endemic areas and immigrants from these areas need to be adequately screened and treated. HBeAg-negative chronic hepatitis is increasingly recognized with additional challenges in management. Programs implementing primary prophylaxis strategies such as vaccination of high-risk adult and adolescent groups should continue.

Fabrizi F, Bunnapradist S, Lunghi G, Aucella F, Martin P. · The Center for Liver and Kidney Diseases and Transplantation, Cedars-Sinai Medical Center and UCLA School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. · Minerva Urol Nefrol. · Pubmed #15467503 links to  free full text

Abstract: Hepatitis C virus (HCV) infection is frequent among patients receiving long-term dialysis in developed and developing countries. It is difficult to assess the natural history of HCV in the dialysis population; however, recent studies have demonstrated that positive anti-HCV status is a significant and independent risk factor for mortality among dialysis patients. Recent meta-analyses have shown that interferon (IFN) initial monotherapy is effective in the treatment of chronic hepatitis C among dialysis patients, but tolerance to IFN mono-therapy was rather poor. Large, multicenter and prospective trials based on pegylated IFN for the treatment of chronic hepatitis C are planned. The frequency of HBV infection in patients undergoing maintenance dialysis in the industrialized world is low but not negligible; persistent HBsAg seropositivity is much higher in less-developed countries. Recent surveys have shown that detectable HBsAg/ HBV DNA status in serum is an independent and significant predictive factor for hepatocellular dysfunction in dialysis patients. No significant difference in morbidity and mortality between dialysis patients according to hepatitis B surface antigen status has been consistently shown. Preliminary reports suggest that lamivudine appears to be safe and effective in patients receiving long-term dialysis.

Fabrizi F, Martin P, Bunnapradist S. · Center for Liver and Kidney Diseases and Transplantation, Cedars-Sinai Medical Center, University of California-Los Angeles School of Medicine, 8635 West Third Street, Suite 590W, Los Angeles, CA 90048, USA. · Gastroenterol Clin North Am. · Pubmed #15324949 No free full text.

Abstract: In the last several years, numerous studies on the natural history and outcomes of viral hepatitis in dialysis and transplantation have been reported. Despite these, the management of hepatitis C virus or hepatitis B virus-related liver disease in end-stage renal disease continues to be an area of controversy. This article aims to address the current therapeutic options for patients with renal disease and chronic viral hepatitis.

Torno MS, Witt MD, Sue DY. · Department of Medicine, David Geffen School of Medicine at University of California at Los Angeles, Harbor-UCLA Medical Center, Torrance, USA. · Clin Infect Dis. · Pubmed #15307020 No free full text.

Abstract: A wide array of diagnoses must be considered when a patient with advanced liver disease and human immunodeficiency virus (HIV) infection presents with hypoxemia. It is important to entertain the possibility of hepatopulmonary syndrome (HPS) in such patients, a diagnosis that must be confirmed with a contrast-enhanced echocardiogram (bubble study). We describe a case of HPS diagnosed in a patient with HIV infection and chronic liver disease and review the literature on HPS.

Pak E, Esrason KT, Wu VH. · Kaiser Permanente, Los Angeles Medical Center, Los Angeles, California, USA. · Prog Transplant. · Pubmed #15264453 No free full text.

Abstract: The surge in consumption of herbal remedies has been stimulated by several factors, including the notion that all herbal products are safe and effective, consumers becoming more proactive in self-treating, and lack of regulation by the Food and Drug Administration. Although herbal remedies are generally perceived as harmless, reports of hepatotoxicity associated with herbal use are accumulating, suggesting they are not completely innocuous. On the basis of various case reports, the liver injury from herbal remedies has ranged from mild elevations of liver enzymes to fulminant liver failure requiring liver transplantation. Although regulation by the Food and Drug Administration may be part of the solution, increasing public awareness and educating healthcare professionals about the potential dangers of herbal preparations will need to be implemented. This article reviews the hepatotoxicity of herbal remedies as reported in the literature and discusses issues related to regulation of herbal preparations.

Gunawan B, Kaplowitz N. · USC Research Center for Liver Diseases, The Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. · Drug Metab Rev. · Pubmed #15237856 No free full text.

Abstract: Drug-induced hepatotoxicity is an important cause of liver disease with significant medical, economic, legal, and regulatory implications. Clinically, it presents a diagnostic challenge to health care professionals since drug-induced liver disease can mimic the clinicopathologic features of all other acute and chronic liver diseases. However, individual drugs tend to have a characteristic clinical signature. Early identification of hepatotoxicity by either laboratory monitoring or patients' awareness as a result of education may avert serious liver injury in delayed idiosyncratic toxicity. Most adverse hepatic reactions require metabolism of the drug to reactive metabolites and free radicals, which then either lead to direct overwhelming lethal insult, nonlethal sensitization to the lethal effects of the innate immune system, or haptenization eliciting an immunoallergic response of the adaptive immune system. Besides licensed drugs, herbal and natural supplements are recognized as causing hepatotoxicity with increasing frequency as patients turn more and more to alternative medicine.

Fabrizi F, Bunnapradist S, Martin P. · Center for Liver and Kidney Diseases and Transplantation, Cedars-Sinai Medical Center and Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, California 90048, USA. · Semin Liver Dis. · Pubmed #15192803 No free full text.

Abstract: Controlling the spread of hepatitis B virus (HBV) infection in dialysis units has been one of major triumphs in the management of end-stage renal disease. However, HBV incidence and prevalence rates remain high in dialysis patients in less-developed countries, and HBV within dialysis units continues to spread in the industrialized world. Overall response rates to HBV vaccination are lower in dialysis patients than in the nondialysis population. Lamivudine is effective in the treatment of HBV infection in the dialysis setting. Presence of hepatitis B surface antigen (HbsAg) has a negative impact on patient survival after renal transplantation. Several issues remain unanswered with regard to the management of HBV infection in dialysis patients, including the management of lamivudine resistance and the optimal timing and duration of antiviral therapy. Liver biopsy prior to renal transplantation is crucial in order to identify and exclude patients with advanced fibrosis or even cirrhosis.

Ji C, Kaplowitz N. · Faculty of Medicine, Gastroenterology/Liver Division, Keck School of Medicine, University of Southern California, HMR-101, 2011 Zonal Avenue, Los Angeles, CA 90033, USA. · World J Gastroenterol. · Pubmed #15188490 links to  free full text

Abstract: Deficiencies in vitamins or other factors (B6, B12, folic acid, betaine) and genetic disorders for the metabolism of the non-protein amino acid-homocysteine (Hcy) lead to hyperhomocysteinemia (HHcy). HHcy is an integral component of several disorders including cardiovascular disease, neurodegeneration, diabetes and alcoholic liver disease. HHcy unleashes mediators of inflammation such as NFkappaB, IL-1beta, IL-6, and IL-8, increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide (NO), and induces endoplasmic reticulum (ER) stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation, and inflammation. Animal models have played an important role in determining the biological effects of HHcy. ER stress may also be involved in other liver diseases such as alpha (1)-antitrypsin (alpha(1)-AT) deficiency and hepatitis C and/or B virus infection. Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury, study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans, and examine polymorphism of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease.

Dasgupta A, Das S, Izumi R, Venkatesan A, Barat B. · Department of Microbiology, Immunology and Molecular Genetics, UCLA School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA. · FEMS Microbiol Lett. · Pubmed #15135522 No free full text.

Abstract: A number of RNA-containing viruses such as hepatitis C (HCV) and poliovirus (PV) that infect human beings and cause serious diseases use a common mechanism for synthesis of viral proteins, termed internal ribosome entry site (IRES)-mediated translation. This mode of translation initiation involves entry of 40S ribosome internally to the 5' untranslated region (UTR) of viral RNA. Cap-dependent translation of cellular mRNAs, on the other hand, requires recognition of mRNA 5' cap by the translation machinery. In this review, we discuss two inhibitors that specifically inhibit viral IRES-mediated translation without interfering with cellular cap-dependent translation. We present evidence, which suggest that one of these inhibitors, a small RNA (called IRNA) originally isolated from the yeast Saccharomyces cerevisiae, inhibits viral IRES-mediated translation by sequestering both noncanonical transacting factors and canonical initiation factors required for IRES-mediated translation. The other inhibitor, a small peptide from the lupus autoantigen La (called LAP), appears to block binding of cellular transacting factors to viral IRES elements. These results suggest that it might be possible to target viral IRES-mediated translation for future development of therapeutic agents effective against a number of RNA viruses including HCV that exclusively use cap-independent translation for synthesis of viral proteins.

Nissen NN, Cavazzoni E, Tran TT, Poordad FP. · Center for Liver Diseases and Transplantation, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Cancer J. · Pubmed #15130268 No free full text.

Abstract: Liver transplantation (LT) has been utilized in the treatment of primary hepatic malignancy for decades. Hepatocellular cancer (HCC) remains the most common malignant condition treated with LT, with almost 400 such transplants performed annually in the US. Refinement in the selection criteria for LT in patients with HCC has led to survival rates similar to those for LT in nonmalignant conditions. Excellent results have also been reported following LT for select patients with epithelioid hemangioendothelioma and hepatoblastoma. Patients with cholangiocarcinoma treated with LT have generally faired poorly, with survival rates far below that of LT for nonmalignant conditions. Improved survival has recently been reported following LT for cholangiocarcinoma in highly select patients treated with aggressive neoadjuvant therapy. The future utility of LT in the treatment of malignancy will be influenced by several factors, including a profound organ donor shortage faced worldwide; increasing prevalence of hepatitis C, HCC and cirrhosis; and the evolution of live donor liver transplantation.