August 2006 HepTalk Listserv

Transcription

1 August 2006 HepTalk Listserv Again in the mnth f August we welcme many new members t the HepTalk Listserv! Our cncentratin fr this mnth is Liver Cancer and Hep B and C. We present tw articles in full and three abstracts: 1. Deadly Liver Cancer Creeps In [Primary liver cancer] cases are rising as rapidly as 4.5 percent amng black men and 5 percent amng Hispanic wmen...the striking increase in liver cancers here and in ther develped cuntries is a result f chrnic and usually silent infectins by the hepatitis B and C viruses, which are spread by bld and attack the liver. 2. Liver Transplants The mst cmmn indicatins fr liver transplantatin in the United States are hepatitis C virus (30%) and alchlic liver disease (18%). 3. Regular Surveillance fr Hepatcellular Carcinma Imprves Survival The big deal is catch them early s they are still candidates fr a curative therapy which is transplantatin, said Alan Hemming, MD. 4. The cntributins f hepatitis B virus and hepatitis C virus infectins t cirrhsis and primary liver cancer wrldwide. Glbally, 57% f cirrhsis was attributable t either HBV (30%) r HCV (27%) and 78% f HCC was attributable t HBV (53%) r HCV (25%). 5. Systemic Therapy f Advanced Hepatcellular Carcinma: Hw Hpeful Shuld We Be? Fr thse f yu just jining, be sure t check the Listserv Archives at r the listserv administratr, Kath Andersn, at dempander@earthlink.net t have a previus editin ed directly t yu. Yu can als cntact the listserv administratr if thers at yur clinic wuld like t be n the listserv, r if yu have questins abut the listserv r resurces listed here, r if yu wuld like t add smething t the psts, r t unsubscribe frm the list. The fllwing is a list f the mnthly tpics in 2006: January 2006: Updated Advisry Cmmittee n Immunizatin Practices (ACIP) f the US Centers fr Disease Cntrl and Preventin (CDC) cmprehensive guidelines fr the eradicatin f hepatitis B virus (HBV) in the United States. February 2006: Update n Hepatitis C. March/April 2006: Crss cultural cmmunicatin. April 2006: Hepatitis A and preventin, with guest editr Amy Liebman, MPA. May 2006: tw successful adult immunizatin prgrams, ne in Pennsylvania and ne in New Yrk. Each invlves cperatin between state and lcal health departments and cmmunity clinics in rder t prvide immunizatins, including Hepatitis A and B, t migrant seasnal farmwrkers. The Pennsylvannia prgram wrks with a HepTalk clinic participant. June /July 2006: Cultural Cmpetency and Hepatitis, with guest editr Dr. Jennie McLauren July 2006: Hepatitis B Updates

2 1. Deadly Liver Cancer Creeps In Published Tuesday, Octber 18, 2005 Yu dn't hear much abut liver cancer, but its incidence is increasing faster than that f any ther cancer in the United States. That increase is expected t cntinue fr tw mre decades. Liver cancer is als ne f the mst deadly cancers, typically fatal within a year f diagnsis, unless, as rarely ccurs, it is fund very early. This fact alne suggests that peple at high risk f develping the cancer may want t cnsider peridic screening with whatever tests are available. That in turn suggests that peple at high risk shuld knw that they are and find ut whether screening will be effective. Many peple are cnfused abut liver cancer. Only cancers that riginate in the liver are liver cancers. Cancers f the cln, lung r breast, amng thers, ften spread t the liver, prmpting the cnfusin. But every cancer, regardless f where it may spread, retains the name and cellular characteristics f its rigin. Liver cancer is ne f the mst cmmn cancers in the wrld, especially prevalent in Sutheast Asia and sub-saharan Africa. In the last quarter-century, Japan, fr example, has experienced an epidemic f liver cancer, nw the third leading cause f cancer deaths amng its men and the fifth leading cause amng the wmen. A RISING SCOURGE Primary liver cancer is still relatively rare in the United States, where it is the 20th mst cmmn type f cancer. But earlier this mnth, The Assciated Press reprted, cases are rising as rapidly as 4.5 percent amng black men and 5 percent amng Hispanic wmen. Because liver cancer is usually nt fund befre symptms f advanced disease develp, it is als the eighth mst cmmn cause f cancer deaths in this cuntry. The striking increase in liver cancers here and in ther develped cuntries is a result f chrnic and usually silent infectins by the hepatitis B and C viruses, which are spread by bld and attack the liver. These viral infectins, which damage liver cells, can lead t primary liver cancer 30 years r mre after an infectin takes hld. Genetic material f the hepatitis B virus incrprates itself int the DNA f liver cells, subverting nrmal functins and, ultimately, causing cancer. The hepatitis C virus wrks differently: It is believed t disrupt the actin f a gene called P53 that nrmally suppresses tumr frmatin. Like hepatitis B, chrnic hepatitis C infectins can als cause cirrhsis, a scarring f the liver. When the damaged liver tries t repair itself, mutatins can ccur that result in uncntrlled cell grwth. Abut 5 percent f peple with cirrhsis frm any cause eventually develp liver cancer. But with screening f bld supplies fr hepatitis B virus in place since the late 1980s and with current immunizatins f infants and sme adults with hepatitis B vaccine,

3 the incidence f liver cancer brught n by this virus shuld be reduced in years t cme. Althugh ptential bld dnrs and dnatins are nw checked fr the hepatitis C virus, many peple became infected befre the virus was identified. N vaccine has been develped against this infectin. Many peple cntinue t put themselves at risk f develping a hepatitis C infectin thrugh expsure t cntaminated needles as a result f drug use, tatting and bdy piercing, and unprtected sex with peple wh may carry the virus. Hepatitis C accunts fr half the cases f primary liver cancer in the United States. Anther imprtant cause f liver cancer is alchl abuse. Alchl damages the liver and ver the years can result in cirrhsis. In fact, cirrhsis frm chrnic alchl cnsumptin, especially when cmbined with a chrnic hepatitis C infectin, is the mst cmmn cause f liver cancer in the develped wrld. Further, it is mre likely t develp a decade r mre after a persn with alchlinduced cirrhsis stps drinking, when the liver generates new cells t repair the damage caused by alchl. Of curse, peple wh cntinue t abuse alchl risk an early demise frm liver failure. Other factrs knwn t cause liver cancer are expsure t certain industrial chemicals like vinyl chlride and a pisn called aflatxin B, prduced by a fungus, Aspergillus flavus, that can grw n fds like peanuts and ther nuts, rice, sybeans, crn and wheat. The Fd and Drug Administratin mnitrs the American fd supply fr this txin. But in suthern China and sub-saharan Africa, chrnic cnsumptin f aflatxin B, believed t suppress the P53 gene, is a leading cause f liver cancer. Cncerns have als been raised abut substances like estrgen and anablic sterids that can cause the develpment f benign liver tumrs, which may ultimately becme malignant. A genetic disease called hemchrmatsis, which causes excess irn t accumulate in the liver and ther rgans, als results in liver cancer in up t 30 percent f the peple with this disrder. Other risk factrs include smking, diabetes and mutatins in the genes BRCA1 and 2, which are mst ften linked t breast and varian cancers. As with the viral infectins that can cause it, liver cancer is ften a silent disease. Symptms typically result nly when the cancer grws t a size that cannt be cured by simple surgery r when it spreads t ther rgans. After that pint, it cannt be cured. The symptms include pain in the upper right side f the abdmen, pssibly extending t the back and shulder; a swllen abdmen; weight lss; lss f appetite and feelings f fullness; weakness r fatigue; nausea and vmiting; fever; and jaundice, evidenced by yellwing f the skin and eyes and by dark urine. Peple at high risk f develping liver cancer are nt likely t want t wait until they have symptms t find ut that cancer -- mst likely advanced cancer -- is the cause. FLAWS IN SCREENING Far better t find a liver cancer while it is still a silent disease, because early detectin

4 is crucial. Liver cancer grws quickly, dubling in size every fur mnths. There is still n cmpletely accurate screening test fr liver cancer. A bld test fr alphafetprtein (AFP) is smetimes used, thugh ther cnditins, including nncancerus liver diseases, can cause AFP levels t increase. Abdminal ultrasund, a nninvasive test that des nt invlve expsure t radiatin r dyes, can smetimes reveal an early liver tumr. A CT scan, with r withut a dye, uses X-rays t prduce crss-sectin images f the liver, and an MRI can create a similar image. If a suspicius lesin is fund, a bipsy can determine whether it is cancer. If the liver is nt cirrhtic and the tumr is small, cnfined t ne lbe f the liver and nt near a main artery, vein r bile duct, surgery can be curative. If the cancer is mre advanced, treatments like chemtherapy, radi frequency ablatin and alchl injectin int the tumr can slw its prgress. The surest cure fr an early liver cancer is a liver transplant. The patient's entire liver is remved and replaced with a healthy liver frm a cadaver r a lbe frm a living dnr. Because the liver regenerates, the dnr and recipient sn have fullsize livers. Abut 18,000 patients are waiting fr liver transplants, but nly 4,000 cadaver rgans becme available each year. Often while patients wait fr dnr rgans, their cancers becme t large t be cured by transplants. Jane Brdy cvers science and bilgy fr The New Yrk Times. 2. Liver Transplants June 30, 2006 Authr: Lemi Luu, MD, Staff Physician, Sectin f Emergency Medicine, Yale-New Haven Hspital Backgrund Applicatin and success f rthtpic liver transplantatin (OLT) has cntinued t grw, and liver transplantatin has becme accepted therapy frseveral causes f irreversible liver disease. As f 2005, 76,575 liver transplants had been reprted t the United Organ Sharing netwrk since it created a natinal database in In 2005, 6,444 liver transplants were perfrmed and 17,645 patients were n the waiting list fr transplantatin. With the increased number f transplants, chances are greater that a transplant patient will present t the ED. Basic knwledge f medical care invlved in treatment f the transplant patient will assist ED physicians in evaluatin. The mst cmmn indicatins fr liver transplantatin in the United States are hepatitis C virus (30%) and alchlic liver disease (18%). Others include idipathic/autimmune liver disease (12%), primary biliary cirrhsis (10%), primary sclersing chlangitis (8%), acute liver failure (7%), hepatitis B virus (6%), metablic liver disease (eg, inbrn errrs f metablism) (3%), cancer (3%), and thers (3%). Biliary atresia is a cmmn indicatin in pediatric patients. Chances f survival fllwing rthtpic liver transplantatin are gd, with a 5-year survival rate f 72%. The mst cmmn causes f death in liver transplant patients (beynd the early in-hspital transplant perid) are infectin, rejectin, and malignancy. 3. Regular Surveillance fr Hepatcellular Carcinma Imprves Survival Katherine Kahn, DVM July 31, 2006 (Bstn) Wrld Transplant Cngress 2006: Abstract 776. Presented July 26, J Hepatl Jun 23; [Epub ahead f print]

5 Rutine surveillance fr hepatcellular carcinma (HCC) in patients with cirrhsis results in earlier diagnsis f HCC, imprves access t liver transplantatin, and imprves survival times, a new study reveals. Richard Stravitz, MD, assciate prfessr f medicine in hepatlgy at the Virginia Cmmnwealth University in Richmnd, presented the findings here at the Wrld Transplant Cngress. "Befre liver transplantatin there wasn't much yu culd d with a diagnsis f HCC," Dr. Stravitz tld Medscape. "Nw that we have liver transplantatin, the questin is whether surveillance detects cancers earlier s that we can transplant patients and have imprved utcmes." T examine this further, Dr. Stravitz and cinvestigatrs retrspectively reviewed the recrds f 296 patients with cirrhsis and HCC that had been diagnsed and treated between 1997 and 2005 at the Virginia Cmmnwealth University Medical Center and its Veterans Affairs affiliate. Of these patients, 86% were men, 62% were white, and 76% were yunger than 65 years. The researchers assigned patients t 1 f 3 grups, representing different levels f quality f surveillance. The standard-f-care surveillance grup included patients wh had received an ultrasund r ther abdminal imaging at least nce in the year prir t HCC diagnsis. The substandard surveillance grup included patients wh were knwn t have cirrhsis but did nt underg imaging in the year prir t a HCC diagnsis. The unrecgnized cirrhsis grup included patients wh received n surveillance prir t a HCC diagnsis. The majrity f patients (63%) had underlying hepatitis C as the cause f cirrhsis, with 41% having alchl abuse as a cntributing factr in additin t hepatitis C. Eleven percent had alchlic cirrhsis and 10% had nnalchlic steathepatitis r cryptgenic cirrhsis. Nine percent had cirrhsis frm ther causes, and 7% had cirrhsis frm hepatitis B virus. Half f the patients had stage I (9%) and stage II (41%) HCC at time f diagnsis, while half had stage III (19%) and stage IV (31%) HCC. The quality f surveillance was strngly linked t tumr stage at diagnsis. Whereas almst 70% f patients wh underwent standard-f-care surveillance had stage I r II HCC at initial diagnsis, nly 35% f thse wh received substandard surveillance had stage I r II. "Still, even substandard surveillance was better than n surveillance, since fewer than 20% f patients with unrecgnized cirrhsis had HCC within Milan criteria at diagnsis," Dr. Stravitz said during his presentatin. Nt surprisingly, survival was clsely linked with the tumr stage at diagnsis, with mean survival fr stage I patients near 60 mnths and decreasing t a mean f 26 mnths fr stage II, 14 mnths fr stage II and 5 mnths fr stage IV. Quality f surveillance als significantly crrelated with whether a patient underwent liver transplantatin. While 32% f the standard-f-care grup received liver transplants, 13% f the substandard surveillance grup and 7% f the grup that had n surveillance received liver transplants (P <.001). Thse patients wh underwent liver transplantatin (n = 60) had a much greater increase in mean survival time cmpared with thse wh did nt receive liver transplants (n = 205), with 81% f thse receiving transplants having a mean survival f 3 years vs 12% fr thse nt transplanted (P <.001). Survival als crrelated significantly with quality f surveillance. "Mean 3-year survival

6 in patients wh received standard-f-care surveillance was 40% as cmpared t 27% in thse with substandard surveillance, but nly 12% in patients with unrecgnized cirrhsis," Dr. Stravitz said. Sessin cchair William Chapman, MD, cmmented t Medscape, "Even in ur best medical centers, surveillance prgrams fail frequently. Even amng transplant centers and physicians that treat patients with liver disease, we d nt have a systematic apprach t surveillance." Dr. Chapman is chief f the abdminal transplantatin sectin at Washingtn University Schl f Medicine in St. Luis, Missuri. "The big deal is catch them early s they are still candidates fr a curative therapy which is transplantatin," said Alan Hemming, MD, sessin cchair and chief f the divisin f transplantatin and hepatbiliary surgery at the University f Flrida in Gainesville. "But it's hit r miss even in ur prgram. Althugh we apply set criteria and patients get screened at set intervals, that interval may nt be adequate." Dr. Stravitz and clleagues were surprised t find that mre than 80% f patients wh did nt receive surveillance did have labratry markers fr cirrhsis that went unrecgnized. "The bttm line is if a physician sees labratry abnrmalities in a patient such as thrmbcytpenia, lw platelet cunt, an AST/ALT rati f greater than 1 and these may be subtle then that patient needs t be referred fr surveillance," he tld Medscape. The study was independently funded. The authrs reprt n relevant financial relatinships. 4. The cntributins f hepatitis B virus and hepatitis C virus infectins t cirrhsis and primary liver cancer wrldwide. Perz JF, Armstrng GL, Farringtn LA, Hutin YJ, Bell BP. Centers fr Disease Cntrl and Preventin, Natinal Center fr Infectius Diseases, Divisin f Viral Hepatitis, Epidemilgy Branch, Atlanta, GA 30333, USA. BACKGROUND/AIMS: End-stage liver disease accunts fr ne in frty deaths wrldwide. Chrnic infectins with hepatitis B virus (HBV) and hepatitis C virus (HCV) are well-recgnized risk factrs fr cirrhsis and liver cancer, but estimates f their cntributins t wrldwide disease burden have been lacking. METHODS: The prevalence f serlgic markers f HBV and HCV infectins amng patients diagnsed with cirrhsis r hepatcellular carcinma (HCC) was btained frm representative samples f published reprts. Attributable fractins f cirrhsis and HCC due t these infectins were estimated fr 11 WHO-based regins. RESULTS: Glbally, 57% f cirrhsis was attributable t either HBV (30%) r HCV (27%) and 78% f HCC was attributable t HBV (53%) r HCV (25%). Reginally, these infectins usually accunted fr >50% f HCC and cirrhsis. Applied t 2002 wrldwide mrtality estimates, these fractins represent 929,000 deaths due t chrnic HBV and HCV infectins, including 446,000 cirrhsis deaths (HBV: n=235,000; HCV: n=211,000) and 483,000 liver cancer deaths (HBV: n=328,000; HCV: n=155,000). CONCLUSIONS: HBV and HCV infectins accunt fr the majrity f cirrhsis and primary liver cancer thrughut mst f the wrld, highlighting the need fr prgrams t prevent new infectins and prvide medical management and treatment fr thse already infected. PMID: [PubMed - as supplied by publisher] 5. Systemic Therapy f Advanced Hepatcellular Carcinma: Hw Hpeful Shuld We Be? Andrew X. Zhu Massachusetts General Hspital Cancer Center, Harvard Medical Schl, Bstn, Massachusetts, USA The Onclgist, Vl. 11, N. 7, , July 2006; di: /thenclgist

7 Crrespndence: Andrew X. Zhu, M.D., Ph.D., Tucker Gsnell Center fr Gastrintestinal Cancers, Massachusetts General Hspital Cancer Center, 100 Blssm Street, Cx 640, Bstn, Massachusetts 02114, USA. Telephne: ; Fax: ; Received April 3, 2006; accepted fr publicatin May 10, ABSTRACT Wrldwide, hepatcellular carcinma (HCC) is the fifth mst cmmn cancer and the third mst cmmn cause f cancer-related death. In the U.S., 18,510 new cancers f the liver and intrahepatic bile duct are expected in 2006, with an estimated 16,200 deaths. The incidence rates fr HCC in the U.S. cntinued t rise steadily thrugh 1998 and dubled during the perid 1975ˆ1995. Unresectable r metastatic HCC carries a pr prgnsis, and systemic therapy with cyttxic agents prvides marginal benefit. A majrity f HCC patients (>80%) presents with advanced r unresectable disease. Even fr thse with resected disease, the recurrence rate can be as high as 50% at 2 years. Because f the pr track recrd f systemic therapy in HCC, there has been a sense f nihilism fr this disease in the nclgy cmmunity fr decades. Hwever, with the arrival f newly develped mlecularly targeted agents and the success f sme f these agents in ther traditinally challenging cancers, like renal cell carcinma, there has recently been renewed interest in develping systemic therapy fr HCC. This review attempts t cncisely summarize the histrical perspective and the current status f systemic therapy develpment in HCC. HepTalk is a prject f the Migrant Clinicians Netwrk and Cmmunity Health Educatin Cncepts. HepTalk is funded by the Centers fr Disease Cntrl and Preventin. The gal f HepTalk is t help clinicians serving migrants and recent immigrants engage in prductive discussins abut hepatitis risks with their clients and help them make preventin plans. The HepTalk listserv is a supprt service fr clinics participating in the prject. This is a pst-nly listserv and pstings will cme frm HepTalk staff abut nce a mnth. If thers at yur clinic wuld like t be n the listserv, r if yu have questins abut the listserv r resurces listed here, r if yu wuld like t add smething t the psts, please cntact Kathryn Andersn, HepTalk training and educatin crdinatr and listserv administratr, at dempander@earthlink.net. Yu can als cntact the listserv administratr if yu wuld like t unsubscribe frm the list.