Hepatotoxicity during legacy cancer chemotherapy in patients infected with hepatitis C virus: A retrospective cohort study.

BACKGROUND: The rates and causes of significant hepatotoxicity with cancer chemotherapy (CCT) in patients infected with hepatitis C virus (HCV) are incompletely characterized. METHODS: We compared rates of grade 3 or 4 hepatotoxicity, defined as elevated transaminases, during CCT in patients who are mono-infected with HCV compared with rates in controls matched on demographics, diagnosis, and rituximab use. We excluded patients with hepatobiliary cancers, hepatitis B virus or human immunodeficiency virus infection. Hepatotoxicity was attributed to a medical cause, cancer progression, or CCT, including HCV flare. RESULTS: Patients with HCV (n = 196) had a higher rate of cirrhosis than the 1,130 matched controls (21.9% versus 4%; P <0.001). Their higher rate of overall hepatotoxicity (8.7% versus 4.5% of controls, P = 0.01) was due to higher rate of CCT-related hepatotoxicity (4.1% versus 1.2%, P = 0.01). On multivariable analysis, the largest risk factor for overall hepatotoxicity was cirrhosis, and the only risk factor for CCT-related hepatotoxicity was HCV infection. Among those with HCV, the only significant risk factor for hepatotoxicity was rituximab use. Hepatotoxicity caused by CCT delayed or altered treatment in only 3 HCV patients and 1 control (1.5% versus 0.1%, P = 0.01). CONCLUSIONS: Most patients with HCV can safely be treated with cancer chemotherapy. Cirrhosis and HCV infection contributed to increased hepatotoxicity in subjects on CCT. Among HCV patients, rituximab use was the major risk factor for increased hepatotoxicity. Hepatotoxicity due to CCT itself rarely altered or delayed CCT. Nonetheless, HCV-positive patients should be monitored carefully during CCT.

Iron deficiency and symptoms in women aged 20-49 years and relation to upper gastrointestinal and colon cancers.

OBJECTIVE: Iron deficiency anaemia (IDA) in women aged 20-49 years may be caused by menses or gastrointestinal cancer. Data are sparse on the yield of endoscopy/colonoscopy in this population. Our aim was to determine the association of IDA and symptoms with cancers. DESIGN: Retrospective cohort study within Kaiser Permanente Northern California. Participants were women aged 20-49 years tested for iron stores and anaemia during 1998, 2004 and 2010 and followed for 5 years for outcomes of oesophageal, gastric and colon cancers. Symptoms from the three prior years were grouped into dysphagia, upper gastrointestinal (UGI), lower gastrointestinal (LGI), rectal bleeding and weight loss. RESULTS: Among 9783 anaemic women aged 20-49 years, there were no oesophageal, 6 gastric and 26 colon cancers. Incidences per 1000 for gastric cancer with and without iron deficiency (ID) were 0.60 (95% CI 0.23 to 1.55) and 0.63 (95% CI 0.17 to 2.31), and for colon cancer, 2.72 (95% CI 1.72 to 4.29) and 2.53 (95% CI 1.29 to 4.99). Endoscopies for UGI or dysphagia symptoms rather than bidirectional endoscopy for ID yielded more gastric cancers (n=5 and n=4, respectively) with fewer procedures (3793 instead of 6627). Colonoscopies for LGI or rectal bleed instead of for ID would detect more colon cancers (n=19 and n=18) with about 40% of the procedures (=2793/6627). CONCLUSIONS: UGI and colon cancers were rare in women of menstruating age and when controlled for anaemia were as common without as with ID. Using symptoms rather than IDA as an indication for endoscopy found equal numbers of cancers with fewer procedures.

Management of Incidentally Detected Gallbladder Polyps: Society of Radiologists in Ultrasound Consensus Conference Recommendations.

Gallbladder polyps (also known as polypoid lesions of the gallbladder) are a common incidental finding. The vast majority of gallbladder polyps smaller than 10 mm are not true neoplastic polyps but are benign cholesterol polyps with no inherent risk of malignancy. In addition, recent studies have shown that the overall risk of gallbladder cancer is not increased in patients with small gallbladder polyps, calling into question the rationale for frequent and prolonged follow-up of these common lesions. In 2021, a Society of Radiologists in Ultrasound, or SRU, consensus conference was convened to provide recommendations for the management of incidentally detected gallbladder polyps at US. See also the editorial by Sidhu and Rafailidis in this issue.

Survey Study on the Experience, Practice Patterns, and Preferences of the Fellows of the Society of Radiologists in Ultrasound for Evaluation and Management of Gallbladder Polyps Detected With Ultrasound.

ABSTRACT: Gallbladder polyps (GPs) are a common incidental finding on ultrasound; however, important differences in recommended management exist among professional society guidelines.An electronic survey was sent to 189 fellows of the Society of Radiologists in Ultrasound. Main outcomes included preferences and current practice patterns for evaluation, management, and surveillance of GPs as well as personal lifetime experience with gallbladder sonography and GPs.A total of 64 subjects (34%) with experience in gallbladder sonography completed the study. The estimated combined total number of gallbladder scans seen by the responders was 3,071,880. None of fellows had ever seen a pedunculated GP <1 cm detected on ultrasound that was proven to be malignant at the time of detection or during subsequent follow-up. All of the fellows used size as a feature to stratify recommendations. The median size threshold currently used by Society of Radiologists in Ultrasound fellows for recommending ultrasound follow-up was 6 mm, and their preferred threshold was 7 mm. The median size threshold for recommending surgical consultation was 10 mm, and the preferred threshold was 10 mm. Wall thickening and shape were considered important factors by 76% and 67% of respondents, respectively.Society of Radiologists in Ultrasound fellows tend to provide recommendations most similar to the American College of Radiology and Canadian Association of Radiology guidelines for management of GPs. Many would prefer guidelines that result in fewer recommendations for follow-up and surgical consultation. Despite a substantial combined experience, this survey did not uncover any case of a small GP that was malignant.

Outcomes of Gallbladder Polyps and Their Association With Gallbladder Cancer in a 20-Year Cohort.

Importance: Gallbladder polyps (GP) are found in more than 4% of adult abdominal ultrasonographs. Their growth pattern and association with gallbladder cancer (GBC) are poorly defined. Objective: To determine the growth pattern of GPs and their association with GBC. Design, Setting, and Participants: This cohort study included 622 227 adult members (ie, aged 18 years or older) of Kaiser Permanente Northern California, an integrated health care delivery system, enrolled between January 1, 1995, and December 31, 2014. The GBC cohort comprised a total of 365 adults with GBC and prior ultrasonography, and the GP cohort comprised 35 970 adults with GPs present on ultrasonography. Data analysis was performed from March 2016 to November 2019. Exposures: Gallbladder polyps (quantitative size, <6 mm, 6 to <10 mm, and ≥10 mm or qualitative size [ie, tiny, small, moderate, and large]). Main Outcomes and Measures: For the GBC cohort, proportion of patients with GBC with polyps identified on preceding ultrasonograph. For the GP cohort, rates of GBC among those with polyps according to size and rate of GP growth of at least 2 mm over time. Results: The GBC cohort comprised 365 individuals (267 [73.1%] women; 173 [47.4%] white patients; median [interquartile range] age, 71 [61-79] years). After excluding 14 patients who did not have evaluation of polyp size, the final GP cohort comprised 35 856 adults, with 18 645 (52.0%) women, a median (interquartile range) age 50 (40-60) years, and 15 573 (43.3%) white patients. Gallbladder polyps were found in 22 patients (6.0%) in the GBC cohort and in 35 870 of 622 227 adults (5.8%) who underwent abdominal ultrasonography. Of these, 19 (0.053%) were diagnosed with GBC, similar to those without GP (316 of 586 357 [0.054%]). The unadjusted GBC rate per 100 000 person-years was 11.3 (95% CI, 6.2-16.3) overall and increased with polyp size, from 1.3 (95% CI, 0-4.0) with initial size of less than 6 mm (n = 17 531) to 128.2 (95% CI, 39.4-217.0) with initial size of 10 mm or larger (n = 2055). In those observed for at least 1 year, the rate was 3.6 (95% CI, 0.7-6.5) per 100 000 person-years. In 6359 patients with evaluable follow-up, unadjusted cumulative probabilities of polyp growth of at least 2 mm at 10 years were 66.2% (95% CI, 62.3%-70.0%) in polyps initially less than 6 mm and 52.9% (95% CI, 47.1%-59.0%) in polyps initially 6 mm to less than 10 mm. Conclusions and Relevance: In this study, GBC rates were low and similar among patients with and without GPs. Growth of 2 mm or more appeared to be part of GP natural history. The results call into question the strategy of proactively following GP to detect GBC.

Incidence of Hepatitis B Virus Reactivation and Hepatotoxicity in Patients Receiving Long-term Treatment With Tumor Necrosis Factor Antagonists.

BACKGROUND & AIMS: Tumor necrosis factor (TNF) antagonists are the first-line treatment for many autoimmune diseases. However, they have been associated with reactivation of hepatitis B virus (HBV). We determined the rate of HBV reactivation and hepatotoxicity grade 3 or 4 (HT ≥3) in patients treated with an anti-TNF agent for an autoimmune disease. METHODS: We collected data from 8887 adult patients in the Kaiser Permanente Northern California database who began treatment with TNF antagonists for autoimmune diseases (dermatologic, rheumatologic, or gastrointestinal) from 2001 through 2010, followed through December 2012. We obtained data on HBV infection (52% of patients were screened for HBV before treatment), demographic features, comorbidities, and use of immunosuppressive agents. HBV reactivation was defined as 1 of the following: >1 log increase in HBV DNA, HBV DNA-positive when previously negative, HBV DNA >2000 IU/mL if no baseline level was available, or reverse seroconversion. HT ≥3 was defined according to the National Cancer Institute Common Toxicity Criteria. We performed multivariable logistic regression to identify factors associated with HT ≥3. RESULTS: Twenty-three patients tested positive for HB surface antigen (HBsAg) at baseline and 9 of these had HBV reactivation; of the 4267 patients with unknown HBV status at baseline, 2 had HBV reactivation. None of the 178 patients who were HBsAg negative and positive for the hepatitis B core antibody (anti-HBc+) had HBV reactivation. HBV reactivation occurred in 1/5 HBsAg+ patients who received prophylactic antiviral therapy and 8/18 who did not (P = .61). No one with HBV reactivation had liver failure. HT ≥3 occurred in 273 patients (2.7%), but only 3 cases were attributed to HBV. Cirrhosis was significantly associated with HT ≥3 (P < .001). CONCLUSION: In a retrospective analysis of patients treated with TNF antagonists for autoimmune diseases, we found HBV reactivation in 39% of patients who were HBsAg+ before therapy, but not in any patients who were HBsAg-negative and anti-HBc+ before therapy. Patients should be screened for HBV infection before anti-TNF therapy; HBsAg+ patients should receive prophylactic antiviral therapy, but not HBsAg-negative, anti-HBc+ patients.

Rate of seeding with biopsies and ablations of hepatocellular carcinoma: A retrospective cohort study.

Biopsies of liver masses that prove to be hepatocellular carcinomas (HCCs) are associated with a risk of seeding the abdominal or chest wall with tumor cells. The reported frequency of seeding varies greatly in the literature. We performed a retrospective cohort study in a large integrated health care system to examine rates of seeding in patients with HCC who had targeted liver biopsies, ablations, or both performed by community radiologists. We reviewed pathology and radiology records to determine the occurrence of wall seeding, defined as a chest or abdominal wall lesion along a definite or probable needle tract. A total of 1,015 patients had targeted liver biopsies (795), ablations (72), or both (148). Multiple procedures were done in 284 patients (28%). Six cases of seeding were identified. The rate of wall seeding was 2/795 patients (0.13%; 95% confidence interval [CI], 0.00%-0.60%) if only biopsies were done versus 4/220 (1.82%; 95% CI, 0.05%-3.58%) if ablations were performed (P = 0.01). The rate was 0/72 (0.00%; 95% CI, 0.00%-0.04%) with ablations alone and 4/148 (2.70%; 95% CI, 0.74%-6.78%) if both procedures were done (P = 0.31). Of those with 1 year follow-up (n = 441), the rate of seeding was 2/269 (0.74%; 95% CI, 0.00%-1.77%) if biopsies alone were done and 4/172 (2.33%; 95% CI, 0.07%-4.58%) if ablations were done. In none of the cases was the seeding a proximate cause of death. Conclusion: Biopsies of liver masses are associated with a low rate of wall seeding when performed in a community setting and when they are the sole procedures. Ablations may have a higher rate of seeding, particularly if done with biopsies, but are still rare. (Hepatology Communications 2017;1:841-851).

Causes of death in patients with hepatitis B: a natural history cohort study in the United States.

UNLABELLED: The natural history of hepatitis B virus (HBV) infection in a U.S. population has not been well described. We identified the causes of death in 6,689 health plan members infected with HBV who were followed between March 1, 1996 and December 31, 2005. Causes of death were grouped into HBV-related (subdivided into decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]), cancer, cardiovascular, and other/unknown. The study cohort included 3,244 females and 3,445 males; 68.3% were of Asian-Pacific Islander (API) descent, 11.8% were white (non-Hispanic), and 19.9% were of other or unknown race. Exposure to HBV antivirals and preexisting comorbidities were uncommon. Males had higher overall 10-year death rates than females, both for total deaths (8.9% versus 4.1%) and for HBV-related deaths (4.8% versus 1.2%). The death rate rose markedly with increasing age, and approximately 40% of all deaths in subjects over the age of 40 were HBV related. The death rate from HCC was twice that of DCC. HCC deaths represented 70% of cancer deaths in males and 37% in females. On multivariable analysis, when subjects with antecedent HCC and DCC were excluded, the only significant predictor of HBV mortality in both sexes was age. CONCLUSION: HBV was the cause of death in over 40% of those who died during the study, and the mortality increased markedly with increasing age over 40 in males and over 50 in females. HBV-related mortality was four times more common in males than in females and was as common in non-Asians as in those of API origin. HBV-related deaths were twice as common from HCC as from DCC.

Prescribing proton pump inhibitors for initial treatment of acid-related gastrointestinal diseases in a managed care population.

OBJECTIVE: To determine whether health services use by patients with selected acid-related gastrointestinal disorders (peptic ulcer disease, gastroesophageal reflux disease, and gastritis or dyspepsia) is lower after initial treatment with proton pump inhibitors (PPIs) than with histamine2 receptor antagonists (H2RAs). STUDY DESIGN: Retrospective, 2-year longitudinal study. PATIENTS AND METHODS: Among continuous enrollees from December 1, 1996, to June 1, 2002, in a group model health maintenance organization, 13,971 members were electronically selected who began receiving antisecretory therapy during that period and who had no previous drug therapy, endoscopy, or hospitalization for gastrointestinal disease. Adjusted medical costs and healthcare use related to gastrointestinal disease (measured by office visits, endoscopy, or imaging and hospital admissions) and factors associated with initial and subsequent drug therapy were analyzed using a 2-stage model. This method adjusted for unobservable confounders, primarily drug selection bias, an inherent limitation of retrospective database studies. RESULTS: Drug costs were more than 4-fold higher (P < .001) when PPIs rather than H2RAs were prescribed initially, but non-drug costs and health services use showed no decrease. A history of physicians' prescribing PPIs in the prior 12 months was associated with prescribing PPIs as initial therapy (odds ratio, 4.29; 95% confidence interval, 3.74-4.90) and with step-up therapy (change from H2RAs to PPIs). A history of physicians' prescribing H2RAs in the prior 12 months was associated with step-down therapy (change from PPIs to H2RAs). CONCLUSION: Prescribing PPI compared with H2RA therapy as initial therapy for acid-related gastrointestinal disease produced no decrease in nondrug costs or health services use.